Speciality
Spotlight

 




 


Cardiology


 


   





  • Tunio
    AS, Hingorani A, Ascher E

    The
    Impact of an Occluded Internal Carotid Artery on the
    Mortality and Morbidity of Patients Undergoing
    Coronary Artery Bypass Grafting



    Amer
    J Surg 178: 201-205


       

    Stroke
    is a major problem in patients undergoing coronary
    artery bypass grafting [CABG]. Although other
    mechanisms may be involved, concomitant carotid
    artery disease is likely major contributor to
    perioperative stroke.
    The effects of internal carotid artery [ICA]  stenosis or occlusion on perioperative stroke rate and
    mortality among patients with CABG were analyzed.

           

    The retrospective study included 3344 patients
    undergoing CABG at one center over 3.5 years [59% of the patients were men]. In each case a
    preoperative duplex scan of the carotid artery was
    available for review.
    About 93% of the patients had ICA stenosis
    less than 60% [ Group A]; 5% had ICA stenosis of 60
    to 99% [Group B]; and 2% had total ICA occlusion
    [Group C]. Further in group C, 87% of the patients
    had in addition 60% stenosis of the contralateral
    ICA and the rest had stenosis of 60% to 99%. In
    Group B 40% of the patients, and in Group C 3% of
    the patients, underwent concomitant carotid
    endarterectomy [CEA] along with CABG.

       

    The 3 groups were comparable in terms of age,
    surgical indications, diabetes, hypertension, and
    smoking.
    The mean pump time was 125 to 138 minutes and
    the aortic cross clamp time was 75 to 78 minutes.
    Thirty day stroke rate was 1.6% in Group A;
    3.8% in Group B, and 6.5% in Group C. Within Group
    C, the perioperative stroke rate was 25% for
    patients with contralateral stenosis compared with
    3.8% for those without contralateral stenosis.
    Among patients undergoing concomitant CEA for
    severe stenosis in the contralateral ICA, the stroke
    rate was 100% in Group C versus 4.2% in Group B.
    Thirty day mortality was 3.6% in Group A, 6.6% in  Group B and  8.6% 
    in  Group
    C.

       

    The presence of concomitant ICA stenosis in patients
    undergoing CABG, is associated with increased
    perioperative morbidity and mortality.
    This is the first large study of the effects
    of ICA occlusion on 
    CABG. The
    findings support the safety of simultaneous CEA and
    CABG.

       

  • White
    CM, Dunn A, Tsikouris J, et al [Hartford Hospital,
    Conn., Univ of Connecticut, Storrs]


    An
    Assessment of the Safety of Short-Term Amiodarone
    Therapy in Cardiac Surgical Patients with Fentanyl
    Isoflurane Anesthesia



    Anesth Analg 89: 585-589, 1999


       

    Chronic
    amiodarone use, in combination with fentanyl
    anesthesias, may cause atrioventricular blockade,
    symptomatic bradycardia, sinus arrest, and severe
    hypotension. The
    effect of short-term amiodarone use has not been
    investigated. The
    effect on hemodynamics of fentanyl-containing
    anesthesia, administered to elderly patients
    receiving short-term amiodarone therapy before
    coronary artery bypass graft [CABG] or vascular
    surgery, was investigated in a prospective,
    randomized, double-blind, placebo-controlled trial.

        

    Elderly
    CABG patients were randomly allocated to receive
    amiodarone 3.4 g over 5 days, or 2.2 g over 24 hours
    [n=45] or placebo [n=39], before CABG. Fluid balance, use of dopamine, use of vaso-pressor catecholamines,
    and use of phospho- diasterase inhibitor or
    intra-aortic balloon pump were recorded.
    Systolic, diastolic and central venous
    pressures were measured, before anesthesia, before
    cardiopulmonary bypass [CPB] and after CPB.
    Heart rates were recorded before induction of
    anesthesia and after CPB.

        

    Results
    showed fluid status increase by 2L in 2 [4.4%]
    amiodarone patients and in 4 [10.3%] placebo
    patients. No
    patient required dopamine or an intra-aortic baloon
    pump. Epinephrine or derivative was administered to
    8 [17.8%] amiodarone and 5 [12.8%] placebo patients
    and milrinone to 1 [2.2%] amiodarone and 2 [5.1%]
    placebo patients. Preanesthesia and post PCB
    systolic blood pressure, were significantly lower in
    amiodarone patients.
    Further, amiodarone patients received less
    fluid and had a lower net increase in fluid status,
    than the placebo patients, although the differences
    were not significant.

        

    Thus
    short term amiodarone therapy does not lead to
    hemodynamic instability in CABG patients receiving
    fentanyl anesthesia regimens.

      
         

  • Westaby
    Stephen, Banning Adrian P, et al [ Oxford Heart Centre, John
    Radciliffe Hospital, Oxford ]


    First permanent implant of the Jarvik 2000 Heart

    The
    Lancet [ Vol-356], Number-9233, 9 September, 2000, Pg. No – 900


       

    In
    patients with heart failure, implantation of the Jarvik 2000 heart
    improves all the abnormalities significantly. After six weeks, there
    is a improvement in exercise tolerance, myocardial function and
    endorgan function. Symptoms of heart failure are reversed and there
    are no adverse effects in the short term. The device is very small
    and is implanted  in  the skull with electrical connection which controls the
    pumping device situated in the heart.

      

  • Presented
    at XII International symposium
    on Atherosclerosis, Stockholm, Sweden.


    Superstatin boosts Astra Zeneca

    Scrip
    no.2554, July 5, 2000, p.18


        

    Rosuvastatin
    (ZD4522) is the most potent cholesterol lowering agent known. 
    It lowers LDL cholesterol by 65% as compared to 25% by
    current statins.

       

    It
    does not produce hepatotoxicity or myotoxicity.
    Liver enzymes and CPK remain normal.
    It has a long half-life (once a day dosing). 
    Rosuvastatin is not metabolised by the liver.

        

  • JS
    Davies, MF Scanlon (Univ of Wales, Cardiff)  

    Hypopituitarism After
    Coronary Artery Bypass Grafting
    . 

    BMJ 316: 682-685, 1998.


        

    Silent
    pituitary infarction may be present after coronary artery bypass
    grafting (CABG).  Increased
    awareness of this uncommon condition should facilitate earlier
    treatment.

         

  • N
    Fuenmanyor, E Moreira, LX Cubeddu, (Central Univ of Venezuela,
    Caracas)


    Salt Sensitivity is Associated
    with Insulin Resistance in Essential Hypertension.

    Am
    J Hypertens 11: 397-402, 1998.


        


    Patients with essential hypertension may be salt sensitive or salt
    resistant.
    Hypertension in salt sensitive patients is associated with
    insulin resistance. In salt
    sensitive patients, high salt intake leads to increase in blood
    pressure, induced hyperinsulinemia, and worsening of diabetes.

       

  • R
    Locher, PM Suter, W Vetter (Univ Hosp, Zurich, Switzerland)


    Ethanol Suppresses Smooth
    Muscle Cell Proliferation in the Postprandial State: 
    A
    New
    Antiatherosclerotic Mechanism of Ethanol?

    Am
    J Clin Nutr 67 : 338-341, 1998


       

    It
    is known that smooth muscle cell proliferation in the postprandial
    state (after food) may lead to narrowing of arteries.
    It is well known that ethanol (alcohol) raises HDL
    cholesterol and thereby gives protection against atherosclerosis and
    heart attack. It now appears
    that ethanol (alcohol) also suppresses the proliferation of smooth
    muscle cells and thereby gives additional protection in patients
    against atherosclerosis.

       

  • Arrowsmith
    J, Usganocar RP, Dickson WA [Morrston Hosp. Swansea UK]


    Electrical Injury and Frequency of Cardiac Complications
     


    Burns 23 : 576-578, 1997


       


    Cardiac abnormalities caused by electrical injury are most often
    apparent at the time of injury. They can also develop later, and 24
    hour cardiac monitoring has recommended for patients with electrical
    injuries. Patients who became unconscious after injury and those
    with high voltage injuries were more prove to cardiac complications.

       


    Analysis finds a 3% rate of cardiac abnormalities among patients
    with electrical injuries. For patients who did not lose
    consciousness at the time of injury and who have normal admission
    ECG, cardiac complications are unlikely to develop later.

        

  • Gilles
    Dreyfus, Sherban Mihealainu (Universite Paris V, France)

    The Batista Procedure – Editorial

    Heart 2001; 85: 1-2

           

    Until recently refractory congestive heart failure under optimum
    medical treatment would only be treated surgically by heart
    transplantation. The increasing number of such options of heart
    failure, lack of heart donors and the very high mortality rate of
    10-20% on problems associated with transplantation have prompted a
    search for possible alternative options.

          

    Of the ischaemic cardiomyopathies some good options are available.
    The most practical and easily available option is myocardial
    revascularization with either a bypass surgery or angioplasty.
    However, a new option is now available of performing mitral valve
    repair to correct mitral regurgitation, which is common in failing
    hearts. One of the reasons for refractoriness of the heart failure
    is the waste of effort caused by mitral regurgitation. Correction of
    mitral regurgitation has excellent results. The operative mortality
    is very low less than 2%. Survival rates are excellent 92% surviving
    for 1year and 72% at 2 years.

        

    The problem really is dilated cardiomyopathy. Although correction of
    mitral regurgitation gives some improvement, it is not adequate.
    Resection of myocardium to reduce the left ventricular cavity
    combined with the mechanical support of a left Ventricular Assist
    Device gives better results. The procedure is still under trial.

        

  • Ian
    B Wilman, David J Webb, et al (Dept of Cardiology, Univ
    Wales College of Medicine, UK)

    Isolated systolic hypertension: a radical rethink.

    BMJ No.7251, June 24, 2000,pg.1685.

         

    The association between hypertension and a ‘hardening’ of the pulse
    and apoplexy has been recognised for hundreds of years. Isolated
    systolic hypertension affects around half of people aged over 60
    years. It confers a substantial cardiovascular risk. Despite this,
    it remains underdiagnosed, and largely untreated, but the benefits
    of treatment are established.

       

    The relative risk reduction of cardiovascular events in elderly
    people with isolated systolic hypertension is similar to that in
    younger people. However, as elderly people are at much higher
    absolute risk of such events, they stand to benefit more from
    treatment than younger people. Elderly people tolerate
    antihypertensive drugs with few side effects.

         

    The latest WHO and International Society for hypertension guidelines
    for management of hypertension emphasise the importance of arterial
    stiffness and pulse pressure as predictors of cardiovascular risk
    and call for further indices of arterial stiffness.

      

  • Lars
    Kober, Poul Erik Bloch et al

    Effect of Dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomized trial.

    Lancet, vol.356, Dec.16, 2000. Pg.2052-2057.

        

    Dofetilide, a new class III antiarrhythmic agent, selectively
    inhibits the rapid component of the delayed potassium current, which
    prolongs refractory period. It does not affect cardiac conduction or
    sinus-node function. It is effective in supraventricular
    arrhythmias.

       

    Arrhythmias cause much morbidity and mortality after MI, but in
    previous trials, antiarrhythmic drug therapy has not been
    convincingly effective. Dofetilide was investigated for effects on
    all cause mortality and morbidity in patients with LV dysfunction
    after MI.

       

    Treatment with dofetilide did not affect all-cause mortality,
    cardiac mortality or total arrhythmic deaths. It was effective in
    treating atrial flutter or fibrillation in patients with severe LV
    dysfunction and recent MI.

       

  • The
    ESPRIT investigators


    Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised placebo-controlled trial.



    Lancet, vol.356, Dec.16, 2000, pg. 2037-2044


        

    The platelet glycoprotein IIb/IIIa inhibitors, although effective in
    reducing ischaemic complications of percutaneous coronary
    intervention, are used in few coronary stent implantation
    procedures. ESPRIT is a randomized placebo-controlled trial to
    assess whether a novel, double-bolus dose of eptifibatide could
    improve outcomes of patients undergoing coronary stenting.

       

    Authors recruited 2064 patients undergoing stent implantation – they
    were randomly allocated to receive eptifibatide, given as two 180
    mg/kg boluses 10min. apart and a continuous infusion of 2 mg/kg/min
    for 18-24 hrs. or placebo, in addition to aspirin, heparin and a
    thienopyridine.

       

    It was observed that routine glycoprotein IIb/IIIa inhibitor
    pretreatment with eptifibatide substantially reduces ischaemic
    complications in coronary stent intervention and is better than a
    strategy of reserving treatment to the bailout situation.

       

  • D
    Monkman, East Barnet Health Centre, Hertfordshire

    Treating dyslipidaemia in primary care – The gap between policy and reality is large in the UK.

    BMJ, 25 November,2000, 321(7272), 1299-1300

       

    The consensus that cholesterol is an important reversible risk
    factor for coronary heart disease was reached only comparatively
    recently as a result of studies published in 1994 and 1995. Cost
    considerations in the NHS in UK have limited the use of statins to
    individuals who are at highest risk and the accepted policy is to
    test cholesterol concentrations only when additional risk factors
    are present.



    The ratio of total cholesterol to HDL cholesterol allows the risk of
    coronary heart disease to be calculated for individuals who are
    being considered for primary prevention. Most primary care
    physicians do not perform 3 cholesterol measurements ( one random
    measurement followed by 2 fasting measurements ) when assessing
    patients.

       

  • Marco
    Pahor, Bruce M Psaty, et al (Department of Internal Medicine and
    Department of Public Health Sciences, USA

    Health Outcomes Associated with Calcium Antagonists compared with other First-line Antihypertensive Therapies: a Meta-Analysis of Randomised Controlled Trials.

    Lancet, vol.356, 9 December 2000, pg.1949-1954.

      

    Several randomised trials in hypertension have suggested that
    compared with other drugs, calcium antagonists may be associated
    with a higher risk of coronary events, despite similar blood
    pressure controls. This meta-analysis was carried out to compare the
    effects of calcium antagonists and other antihypertensive drugs on
    major cardiovascular events.

       

    Authors carried out a meta-analysis of trial in hypertension that
    assessed cardiovascular events and included at least 100 patients,
    who were randomly assigned to intermediate-acting or long-acting
    calcium antagonists or other antihypertensive drugs and who were
    followed up for at least 2 years.

       

    The conclusion of this meta-analysis was that in randomised
    controlled trials, calcium antagonists are inferior to other types
    of antihypertensive drugs as first-line agents in reducing the risks
    of several major complications of hypertension. On the basis of
    these data, the long-acting calcium antagonists cannot be
    recommended as first-line therapy for hypertension.

       

  • Blood
    pressure lowering treatment-Trialists Collaboration

    Effects of ACE inhibitors, calcium antagonists, and other blood pressure-lowering drugs: results of prospectively desgined overviews of randomised trials.

    Lancet : vol.356, December 9, 2000, p.1955-64

        

    This programme of overviews of randomised trials was established to
    investigate the effects of ACE inhibitors, calcium antagonists and
    other BP lowering drugs on mortality and major cardiovascular
    morbidity. Separate overviews of trials comparing active treatment
    regimens with placebo, trials comparing more intensive and less
    intensive BP lowering strategies, and trials comparing treatment
    regimens based on different drug classes were done.

       

    The interpretation is that there was strong evidence of benefits of
    ACE inhibitors and calcium antagonists as compared to placebo. There
    is weaker evidence of differences between treatment regimens of
    differing intensities and of differences between treatment regimens
    based on different drug classes.

       

    Commentary: Selection of initial anti-hypertensive drug therapy.

    The study done by Blood Pressure Lowering Treatment (BPLT)
    Trialist’s Collaboration (BPLT) has several methodological
    strengths. The effect of ACE inhibitors on cardiovascular disease
    was impressive and was achieved in the context of small difference
    in BP (3/1 mm Hg) between ACE inhibitor and placebo groups. This
    finding raises the possibility that the beneficial effects of ACE
    inhibitors on cardiovascular disease in the trials were mediated not
    just through the lowering of BP.

       

    There has been intensive debate over the balance between the
    potentially beneficial and detrimental effects of calcium
    antagonists in cardiovascular disease. Overall, the data of BPLT
    provide evidence that calcium antagonists reduce the incidence and
    mortality from cardiovascular disease.

        

    The meta-analysis of Marco Pahor and colleagues focussed specially
    on comparison of calcium antagonists, with diuretics, beta-blockers,
    ACE inhibitors or clonidine.

        

    (1) Diuretics or beta-blockers may be used initially for
    uncomplicated hypertension.

       

    (2) ACE inhibitors -initial choice especially in patients at high
    risk of heart failure.

       

    (3) Caution- for use of calcium antagonists as initial therapy in
    populations at high risk of CHD and heart failure (i.e. Western
    populations).

       

    (4) Calcium antagonists – may be used as initial therapy in patients
    at high-risk of stroke and low risk of CDH (i.e. Asian population).

        

    (5) If more than one drug needs to be used – combination of
    diuretics, beta-blockers, ACE inhibitors or calcium antagonists,
    based on patient’s absolute level of risk for cause-specific
    cardiovascular disease.

       

  • M.I.Phillips,
    S.M. Galli, J.L. Mehta (Department of Physiology and Medicine,
    College of Medicine, University of Florida, Gainesville, Florida,
    USA).

    The Potential Role of Antisense Oligodeoxynucleotide Therapy for Cardiovascular Disease.

    Drugs Aug 2000, 60(2), 239-248.

       

    Sense is a faculty by which conditions or properties are perceived.
    Antisense technology uses preparation of oligodeoxynucleotides. An
    antisense oligodeoxynucleotide (AS-ODN) is a single stranded
    synthetic DNA with a modification and a specific sequence to
    hybridise to a specific messenger RNA (mRNA) and prevent
    translation. So, AS-ODNs are structural modifications which prevent
    normal cell ribosomal translation of mRNA.

       

    Current drugs used in treatment of cardiovascular disease are
    effective but they act for hours or one day. Antisense inhibition is
    being developed for treatment of hypertension, myocardial ischaemia
    and improved allograft survival in human vascular bypass grafts.

        

    AS-ODNs are delivered nonvirally or antisense DNA is delivered in
    viral vectors to inhibit genes associated with vasoconstrictive
    properties. In hypertension, it is known which genes need to be
    controlled. AS-ODN are short, single-stranded DNA that can be
    injected as such or in liposomes. AS-ODN targeted to angiotension
    type 1 (AT1) receptors, angiotensinogen (ATG), angiotensin
    converting enzyme (ACE) and beta-1 receptors effectively reduce
    hypertension in rat models. A single dose is effective for up to 1
    month when delivered with liposomes, No adverse or toxic effects are
    detected and repeated injections are effective.

       

    For viral delivery, adeno-associated virus (AAV) and cytomegalovirus
    are used along with a DNA to ATG, ACE or AT1 receptors. Results in
    rats and transgenic mice show significant prolonged reduction in
    hypertension with a single dose. Left ventricular hypertrophy is
    also reduced.

        

    AS-ODNs to AT1 receptors, ATG and beta-1 receptors provide
    cardioprotection from the effects of myocardial ischaemia 

      

  • Shaffer
    KM, Mullins CE, Grifka RG, et al [ Baylor College of Medicine,
    Houston; Texas Children’s Hospital, Houston]

    Intravascular Stents in Congenital Heart Disease: Short and Long-Term Results From a Large Single-Center Experience

    J Am Coll Cardiol 31: 661-667, 1998

        

    Intravascular stents for the treatment of patients with congenital
    heart disease and vascular stenoses were evaluated by Food and Drug
    Administration [FDA] phase 1 and 2 clinical trials at Texas
    Children’s Hospital. Results of only FDA-approved investigational
    device exemption study of balloon-expandable stents in patients with
    congenital heart disease and vascular stenoses were reported.

        

    All patients enrolled in the study had stenoses requiring treatment.
    Stents were placed in 3 groups of patients: those with postoperative
    pulmonary artery [PA] stenoses, congenital PA stenoses, and stenoses
    of systemic veins/venous anastomoses. A total of 347 stents were
    placed in 200 patients between September 1989 and June 1995. The
    Palmaz stent was used in all cases. Median patient age at
    implantation was 10.5 years. Data were collected before and after
    stent implantation and at follow-up.

          

    All three groups showed marked fall in gradients across the stenoses,
    and marked increase in vessel diameters. Right ventricular pressure
    decreased in both congenital as well as postoperative pulmonary
    stenoses, and perfusion to the lungs increased considerably. The
    changes were seen steady at follow-up catheterization done at a mean
    of 14 months after implantation. There were 4 cases of stent
    migration in the earlier cases and three patients had restenosis.
    Two deaths were directly attributed to stent implantation.

         

    Intravascular stents proved to be safe and effective in the
    management of PA stenoses and other vascular anastomoses; there is
    no long-term morbidity and the favourable results appear immediately
    and continue into follow-up.

        

  • Daniels
    CJ, Cassidy SC, Teske DW, et al [ Columbus Children’s Hospital and
    Ohio State Univ, Columbus]

    Reopening After Successful Coil Occlusion for Patent ductus Arteriorus

    J Am Coll Cardiol 31: 444-450, 1998

        

    A study of children who had undergone successful coil occlusion of
    patent ductus arteriorus [PDA] was conducted to determine the
    frequency of reopening and the factors that may predict reopening.

       

    The patients underwent percutaneous transarterial PDA coil
    occlusion. The length and diameter of PDAs were determined.Doppler
    echocardiography was performed within 24 hours of coil occlusion to
    document success. Patients were reevaluated at 12 months.

       

    Coil occlusion was performed in 22 children with a median age of 4.9
    years. Clinical success with loss of continuous murmur was achieved
    in 91% and in 90% doppler echocardiography was negative for PDA
    shunting. Five patients [22%] were seen to have reopening at
    follow-up. These patients had larger minimal diameter of 1.4 mm vs
    1.2 mm and shorter PDA length 2.9 mm vs 7.1 mm. Angiographic
    appearance in 3 of these patients showed type B PDA [conical with
    short ductal ampulla].

        

    Thus despite successful coil occlusion for PDA, reopening is common.
    Previous reports have indicated that success is associated with
    minimal diameter of the PDA. In particular failure may occur with a
    wide-diameter and short length PDA. Angiographic type B PDA is also
    associated with reopening. 

      

  • PreitoLR,
    DeCamillo DM, Konrad DJ, et al [ Cleveland Clinic Found, Ohio]

    Comparison of Cost and Clinical Outcome Between Transcatheter Coil Occlusion and Surgical Closure of Isolated Patent Ductus Arteriorus

    Pediatrics 101: 1020-1024, 1998

        

    Transcatheter closure of patent ductus arteriorus [PDA] using
    Gianturco coils was retrospectively compared to surgical repair at
    Cleveland Clinic Foundation.

       

    Procedural and recovery costs for 36 patients, aged 13 months to 28
    years, who had coil or surgical closure of PDA between 1993 and
    1996, were determined and compared.

       

    The average cost of coil occlusion was 38% lower than surgical
    closure. But 17% of patients with coil occlusion had residual leaks
    at an average of 6 months after the procedure. There were no other
    short or long term complications in both groups and there were no
    deaths.

       

    Coil occlusion of PDA is a feasible, cheaper alternative to surgical
    repair.

       

  • ElkinsRC,
    Knott-Craig CJ, Ward KE, et al [Univ of Oklahoma, Oklahoma City]

    The Ross Operation in Children : 10-Year Experience

    Ann Thorac Surg 65 : 496-502, 1998

      

    The Ross operation for aortic valve replacement in children has been
    performed for 30 years, but its widespread acceptance was delayed
    because of the procedure’s technical demands and the need to place 2
    valves at risk. With modifications in operative technique, the Ross
    operation in now the operation of choice for children and young
    adults who require aortic valve replacement. Researchers reviewed
    the records of 150 consecutive patients to provide additional
    long-term follow-up of the Ross operation. There were 112 boys and
    38 girls of median age 12 years. Primary diagnosis was aortic
    stenosis in 40, aortic insufficiency in 29, and a combination of
    both in 81. Most had undergone other procedures before the Ross
    operation.

       

    Eight-year survival was 97.3%. Six patients required reoperation
    with restitution of valve function and two with late dysfunction
    required a replacement procedure. At 8 years 90% were free of any
    dysfunction, 94% were free of any obstruction, and 89% were free of
    any gradient across the valve needing a reoperation. All patients
    had active lives unencumbered by the need to take any
    anticoagulants.

       

    The Ross operation in children has an excellent rate of success at a
    low risk. Valve related complications are not life threatening and
    long-term satisfactory valve function can be achieved.

        

  • D’Souza
    SJA, Tsai WS, Silver MM, et al [Univ of Toronto]

    Diagnosis and Management of Stenotic Aorto-Arteriopathy in Childhood

    J Pediatr 132: 1016-1022, 1998

       

    Patients with stenotic aorto-arteriopathy [SAA], an uncommon group
    of vascular diseases, have segmental stenoses of the aorta and its
    branches. The new common type is middle aortic syndrome,
    characterized by severe stenosis of the thoracic and abdominal
    aorta. The differential diagnosis includes mainly Takayasu Arteritis
    [TA] and fibromuscular dystrophy or other noninflammatory
    aortic-arterial diseases. An experience with the management of SAA
    in childhood is reviewed, including the results of several different
    management approaches.

        

    The 16-year experience included 14 children and adolescents with
    acquired SAA. There were 7 boys and 7 girls, aged 4 to 18 years.
    Most of the patients were asymptomatic, with hypertension noted at
    routine examination. Clinical findings included abdominal bruits in
    8, mixed absent/diminished and normal pulses in 8, and leg
    claudication in 4. On angiography, 13 showed involvement of the
    abdominal or descending thoracic aorta. A mid thoracoabdominal
    coarctation was detected in most patients. Eleven patients received
    a diagnosis of TA. It was difficult to distinguish TA from
    fibromuscular dysplasia on clinical or angiographic grounds.

         

    Treatment commenced with antihypertensive therapy. In patients with
    TA, prednisolone did not reverse aortic disease but it did worsen
    the hypertension. Six patients underwent percutaneous transluminal
    balloon angioplasty of renal artery stenoses, but the renal arteries
    restenosed. Renal autotransplantation – excision of the stenotic
    segment of the renal artery with reimplantation of the kidney on to
    the disease free renal artery – was performed in 5 patients. This
    provided temporary improvement in blood pressure in most patients;
    one patient had renal artery thrombosis with deteriorating renal
    function. Three patients underwent balloon angioplasty of the
    abdominal aorta with implantation of stents. In one case this was
    followed by open renal autotransplantation. There were 3 deaths.

        

    Thus diagnosis and management of SAA in children is a difficult
    problem, requiring multiple procedures, aimed mainly at preventing
    end-organ damage.

        

  • Knott-Craig
    CJ. Elkins RC, Lane MM, et al [Univ of Oklahoma, Oklahoma City].

    A 26-year Experience with Surgical Management of Tetralogy of Fallot : Risk Analysis for Mortality or Late Reintervention 

    Ann Thorac Surg 66: 506-511, 1989

        

    Since the early 1990s, the trend in correction of tetralogy of
    Fallot [TOF] has been toward primary repair and away from 2-stage
    repair. The results suggest that primary repair offers improved
    outcomes, although the long term effects on survival and recurrent
    right ventricular outflow tract disease remain unclear. A 26-year
    experience with TOF repair was reviewed to analyze effects of the
    trend toward early repair on early outcomes and recurrent right
    ventricle obstruction.

        

    From 1971 to 1997, 291 patients were operated for repair of TOF at
    the author’s institute; 68% had primary repair, 21% had a staged
    repair and the rest had palliative surgery only. The pathology was
    complex in 23% of patients, most often including pulmonary atresia.
    Follow-up information was available on 90% of the patients, with a
    median duration of follow-up nearly 11 years.

       

    The overall in-hospital mortality rates were 11% for primary repair,
    18% for staged repair and 16% for the rest. During the 1990s the
    mortality rates decreased to 2%, 12% and 0% respectively. After 1990
    the patients age at surgery was 0.6 years, compared with the earlier
    2 years. Significant risk factors for in-hospital death on
    multivariate analysis were hypothermic circulatory arrest, pulmonary
    artery patch angioplasty, earlier years of surgery, and closure of
    the foramen ovale.

       

    Among patients who survived to hospital discharge, the 20-year
    survival was 98% for those with TOF with pulmonary stenosis vs 88%
    for those with pulmonary atresia. Fourteen percent of patients
    required reoperation on the right ventricular outflow tract. The 20
    year rate of freedom from such intervention was 86% for patients
    with pulmonary stenosis vs 43% for those with pulmonary atresia.
    Among the latter group, the rate of freedom from reintervention was
    85% after primary repair vs 91% for those with staged repair.
    Patients less than one year were less likely to be free of
    reintervention, though the difference was not significant.

        

    The long-term retrospective study suggests that survival after
    primary repair of TOF has improved significantly over the years and
    even infants do well. Staged repair has to be reserved for patients
    with complex pathology only. 

        

  • Singh
    GK, Greenberg SB, Yap YS, et al [ St. Louis Univ., St. Christopher
    Hosp. for Children, Philadelphia, Southampton Gen. Hosp. England ]

    Right Ventricular Function and Exercise Performance Late After Primary Repair of Tetralogy of Fallot with Trasannular Patch

    Am J Cardiol 81: 1378-1382, 1998

       

    Current surgical repair of tetralogy of Fallot [TOF] involving
    reconstruction of the right ventricle [RV] usually results in
    chronic pulmonary insufficiency. Exercise performance and RV
    systolic and diastolic functions in a group of patients with
    pulmonary regurgitation, late after primary repair of TOF in
    infancy, was assessed with cine magnetic resonance imaging and
    compared with results in normal individuals.

        

    The study consisted of 10 New York Heart Association [NYHA] class 1
    [n= 7] or II [n=3] patients with chronic pulmonary regurgitation for
    an average of 13.6 years after surgery for TOF with reconstruction
    of the right ventricular outflow tract with a transannular patch, at
    an average age of 6.9 months.

       

    Cine magnetic resonance imaging was performed and ventricular volume
    and function indices were calculated and compared with those of 7
    age and sex matched healthy controls.

        

    All the patients had pulmonary regurgitation and right and left
    ventricular enlargement and lower ejection fractions with diminished
    exercise tolerance correlated with the degree of pulmonary
    regurgitation.

          

  • Preito
    LR, Hordof AJ, Secic M, et al [Columbia Univ, New York; Cleveland
    Clinic Found, Ohio]

    Progressive Tricuspid Valve Disease in Patients with Congenitally Corrected Transposition of Great Arteries

    Circulation 98: 997-1005, 1998

        

    Patients with corrected congenital transposition of the great
    arteries [CTGA] are commonly found to have morphological
    abnormalities of the tricuspid valve, with 20% to 50% having
    clinically significant tricuspid insufficiency [TI]. The progression
    of tricuspid valve disease in such patients is unclear. A long-term
    follow-up study of patients with CTGA, with and without open heart
    surgery, was reported, with special attention to the significance of
    TI or intrinsic right ventricular dysfunction.

        

    The study included 40 patients with CTGA seen at one medical center
    since 1958. Twenty-seven patients were male and 13 female. The mean
    follow-up was 20 years. Potential risk factors for poor outcome were
    evaluated, including age, open heart surgery, TI, cardiac rhythm,
    pulmonary overcirculation, and right ventricular dysfunction.

       

    Twenty-one patients underwent intracardiac repair and 19 had no
    surgery or had closed heart procedures. The only independent
    prognostic factor for death was severe or moderately severe T1 as
    demonstrated by echocardiography and/or angiography. Furthermore,
    the only factor that predicted the presence of T1, was morphological
    abnormalities of the tricuspid valve. The 20-year survival rate was
    93% for patients without T1 vs 49% for those with T1. For patients
    undergoing surgery, survival rate was 34% for patients with T1 vs
    90% for those without T1. Among patients who did not have surgery,
    the 20-year survival rate was 60% with T1 vs 100% without.

       

    Thus presence of T1 in patients with CTGA worsens the prognosis,
    irrespective of whether they are operated or not.

        

  • Niezen
    RA, Helbing WA, van der Wall EE, et al [Leiden Univ. The
    Netherlands]

    Biventricular Systolic Function and Mass Studied with MR Imaging in Children with Pulmonary Regurgitation After Repair of Tetralogy of Fallot

    Radiology 201: 135-140, 1996

       

    Pulmonary Regurgitation [PR] may occur after surgical correction of
    tetralogy of Fallot. With the trend toward earlier correction of
    this congenital condition, there is a longer follow-up period for
    measurement of PR and biventricular function to evaluate the results
    of surgery; this study examined such functions.

       

    The study included 19 children who had been operated at mean age of
    1.5 years. Doppler echocardiography revealed PR in each patient. A
    group of healthy controls was studied for comparison. The mean age
    was 12 years in both groups. The subjects underwent transverse
    gradient-echo MRI of both ventricles, including creation of MR
    velocity maps of pulmonary artery. Measurements of biventricular
    volumes, ejection fraction, myocardial mass, and pulmonary flow
    volumes were made. In addition, 17 patients underwent exercise
    testing.

       

    The patients with corrected tetralogy of Fallot had lower right
    ventricular ejection fractions [ 54% vs 66%] and higher right
    ventricular mass than controls. Left ventricular ejection factor was
    also lower in operated cases than controls [ 52% vs 68%] and was
    significantly correlated with PR. Exercise performance also was seen
    to be reduced in inverse proportion to PR in the operated cases.

       

    Patients operated for correction of tetralogy of Fallot do develop
    pulmonary regurgitation which results in larger biventricular mass
    and reduced ejection fractions; and these effects can be accurately
    measured by MRI.

  • Reddy
    VM, McElhinney DB, Phoon CK, et al [Univ of California, San
    Fransisco]

    Geomatric Mismatch of Pulmonary and Aortic Anuli in Children Undergoing the Ross Procedure : Implications for Surgical Management and Autograft Valve Function

    J Thorac Cardiovasc Surg 115: 1255-1263, 1998

       

    Many children treated with the Ross procedure for congenital heart
    lesions have a significant discrepancy between pulmonary and aortic
    anuli. No systematic study was examined whether such mismatch
    presents a contraindication to the procedure. A review of 41
    children who underwent the procedure focuses on the surgical
    management of geomatric mismatch and its effects on autograft valve
    function.

       

    Patients had a mean age of 7.8 years. The diameter of the pulmonary
    valve was greater by 3 mm than that of the aortic valve in 20 cases,
    equal in 12 cases, and less by 3 mm in 9 cases; the differences
    ranged between + 10 to -12 mm. Aortoventriculoplasty was used to
    correct the mismatch in children with a larger pulmonary anulus;
    whereas in those with a larger aortic anulus, the correction was
    made by a gradual adjustment along the circumference of the
    autograft. Patients were followed up [ mean period 31 months] for
    autograft valvular regurgitation.

        

    Two patients required reoperation for moderate regurgitation. In the
    remaining 38 survivors, regurgitation was absent or trivial in 30,
    mild in 7, and moderate in 1. Regurgitation showed no relation with
    the age of the child, mismatch, or previous or concurrent
    procedures. No patient had significant autograft root dilatation.

       

    Thus geomatric mismatch is no contraindication to the Ross procedure
    in children. 

       

  • Stanger
    P, Silverman NH, Foster E [ Univ of California, San Francisco]

    Diagnostic Accuracy of Pediatric Echocardiograms Performed in Adults Laboratories by Adult Cardiologists 

    Am J Cardiol 83: 908-914, 1999

        

    In the 25 patients with 46 procedure-proved diagnosis the most
    important error in adult -laboratory echography was major in 44%,
    moderate in 28% and minor in 12%. In pediatric-laboratory
    echocardiography, the most important error was major in none,
    moderate in 4% and minor in 4%. 

        

    Among 41 patients with 62 duplicate-observer-verified diagnosis, the
    most important error in adult-laboratory echography was major in
    12%, moderate in 29%, and minor in 12%, compared with no errors in
    pediatric. 

         

    What Was the Nature of Error?

         

    In 53% of the adult-laboratory, echocardiograms, the most important
    error was major or moderate 71% of these were interpretive, 17%
    technical, and 11% both. The incidences of error were unassociated
    with patient age, year of study or the use of color Droppler, or
    complexity of diagnosis. In 29 of these 35 patients,
    pediatric-laboratory echocardiograms altered clinical management,
    including 12 operations and averted 2 operations. In 3 of the 29,
    delayed diagnosis were correlated with fixed pulmonary vascular
    disease, hypoxemic spells, and vascular collapse with severe
    metabolic acidosis which were major complications of delayed or
    missed diagnosis.

          

    Thus, echocardiography should always be done by a pediatric
    cardiologists in a pediatric set up rather than adult cardiologist
    in an adult set up and at least this has shown that a delayed
    diagnosis were associated with clinical problems in 3 children and
    of course it altered the management of surgery and all in 12
    patients an averted 2 operations.

  • Glagovian
    remodelling, plaque composition, and stenosis generation


    Heart 2000; 84: 461 – 462


      


    Angiograms are good at detecting high grade stenosis in the coronary
    arteries but are not insensitive in demonstrating actual extent of
    atherosclerosis. Some plaques grow in to the media of the artery and
    others bulge into the cavity. Quite often there is arterial
    remodelling (compensatory dilatation) called Glagovian remodelling.
    Disruption or rupture of the plaque has certain features. The most
    important features are a large lipid core, a high macrophage content
    and a thin cap.

       

  • Genetics
    of dilated cardiomyopathy: a molecular maze ?


    Heart 2000; 84: 463 – 464

       

    Systematic examination of relatives show that more than 25-30% of
    dilated cardiomyopathy are familial.

       

  • Stent
    magic! The genie has escaped from the bottle


    Heart 2000; 84 : 469-470



    A response to injury in the coronary artery – injury in terms of
    balloon, angioplasty (PTCA) or stent – is activation of cells within
    the arterial wall, the adventitial of the blood, and there is
    cellular proliferation of arterial smooth muscle cells, fibroblasts,
    endothelial cells, monocytes, lymphocytes and leucocytes.

       

    After balloon angioplasty, the response to injury is immediate, but
    short, after a stent. The response to injury is long lasting. It
    makes one wonder why stenting has become so popular and comprises of
    85% of patients with PTCA.

       

  • William
    G Stevenson, Etienne Delacretaz

    Radiofrequency catheter ablation of ventricular tachycardia

    Heart 2000; 84: 553

       

    Ventricular tachycardia is very difficult to treat. Drug treatment
    is often ineffective and defibrillators can terminate one episode
    but do not prevent them. Tachycardias may arise because of
    myocardial ischaemia but sometimes they arise even in the presence
    of normal heart muscle and ECG illustrations, whether it is
    multifocal or has a fixed site. When there is a single fixed site
    the treatment of choice is by radiofrequency ablation, which
    destroys the site of reentering which causes ventricular tachycardia.

        

  • Michael
    Lye, C Donnellan,

    Heart disease in the elderly

    Heart 2000, 84; 560-566

        

    Cardiovascular disease is the most frequent single cause of death in
    persons over 65 years of age. There is usually thickening of the
    left ventricular wall and fibrosis of the valves. 

       

    Peripheral and central arteries develop, and increase thickness.
    Independent of atherosclerosis, lipids are deposited in the vessel
    walls. Normally increases in heart rate in response to exercise are
    diminished and are almost like beta blockade. The diastolic blood
    flow from the atrium to the ventricle is slowed. Left ventricular
    hypertropic occurs even in the absence of disease. There is usually
    potassium retention which makes potassium sparing diuretics risky.

      

  • Raymond
    J Kim, Edwin Wu, et al 

    The Use of Contrast Enhanced Magnetic Resonance Imaging to
    Identify Reversible Myocardial Dysfunction.

    NEJM, Nov.16, 2000, 343(20), p.1445-53.

      

    Recent studies indicate that magnetic resonance imaging (MRI) after
    the administration of contrast material can be used to distinguish
    between reversible and irreversible myocardial ischaemic injury
    regardless of the extent of wall motion or the age of the infarct.
    Authors hypothesised that the results of contrast-enhanced MRI can
    be used to predict whether regions of abnormal ventricular
    contraction will improve after revascularisation in patients with
    coronary artery disease.



    Gadolinium enhanced MRI was performed in 50 patients with
    ventricular dysfunction. Contrast-enhanced MRI showed
    hyperenhancement of myocardial tissue in 40 of 50 patients before
    revascularisation.



    The conclusion was that reversible myocardial dysfunction can be
    identified by contrast-enhanced MRI before coronary
    revascularisation.



    Editorial – pg. 1488-1490. George A Beller.

    Noninvasive assessment of myocardial viability.

    The prognosis is poor for patients with ischaemic cardiomyopathy,
    which is characterised by extensive coronary artery disease and
    diminished global left ventricular function. Chronic left
    ventricular dysfunction in patients with ischaemic cardiomyopathy
    results from either scarring, as a consequence of myocardial
    necrosis or myocardial hibernation. Presence of myocardial
    hibernation suggests that there is sufficient residual blood flow to
    sustain the viability of myocytes but not enough to maintain
    systolic contraction. In the case of hibernating myocardium,
    systolic function improves as perfusion increases with coronary
    revascularisation. Many patients have both scarring and hibernation
    in different regions.

      

    Availability of an accurate, non-invasive method of distinguishing
    viable myocardium from myocardium that has been irreversibly injured
    as a result of hibernation is important. For clinical decision
    making such a tool would enable physicians to identify patients with
    coronary artery disease and left ventricular dysfunction at rest who
    would benefit most from revascularisation strategies.



    Recently, MRI after administration of a gadolinium based contrast
    agent in determining the transmural extent of myocardial viability
    has been investigated. Kim and co-workers tested the hypothesis that
    hyperenhancement of dysfunctional myocardial regions is indicative
    of nonviability. The predictive accuracy of the method was very
    high. Other strengths of the MRI technique are that none of the
    patients were excluded because of a lack of good-quality images or
    incomplete visualization of all myocardial segments and because of
    the very high spatial resolution, the transmural extent of
    myocardial injury can be determined. This latter advantage is
    important because transmural scarring of more than 20-30% of tissue
    correlates with lack of improvement in function after
    revascularisation.

       

  • A.M.
    Feldman, Dennis McNamara,(Univ. of Pittsburgh School of Medicine,
    Pittsburgh)

    Myocarditis – Review Article

    New Eng J Med, Vol.343, Nov.9, 2000, pg.1388-1398.

       

    CAUSES
    OF MYOCARDITIS




INFECTIOUS  

IMMUNE-MEDIATED

TOXIC
MYOCARDITIS

  • Bacterial:
    brucella, Corynebacterium diphtheriae, gonococcus, Haemophilus influenzae, meningococcus, mycobac- terium, Mycoplasma pneumoniae, pneumococcus, salmonella, Serratia marcescens, staphylococcus, Streptococcus pneumoniae, Strep.pyogens, Treponema pallidum, Tropheryma whippelii, and Vibrio cholerae.Spirochetal: borrelia and leptospiraFungal:actinomyces, aspergillus, blasto myces, candida, coccidioides, cryptococcus histoplasma, mucormycoses, nocardia, and sporothrix

      

    Protozoal: Toxoplasma gondii and Trypa nosoma cruziParasitic: ascaris, Echinococcus granulosus Paragonimus westermanii, schistosoma, Taenia solium, Trichinella spiralis, visceral larva migrans, and Wuchereria bancroftiRickettsial: Coxiella burnetii, Rickettsia rickettsii, and Rick, tsutsugamushiViral: coxsackievirus, cytomegalovirus, dengue virus, echovirus, encephalo myocarditis, Epstein-Barr virus, hepatitis A virus, hepatitis C virus, herpes simplex virus, herpes zoster, human immunodeficiency virus, influenza A virus, influenza B virus, Junin virus, lymphocytic chorio- meningitis, measles virus, mumps virus, parvovirus, poliovirus, rabies virus, respiratory syncytial virus, rubella virus, rubeola, vaccinia virus, varicella-zoster virus, variola virus, and yellow fever virus.

  • Allergens:
    acetazolamide amitriptyline,cefaclor, colchicine,
    furosemide, isoniazid, lidocaine,
    methyl dopa,  
    penicillin,
     phenylbutazone,
    phenytoin, reserpine, streptomycin,tetanus
    toxoid
    ,
    tetracycline,
    and thiazides.

      

    Alloantigens:
    heart-transplant rejection

      

    Autoantigens:Chagas’ disease, Chlamydia
    pneumoniae,
     
    Churg-Strauss syndrome, inflam-matory
    bowel disease, giant-cell myocarditis,
    insulin-dependent diabetes mellitus,
    Kawasaki’s disease, myasthenia gravis,
    polymyositis, sarcoidosis, scleroderma,
    systemic lupus erythematosus, thyro
    toxicosis, and Wegener’s granulomatosis.

     

  • Drugs: amphetamines, anthracyclines, catecholamines, cocaine, cyclo- phosphamide, ethanol, fluorouracil, hemetine,
    interleukin-2, lithium, and trastuzumab.Heavy metals: copper, iron, and lead.Physical agents: electric shock, hyperpyrexia, and radiation.Miscellaneous: arsenic, azides, bee and wasp stings, carbonmono- oxide, inhalants, phos phorus, scorpion bites, snake bites and spider bites.

  • Scott Gottlieb, New York

    Cancer drug may cause heart failure

    BMJ, Vol.321, July 29, 2000, pg.259.

      

    Trastuzumab (Herceptin) is a monoclonal antibody that binds to a protein found on the surface of some cells. The protein, HER2, helps to regulate cell growth. By binding to tumour cells, trastuzumab inhibits growth of cancerous cells. It is currently approved for use in metastatic breast cancer.



    Editorial in ‘Circulation’ has reported that heart failure occurs in 7% of women taking trastuzumab alone and this rate increases to 28% in women taking the drug with other chemotherapy drugs.



    A team of researchers is calling for long-term studies investigating the risk of heart failure among women taking trastuzumab.

      

  • Amanda I Adler, Irene M Stratton, et al 

    Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.

    BMJ, Vol.321, Aug.12, 2000, pg.412-419.

      

    The objective of the study was to determine the relation between systolic BP over time and the risk of macrovascular and microvascular complications in patients with type 2 diabetes.



    The incidence of clinical complications was significantly associated with systolic BP except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic BP was associated with reductions in risk of 12% for any complication related to diabetes. No threshold of risk was observed for any endpoint.

      

    The conclusion was that in patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised BP. Any reduction in BP is likely to reduce the risk of complications with the lowest risk being in those with systolic BP less than 120mm Hg.

      

  • Wilson S Colucci, Uri Elkayam et al

    Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure.

    New Eng J Med, vol.343, July 27, 2000, pg.246.

      

    Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. Authros investigated the clinical use of nesiritide in such patients. Nesiritide was infused at rates of 0.015 and 0.03 ug per kg per minute. It decreased pulmonary capillary wedge pressure, reduced dyspnoea and fatigue.



    It was concluded that in patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Intravenous nesiritide is useful for short-term treatment of decompensated congestive heart failure.

         

  • Perez- Castellano N, Garcia EJ, Abeytua M, et al [Gregorio Maranon Univ Gen Hosp, Madrid]

    Influence of Collateral Circulation on In-Hospital Death From Anterior Acute Myocardial Infarction

    J Am Coll Cardiol 31: 512-518, 1998

      

    Nearly 40% of patients exhibit some degree of collateral circulation at the onset of acute myocardial infarction [AMI]. Some studies have shown beneficial effect from the residual blood flow carried by collateral vessels, but there is no evidence that collateral circulation improves prognosis after AMI. A study of 180 patients sought to determine whether the in-hospital prognosis of anterior AMI is influenced by pre-existent collateral circulation to the infarct-related artery.

      

    Eligible patients admitted with suspected anterior wall AMI, showed complete occlusion of the left anterior descending coronary artery at diagnostic coronary angiography, and were treated by primary percutaneous transluminal coronary angioplasty within the first 6 hours of symptom onset. Angiographic assessment of collateral channels to the infarct related artery before angioplasty, established 2 patient groups: 115 patients without collateral vessels [group A] and 65 patients with collateral vessels [ group B].

      

    The two groups were similar in baseline characteristics, except that the prevalence of previous angina was greater in group B [34%] than in group A [15%]. More hospital deaths occurred in group A [23% than in group B [8%]. Cardiogenic shock, which accounted for 74% of deaths, developed in 26% of patients in group A versus 6% in group B. A progressive decrease in the in-hospital mortality rate was noted with increasing grades of collateral circulation.

       

    Thus the absence of collateral circulation appeared to be a strong predictor of both cardiogenic shock [ odds ratio 5.6] and in-hospital deaths [odds ratio 3.4]. By decreasing the incidence of cardiogenic shock, the presence of collateral circulation decreased the incidence of in-hospital deaths.

        

  • Kloner RA, and the TIMI=9B Investigators [Good Samaritan Hosp, Los Angeles; Univ of Southern California, Los Angeles; Harvard Med School, Boston, et al]

    Prospective Temporal Analysis of Onset of Preinfarction Angina Versus Outcome: An Ancillary Study in TIMI-9B

    Circulation 97: 1042-1045, 1998

        

    Preinfarction angina pectoris has been shown in some studies to confer a protective effect on myocardial infarction [MI], possibly by initiating ischemic preconditioning. Few studies have examined the relationship between onset of angina and outcome after MI. The 30-day outcomes after MI were prospectively compared in patients with more than 24-hours or less between onset of angina and MI.

      

    Angina was reported before MI in 425 of 3002 patients in the TIMI-9B study. Major cardiac events within 30 days of hospitalization were recorded.

       

    Patients who had angina 24 hours or less before MI, had significantly lower rates of events than in those who had angina for more than 24 hours before MI. The former had nonsignificantly lower creatinine kinase [CK] values but significantly lower maximum CK values than the latter. A history of angina longer than 24 hours was not associated with reduced rate of cardiac events. The reduced rate of cardiac events in those with angina of 24 hours or less before MI, was not related to ingestion of aspirin use, antianginal drugs, hypertension or hypercholestrolemia.

       

    Patients with preinfarction angina [ of 24 hours or less duration before MI] had better outcomes after MI than those without preinfarction angina.

       

  • Airaksinen
    KEJ, Ikaheimo MJ, Linnaluoto M, et al [Univ of Oulu, Finland; Univ of Tampere, Finland]

    Gender Difference in Autonomic and Hemodynamic Reactions to Abrupt Coronary Occlusion

    J Am Coll Cardiol 31: 301-306, 1998

       

    The clinical presentation of acute ischemic events may be modified by changes in heart rate, blood pressure, and heart rate variability. In patients with coronary artery disease, a temporal relationship between changes in heart rate variability and life-threatening ventricular tachyarrhythmias has also been demonstrated. In the autonomic modulation of heart rate, recent research has shown that there are gender-related differences. In a prospective series of patients having clinically indicated coronary angioplasty, potential gender related differences in autonomic responses to abrupt coronary artery occlusions were assessed.

       

    In 149 men and 65 women referred for single vessel coronary angioplasty, the changes in heart rate, heart rate variability, blood pressure, and the occurrence of ventricular ectopic beats during a 2-minute coronary artery occlusion were analyzed. By analyzing a control group of 19 patients with no ischemia during a 2-minute ballon inflation in a totally occluded coronary artery, the ranges of non-specific responses were determined. During the occlusion, women had ST segment changes and chest pain more often than men. Women had significant bradycardia [ 31% vs 13%] or increase in heart rate variability [ 25% vs 11%] as a sign of vagal activation compared with men. A decrease in blood pressure was caused by coronary occlusion more often in women than men [ 28% vs 11%]. The incidence of Bezold-Jarisch-type reaction[ simultaneous bradycardia and fall in blood pressure] was the most pronounced female preponderance [16% vs 0.7%]. An independent predictor of bradycardia reactions, hypotensive reactions and Bezold-Jarisch-type reactions was female gender, according to logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia. There was borderline significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats.

       

    During abrupt coronary artery occlusion, vagal stimulation is more comon and may have beneficial antiarrythmic effects, modifying the outcome of acute coronary events.

          

  • Shiraki H, Yoshikawa T, Anzai T, et al [Yokohama Municipal Hosp, Japan; Keio Univ, Tokyo]

    Association Between Preinfarction Angina and a Lower Risk of Right Ventricular Infarction

    N Engl J Med 338: 941-947, 1998

       

    When inferior myocardial infarction caused by proximal occlusion of the right coronary artery occurs, the result is right ventricular infarction. Such infarctions are less common than would be expected from the frequency of proximal occlusion of the right coronary artery. The reasons for this are unclear. This study examined the possible relationship between preinfarction angina and right ventricular infarctions, including their short-term outcomes.

      

    The retrospective study included 113 patients with acute inferior wall infarction caused by right coronary artery occlusion. Of these patients, 62 had preinfarction angina [ defined as at least one episode of typical chest pain, lasting less than 30 minutes, during the week before the infarction], and 52 did not.

      

    Patients without preinfarction angina were more likely to have right ventricular infarction [odds ratio 6.3, 95% confidence interval 2.7 to 15.1]. They were also more likely to have complete atrioventricular block [odds ratio 3.6, 95% confidence interval 104 to 10.3], and combined hypotension and shock [odds ratio 12.4, 95% confidence interval 4.5 to 40.6]. The strongest predictors of a reduced rate of ventricular infarction were angina occurring 24 to 72 hours before infarction [adjusted odds ratio 0.2, 95% confidence interval 0 to 0.5]. Patients with preinfarction angina had a lower incidence of ST segment elevation in lead V4R.

      

    Thus amongst patients with acute inferior myocardial infarction, preinfarction angina is independently associated with the absence of right ventricular infarction. The short-term outcomes are also better when preinfarction angina occurs. These favourable outcomes could be due to delayed ischemic preconditioning.

      

  • CSR Baker, LRI Baker (Dept.of Cardiology, UK, St.Bartholemew’s Hospital UK)

    Editorial – Prevention of contrast nephropathy after cardiac catheterisation.

    Heart 2001; 85:361-362

      

    Increasing number of patients are now being exposed to contrast medium for various investigational procedures and the problem of radiocontrast induced nephropathy assumes greater and greater importance (RCIN). 



    This has now become the third most common cause of new onset renal failure in hospital patients. Patients, most at risk are those with impaired renal function as judged by an increase in serum creatinine concentration. Diabetes further amplifies the risk. 



    The volume of contrast medium is also important and the risk of renal failure rises with the dose of 100ml with contrast medium.



    The typical patients with RCIN is non-oliguric. Most patients recover but minority become dialysis dependent. To reduce the risk of development of RCIN, patients with high serum creatinine (indicative of reduction in glomerullar filtration rate) should be prehydrated before exposure to contrast medium.

      

  • General Cardiology

    Diabetic heart disease: clinical considerations

    Heart 2001; 85: 463

      

    Coronary heart disease in diabetics is slightly different than in a non-diabetic because of autonomic neuropathy. Symptoms are comparatively mild. Atherosclerosis is more different and widespread in diabetes. However response to medical treatment is at least as good as in non-diabetes.



    From the surgical point of view, angioplasty and bypass is more difficult in diabetics because of the diffused nature of obstruction in the coronary arteries. However, bypass surgery is to be preferred to angioplasty. ACE inhibitors are of particular value in diabetics and coronary heart diseases, because this group of drugs minimises microvascular complications both in heart and the kidney.

      

  • Nicholas Alp, N. Clarke, A P Banning (Dept. of Cardiology, UK)

    Editorial – How should patients with patent foramen ovale be managed?

    Heart March 2001, vol. 85: 242-244.

      

    Patent foramen ovale is common enough in the normal population to be considered an anatomical variant and for any individual the absolute risk of adverse events from a PFO (patent foramen ovale) is clearly very small.



    It becomes important only where venous thrombosis has occurred in patients with raised right atrial pressure. Because of reversal of shunt, paradoxical embolism may occur.



    At present the closure of large PFO in patients with stroke appears to be reasonable.

      

  • G D O Lowe (Univ. of Glasgow, Dept. of Medicine, UK)

    Who should take aspirin for primary prophylaxis of coronary heart disease?

    Heart, March 2001; vol.85: p.245-46

       

    In this study a very large series of subjects, received a long term aspirin treatment as primary prophylaxis had following results. Meta-analysis in 4 randomised controlled trials showed that there was significant reduction of cardiovascular events in the aspirin group. However, there was also a significant increase in bleeding risk.



    The authors suggest that at lower coronary event rates, i.e. where the coronary event risks is 1.5% per year, aspirin therapy is not worthwhile. However it is worthwhile in patients who have a high coronary event rate.

      

  • J Shepherd (Inst. Of Biochemistry, Glasgow)

    The statin era : in search of the ideal lipid regulating agent.

    Heart – March 2001; 85: 259-264

      

    Characteristics of Statins

      



























    Characteristics 

    Lovastatin 

    Provastatin  


    Simvastatin

    Atorvastatin 


    Fluvastatin

    Cerivastatin

    Maximal
    dose (mg/day)

    80 

    40 

    80

    80  

    40

    0.4

    Maximal
    serum LDL cho-lesterol
    reduction (5)


    40

    34 

    47

    60 

    24

    28

    Serum
    LDL cholesterol

    reduction
    (%)   

    34

    34  

    41

    60  

    24

    28

    Serum
    triglyceride  reduction
    (%) 

    16

    24

    18

    29 

    10

    13

    Serum
    HDL cholesterol 
    increase
    (%)

    8.6

    12 

    12

    6 

    8

    10

    Plasma
    half life (hours)  

    2 

    1-2  

    1-2

    14

     1.2

    2-3

    Effect
    of food on drug absorption 

     Increased 
    absorption  

    Decreased 

    absorption

    None

    None 

    Negligible

    None

    Optimal
    time of administration 

    With meals 

    (morning &Evening)

    Bedtime

    Evening 

    Evening  

    Bedtime  

    Evening

    Penetration
    of central nervous
    system

    Yes  

    No 

    Yes

    No

    No

    Yes

    Renal
    excretion of absorbed
    dose (%)

    10

    20

    13

    2

    <6

    33

    Mechanism
    of Hepatic
    metabolsim

    Cytochrome
     P450  3A4 

    Sulfation 

    P450  3A4

    Cytochrome 

    P450  3A4 

    Cytochrome 

    P450  3A4 

    Cytochrome
    P450  2C9  

    Cytochrome 

    P450 3A4.2C8

  



  • Satyendra
    Giri, C Michael White, et al

    Oral Amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.

    Lancet, Vol.357. March 17, 2001, pg.830-836

       

    Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is not known. Authors assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.

      

    Patients (average age 73 years) received 6G of amiodarone or placebo over 6 days begining on preoperative day 1.

     

    Interpretation of the findings was that oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillarion and reduces the risk of cerebrovascular accidents and ventricular
    tachycardia.

         

  • Doorey A, Patel S, Reese C, et al [ Med Ctr of Delaware, Newark; St.Francis Hosp, Wilmington, Del]

    Dangers of Delay of Either Thrombolysis or Primary Angioplasty in Acute Myocardial Infarction with Increasing Use of Primary Agioplasty

    Am J Cardiol 81: 1173-1177, 1998

        

    Early trials of primary angioplasty in the treatment of patients with acute myocardial infarction [AMI] yielded excellent results, but the therapy has been less successful in clinical practice. Patients treated with primary angioplasty or thrombolysis were examined. 

        

    Three hospitals in Northern Delaware adopted primary angioplasty in 1995, after the release of meta-analysis. When early results were unsatisfactory, factors contributing to these poor outcomes were evaluated. Treatment time intervals and outcomes for consecutive patients who received thrombolysis or angioplasty for AMI over 1 year were assessed. Reperfusion times were of interest because of the delays experienced with primary angioplasty.

      

    In 1994, the hospitals had average thrombolysis time intervals of 20 to 30 minutes. Time intervals to thrombolysis increased at one of the hospitals after the angioplasty protocol was announced in March 1995. Uncertainty about the use of thrombolysis versus primary angioplasty was common, and often caused delays. Of the 37 patients treated with primary angioplasty, 12[32%] required emergency bypass surgery or died. With the increasing use of angioplasty, time intervals to thrombolysis in patients not treated with angioplasty, increased from an average of 29 to 39 minutes.

        

    The considerations of primary angioplasty can impair the timeliness of thrombolysis in patients with AMI. An algorithm should be established to minimise treatment delays. 

        

  • Mahmarian
    JJ, Moye LA, Chinoy DA, et al [ Baylor College of Medicine, Houston; Univ of Texas, Houston; Jacksonville Cardiovascular Clinic, Fla; et al]

    Transdermal Nitroglycerin Patch Therapy Improves Left Ventricular Function and Prevents Remodeling After Acute Myocardial Infarction: Results of a Multicentric Prospective Randomized, Double-Blind Placebo-Controlled Trial

    Circulation 97: 2017-2024, 1998

        

    A multicentric trial examined the effects of transdermal nitroglycerin [NTG] patches on left ventricular [LV] remodeling in patients who survived acute Q-wave myocardial infarction. Prevention of LV dilatation which occurs more often in patients with LV dysfunction, might improve survival.

        

    The double-blind trial randomly assigned 77 patients to placebo and 214 patients to 3 different NTG patch dosages [0.4, 0.8 and 1.6 mg/h]. Patients in four groups were similar in mean age and other baseline characteristics; all underwent baseline gated radionuclide angiography. Dosage of NTG could be reduced, if necessary, to achieve a final tolerated dosage. Patients were evaluated monthly during the 6-month study period. Change in end-diastolic volume index [ESVI] was the primary study end point.

        

    Use of the 0.4 mg/hr NTG patches significantly reduced both ESVI [mean -11.4 mL/m square] and end-diastolic volume index [mean-11.5 mL/m square]. Patients who benefited most from the treatment were those with a baseline LV ejection fraction less than or equal to 40% and only at 0.4 mg /h dose. Withdrawal of NTG patch significantly increased ESVI, but values remained lower than those recorded before treatment. LV dilatation was prevented by transdermal NTG patches, when administered to patients who survived an acute myocardial infarction and had depressed LV function at baseline. Only the lowest dose [0.4 mg/h] was effective, and withdrawal of the patch after 6 months was followed by a significant increase in
    ESVI.

        

  • Franzosi MG, for the ACE inhibitor Collaborative Group [Instituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy]

    Indications for Ace Inhibitors in the Early Treatment of Acute Myocardial Infarction : Systemic Overview of Individual Data From 100000 Patients in Randomized Trials

    Circulation 97: 2202-2212, 1998

        

    Several trials have evaluated the use of angiotensin converting enzyme [ACE] inhibitors in acute myocardial infarction [MI]. Although the utility of ACE inhibitors in MI is beyond question, some important questions remain; such as do some patient benefit more than others and are some patients at greater risk? The authors examined data from 4 large trials to address these questions.

       

    The 4 large randomized trials included a near 100000 patients from varied regions. In each trial, the test group received ACE inhibitors [n=49214] within 0 to 36 hours after MI and dosing continued for 4 to 6 weeks, whereas a placebo group received no
    ACE inhibitors [n=49269].

       

    Survival was significantly greater for patients receiving ACE inhibitors [7.11% deaths] compared to placebo group [ 7.59% deaths]; of the deaths avoided in the first group, most were in the first week. Men and women benefited from treatment to a similar extent as did the patients between 55 and 74 years’ age. ACE inhibitors saved 2.7 lives/1000 in those patients whose baseline heart rates were 100/min or more and 8.7 lives/1000 for those with heart rates between 80 to 90/min. Absolute benefits of ACE inhibitors were significantly greater for patients with previous MI [8.9 lives saved /1000], diabetes [17.3] lives saved/1000], hypertension [9.0 lives saved/1000], and Killip class more than 1 at baseline [14.1 lives saved/1000]. With ACE inhibitors patients with anterior MI had significantly improved survival compared to those with MI at other sites [10.6 lives saved/1000] ACE inhibitors saved 3.8 lives /1000 in low risk patients and 13.6 lives/1000 in high risk patients. ACE inhibitors had a similar effect on nonfatal cardiac failures at 30 days as compared with the controls [14.6% vs 15.2%].

        

    On the negative side, ACE inhibitor therapy was associated with significantly greater hypotension [ 84 cases /1000 treated], cardiogenic shock [4.6 patients/1000 treated], second to third degree atrioventricular block [5.4 cases/1000 treated], and renal dysfunction [6.2 cases 1000 

    treated]. Patients 75 years or older had increased risk of renal dysfunction [17 cases/1000 treated].

       

    ACE inhibitor therapy for 30 days saved about 5 lives /1000 patients. The benefit was greater in the first few days of MI. Patients with higher risk typically benefited more. Hypotension and renal dysfunction were the most common problems.

       

  • Milavetz
    JJ, Giebel DW, Christian TF, et al [Mayo Clinic and Mayo Found, Rochester, Minn]

    Time to Therapy and Salvage in Myocardial Infarction

    J Am Coll Cardiol 31: 1246-1251, 1998

        

    Previous studies have suggested that earlier reperfusion is associated with improved outcome for patients with myocardial infarction [MI]. However, even if perfusion was delayed, some patients have significant myocardial salvage. Time to reperfusion was evaluated as a determinant of myocardial salvage in patients undergoing reperfusion therapy.

        

    The study included 55 patients receiving successful angioplasty or thrombolysis after their first anterior MI. Reperfusion therapy was performed within 2 hours in 10 patients, and after 2 hours in 45 patients. Before reperfusion therapy and at the time of hospital discharge, each patient underwent technetium-99m sestamibi studies to calculate the myocardial salvage index. The low point of the technetium-99m sestamibi curve was used to determine residual flow to the territory of the infarct.

        

    The salvage index ranged from -0.4 to 1.0; 9% of patients had a salvage index of less than 0.10, while 25% had one of the greater than 0.90. Patients undergoing reperfusion therapy within 2 hours or having good residual blood flow were likely to have a high salvage index. Residual blood flow was significantly correlated with salvage only in patients treated after 2 hours. Residual blood flow interacted significantly with time to therapy: each factor influenced the value of the other. None of the historical or hemodynamic variables evaluated was significantly associated with residual flow or myocardial salvage.

        

    Reperfusion therapy provides the best result, if performed within 2 hours after acute MI. Thereafter, salvage rate appears to depend largely on the amount of residual blood flow to the infarct-related artery. These findings emphasize the importance of adequate flow to the infarct territory in myocardial salvage.

        

  • Ross AM, for the GUSTO-1 Angiographic Investigators [ George Washington Univ, Washington, DC; Thoraxcentrium, Rotterdam, the Netherlands; Duke Univ, Durham, NC; et al]

    Extended Mortality Benefit of Early Postinfarction Reperfusion

    Circulation 97: 1549-1556, 1998

        

    Reperfusion therapy aims to restore blood flow to the infarct-related artery after acute myocardical infarction, thus preserving left ventricular function and survival. It was initially expected that successful reperfusion therapy would show increasing benefits over time. However, larger clinical trials of thrombolytic therapy have shown maximum benefit at 4 to 6 weeks, with no subsequent difference in survival. These studies compared the results in terms of assigned treatment, rather than treatment effectiveness. Data from GUSTO-1 study were analyzed to assess the impact of early, complete reperfusion on long-term survival.

      

    The analysis included data on 2431 patients with myocardial infarction who were receiving 1 of 4 regimens of thrombolytic therapy. The patients were categorized as to whether or not they achieved early complete thrombolysis in myocardial infarction grade 3 [TIMI3] flow in the infarct-related artery, and whether they achieved ejection fraction of 40% or less or of greater than 40%. The effects of these variables on 2-year survival were evaluated by Kaplan-Meier curves; Cox regression models were used to define hazard ratios for factors significantly affecting survival.

      

    Survival beyond 30 days was significantly better for patients with early reperfusion and preserved ejection fractions. For patients with TIMI3 flow, compared to those with lesser flow, unadjusted hazard ratio was 0.57 at 30 days and 0.39 at 30 to 688 days or beyond. Achieving early TIMI 3 flow reduced mortality by about 3 patients per 100 in the first month and 5 per 100 thereafter. Preserved ejection fraction was associated with an unadjusted hazard ratio of 0.25 at 30 days and of 

    0.20 thereafter. Lives saved by preserved ejection fraction at these intervals were 9 and 11 per 100, respectively. 

       

    When reperfusion therapy provides early and complete restoration of blood flow to the infarct-related artery, with preservation of left ventricular function, the survival benefit continues beyond the first postinfarction month. The findings emphasize the need for more effective reperfusion approaches. 

         

  • Tiefenbrunn
    AJ, Chandra NC, French WJ, et al [ Washington Univ, St. Louis; John Hopkins Bayview Med Ctr, Baltimore, Md; Harbor Univ of California, Los Angeles Med Ctr, Torrance; et al]

    Clinical Experience with Primary Percutaneous Transluminal Coronary angioplasty Compared with Alteplase [Recombitant Tissue-Type Plasminogen Activator] In Patients with Acute Myocardial Infarction : A Report From the Second National Registry of Myocardial Infarction [NRMI-2]

    J Am Coll Cardiol 31: 1240-1245, 1998

    Results from a number of small studies comparing percutaneous transluminal coronary angioplasty [PTCA] with thrombolytic therapy in patients with acute myocardial infarction, suggest a survival advantage for patients undergoing PTCA. Data from the NRMI-2 were reviewed to describe the comparison of PTCA with alteplase [rt-PA] in a large number of patients.

        

    The phase 4 study collected data from hospitals in 50 states. Eligible patients were transferred to participating hospitals and received treatment, either an IV thrombolytic agent or primary PTCA., within 12 hours of symptom
    onset. From June 1, 1994, through October 31, 1995, 4939 patients underwent primary PTCA and 24705 received rt-PA. Baseline characteristics of the two groups were similar after lytic-ineligible patients and those in cardiogenic shock at admission, were excluded. Patients in rt-PA group had thrombolytic therapy initiated at a median time of 42 minutes after admission; the median time to first balloon inflation was 111 minutes after admission in the PTCA group, a significant difference.

        

    In-hospital mortality was significantly higher in patients in shock after rt-PA [52%] than after PTCA [32%]. Among the rt-PA patients with no shock, the in-hospital mortality
    not was similar in the two groups [5.4% and 5.2% respectively]. The rate of re-infarction did not differ in the two groups [2.9% after rt-PA and 2.5% after PTCA], nor did the combined end point of death and nonfatal stroke.

         

    Thus, in patients not in cardiogenic shock, both methods of treatment gave similar results, in in-hospital mortality, non-fatal stroke and reinfarction. Primary PTCA may be preferable for patients with a contraindication to lytic therapy, for those who are hemodynamically unstable and for those at increased risk of intracranial bleeding.

        

  • Fried LP, for the Cardiovascular Health Study Collaborative Research Group [John
    Hopkins Med Institutions, Baltimore, Md]

    Risk Factors for 5-Year Mortality In Older Adults : The Cardiovascular Health Study

    JAMA 279: 585-592, 1998

        

    Little is known regarding the joint contributions of diseases and disability to mortality. Few population-based studies have information on objectively measured clinical or subclinical diseases to provide insight into how multiple factors contribute to mortality in older adults. In community-dwelling men and women aged 65 years or older, the disease, functional, and personal characteristics that jointly predict mortality were determined. There were 5201 men and women aged 65 years or older from 4 U.S. communities. Also studied were a supplemental cohort of 685 African-American men and women. Demographic characteristics, self-assessed health status, health habits, physical activity, physical function, and medications used were recorded, as well as a self-report of physician diagnosis of myocardial infarction, angina, congestive heart failure, hypertension, stroke, transient ischemic attack, asthma, hearing impairment, visual impairment, and cancer. Other measures included cardiovascular and pulmonary diseases and blood pressure. 

          

    Within 5 years, there were 646 deaths [12%]. Twenty of 78 characteristics were significantly and independently associated with mortality, including increasing age, income less than $ 50,000 per year, male sex, lack of moderate or severe exercise, low weight, high brachial systolic blood pressure [ greater than 169 mm Hg], low tibial systolic blood pressure [less than 127 mm Hg], smoking for more than 50 pack-years, elevated fasting blood glucose level [greater than 130 mg/dL], diuretic use by those without hypertension or congestive heart failure, elevated creatinine level [1.2 mg /dL or greater], low albumin level [37 g/L or less], aortic stenosis and abnormal left ventricular ejection fraction, low forced vital capacity [2.06 mL or less], stenosis of internal carotid artery, major electrocardiographic abnormality, difficulty in any instrumental activity of daily living, congestive heart failure, and low cognitive function by Digit Symbol substitution test score. Mortality was not associated with high-density or low-density lipoprotein cholesterol. The association between age and mortality diminished after adjustment for other factors, but the reduction in mortality with female sex continued. Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults. 

        

    Other predictors were male sex, relative poverty, smoking, physical activity, indicators of frailty, and disability. Objective, quantitative measures of disease were better predictors of mortality than was a clinical history of disease, except for a history of congestive heart failure. 

            

  • Iacoviello L, Di Castelnuovo A, De Knijff P, et al [Istituto di Ricerche Farmacologiche Marigo Negri, Santa Maria Imbaro, Italy; Leiden Univ, The Netherlands]

    Polymorrhisms In the Coagulation Factor VII Gene and The Risk of Myocardial Infarction

    N Eng J Med 338: 79-85, 1998

        

    A growing body of evidence suggests that patients with high blood levels of coagulation factor VII are associated with an elevated risk of ischemic vascular disease. Environmental and genetic factors may affect the level of factor VII in the blood. However, the relationships among genetic polymorphisms of factor VII, blood levels of factor VII, and myocardial infarction risk are unknown. These associations were investigated in a case-control study.

          

    The cases were 165 patients [mean age, 55 years] with familial myocardial infarction. The controls were 225 individuals [ mean age, 56 years] with no personal or family history of cardiovascular disease. Each individual underwent DNA studies for polymorphisms involving R353Q and the hypervariable region 4 of the factor VII gene. Measurements of factor VII clotting activity and antigen levels were obtained as well. The effects of factor VII gene polymorphisms on myocardial infarction risk and on factor VII levels were analyzed.

         

    The risk of myocardial infarction was reduced for patients with QQ genotype [odds ratio, 0.08; 95% confidence interval, 0.01-0.09] and the H7H7 genotype [odds ratio, 0.22; 95% confidence interval, 0.08-0.63]. Analysis of the R353Q polymorphisms suggested that risk was highest with the RR genotype, intermediate with RQ genotype, and lowest for the QQ genotye. When the hypervariable region 4 polymorphism was considered, patients with the H7H5 or H6H5 genotype were at highest risk, followed by the H6H6, H6H7 and H7H7 genotypes. Factor VII antigen level and factor VII clotting activity were reduced for patients with the QQ or H7H7 genotype vs. the RR or H6H6 genotype. Myocardial infarction risk was reduced for patients at the lowest vs. the highest level of factor VII clotting activity [odds ratio, 0.13; 95% confidence interval, 0.05-0.34].

          

    Thus Factor VII gene polymorphisms appear to influence myocardial infarction risk, perhaps acting through differences in factor VII levels. The mechanism by which the polymorphism influences factor VII levels is unknown. The clinical ramifications of these finding must be evaluated in prospective clinical trials.

       

  • Liem AL, van’t Hof AWJ, Hoorntje JCA, et al [ Hosp de Weezenlanden, Zwolle, The Netherlands]

    Influence of Treatment Delay in Infarct Size And Clinical Outcome In Patients with Acute Myocardial Infarction Treated with Primary Angioplasty

    J Am Coll Cardiol 32: 629-633, 1998

         

    There is great relationship between time to treatment and patency rate among patients given thrombolytic therapy for acute myocardial infarction, but this is less evident in patients treated with primary angioplasty. The effect of delay caused by transfer to an angioplasty center was examined in the study of 207 patients.

        

    Outcome was compared for patients transferred from a community hospital to the study institute for primary angioplasty and patients directly admitted to the study institution. Each transferred patient was matched to a direct patient. Primary angioplasty was considered successful if the residual stenosis in the infarct-related artery was less than 50% and if thrombolysis in myocardial infarction grade 3 flow was present after the procedure.

       

    The median additional delay for transfer patients was 43 minutes. Transferred and nontransferred groups were similar in baseline characteristics and in-hospital outcome. At 6 months, 7% of patients in the transfer group and 6% in the nontransfer had died. Reinfarction had occurred in 4% of the former and 3% of the latter group. Left ventricular ejection fraction at 6 months was 47% and 43% respectively in the two groups. Transferred patients also had more extensive enzymatic infarct size.

        

    Although transferred acute myocardial infarction patients had a larger infarct size and lower left ventricular ejection fractions than the patients admitted directly for angioplasty, the patency rate and 6 month outcome were not adversely affected by the delay. 

       

  • Roger Dobson

    Spider venom may prevent atrial fibrillation


    BMJ, Jan.13, 2001, p.71


         

    Venom from a common South African tarantula spider may contain a protein that could prevent atrial fibrillation.

         

    In the research reported in ‘Nature’ US and German scientists investigated what kind of insect venom could block ion channels and prevent cells from swelling and triggering atrial fibrillation. The poison from Chilean Grammostola spatulata tarantula worked with the peptide GSMtx-4 as the active ingredient.

        

    Rabbit hearts were electrically stimulated to produce arrhythmia and extracts of the venom successfully suppressed the arrhythmia that followed 

       

  • Satyendra
    Giri, C Michael White, et al

    Oral Amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.


    Lancet, Vol.357. March 17, 2001, pg. 830-836


          

    Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is not known. Authors assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.

          

    Patients (average age 73 years) received 6G of amiodarone or placebo over 6 days beginning on preoperative day 1.

         

    Interpretation of the findings was that oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.

      

  • Neil R Grubb (Univ. of Edinburgh Cardiovascular Unit)

    Managing out-of-hospital cardiac arrest survivors:

    Cardiological perspective

    Heart 2001; 85: 123-124, p.123

       

    Implantable cardioverter defibrillators (ICDs) significantly reduce the risk of sudden death in specific patient subgroups.

       


    Approximately, 40% of out-of-hospital cardiac arrest victims have the underlying substrate of acute myocardial infarction. The patients are normally suitable for thrombolysis. However, many of the patients were being revived got thoracic trauma during external cardiac massage. Such patients may survive with thrombolysis. X-ray is then necessary before administration of thrombolytic drugs.

        


    Many patients have cardiac arrest without previous myocardial infarction. However most of them are patients of ischaemic heart disease without acute myocardial infarction. At rest they may have normal ECGs. In such patients coronary angiography is mandatory.

      


    Some patients with a normal heart develop cardiac arrest. They usually have right bundle branch block (RBBB), ST segment elevation and are prone to sudden death. For such patients ICD is life-saving.

        

    While ICDs are extremely useful, they should not be used under certain circumstances. Most important are cardiac arrests caused during evolution of myocardial infarction, in those with frequent ventricular arrhythmias and patients having very rapid heart rate.

       

  • U B Fallon, Y Ben-Shlomo, et al (Dept. of Social Medicine, Univ. of Bristol,UK)

    Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up.

    Heart Feb.2001; 85: 153-158

        


    Although there is a hypothesis that a raised homocysteine concentration in blood is a strong independent risk factor for coronary heart disease, randomized controlled studies in a village in Wales showed that there was no co-relation between homocysteine blood levels and coronary heart disease.

       

  • Martin Riedel (Germany)

    Editorial – Emergency diagnosis of pulmonary embolism

    Heart June 2001, vol.85: 607-609

      


    Emergency diagnosis of pulmonary embolism is the first prerequisite of saving the life of the patient. CT has emerged as a very valuable tool. It is both widely available and results are almost as good as angiography.

      


    Transthoracic echocardiography (TTE) is also widely available. It is non-invasive and very accurate in diagnosis of floating emboli. Transesophageal echocardiography (TOE) is perhaps even superior to TTE. It visualizes the proximal pulmonary arteries. When pulmonary embolism is suspected, TTA followed by TOE and CT gives very specific and precise diagnosis to enable surgery if indicated.

       

  • General
    Cardiology


    Heart June 2001, 85: 613

       

    Generally speaking, LBBB is considered to be of serious import but RBBB is thought to be comparatively not very dangerous. After a series of analysis of 200,000 young patients, it has been demonstrated that complete RBBB is not benign and it becomes more important with progress in age or if it complicates myocardial infarction. Partial RBBB does not share this bad prognosis.

      

  • Milton Packer et al.

    Carvedilol and Survival in Chronic Heart Failure


    NEJM, Vol.344(22), p.1649


         


    Although beta-blockers are used to treat mild-to-moderate heart failure, they are usually avoided in patients with severe heart failure because of the concern that they may worsen the condition. In this randomized trial, the effects of carvedilol, which blocks a1 – b1-, and b2-receptors, were studied in patients with severe heart failure. As compared with placebo, carvedilol reduced the risk of death by 35 percent and the combined risk of death or hospitalization by 24 percent.

         

  • Elizabeth
    Barrett-Connor and Deborah L Wingard

    Normal blood glucose and coronary risk

    Dose response effect seems consistent throughout the
    glycaemic continuum.

    BMJ, Vol.322; 6 Jan 2001, p.5

       

    Glycosylated haemoglobin is an accurate indicator of
    blood glucose level over the preceeding 6-12 weeks.
    It is a more precise predictor of coronary heart
    disease risk. Even in patients without diabetes a
    glycosylated haemoglobin level in the higher
    brackets has been shown to be an indicator of
    impending coronary disease. However lowering of
    glycosylated haemoglobin has not been shown to have
    any significant benefit in reducing cardiovascular
    risk.. Anti-hypertensive treatment is far more
    effective

         

  • Bauters C, Hubert E, Prat A, et al [Univ of Lille, France, INSERM CJF, Lille, France]

    Predictors of Restenosis After Coronary Stent Implantation

    J Am Coll Cardiol 31: 1291-1298, 1998

       


    For patients with coronary artery disease, balloon angioplasty and stenting, has become a treatment of choice, for coronary revascularisation, with improvements in the quality of stents. The technique has been widely used in diabetic patients, in rescue situations, and in vessels smaller than 3 mms. The 6-month angiographic outcome after successful coronary stenting was studied.

        


    There were 463 patients who had successful coronary stenting in 500 lesions. All received antiplatelet therapy. There were 19% patients with diabetes, 71% were smokers, 38% had hypertension, 59% had hypercholesterolemia, 49% had family history of coronary artery disease, and 36% had unstable angina. 

       


    At angiographic follow-up, restenosis [defined as 50% or more stenosis of the vessel diameter] was present in 26% of 405 lesions. During the follow-up period mean late lumen loss was 0.79, +/- 0.64 mm.
    A higher late lumen loss was seen in patients with multiple stents. Other independent predictors of stenosis were longer lengths of stenosis, smaller vessel diameters and type of stents used; the authors have had best results with the Palmaz-Scatz stents. The rate of stenosis is high even though the patient sample is poor

       

  • David I Silverman, Warren J Manning

    Editorial – Strategies for cardioversion of atrial fibrillation – time for a change.

    NEJM, Vol. 344, May 10, 2001,pg.1468.

         


    Cardioversion of atrial fibrillation is one of the oldest therapies in cardiovascular medicine. Thromboembolism is a major adverse outcome but warfarin therapy given for 3-4 weeks before cardioversion has reduced this by 80%.

      


    Transthoracic (surface) echocardiography is inadequate for identification of atrial thrombi especially those confined to atrial appendages. Transesophageal echocardiography is accurate for detection of atrial thrombi. 

       

    John Klein and colleagues have used this technique without prior prolonged treatment with anticoagulants for safe and early cardioversion. They enrolled more than 1200 patients in a prospective, randomized study comparing therapy guided by transesophageal echocardiography with the conventional strategy. Their primary findings were that the two strategies were associated with similar rates of embolic events but that the use of transesophageal echocardiography was associated with significantly fewer hemorrhagic complications. This 70-center trial provides reassurance that transesophageal echocardiographic screening for atrial thrombi can be readily and accurately performed in routine clinical practice. Therapeutic levels of anticoagulation should be present at the time of this procedure and continued for at least one month after cardioversion.

       


    The patient most likely to benefit from transesophageal echocardiographic approach is probably the patient who has atrial fibrillation of less than 3 weeks duration or who has an increased risk of haemorrhagic complications during prolonged warfarin therapy.

       

  • Meier CR, Jick SS, Derby LE, et al [ Boston Univ]

    Acute Respiratory -Tract Infections and Risk of First-Time Acute Myocardial Infarction

    Lancet 351: 1467-1471, 1998

       

    More deaths occur from cardiovascular diseases, especially acute myocardial infarction [AMI] in winter than in summer, an association that may be explained by the greater number of acute respiratory-tract infections during cold weather. A large, population-based study explored the link between acute respiratory –tract infections and AMI.

         

    Data were obtained from the UK General Practice Research Database. Cases were patients with first-time diagnosis of AMI during a three-year period [ 1994-1996], no history of clinical risk factors, and were age 75 years or younger. Four controls were matched to each case on the basis of age, sex, and practice attended. In both groups, the date of the last respiratory-tract infection before the index date was identified. In a case cross-over analysis, cases acted as their own controls.

         

    The final database consisted of 1922 cases. In 1994 and 1995, more cases of AMI occurred in the winter, with the highest number [175] in January and the lowest [110] in June. Significantly more cases than controls had an acute respiratory -tract infection in the 10 days before the index-date [2.8% vs 0.9%]. After adjustment for smoking, and bodymass index, the odds ratio for first-time AMI in association with an infection was 3.6 when the infection occurred 1 to 5 days before the index date. The relative risk for AMI was 2.7 in the cross-over analysis when the infection occurred in the 10 days before the index date. Although cause and effect cannot be assumed, findings suggest that there is a seasonal variation in AMI.

       

  • NZ
    Mian, R Bayly, DM Schreck, etal (Muhlenberg Regional Med Ctr, Plain-field, NJ)

    Incidence of Deep Venous Thrombosis Associated with Femoral Venous Catheterization.

    Acad Emerg Med 4:1118-1121, 1997

        

    The study evaluated 42 patients admitted over a 14-month period subjected to a Heparin-coated 7-fr 20-cm femoral venous catheters. Each patient was subjected to a venous duplex sonography within 7 days of catheter removal. 

         


    Although the study has shown 26% of patients to develop DVT, it does not justify the patients undergoing femoral vein catheterization to be subjected to studies for hypercoaguable states. There is always the potential for substantial morbidity following femoral vein catheterization. Hence, the risk and benefit must be considered prior to this procedure, and complications must be anticipated.

          

  • Khan MA, Herzog CA, St. Peter JV, et al (Hennepin County Med Ctr, Minnesota Heart Clinic, Univ of Minnesota, Minneapolis)

    The Prevalence of Cardiac Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs 

    N. Engl J. Med 339: 713-718, 1998 

          


    A number of obese patients on fen-phen an appetite suppressant, have shown multivalvular disease. The prevalence and severity of valve dysfunction in obese patients taking appetite suppressants was compared with those not taking the drugs.

        


    Of 233 patients and 233 controls in the study, significantly more patients than controls, had cardiac valve abnormalities (22.7% vs 1.3%).

         


    Obese patients who took appetite suppressants showed higher prevalence of valvular insufficiency than obese patients not taking appetite suppressants.

          

  • Antonio P, Beltrami, Konrad Urbanek et al

    Evidence that human cardiac myocytes divide after myocardial infaction

    New Eng J.of Med., vol.344, June 2001, pg.1750.

          


    After myocardial infarction, there is scarring of the heart and this is interpreted as evidence that myocytes are unable to divide. Recent observations have provided evidence that myocytes of adult heart proliferate. Authors have studied the extent of mitosis among myocytes after myocardial infarction in humans.

         


    Myocytes were obtained from the border of the infarct, from areas of myocardium distant from the infarct and from normal hearts. Myocytes that had entered the cell cycle in preparation for cell division were measured by labelling the antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined and the mitotic index (ratio of number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. In the infracted hearts, Ki-67 expression was detected in 4 percent of mycocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts.

          


    Authors conclude that these results challenge the dogma that the adult heart is a postmitotic organ and raise the possibility that the regeneration of myocytes may contribute to the increase in muscle mass of the myocardium

        

  • Nadia Rosenthal

    Editorial – High hopes for the heart

    New Eng J of Med. June 7, 2001; vol.344, pg.1785

       


    The heart is less well-equipped to deal with injury as compared to other tissues. This most critical organ is also the most mortal since it has been widely accepted that the muscle cells of the adult heart are incapable of self-renewal.

      


    Beltrami et al found that the number of Ki-67 positive nuclei in actin-positive cells from hearts with MI was 84 times as high. In distant parts of the myocardium of infracted hearts, such cells were 28 times as frequent as in comparable zones of control hearts. Ki-67 is a reliable marker of mitotic activity. This lends support to the notion that necrosis that follows cardiac injury stimulates the compensatory proliferation of muscle cells.

          


    The level of cardiomyocyte proliferation would hardly be extensive enough to counter the massive necrosis that follows a heart attack, but may be sufficient to repair subclinical lesions after blockage of small capillaries. It is not clear how long the level of proliferation would have persisted had the patients lived. Additional revascularization of repaired scar tissue would be critical to ensure survival of new myocardium. None of these processes are normally efficient enough to prevent ventricular remodeling and progression to heart failure.

       


    The same group of investigators recently reported the persistence of bone marrow cells from an adult donor mouse that had been genetically engineered to express green fluorescent protein, after their injection into the infracted area of a recipient mouse heart that had undergone coronary artery ligation. These cells differentiated into cardiomyocytes, endothelial cells and smooth muscle cells and partially restored cardiac function. Another group selected a subpopulation of bone-marrow cells from human donors and marked them in-vitro. When introduced intravenously into the circulation of athymic rats after induction of MI, these cells migrated to the infarcted zone, differentiated into blood vessels, and induced revascularisation of surrounding rat myocardium, resulting in reduction of apoptosis and scar formation and long-term restoration of cardiac function. Successful incorporation of a patients’ own banked stem cells into multiple cardiac tissues might induce repair of a damaged heart.

          


    The current studies challenge the dogma and suggest exciting new therapeutic pathways to explore.

         

  • G Richardson, AR Moore, et al (Dept. of Cardiology, London)

    Copper generates Nitric oxide from S-Nitrosoglutathione to inhibit platelet function – a potential stent coating?

    Heart May 2001; 85(Suppl.1): P1

       


    Copper produces NO from GSNO to inhibit platelet function in vitro. Coverage of stainless steel with small quantities of copper may not induce significant inflammatory responses. Further re-evaluation of copper, as a stent coating to generate NO, is required.

          

  • J P J Halcox, G Zalos, et al (National Insitutes of Health, Bethesda, Maryland, USA)

    Sildenafil: Effects on Human Vascular Function, Platelet Activation and myocardial Ischaemia

    Heart May 2001; 85(Suppl.1): P.24

          


    Sildenafil dilates epicardial coronary arteries, reduces platelet actrivation, and improves endothelial dysfunction in the coronary and peripheral circulations of CAD patients. Sildenafil had an intermediate effect on myocardial ischaemia compared to ISDN and placebo. Thus, PDE5 inhibitors may be of therapeutic value in atherosclerosis.    

         

  • Israel in stem cell breakthroughs

    Scrip No.2667, August 8, 2001, p.22

        

    Researchers in Israel have made advances in stem cell research which could have applications for heart attack and diabetes patients. They have succeeded in producing heart cells from stem cells (cardiomyocytes) and insulin producing islet cells both in the laboratory stage. If they succeed, there will be major changes in the treatment of heart disease and diabetes.

        

  • Aldo P Maggioni

    Secondary prevention: improving outcomes following myocardial infarction.

    Heart 2000; 84(Suppl.1):i5-i7

         

    Early treatment with ACE inhibitors reduces the expansion of infarct and ventricular enlargement. Most (80%) of the benefit is obvious in the first week of onset of symptoms. These benefits achieved during the first week are maintained for atleast 4 years. There is reduction of mortality in all patients.

        

    Therefore ACE inhibitors should be considered in every MI patients as a parallel benefit. The incidence of diabetes is reduced.

       

  • John G F Cleland

    Improving patient outcomes in heart failure: evidence and barriers

    Heart 2000: 84 (Suppl.1): i8-i10.

         

    In the treatment of heart failure, the most important step is initiation of ACE inhibitors. Higher doses are necessary to exert great benefits. There is now conclusive evidence of the benefit of ACE inhibitors with beta blockers for treatment of heart failure.

        

  • M Petrie, J McMurray

    Changes in notions about heart failure

    The Lancet, Vol.358: 11 August 2001, p.432.

       

    Chronic Heart Failure (CHF) has been traditionally thought of as a clinical syndrome of breathlessness, fatigue and salt and water retention. Until lately the focus has been on symptoms and left ventricular systolic dysfunction. 

       

    In large survey of 3960 patients, in person over 45 years, who were examined and investigated in great detail, it was found that approximately half the patients had no symptoms. Left ventricular ejection fraction was seen as diminished in 139 patients out of 3960. Ejection fraction was calculated by echocardiography and when followed up the 5-year mortality rate was 50-75%.

       

    In treatment, ACE inhibitors were the drugs of choice given in adequate doses. Combination with beta blockers further improved the prognosis.

        

  • Helen Frankish

    News -Researchers turn human stem cells into heart tissue

    The Lancet, vol358, August 11, 2001, p.475

       

    A case report is presented whereby injection of human stem cells taken from patient’s hip has been injected into the coronary circulation, which has lead to growth of new myocytes. The work is under progress in Israel. Human stem cells are being experimented with for manufacture of pancreatic beta cells for treatment of diabetes.

         

  • Yoshiki Sawa

    Therapeutic angiogenesis with gene transfection for ischaemic heart disease.

    Drugs of Today, 2001, 37(1), pg.67-71

          

    Genetic engineering studies conducted in the field of cardiovascular medicine have lead to the use of gene therapy as a means of treating ischaemic disease. Folkman et al have shown that tumour growth is facilitated by revascularisation and revascularization factors are involved in tumour growth. The first revascularisation factor used for therapeutic angiogenesis was basic fibroblast growth factor (bFGF). In a rabbit model of acute leg ischaemia, 14 day IM treatment with bFGF at a dose of 1 or 3 mg promoted the formation of collaterals in the legs. Possibility of treating myocardial infarction has also been reported. Intramyocardial injection of vascular endothelial growth factor (VEGF) on induction of myocardial revascularisation has been shown in dogs and pigs.

          

    Clinical trials of gene therapy using VEGF have started at Tufts University in U.S. This therapy is designed to treat severe ischemic disease with revascularisation. VEGF genes were injected locally into myocardium after small thoracotomy. More than 70 patients have undergone this therapy and revascularisation and improved regional blood flow as assessed by angiography and myocardial scintigraphy has been reported. Crystal and coworkers at Cornell University have administered VEGF cDNA on an adenovirus vector into the myocardia of about 30 patients, with or without coronary artery bypass grafting, and reported revascularising effect and safety of this therapy. 

         

    Revascularising effects of HGF:- Hepatocyte growth factor has been shown to be specific to vascular endothelium and does not affect proliferation of vascular smooth muscle.

        

    Studies in rats have shown that HGF increases the number of newly formed blood vessels. HGF is more potent than VEGF and clinically useful. Introduction of HGF gene, which is a revascularisation factor produced endogenously, may be a new means of treating severe ischaemic heart disease.

            

  • S.L. Udupa

    Indigenous drugs and atherosclerosis

    Drugs of Today 2001, 37(1), 37-47

         

    An encouraging field for the application of indigenous drugs is regression of atherosclerosis. Vitamins C and E, carotenoids, flavonoids, terpenoids present in indigenous drugs have been shown to slow down progression of experimental atherosclerosis. Potassium and magnesium found in herbals are also beneficial.

          

    This is a review of some of the Indian indigenous drugs, found to be antiatherogenic. 

         

    The drugs included are: 

    (1) Achyranthus aspera – contains triterpenoids. Hypocholesterolemic effect in rats. 

         

    (2) Allium cepa (onion) – therapeutic effects attributed to sulphur compounds.

         

    (3) Allium satiuum (garlic) – known to have hypoglycaemic, hypocholesterolemic and hypolipidemic effects and protects against the development of atherosclerosis. The inhibition of cholesterol synthesis by garlic may be due to a mixture of multiple compounds of sulfur containing thiosulfinates, ajoenes and dithienes.

         

    (4) Aloe barbedensis – Lipid lowering agent lowers VLDL and LDL and increases HDL.

        

    (5) Capsicum annum (Red pepper). Red pepper or its active principle capsaicin prevented increase in cholesterol levels in rats.

       

    (6) Cicer arientinum – Bengal gram. Hypolipidemic effect
    – due to its isoflavonic component – Biochanin A.

        

    (7) Commiphora mukul – Crude guggul or its oleoresin lowers serum cholesterol in rabbits. Similar effect shown in patients with hypercholesterolemia. Long-term combination treatment with fraction A guggul and cholestyramine resulted in decrease in serum cholesterol and triglyceride levels.

       

    (8) Dolicos lablab – seeds used as pulse in diet. Reduces serum cholesterol in rats.

        

    (9) Emblica officinalis – Its fruit (amla) is probably the richest known natural source of vitamin C. Dietary supplementation with raw amla in normal and hypercholesterolemic subjects resulted in a decrease in cholesterol levels.

        

    (10) Medicago sativa : (Alfalfa). Alfalfa meals prevent hypercholesterolemia, triglyceridemia and atherogenesis in cholesterol fed rabbits.

         

    (11) Plantago ovata – They are a class of gel-forming, nonabsorbable, soluble fibres derived from oat or psyllium seed husk which have been shown to produce cholesterol lowering effects when added as dietary supplements. Addition of psyllium hydrophilic mucilloid to cholestyramine therapy may improve patient compliance by reducing drug-associated GI side-effects.

         

    (12) Terminalia arjuna – Powdered bark is used. Constituent of many Ayurvedic preparations shown to decrease serum cholesterol and blood sugar levels in experimental animals after 3 months of treatment. It is also reported to have antihypertensive and antiarrhythmic properties.

        

    (13) Terminalia belerica – Alcoholic extract has dose-dependent hypotensive effect. It is present in Triphala (T.belerica, T.chebula and E.officinalis).

        

    (14) Terminalia chebula – Reduces cholesterol levels in experimental atherosclerosis in rabbits.

        

    (15) Trichosanthes dioica – Fruit used. Hypoglycemic and hypocholesterolemic effects in normal and mildly diabetic humans.

         

    (16) Trigonella foenum graecum – The seeds (fenugreek)
    – caused cholesterol levels to decrease in diabetic hypercholesterolemic dogs. Also reduces hyperglycemia. Ethanol extract from defatted fenugreek seeds contained saponins that inhibit absorption of taurocholate and deoxycholate.

          

    In type I diabetes, fenugreek diet significantly reduced fasting blood sugar and improved glucose tolerance test. Serum cholesterol, LDL and VLDL and TG were significantly reduced but HDL was unchanged.

          

  • Frank B Hu.

    The role of N-3 polyunsaturated fatty acids in the prevention and treatment of cardiovascular disease.

    Drugs of Today, 2001, 37(1): 49-56

        

    Several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing MI. Epidemiologic and clinical studies have suggested that alpha-linoleic acid (ALA), a short-chain n3-3 fatty acid from plant sources may have similar cardiac benefits as long chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. Reduction of TG levels, reduction of platelet aggregation also contribute. There is growing evidence that fish oil may improve endothelial dysfunction.

        

    Substantial evidence is there for beneficial effects of ALA on CVD. Flaxseed as well as other important dietary sources of ALA e.g. unhydrogenated canola, soyabean oil and walnuts can be incorporated into a healthy and balanced diet for prevention of CVD. This is especially important for persons who do not consume fish.

        

  • G Richardson, AR Moore, et al (Dept. of Cardiology, London)

    Copper generates Nitric oxide from S-Nitrosoglutathione to inhibit platelet function – a potential stent coating?

    Heart May 2001; 85(Suppl.1): P1

         

    Copper produces NO from GSNO to inhibit platelet function in vitro. Coverage of stainless steel with small quantities of copper may not induce significant inflammatory responses. Further re-evaluation of copper, as a stent coating to generate NO, is
    required.

         

  • J P J Halcox, G Zalos, et al (National Insitutes of Health, Bethesda, Maryland, USA)

    Sildenafil: Effects on Human Vascular Function, Platelet Activation and myocardial Ischaemia

    Heart May 2001; 85(Suppl.1): P.24

          

    Sildenafil dilates epicardial coronary arteries, reduces platelet actrivation, and improves endothelial dysfunction in the coronary and peripheral circulations of CAD patients. Sildenafil had an intermediate effect on myocardial ischaemia compared to ISDN and placebo. Thus, PDE5 inhibitors may be of therapeutic value in atherosclerosis.

        

  • Patrick
    Tounian, Yacine Aggoun, et al 

    Presence of Increased Stiffness of the Common Carotid Artery and Endothelial Dysfunction in Severely Obese Children: A Prospective Study 

    Lancet, Vol.358, October 27, 2001, Pg. 1400-04

         


    Summary: Epidemiological studies suggest that obesity induced atherosclerosis may start in childhood, but this process has never been demonstrated.

          


    The authors looked for arterial changes and investigated their relation to cardiovascular risk factors in obese children.

          


    Non-invasive ultrasonographic measurements were made in 48 severely obese children and 27 controls to investigate arterial mechanics and endothelial function. Plasma lipid concentrations, indices of insulin resistance, and body composition were assessed in obese children.

          


    Severe obesity in children is associated with arterial wall stiffness and endothelial dysfunction. Low plasma apolipoprotein-A-I, insulin resistance, and android fat distribution may be the main risk factors for these arterial changes, which are of considerable concern as possible early events in the genesis of atheroma.

         

  • Bruce
    Zuraw

    Commentary – Bradykinin In Protection Against
    Left-Ventricular Hypertrophy

    Lancet, Vol. 358, October 6, 2001, Pg. 1116-18

         

    Summary : Left-Ventricular hypertrophy
    substantially increases risk of sudden death and other
    cardiovascular complications even after adjustment for
    other known risk factors.

        

    On the basis of pressor and remodeling effects of
    angiotensin II, the reninangiotensin system is widely
    thought to play an important part in the development
    of LVH. Efficacy of ACE inhibitors in lessening
    progressive LV remodeling and rates of sudden death in
    patient with LV dysfunction further proves the
    importance of this system.

          

    ACE generates angiotensin II but also degrades
    bradykinin, and bradykinin is the preferred ACE
    substrate. Of the 2 angiotensin receptors that have
    been identified, AT1 receptors mediates the
    pressor effect whereas AT2 receptor
    mediates hypotensive effects.

         

    David Brull and colleagues have reported that
    individuals with the greatest increase in LV mass had
    the highest concentration of ACE and the lowest
    concentration of B2 bradykinin receptor.
    These results strongly support an important role for
    bradykinin in the ACE medicated effect on LVH.

         

    Bradykinin mediates important cardiovascular effects,
    such as increased vascular permeability, enhanced
    myocardial glucose uptake, negative intropism and
    inhibition of myocardial growth. Bradykinin has been
    shown to play an intergral part in protecting
    ischaemic myocardium. Genetically ablating B2
    bradykinin receptors result in enhanced salt-induced
    hypertension and hypertropic cardiomyopathy.

         

    There is also evidence of interaction between
    bradykinin and rein-angiotesin system. It is now seems
    that bradykinin ia an important participant in the
    cardiac effects of the renin-angiotensis system and
    novel pharmaceutical approches to further increase
    bradykinin concentrations may be clinically
    beneficial.

        

    It is important to recognise that the ACE and B2
    bradykinin-receptor polymorphisms account for only a
    fraction of the total variability in the expression of
    LVH.

         

    A complete understanding of LVH variability is certain
    to be extremely complex, involving multiple gene
    interactions as well as gene-environment interactions.

             

  • Franz-Josef Neumann, Adnan Kastrati et al 

    Treatment of Chlamydia pneumoniae Infection with Roxithromycin and Effect on Neointima Proliferation After Coronary Stent Placement (ISAR-3): A Randomised, Double-Blind, Placebo-Controlled Trial 

    Lancet, Vol.357, June 30, 2001, Pg. 2085-89

          

    Summary : Vascular infection with Chlamydia pneumoniae might boost inflammatory responses that play an important role in neointima formation, which is the main cause of restenosis after stenting.

          

    The aim of this study was to investigate whether or not treatment of Chlamydia pneumoniae infection with antibiotics prevents restenosis after stent placement. 

           

    The interpretation of this study was that non-selective use of roxithromycin is inadequate for prevention of restenosis after coronary stenting. There is a differential effect dependent on Chlamydia pneumoniae titres. In patients with high titres, roxithromycin reduced the rate of restenosis.

           

  • C. Varma and S J D Brecker 

    Predictors of Mortality in Acute Myocardial Infarction 

    Lancet, Vol.358, November 3, 2001, Pg. 1473-74

           

    Summary : Initial treatment of myocardial infarction is aimed at establishing coronary artery patency, but it is myocardial viability that determines prognosis. Flow in the related artery is not always associated with myocardial perfusion because of microvascular damage.

          

    Angioplasty is the most successful method of reperfusion, but it is restricted by logistical issues, and for most patients thrombolysis is the initial method of reperfusion. 

           

    The most reliable predictor of outcome after myocardial infarction is the concentration of troponin T. Troponin concentration may start to rise within 6 h of infarction, and takes only 20 min to measure. Other predictors are ST-segment elevation and increased concentrations of kinase. C reactive protein and myoglobin are also of prognostic value.

          

    ECG is still the most widely used diagnostic tool and according to GUSTO-IIb study the 30-day incidence of death or myocardial reinfarction was 10.5% among those with ST-segment depression and 12.4% among those with ST elevation and depression. ST depression is also the strongest predictor of 1-year mortality among patients with acute coronary syndromes.

         

    In a study reported by Klaus Schroder and colleagues, they found that mortality at 180 days was predicted by analysis of just 1 ECG lead (the one with maximum deviation at 90 min) and that the ST deviation (not resolution) in this single lead was a better predictor than sum STR.

           

    Although the investigators used a lens-intensified calliper for their measurements, most of the measures are large enough not to require any special equipment.

            

    Novel adjunctive therapies for reducing microvascular damage and improving myocardial perfusion (myocardium protective agents and vascular growth factors) are being investigated.

             

  • Klaus
    Schroder, Karl Wegscheider et al 

    Extent of ST-Segment Deviation in a Single Electrocardiogram Lead 90 Min After Thrombolysis as a Predictor of Medium-Term Mortality in Acute Myocardial Infarction 

    Lancet, Vol.358, November 3, 2001, Pg. 1479-86

             

    Summary : In evolving myocardial infarction, assessment of the sum of early resolution of ST-segment elevation (sumSTR) has become an established method to predict outcome. 

           

    Authors have found previously that mortality is predicted more accurately by the existing ST-segment deviation in the single ECG lead with maximum deviation (maxSTE) 90 min after start of thrombolysis. Authors compared the power to predict medium-term mortality by these 2 approaches.

          

    Interpretation of this study was that, maxSTE predicts early and medium-term mortality more accurately than does sumSTR. The prognosis for an individual patient can be accurately estimated simply by the ST-segment deviation present in one ECG lead recorded 90 min after
    thrombolysis.

           

  • Gusto V Investigators 

    Reperfusion Therapy for Acute Myocardial Infarction with Fibrinolytic Therapy or Combination Reduced Fibrinolytic Therapy and Platelet Glycoprotein IIb/IIIa Inhibition: The GUSTO V Randomised Trial 

    Lancet, Vol.357, June 16, 2001, Pg. 1905-14

          

    Summary : Plasminogen activator therapy for acute myocardial infarction is limited by lack of achievement of early, complete, and sustained reperfusion in a substantial proportion of patients. Many phase II trials have supported the potential of combined fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition for improving reperfusion.

         

    The authors’ did a randomised, open-label trial to compare the effect of reteplase alone with reteplase plus abciximab in patients with acute myocardial infarction.

          

    Interpretation: Although combined reteplase and abciximab was not superior to standard reteplase, the 0.3% absolute (5% relative) decrease in 30-day mortality fulfilled the criteria of non-inferiority. 

          

    Combination therapy led to a consistent reduction in key secondary complications of myocardial infarction including reinfarction, which was partly counterbalanced by increased non-intracranial bleeding complications.

          

  • Freek W A Verheugt

    Commentary: GUSTO V: The Bottom Line of Fibrinolytic Reperfusion Therapy 

    Lancet, Vol.357, June 16, 2001, Pg. 1898-99

           

    Summary: Several drugs that could provide additional benefit to thrombolytic therapy have been investigated. Addition of heparin has not improved early patency rates or prevented reocclusion and has increased frequency of bleeding especially cerebral bleeding.

          

    Hirudin, a direct inhibitor of thrombin was similar. Aspirin, in addition to streptokinase, decreased mortality and has shown benefit of inhibiting platelet aggregation.

          

    Antagonists to the glycoprotein IIb/IIIa receptor, such as abciximab, eptifibatide or tirofiban, block the final common pathway of platelet aggregation. These drugs given IV have improved outcome of fibrinolytic agent and a glycoprotein protein abciximab has been extensively evaluated.

        

    Addition of full-dose abciximab to half-dose alteplase or to half-dose reteplase resulted in nearly 80% of patients achieving complete reperfusion at 90 min without much increase in side-effects. Patency improved and ECG signs of tissue perfusion were also better with the combination.

         

    Results of GUSTO V has both good and bad news. The good news is the report of the lowest 30 day mortality (less than 6%) and bad news is that concept of an improvement in early patency rates leading to a decrease in mortality was not confirmed.

            

    Future management of MI with ST elevation may involve early medical treatment with a bolus of fibrinolytic or a combination of a fibrinolytic and a glycoprotein blocker- followed immediately by angioplasty.

          

  • The GUSTO IV-ACS Investigators 

    Effect of Glycoprotein IIb/IIIa Receptor Blocker Abciximab on Outocome in Patients with Acute Coronary Syndromes Without Early Coronary Revascularisation: The GUSTO IV-ACS Randomised Trial 

    Lancet, Vol.357, June 16, 2001, Pg. 1915-24

            

    Summary : Glycoprotein IIb/IIIa blockers reduce procedure-related thrombotic complications of percutaneous coronary intervention, and the risk of death and myocardial infarction in patients with acute coronary syndromes.

           

    The effect on risk of death and myocardial infarction is particularly apparent in patients undergoing early percutaneous coronary interventions.

          

    The authors did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early
    revascularisation.

          

    Interpretations : Although the explanations for the findings are unclear, this study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes.

        

  • McKenna CJ, Codd MB, McCann HA, et al (Mater Misericordiae Hosp, Dublin) 

    Alcohol Consumption and Idiopathic Dilated Cardiomyopathy: A Case Control Study

    Am Heart J 135: 833-837, 1998

            

    Alcohol is believed to be a risk factor for idiopathic dilated cardiomyopathy (IDCM). A case control study was made comparing consumption of alcohol in cases with IDCM with that of normal controls.

           

    Patients were 100 adults (73 men and 27 women, with mean age of 54 years) with IDCM. Controls were 211 adults (86 men and 125 women with mean age of 56 years) who were randomly selected from the population. 

            

    All participants filled up questionnaires that addressed the duration and quantity of alcohol intake and alcohol abuse. Additionally 200 first-degree relatives of 56 patients with IDCM were examined by echocardiography to identify any familial disease. 

            

    It was observed, significantly more of patients with IDCM (40 or 40%) exceeded recommended weekly intake of alcohol (21 units for men and 14 units for women) than did the controls. Also significantly more of the patients were alcohol abusers than controls (27% vs 16%).

           

    Of the 56 patients whose relatives were examined, 25 (45%) had a familial tendency to IDCM. These 25 were compared with 31 patients with non-familial tendency and both groups had similar risk factors for IDCM (i.e. viral illness, atopy and pregnancy) in alcohol consumption and alcohol abuse.

            

    Thus alcohol consumption was identified as a possible aetiologic agent in 40% of patients with IDCM. However, 60% of the patients with IDCM were not heavy drinkers and yet had IDCM. Alcohol consumption is one of the factors, among others, involved in the aetiology of IDCM.

            

  • Grunig E, Tasmasn JA, Kucherer H, et al (Univ of Heidelberg, Germany; Univ of Lubeck, Germany) 

    Frequency and Phenotypes of Familial Dilated Cardiomyopathy 

    J Am Coll Cardiol 31: 186-194, 1998

           

    Aetiology of dilated cardiomyopathy (DCM) is unknown and accurate diagnosis remains difficult. Up to 25% of patients were classified as having inherited disease in one recent study. A typical phenotype pattern may often be found in a single family.

         

    To construct pedigrees, 445 consecutive patients with proven DCM were studied together with 970 first and second-degree family members.

          

    In 48 of the 445 patients (10.8%) familial DCM was confirmed; it was suspected in 108 (24.2%). These 156 patients with suspected or confirmed DCM were younger and more often had EKG changes, compared with those with non-familial disease.

          

    Five phenotypes of familial DCM were also identified, namely: 

    DCM with sensoneural hearing loss, 

    DCM with conduction defects, 

    DCM with segmental hypokinesia of the left ventricle, 

    Juvenile DCM with rapid progressive course in male relatives without muscular dystrophy; and 

    DCM with muscular dystrophy.

          

    Thus an inherited disorder may be found in 35% of patients with
    DCM.

           

  • The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators

    Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes Without ST-Segment Elevation 

    The New England Journal of Medicine Vol.345 (7), August 16, 2001, Pg. 494-502

           


    Summary: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. The authors have evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients.

          


    Patients (12,562) who presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) or placebo in addition to aspirin for 3-12 months.

          

    The conclusion was that clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with
    clopidogrel.

            

  • D. P. Wade and J. S. Owen 

    Regulation of the Cholesterol Efflux Gene, ABCA1

    Lancet Vol.357, January 20, 2001, Pg. 161-163

          

    Summary : The possibility of controlling serum LDL cholesterol concentrations with statins is a major advance. But statins are not very effective if dietary cholesterol intake is excessive and they do not rectify low HDL, a risk factor as important as raised LDL for coronary heart disease. So, drugs that raise HDL or impair dietary cholesterol uptake are needed.

           

    Recent discovery suggests that a single protein ABCA1 has key functions in HDL production and cholesterol absorption. The first breakthrough was identification of ABCA1 as the defective gene in Tangier disease, a rare disorder characterised by very low plasma HDL and an inability of cells to excrete cholesterol onto lipid-poor apoA-I, the main HDL precursor.

           

    ABCA1 protein belongs to a superfamily of membrane transporters that bind and hydrolyse ATP to drive diverse substrates across membranes. Cholesterol, and perhaps phospholipid are ABCA1 substrates and their efflux may be aided by binding of apoA-1 to ABCA1.

           

    This step, first stage in reverse cholesterol transport, enables peripheral cells to unload superfluous cholesterol onto HDL for transfer to liver.

           

    Can ABCA1 be upregulated, as a means of atheroprotection? ABCA1 activity can be increased by increasing transcription of the ABCA1 gene. Increase in ABCA1 expression is mediated by 2 members of nuclear receptor superfamily
    – LXR (liver X receptor) and RXR (retinol X receptor).

           

    Insights into potential benefits of upregulating ABCA1 expression will prompt increased efforts to uncover regulatory pathways that provide new targets for pharmacological intervention.

           

  • Walter W. Rosser 

    Aspirin for Primary Prevention of Cardiovascular Events 

    Lancet Vol.357, January 13, 2001, Pg. 84-85

            

    Summary : Whether general practitioners should recommend aspirin to their patients to reduce the risk of heart attack and other cardiovascular events has been confusing. The report on the Primary Prevention Project (PPP) in Lancet provides general practitioners with some evidence.

            

    The PPP study was stopped after about 3.5 years of follow-up because 2 other studies of low doses of aspirin showed a significant beneficial effect of drug. PPP results showed that 100 mg daily of enteric coated aspirin had a protective effect in people with one or more cardiovascular risk factors.

            

    All 3 studies highlight the fact that in hypertensive patients blood pressure must be well controlled because higher the blood pressure greater the risk of haemorrhagic strokes, and aspirin should be prescribed in low doses to avoid bleeding complications.

            

    The 2nd segment of PPP, that of the effect of vitamin E did not provide evidence that the vitamin reduces cardiovascular risk. General practitioners can advise their patients that any beneficial effect that vitamin E might have is weak and awaits discovery.

          

  • Collaborative Group of the Primary Prevention Project (PPP)

    Low-dose Aspirin and Vitamin E in People at Cardiovascular Risk: A Randomised Trial in General Practice 

    Lancet Vol.357, January 13, 2001, Pg. 89-95

              

    Summary : Authors aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors.

               

    They did a randomised controlled open trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly.

              

    Interpretation of the study was that in women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile.

              

    Results on vitamin E’s cardiovascular primary preventive efficacy are not conclusive per se, and are consistent with the negative results of other large published trials on secondary prevention.

          

  • Luchsinger JA, Steinberg JS (Columbia Univ, New York)

    Resolution of Cardiomyopathy After Ablation of Atrial Flutter

    J Am Coll Cardiol 32: 205-210, 1998

              


    Tachycardia-induced cardiomyopathy can lead to congestive heart failure (CHF) and studies have shown that controlling tachycardia improves left ventricular (LV) function. Possible effect of atrial flutter (AFl) in causing cardiomyopathy with LV dysfunction was examined. 

           


    Eleven patients (all men, mean age, 59 years) with refractory AFl who were undergoing radiofrequency ablation (RFA) of AFl, had dilated cardiomyopathy and CHF.

            


    RFA was successful in all eleven patients. 2-dimension echocardiography performed before RFA and a median of 7 months after RFA, showed significant improvements in LV function and complete resolution of CHF. Six patients had normal LV ejection fraction (LVEF).

             


    Thus AFl appears to contribute to LV dysfunction and tachycardia-induced cardiomyopathy which reverse with RFA.

            

  • Corrado D, Basso C, Schiavon M, et al (Univ of Padua, Italy; Natl Health Service, Padua, Italy)

    Screening for Hypertrophic Cardiomyopathy in Young Athletes 

    N Engl J Med 339: 364-369, 1998 

            


    Cardiovascular disease is the most common cause of sudden death in athletes. For athletes over 35 years, atherosclerotic coronary artery disease is the most common cause of sudden death. In younger athletes, hypertrophic cardiomyopathy has been implicated as a cause of sudden death, in a third of competing athletes.

               


    In Italy it is required by law, for every athlete to be clinically examined before entering competitive sports. A consecutive group of 33,375 young athletes who underwent preparticipation screening were studied.

             


    In a group of 269 young people with sudden death, 49 (18.2%) were competitive athletes (mean age 23 years; 44 men and 5 women). Amongst the causes of death, cardiomyopathy accounted for 2% of deaths only. Thus preparticipation screening reduces the incidence of sudden deaths in young athletes due to cardiomyopathy.

              

  • Hunt SA (Stanford Univ, Calif)

    Current Status of Cardiac Transplantation 

    JAMA 280: 1692-1698, 1998 

            


    The article deals with 30 years of heart transplantation and future trends. Heart transplantation is still reserved for those in end stage heart disease. Approximately 2500 heart transplants are being performed in USA per year and the trend has continued for the past decade.

           


    Combination of cyclosporine, azathioprine and corticosteroids remains the main stay for immunosuppression.

            

    Overall 1-year survival rate has remained 80%. The main limitations to heart transplantation are infection, rejection, coronary artery disease and malignancy in the graft.

          


    Future may see discovery of better immunosuppressive drugs. Newer donor materials by way of nonbiologic and mechanical hearts may become available to overcome shortage of donor hearts. Left ventricular assist devices are being devised and used but need more
    developments.

          

  • The Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators

    Thrombin-Specific Anticoagulation with Bivalirudin Versus Heparin in Patients Receiving Fibrinolytic Therapy for Acute Myocardial Infarction: The HERO-2 Randomised Trial 

    Lancet, Vol. 358, December 2001, Pg. 1855-1863

          

    Summary :
    Bivalirudin (Angiomax, previously known as Hirulog) is a direct thrombin-specific anticoagulant. The authors therefore tested the effect on 30-day mortality of bivalirudin (in a dose selected as being the optimum on the basis of HERO-1 efficacy and safety data) versus unfractionated heparin started before streptokinase.

          

    Interpretation :
    Bivalirudin did not reduce mortality compared with unfractionated haparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin.

         

    Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.

          

  • Sheila A. Doggrell 

    Clinical Trials With Glycoprotein IIb/IIIa Antagonists No Benefit Without Bleeding?

    Drugs of Today Vol.37 (8), August 2001, Pg. 509-531

          

    As the glycoprotein GPIIb/IIIa receptor is the final common pathway in platelet aggregation, an antagonist of this receptor can cause profound inhibition of aggregation induced by any agonist.

         

    Abciximab is a chimeric human-mouse monoclonal antibody that is less immunogenic than murine 7E3 Fab. A major clinical trial with abciximab showed that it reduced ischaemic complications of coronary balloon angioplasty in high-risk patients, but increased the risk of bleeding. 

          

    Subsequent studies showed that using less concurrent heparin reduced bleeding. Further studies have shown that the benefits extend to all patients with unstable angina and acute myocardial infarction. Clinical trials with eptifibatide and tirofiban have not shown benefit at the doses used, in angioplasty.

           

    Orally active GPIIb/IIIa antagonists are being developed for use in myocardial infarction. Abciximab can cause thrombocytopenia and all the GPIIb/IIIa antagonists increase the incidence of bleeding but there is no excess intracranial
    hemorrhage.

           

  • Veli-Pekka
    Valkonen, Hannu Paiva, et al 


    Risk of Acute Coronary Events and Serum Concentration of Asymmetrical Dimethylarginine


    Lancet Vol.358, December 22/29, 2001, Pg. 2127-2128

           

    Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease.

           

    The authors investigated the association of ADMA concentration in serum with risk of acute coronary events. They did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (> 0.62
    mmol/L) had a 3.9-fold (95% C1 1.25-12.3, p=0.02) increase in risk of acute coronary events compared with the other quartiles. Their findings suggest that ADMA is a predictor of acute coronary events.

           

  • Sudlow M, Thomson R, Thwaites B, et al (Univ of Newcastle upon Tyne, England; Wansbeck Gen Hosp, Ashington, England)

    Prevalence of Atrial Fibrillation and Eligibility for Anticoagulants in the Community

    Lancet 352: 1167-1171, 1998

          

    The risk of stroke in patients with atrial fibrillation (AF) can be reduced by anticoagulation.

            

    A group of 3,678 people, 65 years and older, were screened by an electrocardiogram (ECG). Those with AF were evaluated further to determine the risk for stroke. ECGs revealed AF in 207 (5.6%). 

          

    Based on different inclusion criteria 41% to 61% of these 207 would have benefited from anticoagulation but only 23% were receiving warfarin.

             

    Thus anticoagulation with warfarin is underused in elderly patients with AF to decrease the incidence of stroke.

            

  • Sudlow M, Thomson R, Rodgers H, et al (Univ of Newcastle upon Tyne, England)

    The Effect of Age and Quality of Life on Doctor’s Decisions to Anticoagulate Patients With Atrial Fibrillation

    Age Ageing 27: 285-289, 1998

           

    Many studies have shown that in selected patients who have atrial fibrillation (AF) anticoagulation reduces the risk of strokes.

           

    Inspite of this a large number of patients who meet medical criteria for anticoagulation, do not receive the same.

          

    A questionnaire was sent to a random 50% of 824 local practitioners and 207 local consultants, seeking their views on use of anticoagulants in patients with AF.

           

    Overall response rates for general practitioners was 56% and consultants 79%. A large proportion (43% to 46%) from both groups felt that patients above age 84 years, should not be treated; a small minority felt it inappropriate to treat patients between 65 and 74 years and above; the criteria for selection being quality of life.

            

    Thus non use of anticoagulants based on age is not justified and amounts to inadequate treatment of such patients. A substantial number of strokes can be prevented with appropriate use of anticoagulants even in elderly patients.

            

  • Teo
    KK, for the Clinical Quality Improvement Network (CQIN) Investigators (Univ of Alberta, Edmonton, Canada)

    Thromboembolic Prophylaxis in 3,575 Hospitalized Patients With Atrial Fibrillation

    Can J Cardiol 14: 695-702, 1998

          

    Atrial fibrillation (AF) becomes more prevalent as population gets older. AF is a major contributing factor in 15% of overall strokes and 36% of strokes in persons over age 80. 

           

    Anticoagulation therapy is under utilized particularly in elderly patients. One of the primary reasons for this is the risk of bleeding. 3,375 patients from 12 hospitals (2005 males and 1570 females) with mean age of 72 years were monitored for use of warfarin or aspirin. 

           

    Thirty three percent of patients did not receive any anticoagulants. Of those on anticoagulants, 24% received warfarin; 35% received aspirin and 8% received both. 

           

    13% of patients had contraindications to warfarin and 6% to aspirin. Warfarin use was less likely in patients over 70 years in age. Thus almost a third of all patients did not receive anticoagulants and another third received only aspirin and only about one third received warfarin which alone provides proper prophylaxis against strokes in such patients.

             

  • Beyth RJ, Quinn LM, Landefeld CS (Case Western Univ, Cleveland, Ohio; Cleveland Veterans Affairs Med Ctr, Ohio; Univ Hosp of Cleveland, Ohio)

    Prospective Evaluation of an Index for Predicting the Risk of Major Bleeding in Outpatients Treated With Warfarin

    Am J Med 105: 91-99, 1998

           

    Anticoagulant-related bleeding reduces the net benefit of therapy. The accuracy and efficacy of the Outpatient Bleeding Risk Index, and its ability to estimate probability of major bleeding, were assessed.

           

    Warfarin therapy was initiated in 264 outpatients; bleeding amounts, rate, frequency and consequences were recorded by physicians.

           

    The rate of major bleeding was 6.5% per year. Four independent risk factors for major bleeding were age 65 years or over, history of gastrointestinal bleeding, history of stroke and 1 or more of 4 specific co-morbid conditions.

            

    The index predicted major bleeding better than did the physicians. The rate of bleeding at 4 years was 3% in 80 patients at low risk, 12% in 166 patients at intermediate risk, and 53% in 18 patients at high risk. Seventeen of the 18 episodes of major bleeding were potentially preventable.

           

    Thus Outpatient Bleeding Risk Index was able to discriminate between patients who would have a major bleed from those who would not, better than the physicians.

          

  • Yetman AT, Hamilton RM, Benson LN, et al (Univ of Toronto)

    Long-term Outcome and Prognostic Determinants in Children With Hypertrophic Cardiomyopathy

    J Am Coll Cardiol 32: 1943-1950, 1998

      

    The outcomes and effects of treatment in children with hypertrophic cardiomyopathy (HCM) are not well characterized.

     

    Ninety-nine HCM patients (71 males, aged 1 day to 17 years) treated between 1958 and 1997 were studied. Diagnoses were made by echocardiography (n=83) and angiography (n=16).

       

    The median age at diagnosis was 5 years. Heart murmurs were present in 41 patients, a family history of HCM in 37 and only an abnormal ECG in 3. Symptoms varied from shortness of breath, chest pain, syncope, palpitations, failure to thrive and sudden death.

      

    Various types of arrhythmias were seen on ECG. Twelve patients had sudden death and 6 others had resuscitated sudden death but survived. Risk factors for sudden death were increased QT interval in ECG and ventricular tachycardia on ambulatory ECG. Thus ECG, ambulatory ECG and angiography data can identify HCM children who are at risk of sudden death.

       

  • Iribarren C, Tekawa IS, Sidney S, et al (Kaiser Permanente Med Care Program, Oakland, Calif)

    Effect of Cigar Smoking on the Risk of Cardiovascular Disease, Chronic Obstructive Pulmonary Disease, and Cancer in Man

    N Engl J Med 340: 1773-1780, 1999

      

    Cigar smoking has increased in recent times. Cigar smoking is known to increase risk of pulmonary disease, its effect on cardiovascular disease has not been studied.

      

    A cohort of 17,774 men (aged 30 to 85 years) enrolled in the study. At baseline 1,546 men reported smoking cigars and 16,228 did not. The two groups were followed up from 1971 to
    1995.

      

    Relative risks for chronic obstructive pulmonary disease (COPD), coronary heart disease, upper digestive tract cancer and lung cancer were higher in cigar smokers as compared to non smokers.

     

    The increase in incidence of coronary heart disease in cigar smokers is moderate but significant.        

  • Ling LH, Oh JK, Schaff HV, et al (Mayo Clinic and Mayo Found, Rochester, Minn)

    Constrictive Pericarditis in the Modern Era: Evolving Clinical Spectrum and Impact on Outcome After Pericardiectomy

    Circulation 100: 1380-1386, 1999

                                              


    There has been changes in the spectrum of constrictive pericarditis (CP) in the United States. There is a decline in the incidence of tuberculous pericarditis and an increase in the frequency of CP after cardiac surgery and mediastinal radiation. The effect of pericardiectomy in such cases was studied.

                                                                

    Files of Mayo Clinic presented 135 patients (67% men) with CP between January 1985 through June 1995. The follow-up was done by mailed questionnaires, hospital records, and calls to patients and physicians. The results of this cohort of patients were compared with another historic cohort from the years 1938 through 1982 at the Mayo Clinic.

                                                                      

    The recent cohort showed increasing incidence of CP following cardiac surgery and mediastinal radiotherapy. Also the patients in the present study reported at a later median age (61 years) as compared with the historic cohort (45 years). There was a decline in mortality from the historic cohort (14%) to the recent cohort (6%).

                                                                           

    Radiation-induced CP had poorer alleviation of symptoms compared to the others.                                   

  • Calkins H, for the Atakr Multicenter Investigators Group (John Hopkins Univ, Baltimore, Md; Stanford Univ, Calif)

    Catheter Ablation of Accessory Pathways, Atrio-ventricular Nodal Reentrant Tachycardia, and the Atrio-ventricular Junction: Final Results of a Prospective, Multicenter Clinical Trial

    Circulation 99: 262-270, 1999

                                                        


    There is growing interest in the use of radiofrequency (RF) catheter ablation procedures for patients with atrio-ventricular node reentrant tachycardia (AVNRT) or arrythmias involving an accessory pathway (AP) or the atrio-ventricular junction (AVJ). 

                                                         

    The study included 1050 patients undergoing 1136 AF ablation procedures at 18 centers. The mean age was 37 years with 31% of the patients being 20 years or younger. Each patient was treated for AVNRT (n=373) or arrythmias related to AP (n=500) or the AVJ (n=121); another 56 patients were treated for more than 1 type of target. Follow-up evaluations were performed at 1 to 24 months after ablation. 

                                                                 

    The acute success rate of ablation was 95% with a median application of 6 RF applications. Success rates by site were 100% for AVJ, 97% for AVNRT, and 93% for AP.

                                                                     

    Major complication rate was 3%, including 3 deaths and 2 strokes, 1 myocardial infarction and 10 cases of complete atrio-ventricular block requiring permanent pacemaker implantation. The recurrence rate was 6%, factors predictive of reentrant arrythmia was right free wall, posterolateral, septal and multiple AP ablations. 

                                                                            

    This prospective multicenter trial confirms that RF catheter ablation is a safe and effective treatment for children and adults with supraventricular tachycardias. The study identifies factors associated with probability of success, major complications, and recurrent arrhythmias.                                       

        

  • Jordan J, Shannon JR, Black BK, et al (Franz Volhard Clinic, Berlin; Vanderbilt Univ, Nashville, Tenn)

    The Pressor Response to Water Drinking in Humans: A Sympathetic Reflex?

    Circulation 101: 504-509, 2000

                                                   


    The short-term effect of water drinking on blood pressure was investigated in patients with orthostatic hypotension caused by autonomic failure. 

                                                               

    The subjects were 47 patients with disabling orthostatic hypotension caused by multiple system atrophy (20 men and 8 women; mean age 66 years), or pure autonomic failure (8 men and 11 women; mean age 72 years). Eleven older (mean age 57 years) and 8 younger (mean age 25 years) control subjects were also studied. Participants drank 480 mL of tap water while sitting and their systolic (SBP) and diastolic (DBP) blood pressures, and heart rate (HR) were measured for 60 minutes.

                                                                 

    Drinking water significantly increased SBP and DBP in patients with multiple system atrophy and pure autonomic failure, within 5 minutes of water ingestion and the effect continued up to 60 minutes. Heart rate also decreased significantly in both groups of patients. Similarly older controls showed significant increase in SBP and decrease in heart rate but younger controls showed no pressor response.

                                                         

    Drinking water did not affect plasma renin activity, vasopressin levels or blood volume of patients but it significantly increased plasma norepinephrine levels in both control groups. The mechanism of action of drinking water is not clear.          

                                 

  • Owen I Miller, Swee Fong Tang et al  

    Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a   
    randomised double-blind study. 

    Lancet, vol.356, 28 Oct.2000, pg.1464.    

                                   

    Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. A randomised double-blind study was carried out to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk.

                          

    Authors enrolled 124 infants with large ventricular and atrioventricular septal defects who had high pulmonary flow, pressure or both and were undergoing corrective surgery for congenital heart disease.

                                

    Interpretation of the study was that, in infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course with no toxic effects.                             

                                   

  • Maheshwari S, Bruckheimer E, Fahey JT, et al (Yale Univ, New Haven,
    Conn) 

    Balloon Angioplasty of Postsurgical Recoarctation in Infants: The Risk of Restenosis and Long-term Follow-up 

    J Am Coll Cardiol 35: 209-213, 2000

                

    The immediate results of balloon angioplasty (BA) for coarctation of the aorta are encouraging. Concerns remain regarding its use in children, particularly infants who are at higher risk for complications because of their small size, smaller vessels, and the potential for restenosis with growth. The long-term results of BA for postsurgical recoarctation were examined in 22 infants. 

                   

    Angioplasty was performed under conscious sedation with local anesthesia. Cardiology charts, recent echocardiogram or MRI, and repeat catheterization (when available) were reviewed retrospectively for the year 1986 through 1996. A successful result was defined as a post BA gradient of 20 mm Hg or less.

                

    Twenty of 22 (91%) infants achieved a successful result, with a decrease in systolic peak pressure gradient from 38 mm Hg to 9 mm Hg and an increase in the coarctation diameter from 2.7 mm to 5.2 mm. At long-term follow-up of 0.6 to 12 years (median 56 months), the restenosis rate after an initial optimal result was 16%. Five (24%) infants needed reintervention (2 initially unsuccessful and 3 recoarctation). The success rate was 95% after 2 procedures. Lower infant weight was associated with a sub-optimal long-term outcome. 

                          

    Infants can undergo BA with good long-term outcome. The risk of restenosis is low in infants who had undergone BA and can be successfully managed with a lower infant weight.                                     

                                                            

  • Zosia Kmietowicz            

    Statins are the new aspirin, Oxford researchers say     

    BMJ, 17 Nov.01, 323, 1145               

                                                 

    Results of the world’s largest trial on statins drug show that in addition to lowering cholesterol, the statins reduce the risk of vascular disease and especially heart attacks and strokes, even in people whose cholesterol concentration is normal. The statins stabilize atherosclerotic plaques by making them firm (less fragile) and causing a capping of the plaques.         

                                   

  • Ralf Koster, Dieter Vieluf, et al   

    Nickel and molybdenum contact allergies in patients with coronary in-stent
    restenosis.   

    The Lancet, vol.356, Dec.2, 2000, pg.1895   

                                             

    Coronary in-stent restenosis might be triggered by contact allergy to nickel, chromate, or molybdenum ions released from stainless-steel stents. Authors investigated the association between allergic reactions to stent components and the occurrence of in-stent
    restenosis.            

                                                          

    Patients with allergic patch-test reactions to nickel and molybdenum had a higher frequency of in-stent restenoses than patients without hypersensitivity. Allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent
    restenosis.        

                                                                      

  • The CAPRICORN Investigators    

    Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction.

    The Lancet, vol.357 (9266), 5 May 2001, pg.1385   

    The beneficial effects of
    ß-blockers on long-term outcome after acute myocardial infarction were shown before the introduction of thrombolysis and angiotensin-converting-enzyme (ACE) inhibitors. Generally, the patients recruited to these trials were at low risk: few had heart failure, and none had measurements of left-ventricular function taken. The long-term efficacy of carvedilol on morbidity and mortality was investigated in patients with left-ventricular dysfunction after acute myocardial infarction treated according to current evidence-based practice.     

                                               

    In a multicentre, randomised placebo-controlled trial, 1959 patients with a proven acute myocardial infarction and a left-ventricular ejection fraction of
    > 40% were randomly assigned 6.25mg carvedilol (n=975) or placebo (n=984). Study medication was progressively increased to a maximum of 25mg twice daily during the next 4-6 weeks, and patients were followed up until the requisite number of primary endpoints had occurred. The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems. Analysis was by intention to treat.   

                                                                

    In patients treated long-term after an acute myocardial infarction complicated by left-ventricular systolic dysfunction, carvedilol reduced the frequency of all-cause and cardiovascular mortality, and recurrent, non-fatal myocardial infarctions. These beneficial effects are additional to those of evidence-based treatments for acute myocardial infarction including ACE inhibitors.    



NEXT




 

 

Speciality Spotlight

 

   

  • Tunio AS, Hingorani A, Ascher E
    The Impact of an Occluded Internal Carotid Artery on the Mortality and Morbidity of Patients Undergoing Coronary Artery Bypass Grafting
    Amer J Surg 178: 201-205
       
    Stroke is a major problem in patients undergoing coronary artery bypass grafting [CABG]. Although other mechanisms may be involved, concomitant carotid artery disease is likely major contributor to perioperative stroke. The effects of internal carotid artery [ICA]  stenosis or occlusion on perioperative stroke rate and mortality among patients with CABG were analyzed.
           
    The retrospective study included 3344 patients undergoing CABG at one center over 3.5 years [59% of the patients were men]. In each case a preoperative duplex scan of the carotid artery was available for review. About 93% of the patients had ICA stenosis less than 60% [ Group A]; 5% had ICA stenosis of 60 to 99% [Group B]; and 2% had total ICA occlusion [Group C]. Further in group C, 87% of the patients had in addition 60% stenosis of the contralateral ICA and the rest had stenosis of 60% to 99%. In Group B 40% of the patients, and in Group C 3% of the patients, underwent concomitant carotid endarterectomy [CEA] along with CABG.
       
    The 3 groups were comparable in terms of age, surgical indications, diabetes, hypertension, and smoking. The mean pump time was 125 to 138 minutes and the aortic cross clamp time was 75 to 78 minutes. Thirty day stroke rate was 1.6% in Group A; 3.8% in Group B, and 6.5% in Group C. Within Group C, the perioperative stroke rate was 25% for patients with contralateral stenosis compared with 3.8% for those without contralateral stenosis. Among patients undergoing concomitant CEA for severe stenosis in the contralateral ICA, the stroke rate was 100% in Group C versus 4.2% in Group B. Thirty day mortality was 3.6% in Group A, 6.6% in  Group B and  8.6%  in  Group C.
       
    The presence of concomitant ICA stenosis in patients undergoing CABG, is associated with increased perioperative morbidity and mortality. This is the first large study of the effects of ICA occlusion on  CABG. The findings support the safety of simultaneous CEA and CABG.
       

  • White CM, Dunn A, Tsikouris J, et al [Hartford Hospital, Conn., Univ of Connecticut, Storrs]
    An Assessment of the Safety of Short-Term Amiodarone Therapy in Cardiac Surgical Patients with Fentanyl Isoflurane Anesthesia
    Anesth Analg 89: 585-589, 1999
       
    Chronic amiodarone use, in combination with fentanyl anesthesias, may cause atrioventricular blockade, symptomatic bradycardia, sinus arrest, and severe hypotension. The effect of short-term amiodarone use has not been investigated. The effect on hemodynamics of fentanyl-containing anesthesia, administered to elderly patients receiving short-term amiodarone therapy before coronary artery bypass graft [CABG] or vascular surgery, was investigated in a prospective, randomized, double-blind, placebo-controlled trial.
        
    Elderly CABG patients were randomly allocated to receive amiodarone 3.4 g over 5 days, or 2.2 g over 24 hours [n=45] or placebo [n=39], before CABG. Fluid balance, use of dopamine, use of vaso-pressor catecholamines, and use of phospho- diasterase inhibitor or intra-aortic balloon pump were recorded. Systolic, diastolic and central venous pressures were measured, before anesthesia, before cardiopulmonary bypass [CPB] and after CPB. Heart rates were recorded before induction of anesthesia and after CPB.
        
    Results showed fluid status increase by 2L in 2 [4.4%] amiodarone patients and in 4 [10.3%] placebo patients. No patient required dopamine or an intra-aortic baloon pump. Epinephrine or derivative was administered to 8 [17.8%] amiodarone and 5 [12.8%] placebo patients and milrinone to 1 [2.2%] amiodarone and 2 [5.1%] placebo patients. Preanesthesia and post PCB systolic blood pressure, were significantly lower in amiodarone patients. Further, amiodarone patients received less fluid and had a lower net increase in fluid status, than the placebo patients, although the differences were not significant.
        
    Thus short term amiodarone therapy does not lead to hemodynamic instability in CABG patients receiving fentanyl anesthesia regimens.
      
         

  • Westaby Stephen, Banning Adrian P, et al [ Oxford Heart Centre, John Radciliffe Hospital, Oxford ]
    First permanent implant of the Jarvik 2000 Heart
    The Lancet [ Vol-356], Number-9233, 9 September, 2000, Pg. No – 900
       
    In patients with heart failure, implantation of the Jarvik 2000 heart improves all the abnormalities significantly. After six weeks, there is a improvement in exercise tolerance, myocardial function and endorgan function. Symptoms of heart failure are reversed and there are no adverse effects in the short term. The device is very small and is implanted  in  the skull with electrical connection which controls the pumping device situated in the heart.
      

  • Presented at XII International symposium on Atherosclerosis, Stockholm, Sweden.
    Superstatin boosts Astra Zeneca
    Scrip no.2554, July 5, 2000, p.18
        
    Rosuvastatin (ZD4522) is the most potent cholesterol lowering agent known.  It lowers LDL cholesterol by 65% as compared to 25% by current statins.
       
    It does not produce hepatotoxicity or myotoxicity. Liver enzymes and CPK remain normal. It has a long half-life (once a day dosing).  Rosuvastatin is not metabolised by the liver.
        

  • JS Davies, MF Scanlon (Univ of Wales, Cardiff)  
    Hypopituitarism After Coronary Artery Bypass Grafting. 
    BMJ 316: 682-685, 1998.

        
    Silent pituitary infarction may be present after coronary artery bypass grafting (CABG).  Increased awareness of this uncommon condition should facilitate earlier treatment.
         

  • N Fuenmanyor, E Moreira, LX Cubeddu, (Central Univ of Venezuela, Caracas)
    Salt Sensitivity is Associated with Insulin Resistance in Essential Hypertension.
    Am J Hypertens 11: 397-402, 1998.
        
    Patients with essential hypertension may be salt sensitive or salt resistant. Hypertension in salt sensitive patients is associated with insulin resistance. In salt sensitive patients, high salt intake leads to increase in blood pressure, induced hyperinsulinemia, and worsening of diabetes.
       

  • R Locher, PM Suter, W Vetter (Univ Hosp, Zurich, Switzerland)
    Ethanol Suppresses Smooth Muscle Cell Proliferation in the Postprandial State:  A New Antiatherosclerotic Mechanism of Ethanol?
    Am J Clin Nutr 67 : 338-341, 1998
       
    It is known that smooth muscle cell proliferation in the postprandial state (after food) may lead to narrowing of arteries. It is well known that ethanol (alcohol) raises HDL cholesterol and thereby gives protection against atherosclerosis and heart attack. It now appears that ethanol (alcohol) also suppresses the proliferation of smooth muscle cells and thereby gives additional protection in patients against atherosclerosis.
       

  • Arrowsmith J, Usganocar RP, Dickson WA [Morrston Hosp. Swansea UK]
    Electrical Injury and Frequency of Cardiac Complications 
    Burns 23 : 576-578, 1997
       
    Cardiac abnormalities caused by electrical injury are most often apparent at the time of injury. They can also develop later, and 24 hour cardiac monitoring has recommended for patients with electrical injuries. Patients who became unconscious after injury and those with high voltage injuries were more prove to cardiac complications.
       
    Analysis finds a 3% rate of cardiac abnormalities among patients with electrical injuries. For patients who did not lose consciousness at the time of injury and who have normal admission ECG, cardiac complications are unlikely to develop later.
        

  • Gilles Dreyfus, Sherban Mihealainu (Universite Paris V, France)
    The Batista Procedure – Editorial
    Heart 2001; 85: 1-2
           
    Until recently refractory congestive heart failure under optimum medical treatment would only be treated surgically by heart transplantation. The increasing number of such options of heart failure, lack of heart donors and the very high mortality rate of 10-20% on problems associated with transplantation have prompted a search for possible alternative options.
          
    Of the ischaemic cardiomyopathies some good options are available. The most practical and easily available option is myocardial revascularization with either a bypass surgery or angioplasty. However, a new option is now available of performing mitral valve repair to correct mitral regurgitation, which is common in failing hearts. One of the reasons for refractoriness of the heart failure is the waste of effort caused by mitral regurgitation. Correction of mitral regurgitation has excellent results. The operative mortality is very low less than 2%. Survival rates are excellent 92% surviving for 1year and 72% at 2 years.
        
    The problem really is dilated cardiomyopathy. Although correction of mitral regurgitation gives some improvement, it is not adequate. Resection of myocardium to reduce the left ventricular cavity combined with the mechanical support of a left Ventricular Assist Device gives better results. The procedure is still under trial.
        

  • Ian B Wilman, David J Webb, et al (Dept of Cardiology, Univ Wales College of Medicine, UK)
    Isolated systolic hypertension: a radical rethink.
    BMJ No.7251, June 24, 2000,pg.1685.
         
    The association between hypertension and a ‘hardening’ of the pulse and apoplexy has been recognised for hundreds of years. Isolated systolic hypertension affects around half of people aged over 60 years. It confers a substantial cardiovascular risk. Despite this, it remains underdiagnosed, and largely untreated, but the benefits of treatment are established.
       
    The relative risk reduction of cardiovascular events in elderly people with isolated systolic hypertension is similar to that in younger people. However, as elderly people are at much higher absolute risk of such events, they stand to benefit more from treatment than younger people. Elderly people tolerate antihypertensive drugs with few side effects.
         
    The latest WHO and International Society for hypertension guidelines for management of hypertension emphasise the importance of arterial stiffness and pulse pressure as predictors of cardiovascular risk and call for further indices of arterial stiffness.
      

  • Lars Kober, Poul Erik Bloch et al
    Effect of Dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomized trial.
    Lancet, vol.356, Dec.16, 2000. Pg.2052-2057.
        
    Dofetilide, a new class III antiarrhythmic agent, selectively inhibits the rapid component of the delayed potassium current, which prolongs refractory period. It does not affect cardiac conduction or sinus-node function. It is effective in supraventricular arrhythmias.
       
    Arrhythmias cause much morbidity and mortality after MI, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide was investigated for effects on all cause mortality and morbidity in patients with LV dysfunction after MI.
       
    Treatment with dofetilide did not affect all-cause mortality, cardiac mortality or total arrhythmic deaths. It was effective in treating atrial flutter or fibrillation in patients with severe LV dysfunction and recent MI.
       

  • The ESPRIT investigators
    Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised placebo-controlled trial.
    Lancet, vol.356, Dec.16, 2000, pg. 2037-2044
        
    The platelet glycoprotein IIb/IIIa inhibitors, although effective in reducing ischaemic complications of percutaneous coronary intervention, are used in few coronary stent implantation procedures. ESPRIT is a randomized placebo-controlled trial to assess whether a novel, double-bolus dose of eptifibatide could improve outcomes of patients undergoing coronary stenting.
       
    Authors recruited 2064 patients undergoing stent implantation – they were randomly allocated to receive eptifibatide, given as two 180 mg/kg boluses 10min. apart and a continuous infusion of 2 mg/kg/min for 18-24 hrs. or placebo, in addition to aspirin, heparin and a thienopyridine.
       
    It was observed that routine glycoprotein IIb/IIIa inhibitor pretreatment with eptifibatide substantially reduces ischaemic complications in coronary stent intervention and is better than a strategy of reserving treatment to the bailout situation.
       

  • D Monkman, East Barnet Health Centre, Hertfordshire
    Treating dyslipidaemia in primary care – The gap between policy and reality is large in the UK.
    BMJ, 25 November,2000, 321(7272), 1299-1300
       
    The consensus that cholesterol is an important reversible risk factor for coronary heart disease was reached only comparatively recently as a result of studies published in 1994 and 1995. Cost considerations in the NHS in UK have limited the use of statins to individuals who are at highest risk and the accepted policy is to test cholesterol concentrations only when additional risk factors are present.

    The ratio of total cholesterol to HDL cholesterol allows the risk of coronary heart disease to be calculated for individuals who are being considered for primary prevention. Most primary care physicians do not perform 3 cholesterol measurements ( one random measurement followed by 2 fasting measurements ) when assessing patients.
       

  • Marco Pahor, Bruce M Psaty, et al (Department of Internal Medicine and Department of Public Health Sciences, USA
    Health Outcomes Associated with Calcium Antagonists compared with other First-line Antihypertensive Therapies: a Meta-Analysis of Randomised Controlled Trials.
    Lancet, vol.356, 9 December 2000, pg.1949-1954.
      
    Several randomised trials in hypertension have suggested that compared with other drugs, calcium antagonists may be associated with a higher risk of coronary events, despite similar blood pressure controls. This meta-analysis was carried out to compare the effects of calcium antagonists and other antihypertensive drugs on major cardiovascular events.
       
    Authors carried out a meta-analysis of trial in hypertension that assessed cardiovascular events and included at least 100 patients, who were randomly assigned to intermediate-acting or long-acting calcium antagonists or other antihypertensive drugs and who were followed up for at least 2 years.
       
    The conclusion of this meta-analysis was that in randomised controlled trials, calcium antagonists are inferior to other types of antihypertensive drugs as first-line agents in reducing the risks of several major complications of hypertension. On the basis of these data, the long-acting calcium antagonists cannot be recommended as first-line therapy for hypertension.
       

  • Blood pressure lowering treatment-Trialists Collaboration
    Effects of ACE inhibitors, calcium antagonists, and other blood pressure-lowering drugs: results of prospectively desgined overviews of randomised trials.
    Lancet : vol.356, December 9, 2000, p.1955-64
        
    This programme of overviews of randomised trials was established to investigate the effects of ACE inhibitors, calcium antagonists and other BP lowering drugs on mortality and major cardiovascular morbidity. Separate overviews of trials comparing active treatment regimens with placebo, trials comparing more intensive and less intensive BP lowering strategies, and trials comparing treatment regimens based on different drug classes were done.
       
    The interpretation is that there was strong evidence of benefits of ACE inhibitors and calcium antagonists as compared to placebo. There is weaker evidence of differences between treatment regimens of differing intensities and of differences between treatment regimens based on different drug classes.
       
    Commentary: Selection of initial anti-hypertensive drug therapy.
    The study done by Blood Pressure Lowering Treatment (BPLT) Trialist’s Collaboration (BPLT) has several methodological strengths. The effect of ACE inhibitors on cardiovascular disease was impressive and was achieved in the context of small difference in BP (3/1 mm Hg) between ACE inhibitor and placebo groups. This finding raises the possibility that the beneficial effects of ACE inhibitors on cardiovascular disease in the trials were mediated not just through the lowering of BP.
       
    There has been intensive debate over the balance between the potentially beneficial and detrimental effects of calcium antagonists in cardiovascular disease. Overall, the data of BPLT provide evidence that calcium antagonists reduce the incidence and mortality from cardiovascular disease.
        
    The meta-analysis of Marco Pahor and colleagues focussed specially on comparison of calcium antagonists, with diuretics, beta-blockers, ACE inhibitors or clonidine.
        
    (1) Diuretics or beta-blockers may be used initially for uncomplicated hypertension.
       
    (2) ACE inhibitors -initial choice especially in patients at high risk of heart failure.
       
    (3) Caution- for use of calcium antagonists as initial therapy in populations at high risk of CHD and heart failure (i.e. Western populations).
       
    (4) Calcium antagonists – may be used as initial therapy in patients at high-risk of stroke and low risk of CDH (i.e. Asian population).
        
    (5) If more than one drug needs to be used – combination of diuretics, beta-blockers, ACE inhibitors or calcium antagonists, based on patient’s absolute level of risk for cause-specific cardiovascular disease.
       

  • M.I.Phillips, S.M. Galli, J.L. Mehta (Department of Physiology and Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA).
    The Potential Role of Antisense Oligodeoxynucleotide Therapy for Cardiovascular Disease.
    Drugs Aug 2000, 60(2), 239-248.
       
    Sense is a faculty by which conditions or properties are perceived. Antisense technology uses preparation of oligodeoxynucleotides. An antisense oligodeoxynucleotide (AS-ODN) is a single stranded synthetic DNA with a modification and a specific sequence to hybridise to a specific messenger RNA (mRNA) and prevent translation. So, AS-ODNs are structural modifications which prevent normal cell ribosomal translation of mRNA.
       
    Current drugs used in treatment of cardiovascular disease are effective but they act for hours or one day. Antisense inhibition is being developed for treatment of hypertension, myocardial ischaemia and improved allograft survival in human vascular bypass grafts.
        
    AS-ODNs are delivered nonvirally or antisense DNA is delivered in viral vectors to inhibit genes associated with vasoconstrictive properties. In hypertension, it is known which genes need to be controlled. AS-ODN are short, single-stranded DNA that can be injected as such or in liposomes. AS-ODN targeted to angiotension type 1 (AT1) receptors, angiotensinogen (ATG), angiotensin converting enzyme (ACE) and beta-1 receptors effectively reduce hypertension in rat models. A single dose is effective for up to 1 month when delivered with liposomes, No adverse or toxic effects are detected and repeated injections are effective.
       
    For viral delivery, adeno-associated virus (AAV) and cytomegalovirus are used along with a DNA to ATG, ACE or AT1 receptors. Results in rats and transgenic mice show significant prolonged reduction in hypertension with a single dose. Left ventricular hypertrophy is also reduced.
        
    AS-ODNs to AT1 receptors, ATG and beta-1 receptors provide cardioprotection from the effects of myocardial ischaemia 
      

  • Shaffer KM, Mullins CE, Grifka RG, et al [ Baylor College of Medicine, Houston; Texas Children’s Hospital, Houston]
    Intravascular Stents in Congenital Heart Disease: Short and Long-Term Results From a Large Single-Center Experience
    J Am Coll Cardiol 31: 661-667, 1998
        
    Intravascular stents for the treatment of patients with congenital heart disease and vascular stenoses were evaluated by Food and Drug Administration [FDA] phase 1 and 2 clinical trials at Texas Children’s Hospital. Results of only FDA-approved investigational device exemption study of balloon-expandable stents in patients with congenital heart disease and vascular stenoses were reported.
        
    All patients enrolled in the study had stenoses requiring treatment. Stents were placed in 3 groups of patients: those with postoperative pulmonary artery [PA] stenoses, congenital PA stenoses, and stenoses of systemic veins/venous anastomoses. A total of 347 stents were placed in 200 patients between September 1989 and June 1995. The Palmaz stent was used in all cases. Median patient age at implantation was 10.5 years. Data were collected before and after stent implantation and at follow-up.
          
    All three groups showed marked fall in gradients across the stenoses, and marked increase in vessel diameters. Right ventricular pressure decreased in both congenital as well as postoperative pulmonary stenoses, and perfusion to the lungs increased considerably. The changes were seen steady at follow-up catheterization done at a mean of 14 months after implantation. There were 4 cases of stent migration in the earlier cases and three patients had restenosis. Two deaths were directly attributed to stent implantation.
         
    Intravascular stents proved to be safe and effective in the management of PA stenoses and other vascular anastomoses; there is no long-term morbidity and the favourable results appear immediately and continue into follow-up.
        

  • Daniels CJ, Cassidy SC, Teske DW, et al [ Columbus Children’s Hospital and Ohio State Univ, Columbus]
    Reopening After Successful Coil Occlusion for Patent ductus Arteriorus
    J Am Coll Cardiol 31: 444-450, 1998
        
    A study of children who had undergone successful coil occlusion of patent ductus arteriorus [PDA] was conducted to determine the frequency of reopening and the factors that may predict reopening.
       
    The patients underwent percutaneous transarterial PDA coil occlusion. The length and diameter of PDAs were determined.Doppler echocardiography was performed within 24 hours of coil occlusion to document success. Patients were reevaluated at 12 months.
       
    Coil occlusion was performed in 22 children with a median age of 4.9 years. Clinical success with loss of continuous murmur was achieved in 91% and in 90% doppler echocardiography was negative for PDA shunting. Five patients [22%] were seen to have reopening at follow-up. These patients had larger minimal diameter of 1.4 mm vs 1.2 mm and shorter PDA length 2.9 mm vs 7.1 mm. Angiographic appearance in 3 of these patients showed type B PDA [conical with short ductal ampulla].
        
    Thus despite successful coil occlusion for PDA, reopening is common. Previous reports have indicated that success is associated with minimal diameter of the PDA. In particular failure may occur with a wide-diameter and short length PDA. Angiographic type B PDA is also associated with reopening. 
      

  • PreitoLR, DeCamillo DM, Konrad DJ, et al [ Cleveland Clinic Found, Ohio]
    Comparison of Cost and Clinical Outcome Between Transcatheter Coil Occlusion and Surgical Closure of Isolated Patent Ductus Arteriorus
    Pediatrics 101: 1020-1024, 1998
        
    Transcatheter closure of patent ductus arteriorus [PDA] using Gianturco coils was retrospectively compared to surgical repair at Cleveland Clinic Foundation.
       
    Procedural and recovery costs for 36 patients, aged 13 months to 28 years, who had coil or surgical closure of PDA between 1993 and 1996, were determined and compared.
       
    The average cost of coil occlusion was 38% lower than surgical closure. But 17% of patients with coil occlusion had residual leaks at an average of 6 months after the procedure. There were no other short or long term complications in both groups and there were no deaths.
       
    Coil occlusion of PDA is a feasible, cheaper alternative to surgical repair.
       

  • ElkinsRC, Knott-Craig CJ, Ward KE, et al [Univ of Oklahoma, Oklahoma City]
    The Ross Operation in Children : 10-Year Experience
    Ann Thorac Surg 65 : 496-502, 1998
      
    The Ross operation for aortic valve replacement in children has been performed for 30 years, but its widespread acceptance was delayed because of the procedure’s technical demands and the need to place 2 valves at risk. With modifications in operative technique, the Ross operation in now the operation of choice for children and young adults who require aortic valve replacement. Researchers reviewed the records of 150 consecutive patients to provide additional long-term follow-up of the Ross operation. There were 112 boys and 38 girls of median age 12 years. Primary diagnosis was aortic stenosis in 40, aortic insufficiency in 29, and a combination of both in 81. Most had undergone other procedures before the Ross operation.
       
    Eight-year survival was 97.3%. Six patients required reoperation with restitution of valve function and two with late dysfunction required a replacement procedure. At 8 years 90% were free of any dysfunction, 94% were free of any obstruction, and 89% were free of any gradient across the valve needing a reoperation. All patients had active lives unencumbered by the need to take any anticoagulants.
       
    The Ross operation in children has an excellent rate of success at a low risk. Valve related complications are not life threatening and long-term satisfactory valve function can be achieved.
        

  • D’Souza SJA, Tsai WS, Silver MM, et al [Univ of Toronto]
    Diagnosis and Management of Stenotic Aorto-Arteriopathy in Childhood
    J Pediatr 132: 1016-1022, 1998
       
    Patients with stenotic aorto-arteriopathy [SAA], an uncommon group of vascular diseases, have segmental stenoses of the aorta and its branches. The new common type is middle aortic syndrome, characterized by severe stenosis of the thoracic and abdominal aorta. The differential diagnosis includes mainly Takayasu Arteritis [TA] and fibromuscular dystrophy or other noninflammatory aortic-arterial diseases. An experience with the management of SAA in childhood is reviewed, including the results of several different management approaches.
        
    The 16-year experience included 14 children and adolescents with acquired SAA. There were 7 boys and 7 girls, aged 4 to 18 years. Most of the patients were asymptomatic, with hypertension noted at routine examination. Clinical findings included abdominal bruits in 8, mixed absent/diminished and normal pulses in 8, and leg claudication in 4. On angiography, 13 showed involvement of the abdominal or descending thoracic aorta. A mid thoracoabdominal coarctation was detected in most patients. Eleven patients received a diagnosis of TA. It was difficult to distinguish TA from fibromuscular dysplasia on clinical or angiographic grounds.
         
    Treatment commenced with antihypertensive therapy. In patients with TA, prednisolone did not reverse aortic disease but it did worsen the hypertension. Six patients underwent percutaneous transluminal balloon angioplasty of renal artery stenoses, but the renal arteries restenosed. Renal autotransplantation – excision of the stenotic segment of the renal artery with reimplantation of the kidney on to the disease free renal artery – was performed in 5 patients. This provided temporary improvement in blood pressure in most patients; one patient had renal artery thrombosis with deteriorating renal function. Three patients underwent balloon angioplasty of the abdominal aorta with implantation of stents. In one case this was followed by open renal autotransplantation. There were 3 deaths.
        
    Thus diagnosis and management of SAA in children is a difficult problem, requiring multiple procedures, aimed mainly at preventing end-organ damage.
        

  • Knott-Craig CJ. Elkins RC, Lane MM, et al [Univ of Oklahoma, Oklahoma City].
    A 26-year Experience with Surgical Management of Tetralogy of Fallot : Risk Analysis for Mortality or Late Reintervention 
    Ann Thorac Surg 66: 506-511, 1989
        
    Since the early 1990s, the trend in correction of tetralogy of Fallot [TOF] has been toward primary repair and away from 2-stage repair. The results suggest that primary repair offers improved outcomes, although the long term effects on survival and recurrent right ventricular outflow tract disease remain unclear. A 26-year experience with TOF repair was reviewed to analyze effects of the trend toward early repair on early outcomes and recurrent right ventricle obstruction.
        
    From 1971 to 1997, 291 patients were operated for repair of TOF at the author’s institute; 68% had primary repair, 21% had a staged repair and the rest had palliative surgery only. The pathology was complex in 23% of patients, most often including pulmonary atresia. Follow-up information was available on 90% of the patients, with a median duration of follow-up nearly 11 years.
       
    The overall in-hospital mortality rates were 11% for primary repair, 18% for staged repair and 16% for the rest. During the 1990s the mortality rates decreased to 2%, 12% and 0% respectively. After 1990 the patients age at surgery was 0.6 years, compared with the earlier 2 years. Significant risk factors for in-hospital death on multivariate analysis were hypothermic circulatory arrest, pulmonary artery patch angioplasty, earlier years of surgery, and closure of the foramen ovale.
       
    Among patients who survived to hospital discharge, the 20-year survival was 98% for those with TOF with pulmonary stenosis vs 88% for those with pulmonary atresia. Fourteen percent of patients required reoperation on the right ventricular outflow tract. The 20 year rate of freedom from such intervention was 86% for patients with pulmonary stenosis vs 43% for those with pulmonary atresia. Among the latter group, the rate of freedom from reintervention was 85% after primary repair vs 91% for those with staged repair. Patients less than one year were less likely to be free of reintervention, though the difference was not significant.
        
    The long-term retrospective study suggests that survival after primary repair of TOF has improved significantly over the years and even infants do well. Staged repair has to be reserved for patients with complex pathology only. 
        

  • Singh GK, Greenberg SB, Yap YS, et al [ St. Louis Univ., St. Christopher Hosp. for Children, Philadelphia, Southampton Gen. Hosp. England ]
    Right Ventricular Function and Exercise Performance Late After Primary Repair of Tetralogy of Fallot with Trasannular Patch
    Am J Cardiol 81: 1378-1382, 1998
       
    Current surgical repair of tetralogy of Fallot [TOF] involving reconstruction of the right ventricle [RV] usually results in chronic pulmonary insufficiency. Exercise performance and RV systolic and diastolic functions in a group of patients with pulmonary regurgitation, late after primary repair of TOF in infancy, was assessed with cine magnetic resonance imaging and compared with results in normal individuals.
        
    The study consisted of 10 New York Heart Association [NYHA] class 1 [n= 7] or II [n=3] patients with chronic pulmonary regurgitation for an average of 13.6 years after surgery for TOF with reconstruction of the right ventricular outflow tract with a transannular patch, at an average age of 6.9 months.
       
    Cine magnetic resonance imaging was performed and ventricular volume and function indices were calculated and compared with those of 7 age and sex matched healthy controls.
        
    All the patients had pulmonary regurgitation and right and left ventricular enlargement and lower ejection fractions with diminished exercise tolerance correlated with the degree of pulmonary regurgitation.
          

  • Preito LR, Hordof AJ, Secic M, et al [Columbia Univ, New York; Cleveland Clinic Found, Ohio]
    Progressive Tricuspid Valve Disease in Patients with Congenitally Corrected Transposition of Great Arteries
    Circulation 98: 997-1005, 1998
        
    Patients with corrected congenital transposition of the great arteries [CTGA] are commonly found to have morphological abnormalities of the tricuspid valve, with 20% to 50% having clinically significant tricuspid insufficiency [TI]. The progression of tricuspid valve disease in such patients is unclear. A long-term follow-up study of patients with CTGA, with and without open heart surgery, was reported, with special attention to the significance of TI or intrinsic right ventricular dysfunction.
        
    The study included 40 patients with CTGA seen at one medical center since 1958. Twenty-seven patients were male and 13 female. The mean follow-up was 20 years. Potential risk factors for poor outcome were evaluated, including age, open heart surgery, TI, cardiac rhythm, pulmonary overcirculation, and right ventricular dysfunction.
       
    Twenty-one patients underwent intracardiac repair and 19 had no surgery or had closed heart procedures. The only independent prognostic factor for death was severe or moderately severe T1 as demonstrated by echocardiography and/or angiography. Furthermore, the only factor that predicted the presence of T1, was morphological abnormalities of the tricuspid valve. The 20-year survival rate was 93% for patients without T1 vs 49% for those with T1. For patients undergoing surgery, survival rate was 34% for patients with T1 vs 90% for those without T1. Among patients who did not have surgery, the 20-year survival rate was 60% with T1 vs 100% without.
       
    Thus presence of T1 in patients with CTGA worsens the prognosis, irrespective of whether they are operated or not.
        

  • Niezen RA, Helbing WA, van der Wall EE, et al [Leiden Univ. The Netherlands]
    Biventricular Systolic Function and Mass Studied with MR Imaging in Children with Pulmonary Regurgitation After Repair of Tetralogy of Fallot
    Radiology 201: 135-140, 1996
       
    Pulmonary Regurgitation [PR] may occur after surgical correction of tetralogy of Fallot. With the trend toward earlier correction of this congenital condition, there is a longer follow-up period for measurement of PR and biventricular function to evaluate the results of surgery; this study examined such functions.
       
    The study included 19 children who had been operated at mean age of 1.5 years. Doppler echocardiography revealed PR in each patient. A group of healthy controls was studied for comparison. The mean age was 12 years in both groups. The subjects underwent transverse gradient-echo MRI of both ventricles, including creation of MR velocity maps of pulmonary artery. Measurements of biventricular volumes, ejection fraction, myocardial mass, and pulmonary flow volumes were made. In addition, 17 patients underwent exercise testing.
       
    The patients with corrected tetralogy of Fallot had lower right ventricular ejection fractions [ 54% vs 66%] and higher right ventricular mass than controls. Left ventricular ejection factor was also lower in operated cases than controls [ 52% vs 68%] and was significantly correlated with PR. Exercise performance also was seen to be reduced in inverse proportion to PR in the operated cases.
       
    Patients operated for correction of tetralogy of Fallot do develop pulmonary regurgitation which results in larger biventricular mass and reduced ejection fractions; and these effects can be accurately measured by MRI.

  • Reddy VM, McElhinney DB, Phoon CK, et al [Univ of California, San Fransisco]
    Geomatric Mismatch of Pulmonary and Aortic Anuli in Children Undergoing the Ross Procedure : Implications for Surgical Management and Autograft Valve Function
    J Thorac Cardiovasc Surg 115: 1255-1263, 1998
       
    Many children treated with the Ross procedure for congenital heart lesions have a significant discrepancy between pulmonary and aortic anuli. No systematic study was examined whether such mismatch presents a contraindication to the procedure. A review of 41 children who underwent the procedure focuses on the surgical management of geomatric mismatch and its effects on autograft valve function.
       
    Patients had a mean age of 7.8 years. The diameter of the pulmonary valve was greater by 3 mm than that of the aortic valve in 20 cases, equal in 12 cases, and less by 3 mm in 9 cases; the differences ranged between + 10 to -12 mm. Aortoventriculoplasty was used to correct the mismatch in children with a larger pulmonary anulus; whereas in those with a larger aortic anulus, the correction was made by a gradual adjustment along the circumference of the autograft. Patients were followed up [ mean period 31 months] for autograft valvular regurgitation.
        
    Two patients required reoperation for moderate regurgitation. In the remaining 38 survivors, regurgitation was absent or trivial in 30, mild in 7, and moderate in 1. Regurgitation showed no relation with the age of the child, mismatch, or previous or concurrent procedures. No patient had significant autograft root dilatation.
       
    Thus geomatric mismatch is no contraindication to the Ross procedure in children. 
       

  • Stanger P, Silverman NH, Foster E [ Univ of California, San Francisco]
    Diagnostic Accuracy of Pediatric Echocardiograms Performed in Adults Laboratories by Adult Cardiologists 
    Am J Cardiol 83: 908-914, 1999
        
    In the 25 patients with 46 procedure-proved diagnosis the most important error in adult -laboratory echography was major in 44%, moderate in 28% and minor in 12%. In pediatric-laboratory echocardiography, the most important error was major in none, moderate in 4% and minor in 4%. 
        
    Among 41 patients with 62 duplicate-observer-verified diagnosis, the most important error in adult-laboratory echography was major in 12%, moderate in 29%, and minor in 12%, compared with no errors in pediatric. 
         
    What Was the Nature of Error?
         
    In 53% of the adult-laboratory, echocardiograms, the most important error was major or moderate 71% of these were interpretive, 17% technical, and 11% both. The incidences of error were unassociated with patient age, year of study or the use of color Droppler, or complexity of diagnosis. In 29 of these 35 patients, pediatric-laboratory echocardiograms altered clinical management, including 12 operations and averted 2 operations. In 3 of the 29, delayed diagnosis were correlated with fixed pulmonary vascular disease, hypoxemic spells, and vascular collapse with severe metabolic acidosis which were major complications of delayed or missed diagnosis.
          
    Thus, echocardiography should always be done by a pediatric cardiologists in a pediatric set up rather than adult cardiologist in an adult set up and at least this has shown that a delayed diagnosis were associated with clinical problems in 3 children and of course it altered the management of surgery and all in 12 patients an averted 2 operations.

  • Glagovian remodelling, plaque composition, and stenosis generation
    Heart 2000; 84: 461 – 462
      

    Angiograms are good at detecting high grade stenosis in the coronary arteries but are not insensitive in demonstrating actual extent of atherosclerosis. Some plaques grow in to the media of the artery and others bulge into the cavity. Quite often there is arterial remodelling (compensatory dilatation) called Glagovian remodelling. Disruption or rupture of the plaque has certain features. The most important features are a large lipid core, a high macrophage content and a thin cap.
       

  • Genetics of dilated cardiomyopathy: a molecular maze ?
    Heart 2000; 84: 463 – 464
       
    Systematic examination of relatives show that more than 25-30% of dilated cardiomyopathy are familial.
       

  • Stent magic! The genie has escaped from the bottle
    Heart 2000; 84 : 469-470

    A response to injury in the coronary artery – injury in terms of balloon, angioplasty (PTCA) or stent – is activation of cells within the arterial wall, the adventitial of the blood, and there is cellular proliferation of arterial smooth muscle cells, fibroblasts, endothelial cells, monocytes, lymphocytes and leucocytes.
       
    After balloon angioplasty, the response to injury is immediate, but short, after a stent. The response to injury is long lasting. It makes one wonder why stenting has become so popular and comprises of 85% of patients with PTCA.
       

  • William G Stevenson, Etienne Delacretaz
    Radiofrequency catheter ablation of ventricular tachycardia
    Heart 2000; 84: 553
       
    Ventricular tachycardia is very difficult to treat. Drug treatment is often ineffective and defibrillators can terminate one episode but do not prevent them. Tachycardias may arise because of myocardial ischaemia but sometimes they arise even in the presence of normal heart muscle and ECG illustrations, whether it is multifocal or has a fixed site. When there is a single fixed site the treatment of choice is by radiofrequency ablation, which destroys the site of reentering which causes ventricular tachycardia.
        

  • Michael Lye, C Donnellan,
    Heart disease in the elderly
    Heart 2000, 84; 560-566
        
    Cardiovascular disease is the most frequent single cause of death in persons over 65 years of age. There is usually thickening of the left ventricular wall and fibrosis of the valves. 
       
    Peripheral and central arteries develop, and increase thickness. Independent of atherosclerosis, lipids are deposited in the vessel walls. Normally increases in heart rate in response to exercise are diminished and are almost like beta blockade. The diastolic blood flow from the atrium to the ventricle is slowed. Left ventricular hypertropic occurs even in the absence of disease. There is usually potassium retention which makes potassium sparing diuretics risky.
      

  • Raymond J Kim, Edwin Wu, et al 
    The Use of Contrast Enhanced Magnetic Resonance Imaging to Identify Reversible Myocardial Dysfunction.
    NEJM, Nov.16, 2000, 343(20), p.1445-53.
      
    Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischaemic injury regardless of the extent of wall motion or the age of the infarct. Authors hypothesised that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularisation in patients with coronary artery disease.

    Gadolinium enhanced MRI was performed in 50 patients with ventricular dysfunction. Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularisation.

    The conclusion was that reversible myocardial dysfunction can be identified by contrast-enhanced MRI before coronary revascularisation.

    Editorial – pg. 1488-1490. George A Beller.
    Noninvasive assessment of myocardial viability.
    The prognosis is poor for patients with ischaemic cardiomyopathy, which is characterised by extensive coronary artery disease and diminished global left ventricular function. Chronic left ventricular dysfunction in patients with ischaemic cardiomyopathy results from either scarring, as a consequence of myocardial necrosis or myocardial hibernation. Presence of myocardial hibernation suggests that there is sufficient residual blood flow to sustain the viability of myocytes but not enough to maintain systolic contraction. In the case of hibernating myocardium, systolic function improves as perfusion increases with coronary revascularisation. Many patients have both scarring and hibernation in different regions.
      
    Availability of an accurate, non-invasive method of distinguishing viable myocardium from myocardium that has been irreversibly injured as a result of hibernation is important. For clinical decision making such a tool would enable physicians to identify patients with coronary artery disease and left ventricular dysfunction at rest who would benefit most from revascularisation strategies.

    Recently, MRI after administration of a gadolinium based contrast agent in determining the transmural extent of myocardial viability has been investigated. Kim and co-workers tested the hypothesis that hyperenhancement of dysfunctional myocardial regions is indicative of nonviability. The predictive accuracy of the method was very high. Other strengths of the MRI technique are that none of the patients were excluded because of a lack of good-quality images or incomplete visualization of all myocardial segments and because of the very high spatial resolution, the transmural extent of myocardial injury can be determined. This latter advantage is important because transmural scarring of more than 20-30% of tissue correlates with lack of improvement in function after revascularisation.
       

  • A.M. Feldman, Dennis McNamara,(Univ. of Pittsburgh School of Medicine, Pittsburgh)
    Myocarditis – Review Article
    New Eng J Med, Vol.343, Nov.9, 2000, pg.1388-1398.
       
    CAUSES OF MYOCARDITIS

INFECTIOUS  

IMMUNE-MEDIATED

TOXIC MYOCARDITIS

  • Bacterial: brucella, Corynebacterium diphtheriae, gonococcus, Haemophilus influenzae, meningococcus, mycobac- terium, Mycoplasma pneumoniae, pneumococcus, salmonella, Serratia marcescens, staphylococcus, Streptococcus pneumoniae, Strep.pyogens, Treponema pallidum, Tropheryma whippelii, and Vibrio cholerae.Spirochetal: borrelia and leptospiraFungal:actinomyces, aspergillus, blasto myces, candida, coccidioides, cryptococcus histoplasma, mucormycoses, nocardia, and sporothrix
      
    Protozoal: Toxoplasma gondii and Trypa nosoma cruziParasitic: ascaris, Echinococcus granulosus Paragonimus westermanii, schistosoma, Taenia solium, Trichinella spiralis, visceral larva migrans, and Wuchereria bancroftiRickettsial: Coxiella burnetii, Rickettsia rickettsii, and Rick, tsutsugamushiViral: coxsackievirus, cytomegalovirus, dengue virus, echovirus, encephalo myocarditis, Epstein-Barr virus, hepatitis A virus, hepatitis C virus, herpes simplex virus, herpes zoster, human immunodeficiency virus, influenza A virus, influenza B virus, Junin virus, lymphocytic chorio- meningitis, measles virus, mumps virus, parvovirus, poliovirus, rabies virus, respiratory syncytial virus, rubella virus, rubeola, vaccinia virus, varicella-zoster virus, variola virus, and yellow fever virus.

  • Allergens: acetazolamide amitriptyline,cefaclor, colchicine, furosemide, isoniazid, lidocaine, methyl dopa,   penicillin, phenylbutazone, phenytoin, reserpine, streptomycin,tetanus toxoid, tetracycline, and thiazides.
      
    Alloantigens: heart-transplant rejection
      
    Autoantigens:Chagas’ disease, Chlamydia pneumoniae,  Churg-Strauss syndrome, inflam-matory bowel disease, giant-cell myocarditis, insulin-dependent diabetes mellitus, Kawasaki’s disease, myasthenia gravis, polymyositis, sarcoidosis, scleroderma, systemic lupus erythematosus, thyro toxicosis, and Wegener’s granulomatosis.

     

  • Drugs: amphetamines, anthracyclines, catecholamines, cocaine, cyclo- phosphamide, ethanol, fluorouracil, hemetine, interleukin-2, lithium, and trastuzumab.Heavy metals: copper, iron, and lead.Physical agents: electric shock, hyperpyrexia, and radiation.Miscellaneous: arsenic, azides, bee and wasp stings, carbonmono- oxide, inhalants, phos phorus, scorpion bites, snake bites and spider bites.

  • Scott Gottlieb, New York
    Cancer drug may cause heart failure
    BMJ, Vol.321, July 29, 2000, pg.259.
      
    Trastuzumab (Herceptin) is a monoclonal antibody that binds to a protein found on the surface of some cells. The protein, HER2, helps to regulate cell growth. By binding to tumour cells, trastuzumab inhibits growth of cancerous cells. It is currently approved for use in metastatic breast cancer.

    Editorial in ‘Circulation’ has reported that heart failure occurs in 7% of women taking trastuzumab alone and this rate increases to 28% in women taking the drug with other chemotherapy drugs.

    A team of researchers is calling for long-term studies investigating the risk of heart failure among women taking trastuzumab.
      

  • Amanda I Adler, Irene M Stratton, et al 
    Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.
    BMJ, Vol.321, Aug.12, 2000, pg.412-419.
      
    The objective of the study was to determine the relation between systolic BP over time and the risk of macrovascular and microvascular complications in patients with type 2 diabetes.

    The incidence of clinical complications was significantly associated with systolic BP except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic BP was associated with reductions in risk of 12% for any complication related to diabetes. No threshold of risk was observed for any endpoint.
      
    The conclusion was that in patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised BP. Any reduction in BP is likely to reduce the risk of complications with the lowest risk being in those with systolic BP less than 120mm Hg.
      

  • Wilson S Colucci, Uri Elkayam et al
    Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure.
    New Eng J Med, vol.343, July 27, 2000, pg.246.
      
    Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. Authros investigated the clinical use of nesiritide in such patients. Nesiritide was infused at rates of 0.015 and 0.03 ug per kg per minute. It decreased pulmonary capillary wedge pressure, reduced dyspnoea and fatigue.

    It was concluded that in patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Intravenous nesiritide is useful for short-term treatment of decompensated congestive heart failure.
         

  • Perez- Castellano N, Garcia EJ, Abeytua M, et al [Gregorio Maranon Univ Gen Hosp, Madrid]
    Influence of Collateral Circulation on In-Hospital Death From Anterior Acute Myocardial Infarction
    J Am Coll Cardiol 31: 512-518, 1998
      
    Nearly 40% of patients exhibit some degree of collateral circulation at the onset of acute myocardial infarction [AMI]. Some studies have shown beneficial effect from the residual blood flow carried by collateral vessels, but there is no evidence that collateral circulation improves prognosis after AMI. A study of 180 patients sought to determine whether the in-hospital prognosis of anterior AMI is influenced by pre-existent collateral circulation to the infarct-related artery.
      
    Eligible patients admitted with suspected anterior wall AMI, showed complete occlusion of the left anterior descending coronary artery at diagnostic coronary angiography, and were treated by primary percutaneous transluminal coronary angioplasty within the first 6 hours of symptom onset. Angiographic assessment of collateral channels to the infarct related artery before angioplasty, established 2 patient groups: 115 patients without collateral vessels [group A] and 65 patients with collateral vessels [ group B].
      
    The two groups were similar in baseline characteristics, except that the prevalence of previous angina was greater in group B [34%] than in group A [15%]. More hospital deaths occurred in group A [23% than in group B [8%]. Cardiogenic shock, which accounted for 74% of deaths, developed in 26% of patients in group A versus 6% in group B. A progressive decrease in the in-hospital mortality rate was noted with increasing grades of collateral circulation.
       
    Thus the absence of collateral circulation appeared to be a strong predictor of both cardiogenic shock [ odds ratio 5.6] and in-hospital deaths [odds ratio 3.4]. By decreasing the incidence of cardiogenic shock, the presence of collateral circulation decreased the incidence of in-hospital deaths.
        

  • Kloner RA, and the TIMI=9B Investigators [Good Samaritan Hosp, Los Angeles; Univ of Southern California, Los Angeles; Harvard Med School, Boston, et al]
    Prospective Temporal Analysis of Onset of Preinfarction Angina Versus Outcome: An Ancillary Study in TIMI-9B
    Circulation 97: 1042-1045, 1998
        
    Preinfarction angina pectoris has been shown in some studies to confer a protective effect on myocardial infarction [MI], possibly by initiating ischemic preconditioning. Few studies have examined the relationship between onset of angina and outcome after MI. The 30-day outcomes after MI were prospectively compared in patients with more than 24-hours or less between onset of angina and MI.
      
    Angina was reported before MI in 425 of 3002 patients in the TIMI-9B study. Major cardiac events within 30 days of hospitalization were recorded.
       
    Patients who had angina 24 hours or less before MI, had significantly lower rates of events than in those who had angina for more than 24 hours before MI. The former had nonsignificantly lower creatinine kinase [CK] values but significantly lower maximum CK values than the latter. A history of angina longer than 24 hours was not associated with reduced rate of cardiac events. The reduced rate of cardiac events in those with angina of 24 hours or less before MI, was not related to ingestion of aspirin use, antianginal drugs, hypertension or hypercholestrolemia.
       
    Patients with preinfarction angina [ of 24 hours or less duration before MI] had better outcomes after MI than those without preinfarction angina.
       

  • Airaksinen KEJ, Ikaheimo MJ, Linnaluoto M, et al [Univ of Oulu, Finland; Univ of Tampere, Finland]
    Gender Difference in Autonomic and Hemodynamic Reactions to Abrupt Coronary Occlusion
    J Am Coll Cardiol 31: 301-306, 1998
       
    The clinical presentation of acute ischemic events may be modified by changes in heart rate, blood pressure, and heart rate variability. In patients with coronary artery disease, a temporal relationship between changes in heart rate variability and life-threatening ventricular tachyarrhythmias has also been demonstrated. In the autonomic modulation of heart rate, recent research has shown that there are gender-related differences. In a prospective series of patients having clinically indicated coronary angioplasty, potential gender related differences in autonomic responses to abrupt coronary artery occlusions were assessed.
       
    In 149 men and 65 women referred for single vessel coronary angioplasty, the changes in heart rate, heart rate variability, blood pressure, and the occurrence of ventricular ectopic beats during a 2-minute coronary artery occlusion were analyzed. By analyzing a control group of 19 patients with no ischemia during a 2-minute ballon inflation in a totally occluded coronary artery, the ranges of non-specific responses were determined. During the occlusion, women had ST segment changes and chest pain more often than men. Women had significant bradycardia [ 31% vs 13%] or increase in heart rate variability [ 25% vs 11%] as a sign of vagal activation compared with men. A decrease in blood pressure was caused by coronary occlusion more often in women than men [ 28% vs 11%]. The incidence of Bezold-Jarisch-type reaction[ simultaneous bradycardia and fall in blood pressure] was the most pronounced female preponderance [16% vs 0.7%]. An independent predictor of bradycardia reactions, hypotensive reactions and Bezold-Jarisch-type reactions was female gender, according to logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia. There was borderline significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats.
       
    During abrupt coronary artery occlusion, vagal stimulation is more comon and may have beneficial antiarrythmic effects, modifying the outcome of acute coronary events.
          

  • Shiraki H, Yoshikawa T, Anzai T, et al [Yokohama Municipal Hosp, Japan; Keio Univ, Tokyo]
    Association Between Preinfarction Angina and a Lower Risk of Right Ventricular Infarction
    N Engl J Med 338: 941-947, 1998
       
    When inferior myocardial infarction caused by proximal occlusion of the right coronary artery occurs, the result is right ventricular infarction. Such infarctions are less common than would be expected from the frequency of proximal occlusion of the right coronary artery. The reasons for this are unclear. This study examined the possible relationship between preinfarction angina and right ventricular infarctions, including their short-term outcomes.
      
    The retrospective study included 113 patients with acute inferior wall infarction caused by right coronary artery occlusion. Of these patients, 62 had preinfarction angina [ defined as at least one episode of typical chest pain, lasting less than 30 minutes, during the week before the infarction], and 52 did not.
      
    Patients without preinfarction angina were more likely to have right ventricular infarction [odds ratio 6.3, 95% confidence interval 2.7 to 15.1]. They were also more likely to have complete atrioventricular block [odds ratio 3.6, 95% confidence interval 104 to 10.3], and combined hypotension and shock [odds ratio 12.4, 95% confidence interval 4.5 to 40.6]. The strongest predictors of a reduced rate of ventricular infarction were angina occurring 24 to 72 hours before infarction [adjusted odds ratio 0.2, 95% confidence interval 0 to 0.5]. Patients with preinfarction angina had a lower incidence of ST segment elevation in lead V4R.
      
    Thus amongst patients with acute inferior myocardial infarction, preinfarction angina is independently associated with the absence of right ventricular infarction. The short-term outcomes are also better when preinfarction angina occurs. These favourable outcomes could be due to delayed ischemic preconditioning.
      

  • CSR Baker, LRI Baker (Dept.of Cardiology, UK, St.Bartholemew’s Hospital UK)
    Editorial – Prevention of contrast nephropathy after cardiac catheterisation.
    Heart 2001; 85:361-362
      
    Increasing number of patients are now being exposed to contrast medium for various investigational procedures and the problem of radiocontrast induced nephropathy assumes greater and greater importance (RCIN). 

    This has now become the third most common cause of new onset renal failure in hospital patients. Patients, most at risk are those with impaired renal function as judged by an increase in serum creatinine concentration. Diabetes further amplifies the risk. 

    The volume of contrast medium is also important and the risk of renal failure rises with the dose of 100ml with contrast medium.

    The typical patients with RCIN is non-oliguric. Most patients recover but minority become dialysis dependent. To reduce the risk of development of RCIN, patients with high serum creatinine (indicative of reduction in glomerullar filtration rate) should be prehydrated before exposure to contrast medium.
      

  • General Cardiology
    Diabetic heart disease: clinical considerations
    Heart 2001; 85: 463
      
    Coronary heart disease in diabetics is slightly different than in a non-diabetic because of autonomic neuropathy. Symptoms are comparatively mild. Atherosclerosis is more different and widespread in diabetes. However response to medical treatment is at least as good as in non-diabetes.

    From the surgical point of view, angioplasty and bypass is more difficult in diabetics because of the diffused nature of obstruction in the coronary arteries. However, bypass surgery is to be preferred to angioplasty. ACE inhibitors are of particular value in diabetics and coronary heart diseases, because this group of drugs minimises microvascular complications both in heart and the kidney.
      

  • Nicholas Alp, N. Clarke, A P Banning (Dept. of Cardiology, UK)
    Editorial – How should patients with patent foramen ovale be managed?
    Heart March 2001, vol. 85: 242-244.
      
    Patent foramen ovale is common enough in the normal population to be considered an anatomical variant and for any individual the absolute risk of adverse events from a PFO (patent foramen ovale) is clearly very small.

    It becomes important only where venous thrombosis has occurred in patients with raised right atrial pressure. Because of reversal of shunt, paradoxical embolism may occur.

    At present the closure of large PFO in patients with stroke appears to be reasonable.
      

  • G D O Lowe (Univ. of Glasgow, Dept. of Medicine, UK)
    Who should take aspirin for primary prophylaxis of coronary heart disease?
    Heart, March 2001; vol.85: p.245-46
       
    In this study a very large series of subjects, received a long term aspirin treatment as primary prophylaxis had following results. Meta-analysis in 4 randomised controlled trials showed that there was significant reduction of cardiovascular events in the aspirin group. However, there was also a significant increase in bleeding risk.

    The authors suggest that at lower coronary event rates, i.e. where the coronary event risks is 1.5% per year, aspirin therapy is not worthwhile. However it is worthwhile in patients who have a high coronary event rate.
      

  • J Shepherd (Inst. Of Biochemistry, Glasgow)
    The statin era : in search of the ideal lipid regulating agent.
    Heart – March 2001; 85: 259-264
      
    Characteristics of Statins
      

    Characteristics 

    Lovastatin 

    Provastatin  

    Simvastatin

    Atorvastatin 

    Fluvastatin

    Cerivastatin

    Maximal dose (mg/day)

    80 

    40 

    80

    80  

    40

    0.4

    Maximal serum LDL cho-lesterol reduction (5)

    40

    34 

    47

    60 

    24

    28

    Serum LDL cholesterol
    reduction (%)   

    34

    34  

    41

    60  

    24

    28

    Serum triglyceride  reduction (%) 

    16

    24

    18

    29 

    10

    13

    Serum HDL cholesterol  increase (%)

    8.6

    12 

    12

    6 

    8

    10

    Plasma half life (hours)  

    2 

    1-2  

    1-2

    14

     1.2

    2-3

    Effect of food on drug absorption 

     Increased  absorption  

    Decreased 
    absorption

    None

    None 

    Negligible

    None

    Optimal time of administration 

    With meals 
    (morning &Evening)

    Bedtime

    Evening 

    Evening  

    Bedtime  

    Evening

    Penetration of central nervous system

    Yes  

    No 

    Yes

    No

    No

    Yes

    Renal excretion of absorbed dose (%)

    10

    20

    13

    2

    <6

    33

    Mechanism of Hepatic metabolsim

    Cytochrome  P450  3A4 

    Sulfation 
    P450  3A4

    Cytochrome 
    P450  3A4 

    Cytochrome 
    P450  3A4 

    Cytochrome P450  2C9  

    Cytochrome 
    P450 3A4.2C8

  

  • Satyendra Giri, C Michael White, et al
    Oral Amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.
    Lancet, Vol.357. March 17, 2001, pg.830-836
       
    Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is not known. Authors assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.
      
    Patients (average age 73 years) received 6G of amiodarone or placebo over 6 days begining on preoperative day 1.
     
    Interpretation of the findings was that oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillarion and reduces the risk of cerebrovascular accidents and ventricular tachycardia.
         

  • Doorey A, Patel S, Reese C, et al [ Med Ctr of Delaware, Newark; St.Francis Hosp, Wilmington, Del]
    Dangers of Delay of Either Thrombolysis or Primary Angioplasty in Acute Myocardial Infarction with Increasing Use of Primary Agioplasty
    Am J Cardiol 81: 1173-1177, 1998
        
    Early trials of primary angioplasty in the treatment of patients with acute myocardial infarction [AMI] yielded excellent results, but the therapy has been less successful in clinical practice. Patients treated with primary angioplasty or thrombolysis were examined. 
        
    Three hospitals in Northern Delaware adopted primary angioplasty in 1995, after the release of meta-analysis. When early results were unsatisfactory, factors contributing to these poor outcomes were evaluated. Treatment time intervals and outcomes for consecutive patients who received thrombolysis or angioplasty for AMI over 1 year were assessed. Reperfusion times were of interest because of the delays experienced with primary angioplasty.
      
    In 1994, the hospitals had average thrombolysis time intervals of 20 to 30 minutes. Time intervals to thrombolysis increased at one of the hospitals after the angioplasty protocol was announced in March 1995. Uncertainty about the use of thrombolysis versus primary angioplasty was common, and often caused delays. Of the 37 patients treated with primary angioplasty, 12[32%] required emergency bypass surgery or died. With the increasing use of angioplasty, time intervals to thrombolysis in patients not treated with angioplasty, increased from an average of 29 to 39 minutes.
        
    The considerations of primary angioplasty can impair the timeliness of thrombolysis in patients with AMI. An algorithm should be established to minimise treatment delays. 
        

  • Mahmarian JJ, Moye LA, Chinoy DA, et al [ Baylor College of Medicine, Houston; Univ of Texas, Houston; Jacksonville Cardiovascular Clinic, Fla; et al]
    Transdermal Nitroglycerin Patch Therapy Improves Left Ventricular Function and Prevents Remodeling After Acute Myocardial Infarction: Results of a Multicentric Prospective Randomized, Double-Blind Placebo-Controlled Trial
    Circulation 97: 2017-2024, 1998
        
    A multicentric trial examined the effects of transdermal nitroglycerin [NTG] patches on left ventricular [LV] remodeling in patients who survived acute Q-wave myocardial infarction. Prevention of LV dilatation which occurs more often in patients with LV dysfunction, might improve survival.
        
    The double-blind trial randomly assigned 77 patients to placebo and 214 patients to 3 different NTG patch dosages [0.4, 0.8 and 1.6 mg/h]. Patients in four groups were similar in mean age and other baseline characteristics; all underwent baseline gated radionuclide angiography. Dosage of NTG could be reduced, if necessary, to achieve a final tolerated dosage. Patients were evaluated monthly during the 6-month study period. Change in end-diastolic volume index [ESVI] was the primary study end point.
        
    Use of the 0.4 mg/hr NTG patches significantly reduced both ESVI [mean -11.4 mL/m square] and end-diastolic volume index [mean-11.5 mL/m square]. Patients who benefited most from the treatment were those with a baseline LV ejection fraction less than or equal to 40% and only at 0.4 mg /h dose. Withdrawal of NTG patch significantly increased ESVI, but values remained lower than those recorded before treatment. LV dilatation was prevented by transdermal NTG patches, when administered to patients who survived an acute myocardial infarction and had depressed LV function at baseline. Only the lowest dose [0.4 mg/h] was effective, and withdrawal of the patch after 6 months was followed by a significant increase in ESVI.
        

  • Franzosi MG, for the ACE inhibitor Collaborative Group [Instituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy]
    Indications for Ace Inhibitors in the Early Treatment of Acute Myocardial Infarction : Systemic Overview of Individual Data From 100000 Patients in Randomized Trials
    Circulation 97: 2202-2212, 1998
        
    Several trials have evaluated the use of angiotensin converting enzyme [ACE] inhibitors in acute myocardial infarction [MI]. Although the utility of ACE inhibitors in MI is beyond question, some important questions remain; such as do some patient benefit more than others and are some patients at greater risk? The authors examined data from 4 large trials to address these questions.
       
    The 4 large randomized trials included a near 100000 patients from varied regions. In each trial, the test group received ACE inhibitors [n=49214] within 0 to 36 hours after MI and dosing continued for 4 to 6 weeks, whereas a placebo group received no ACE inhibitors [n=49269].
       
    Survival was significantly greater for patients receiving ACE inhibitors [7.11% deaths] compared to placebo group [ 7.59% deaths]; of the deaths avoided in the first group, most were in the first week. Men and women benefited from treatment to a similar extent as did the patients between 55 and 74 years’ age. ACE inhibitors saved 2.7 lives/1000 in those patients whose baseline heart rates were 100/min or more and 8.7 lives/1000 for those with heart rates between 80 to 90/min. Absolute benefits of ACE inhibitors were significantly greater for patients with previous MI [8.9 lives saved /1000], diabetes [17.3] lives saved/1000], hypertension [9.0 lives saved/1000], and Killip class more than 1 at baseline [14.1 lives saved/1000]. With ACE inhibitors patients with anterior MI had significantly improved survival compared to those with MI at other sites [10.6 lives saved/1000] ACE inhibitors saved 3.8 lives /1000 in low risk patients and 13.6 lives/1000 in high risk patients. ACE inhibitors had a similar effect on nonfatal cardiac failures at 30 days as compared with the controls [14.6% vs 15.2%].
        
    On the negative side, ACE inhibitor therapy was associated with significantly greater hypotension [ 84 cases /1000 treated], cardiogenic shock [4.6 patients/1000 treated], second to third degree atrioventricular block [5.4 cases/1000 treated], and renal dysfunction [6.2 cases 1000 
    treated]. Patients 75 years or older had increased risk of renal dysfunction [17 cases/1000 treated].
       
    ACE inhibitor therapy for 30 days saved about 5 lives /1000 patients. The benefit was greater in the first few days of MI. Patients with higher risk typically benefited more. Hypotension and renal dysfunction were the most common problems.
       

  • Milavetz JJ, Giebel DW, Christian TF, et al [Mayo Clinic and Mayo Found, Rochester, Minn]
    Time to Therapy and Salvage in Myocardial Infarction
    J Am Coll Cardiol 31: 1246-1251, 1998
        
    Previous studies have suggested that earlier reperfusion is associated with improved outcome for patients with myocardial infarction [MI]. However, even if perfusion was delayed, some patients have significant myocardial salvage. Time to reperfusion was evaluated as a determinant of myocardial salvage in patients undergoing reperfusion therapy.
        
    The study included 55 patients receiving successful angioplasty or thrombolysis after their first anterior MI. Reperfusion therapy was performed within 2 hours in 10 patients, and after 2 hours in 45 patients. Before reperfusion therapy and at the time of hospital discharge, each patient underwent technetium-99m sestamibi studies to calculate the myocardial salvage index. The low point of the technetium-99m sestamibi curve was used to determine residual flow to the territory of the infarct.
        
    The salvage index ranged from -0.4 to 1.0; 9% of patients had a salvage index of less than 0.10, while 25% had one of the greater than 0.90. Patients undergoing reperfusion therapy within 2 hours or having good residual blood flow were likely to have a high salvage index. Residual blood flow was significantly correlated with salvage only in patients treated after 2 hours. Residual blood flow interacted significantly with time to therapy: each factor influenced the value of the other. None of the historical or hemodynamic variables evaluated was significantly associated with residual flow or myocardial salvage.
        
    Reperfusion therapy provides the best result, if performed within 2 hours after acute MI. Thereafter, salvage rate appears to depend largely on the amount of residual blood flow to the infarct-related artery. These findings emphasize the importance of adequate flow to the infarct territory in myocardial salvage.
        

  • Ross AM, for the GUSTO-1 Angiographic Investigators [ George Washington Univ, Washington, DC; Thoraxcentrium, Rotterdam, the Netherlands; Duke Univ, Durham, NC; et al]
    Extended Mortality Benefit of Early Postinfarction Reperfusion
    Circulation 97: 1549-1556, 1998
        
    Reperfusion therapy aims to restore blood flow to the infarct-related artery after acute myocardical infarction, thus preserving left ventricular function and survival. It was initially expected that successful reperfusion therapy would show increasing benefits over time. However, larger clinical trials of thrombolytic therapy have shown maximum benefit at 4 to 6 weeks, with no subsequent difference in survival. These studies compared the results in terms of assigned treatment, rather than treatment effectiveness. Data from GUSTO-1 study were analyzed to assess the impact of early, complete reperfusion on long-term survival.
      
    The analysis included data on 2431 patients with myocardial infarction who were receiving 1 of 4 regimens of thrombolytic therapy. The patients were categorized as to whether or not they achieved early complete thrombolysis in myocardial infarction grade 3 [TIMI3] flow in the infarct-related artery, and whether they achieved ejection fraction of 40% or less or of greater than 40%. The effects of these variables on 2-year survival were evaluated by Kaplan-Meier curves; Cox regression models were used to define hazard ratios for factors significantly affecting survival.
      
    Survival beyond 30 days was significantly better for patients with early reperfusion and preserved ejection fractions. For patients with TIMI3 flow, compared to those with lesser flow, unadjusted hazard ratio was 0.57 at 30 days and 0.39 at 30 to 688 days or beyond. Achieving early TIMI 3 flow reduced mortality by about 3 patients per 100 in the first month and 5 per 100 thereafter. Preserved ejection fraction was associated with an unadjusted hazard ratio of 0.25 at 30 days and of 
    0.20 thereafter. Lives saved by preserved ejection fraction at these intervals were 9 and 11 per 100, respectively. 
       
    When reperfusion therapy provides early and complete restoration of blood flow to the infarct-related artery, with preservation of left ventricular function, the survival benefit continues beyond the first postinfarction month. The findings emphasize the need for more effective reperfusion approaches. 
         

  • Tiefenbrunn AJ, Chandra NC, French WJ, et al [ Washington Univ, St. Louis; John Hopkins Bayview Med Ctr, Baltimore, Md; Harbor Univ of California, Los Angeles Med Ctr, Torrance; et al]
    Clinical Experience with Primary Percutaneous Transluminal Coronary angioplasty Compared with Alteplase [Recombitant Tissue-Type Plasminogen Activator] In Patients with Acute Myocardial Infarction : A Report From the Second National Registry of Myocardial Infarction [NRMI-2]
    J Am Coll Cardiol 31: 1240-1245, 1998
    Results from a number of small studies comparing percutaneous transluminal coronary angioplasty [PTCA] with thrombolytic therapy in patients with acute myocardial infarction, suggest a survival advantage for patients undergoing PTCA. Data from the NRMI-2 were reviewed to describe the comparison of PTCA with alteplase [rt-PA] in a large number of patients.
        
    The phase 4 study collected data from hospitals in 50 states. Eligible patients were transferred to participating hospitals and received treatment, either an IV thrombolytic agent or primary PTCA., within 12 hours of symptom onset. From June 1, 1994, through October 31, 1995, 4939 patients underwent primary PTCA and 24705 received rt-PA. Baseline characteristics of the two groups were similar after lytic-ineligible patients and those in cardiogenic shock at admission, were excluded. Patients in rt-PA group had thrombolytic therapy initiated at a median time of 42 minutes after admission; the median time to first balloon inflation was 111 minutes after admission in the PTCA group, a significant difference.
        
    In-hospital mortality was significantly higher in patients in shock after rt-PA [52%] than after PTCA [32%]. Among the rt-PA patients with no shock, the in-hospital mortality not was similar in the two groups [5.4% and 5.2% respectively]. The rate of re-infarction did not differ in the two groups [2.9% after rt-PA and 2.5% after PTCA], nor did the combined end point of death and nonfatal stroke.
         
    Thus, in patients not in cardiogenic shock, both methods of treatment gave similar results, in in-hospital mortality, non-fatal stroke and reinfarction. Primary PTCA may be preferable for patients with a contraindication to lytic therapy, for those who are hemodynamically unstable and for those at increased risk of intracranial bleeding.
        

  • Fried LP, for the Cardiovascular Health Study Collaborative Research Group [John Hopkins Med Institutions, Baltimore, Md]
    Risk Factors for 5-Year Mortality In Older Adults : The Cardiovascular Health Study
    JAMA 279: 585-592, 1998
        
    Little is known regarding the joint contributions of diseases and disability to mortality. Few population-based studies have information on objectively measured clinical or subclinical diseases to provide insight into how multiple factors contribute to mortality in older adults. In community-dwelling men and women aged 65 years or older, the disease, functional, and personal characteristics that jointly predict mortality were determined. There were 5201 men and women aged 65 years or older from 4 U.S. communities. Also studied were a supplemental cohort of 685 African-American men and women. Demographic characteristics, self-assessed health status, health habits, physical activity, physical function, and medications used were recorded, as well as a self-report of physician diagnosis of myocardial infarction, angina, congestive heart failure, hypertension, stroke, transient ischemic attack, asthma, hearing impairment, visual impairment, and cancer. Other measures included cardiovascular and pulmonary diseases and blood pressure. 
          
    Within 5 years, there were 646 deaths [12%]. Twenty of 78 characteristics were significantly and independently associated with mortality, including increasing age, income less than $ 50,000 per year, male sex, lack of moderate or severe exercise, low weight, high brachial systolic blood pressure [ greater than 169 mm Hg], low tibial systolic blood pressure [less than 127 mm Hg], smoking for more than 50 pack-years, elevated fasting blood glucose level [greater than 130 mg/dL], diuretic use by those without hypertension or congestive heart failure, elevated creatinine level [1.2 mg /dL or greater], low albumin level [37 g/L or less], aortic stenosis and abnormal left ventricular ejection fraction, low forced vital capacity [2.06 mL or less], stenosis of internal carotid artery, major electrocardiographic abnormality, difficulty in any instrumental activity of daily living, congestive heart failure, and low cognitive function by Digit Symbol substitution test score. Mortality was not associated with high-density or low-density lipoprotein cholesterol. The association between age and mortality diminished after adjustment for other factors, but the reduction in mortality with female sex continued. Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults. 
        
    Other predictors were male sex, relative poverty, smoking, physical activity, indicators of frailty, and disability. Objective, quantitative measures of disease were better predictors of mortality than was a clinical history of disease, except for a history of congestive heart failure. 
            

  • Iacoviello L, Di Castelnuovo A, De Knijff P, et al [Istituto di Ricerche Farmacologiche Marigo Negri, Santa Maria Imbaro, Italy; Leiden Univ, The Netherlands]
    Polymorrhisms In the Coagulation Factor VII Gene and The Risk of Myocardial Infarction
    N Eng J Med 338: 79-85, 1998
        
    A growing body of evidence suggests that patients with high blood levels of coagulation factor VII are associated with an elevated risk of ischemic vascular disease. Environmental and genetic factors may affect the level of factor VII in the blood. However, the relationships among genetic polymorphisms of factor VII, blood levels of factor VII, and myocardial infarction risk are unknown. These associations were investigated in a case-control study.
          
    The cases were 165 patients [mean age, 55 years] with familial myocardial infarction. The controls were 225 individuals [ mean age, 56 years] with no personal or family history of cardiovascular disease. Each individual underwent DNA studies for polymorphisms involving R353Q and the hypervariable region 4 of the factor VII gene. Measurements of factor VII clotting activity and antigen levels were obtained as well. The effects of factor VII gene polymorphisms on myocardial infarction risk and on factor VII levels were analyzed.
         
    The risk of myocardial infarction was reduced for patients with QQ genotype [odds ratio, 0.08; 95% confidence interval, 0.01-0.09] and the H7H7 genotype [odds ratio, 0.22; 95% confidence interval, 0.08-0.63]. Analysis of the R353Q polymorphisms suggested that risk was highest with the RR genotype, intermediate with RQ genotype, and lowest for the QQ genotye. When the hypervariable region 4 polymorphism was considered, patients with the H7H5 or H6H5 genotype were at highest risk, followed by the H6H6, H6H7 and H7H7 genotypes. Factor VII antigen level and factor VII clotting activity were reduced for patients with the QQ or H7H7 genotype vs. the RR or H6H6 genotype. Myocardial infarction risk was reduced for patients at the lowest vs. the highest level of factor VII clotting activity [odds ratio, 0.13; 95% confidence interval, 0.05-0.34].
          
    Thus Factor VII gene polymorphisms appear to influence myocardial infarction risk, perhaps acting through differences in factor VII levels. The mechanism by which the polymorphism influences factor VII levels is unknown. The clinical ramifications of these finding must be evaluated in prospective clinical trials.
       

  • Liem AL, van’t Hof AWJ, Hoorntje JCA, et al [ Hosp de Weezenlanden, Zwolle, The Netherlands]
    Influence of Treatment Delay in Infarct Size And Clinical Outcome In Patients with Acute Myocardial Infarction Treated with Primary Angioplasty
    J Am Coll Cardiol 32: 629-633, 1998
         
    There is great relationship between time to treatment and patency rate among patients given thrombolytic therapy for acute myocardial infarction, but this is less evident in patients treated with primary angioplasty. The effect of delay caused by transfer to an angioplasty center was examined in the study of 207 patients.
        
    Outcome was compared for patients transferred from a community hospital to the study institute for primary angioplasty and patients directly admitted to the study institution. Each transferred patient was matched to a direct patient. Primary angioplasty was considered successful if the residual stenosis in the infarct-related artery was less than 50% and if thrombolysis in myocardial infarction grade 3 flow was present after the procedure.
       
    The median additional delay for transfer patients was 43 minutes. Transferred and nontransferred groups were similar in baseline characteristics and in-hospital outcome. At 6 months, 7% of patients in the transfer group and 6% in the nontransfer had died. Reinfarction had occurred in 4% of the former and 3% of the latter group. Left ventricular ejection fraction at 6 months was 47% and 43% respectively in the two groups. Transferred patients also had more extensive enzymatic infarct size.
        
    Although transferred acute myocardial infarction patients had a larger infarct size and lower left ventricular ejection fractions than the patients admitted directly for angioplasty, the patency rate and 6 month outcome were not adversely affected by the delay. 
       

  • Roger Dobson
    Spider venom may prevent atrial fibrillation
    BMJ, Jan.13, 2001, p.71
         
    Venom from a common South African tarantula spider may contain a protein that could prevent atrial fibrillation.
         
    In the research reported in ‘Nature’ US and German scientists investigated what kind of insect venom could block ion channels and prevent cells from swelling and triggering atrial fibrillation. The poison from Chilean Grammostola spatulata tarantula worked with the peptide GSMtx-4 as the active ingredient.
        
    Rabbit hearts were electrically stimulated to produce arrhythmia and extracts of the venom successfully suppressed the arrhythmia that followed 
       

  • Satyendra Giri, C Michael White, et al
    Oral Amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.
    Lancet, Vol.357. March 17, 2001, pg. 830-836
          
    Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is not known. Authors assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery.
          
    Patients (average age 73 years) received 6G of amiodarone or placebo over 6 days beginning on preoperative day 1.
         
    Interpretation of the findings was that oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.
      

  • Neil R Grubb (Univ. of Edinburgh Cardiovascular Unit)
    Managing out-of-hospital cardiac arrest survivors:
    Cardiological perspective
    Heart 2001; 85: 123-124, p.123
       
    Implantable cardioverter defibrillators (ICDs) significantly reduce the risk of sudden death in specific patient subgroups.
       
    Approximately, 40% of out-of-hospital cardiac arrest victims have the underlying substrate of acute myocardial infarction. The patients are normally suitable for thrombolysis. However, many of the patients were being revived got thoracic trauma during external cardiac massage. Such patients may survive with thrombolysis. X-ray is then necessary before administration of thrombolytic drugs.
        
    Many patients have cardiac arrest without previous myocardial infarction. However most of them are patients of ischaemic heart disease without acute myocardial infarction. At rest they may have normal ECGs. In such patients coronary angiography is mandatory.
      
    Some patients with a normal heart develop cardiac arrest. They usually have right bundle branch block (RBBB), ST segment elevation and are prone to sudden death. For such patients ICD is life-saving.
        
    While ICDs are extremely useful, they should not be used under certain circumstances. Most important are cardiac arrests caused during evolution of myocardial infarction, in those with frequent ventricular arrhythmias and patients having very rapid heart rate.
       

  • U B Fallon, Y Ben-Shlomo, et al (Dept. of Social Medicine, Univ. of Bristol,UK)
    Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow up.
    Heart Feb.2001; 85: 153-158
        

    Although there is a hypothesis that a raised homocysteine concentration in blood is a strong independent risk factor for coronary heart disease, randomized controlled studies in a village in Wales showed that there was no co-relation between homocysteine blood levels and coronary heart disease.
       

  • Martin Riedel (Germany)
    Editorial – Emergency diagnosis of pulmonary embolism
    Heart June 2001, vol.85: 607-609
      
    Emergency diagnosis of pulmonary embolism is the first prerequisite of saving the life of the patient. CT has emerged as a very valuable tool. It is both widely available and results are almost as good as angiography.
      
    Transthoracic echocardiography (TTE) is also widely available. It is non-invasive and very accurate in diagnosis of floating emboli. Transesophageal echocardiography (TOE) is perhaps even superior to TTE. It visualizes the proximal pulmonary arteries. When pulmonary embolism is suspected, TTA followed by TOE and CT gives very specific and precise diagnosis to enable surgery if indicated.
       

  • General Cardiology
    Heart June 2001, 85: 613
       
    Generally speaking, LBBB is considered to be of serious import but RBBB is thought to be comparatively not very dangerous. After a series of analysis of 200,000 young patients, it has been demonstrated that complete RBBB is not benign and it becomes more important with progress in age or if it complicates myocardial infarction. Partial RBBB does not share this bad prognosis.
      

  • Milton Packer et al.
    Carvedilol and Survival in Chronic Heart Failure
    NEJM, Vol.344(22), p.1649
         
    Although beta-blockers are used to treat mild-to-moderate heart failure, they are usually avoided in patients with severe heart failure because of the concern that they may worsen the condition. In this randomized trial, the effects of carvedilol, which blocks a1 – b1-, and b2-receptors, were studied in patients with severe heart failure. As compared with placebo, carvedilol reduced the risk of death by 35 percent and the combined risk of death or hospitalization by 24 percent.
         

  • Elizabeth Barrett-Connor and Deborah L Wingard
    Normal blood glucose and coronary risk
    Dose response effect seems consistent throughout the glycaemic continuum.
    BMJ, Vol.322; 6 Jan 2001, p.5
       
    Glycosylated haemoglobin is an accurate indicator of blood glucose level over the preceeding 6-12 weeks. It is a more precise predictor of coronary heart disease risk. Even in patients without diabetes a glycosylated haemoglobin level in the higher brackets has been shown to be an indicator of impending coronary disease. However lowering of glycosylated haemoglobin has not been shown to have any significant benefit in reducing cardiovascular risk.. Anti-hypertensive treatment is far more effective
         

  • Bauters C, Hubert E, Prat A, et al [Univ of Lille, France, INSERM CJF, Lille, France]
    Predictors of Restenosis After Coronary Stent Implantation
    J Am Coll Cardiol 31: 1291-1298, 1998
       
    For patients with coronary artery disease, balloon angioplasty and stenting, has become a treatment of choice, for coronary revascularisation, with improvements in the quality of stents. The technique has been widely used in diabetic patients, in rescue situations, and in vessels smaller than 3 mms. The 6-month angiographic outcome after successful coronary stenting was studied.
        
    There were 463 patients who had successful coronary stenting in 500 lesions. All received antiplatelet therapy. There were 19% patients with diabetes, 71% were smokers, 38% had hypertension, 59% had hypercholesterolemia, 49% had family history of coronary artery disease, and 36% had unstable angina. 
       
    At angiographic follow-up, restenosis [defined as 50% or more stenosis of the vessel diameter] was present in 26% of 405 lesions. During the follow-up period mean late lumen loss was 0.79, +/- 0.64 mm. A higher late lumen loss was seen in patients with multiple stents. Other independent predictors of stenosis were longer lengths of stenosis, smaller vessel diameters and type of stents used; the authors have had best results with the Palmaz-Scatz stents. The rate of stenosis is high even though the patient sample is poor
       

  • David I Silverman, Warren J Manning
    Editorial – Strategies for cardioversion of atrial fibrillation – time for a change.
    NEJM, Vol. 344, May 10, 2001,pg.1468.
         
    Cardioversion of atrial fibrillation is one of the oldest therapies in cardiovascular medicine. Thromboembolism is a major adverse outcome but warfarin therapy given for 3-4 weeks before cardioversion has reduced this by 80%.
      
    Transthoracic (surface) echocardiography is inadequate for identification of atrial thrombi especially those confined to atrial appendages. Transesophageal echocardiography is accurate for detection of atrial thrombi. 
       
    John Klein and colleagues have used this technique without prior prolonged treatment with anticoagulants for safe and early cardioversion. They enrolled more than 1200 patients in a prospective, randomized study comparing therapy guided by transesophageal echocardiography with the conventional strategy. Their primary findings were that the two strategies were associated with similar rates of embolic events but that the use of transesophageal echocardiography was associated with significantly fewer hemorrhagic complications. This 70-center trial provides reassurance that transesophageal echocardiographic screening for atrial thrombi can be readily and accurately performed in routine clinical practice. Therapeutic levels of anticoagulation should be present at the time of this procedure and continued for at least one month after cardioversion.
       
    The patient most likely to benefit from transesophageal echocardiographic approach is probably the patient who has atrial fibrillation of less than 3 weeks duration or who has an increased risk of haemorrhagic complications during prolonged warfarin therapy.
       

  • Meier CR, Jick SS, Derby LE, et al [ Boston Univ]
    Acute Respiratory -Tract Infections and Risk of First-Time Acute Myocardial Infarction
    Lancet 351: 1467-1471, 1998
       
    More deaths occur from cardiovascular diseases, especially acute myocardial infarction [AMI] in winter than in summer, an association that may be explained by the greater number of acute respiratory-tract infections during cold weather. A large, population-based study explored the link between acute respiratory –tract infections and AMI.
         
    Data were obtained from the UK General Practice Research Database. Cases were patients with first-time diagnosis of AMI during a three-year period [ 1994-1996], no history of clinical risk factors, and were age 75 years or younger. Four controls were matched to each case on the basis of age, sex, and practice attended. In both groups, the date of the last respiratory-tract infection before the index date was identified. In a case cross-over analysis, cases acted as their own controls.
         
    The final database consisted of 1922 cases. In 1994 and 1995, more cases of AMI occurred in the winter, with the highest number [175] in January and the lowest [110] in June. Significantly more cases than controls had an acute respiratory -tract infection in the 10 days before the index-date [2.8% vs 0.9%]. After adjustment for smoking, and bodymass index, the odds ratio for first-time AMI in association with an infection was 3.6 when the infection occurred 1 to 5 days before the index date. The relative risk for AMI was 2.7 in the cross-over analysis when the infection occurred in the 10 days before the index date. Although cause and effect cannot be assumed, findings suggest that there is a seasonal variation in AMI.
       

  • NZ Mian, R Bayly, DM Schreck, etal (Muhlenberg Regional Med Ctr, Plain-field, NJ)
    Incidence of Deep Venous Thrombosis Associated with Femoral Venous Catheterization.
    Acad Emerg Med 4:1118-1121, 1997
        
    The study evaluated 42 patients admitted over a 14-month period subjected to a Heparin-coated 7-fr 20-cm femoral venous catheters. Each patient was subjected to a venous duplex sonography within 7 days of catheter removal. 
         
    Although the study has shown 26% of patients to develop DVT, it does not justify the patients undergoing femoral vein catheterization to be subjected to studies for hypercoaguable states. There is always the potential for substantial morbidity following femoral vein catheterization. Hence, the risk and benefit must be considered prior to this procedure, and complications must be anticipated.
          

  • Khan MA, Herzog CA, St. Peter JV, et al (Hennepin County Med Ctr, Minnesota Heart Clinic, Univ of Minnesota, Minneapolis)
    The Prevalence of Cardiac Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs 
    N. Engl J. Med 339: 713-718, 1998 
          
    A number of obese patients on fen-phen an appetite suppressant, have shown multivalvular disease. The prevalence and severity of valve dysfunction in obese patients taking appetite suppressants was compared with those not taking the drugs.
        
    Of 233 patients and 233 controls in the study, significantly more patients than controls, had cardiac valve abnormalities (22.7% vs 1.3%).
         
    Obese patients who took appetite suppressants showed higher prevalence of valvular insufficiency than obese patients not taking appetite suppressants.
          

  • Antonio P, Beltrami, Konrad Urbanek et al
    Evidence that human cardiac myocytes divide after myocardial infaction
    New Eng J.of Med., vol.344, June 2001, pg.1750.
          
    After myocardial infarction, there is scarring of the heart and this is interpreted as evidence that myocytes are unable to divide. Recent observations have provided evidence that myocytes of adult heart proliferate. Authors have studied the extent of mitosis among myocytes after myocardial infarction in humans.
         
    Myocytes were obtained from the border of the infarct, from areas of myocardium distant from the infarct and from normal hearts. Myocytes that had entered the cell cycle in preparation for cell division were measured by labelling the antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined and the mitotic index (ratio of number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. In the infracted hearts, Ki-67 expression was detected in 4 percent of mycocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts.
          
    Authors conclude that these results challenge the dogma that the adult heart is a postmitotic organ and raise the possibility that the regeneration of myocytes may contribute to the increase in muscle mass of the myocardium
        

  • Nadia Rosenthal
    Editorial – High hopes for the heart
    New Eng J of Med. June 7, 2001; vol.344, pg.1785
       
    The heart is less well-equipped to deal with injury as compared to other tissues. This most critical organ is also the most mortal since it has been widely accepted that the muscle cells of the adult heart are incapable of self-renewal.
      
    Beltrami et al found that the number of Ki-67 positive nuclei in actin-positive cells from hearts with MI was 84 times as high. In distant parts of the myocardium of infracted hearts, such cells were 28 times as frequent as in comparable zones of control hearts. Ki-67 is a reliable marker of mitotic activity. This lends support to the notion that necrosis that follows cardiac injury stimulates the compensatory proliferation of muscle cells.
          
    The level of cardiomyocyte proliferation would hardly be extensive enough to counter the massive necrosis that follows a heart attack, but may be sufficient to repair subclinical lesions after blockage of small capillaries. It is not clear how long the level of proliferation would have persisted had the patients lived. Additional revascularization of repaired scar tissue would be critical to ensure survival of new myocardium. None of these processes are normally efficient enough to prevent ventricular remodeling and progression to heart failure.
       
    The same group of investigators recently reported the persistence of bone marrow cells from an adult donor mouse that had been genetically engineered to express green fluorescent protein, after their injection into the infracted area of a recipient mouse heart that had undergone coronary artery ligation. These cells differentiated into cardiomyocytes, endothelial cells and smooth muscle cells and partially restored cardiac function. Another group selected a subpopulation of bone-marrow cells from human donors and marked them in-vitro. When introduced intravenously into the circulation of athymic rats after induction of MI, these cells migrated to the infarcted zone, differentiated into blood vessels, and induced revascularisation of surrounding rat myocardium, resulting in reduction of apoptosis and scar formation and long-term restoration of cardiac function. Successful incorporation of a patients’ own banked stem cells into multiple cardiac tissues might induce repair of a damaged heart.
          
    The current studies challenge the dogma and suggest exciting new therapeutic pathways to explore.
         

  • G Richardson, AR Moore, et al (Dept. of Cardiology, London)
    Copper generates Nitric oxide from S-Nitrosoglutathione to inhibit platelet function – a potential stent coating?
    Heart May 2001; 85(Suppl.1): P1
       
    Copper produces NO from GSNO to inhibit platelet function in vitro. Coverage of stainless steel with small quantities of copper may not induce significant inflammatory responses. Further re-evaluation of copper, as a stent coating to generate NO, is required.
          

  • J P J Halcox, G Zalos, et al (National Insitutes of Health, Bethesda, Maryland, USA)
    Sildenafil: Effects on Human Vascular Function, Platelet Activation and myocardial Ischaemia
    Heart May 2001; 85(Suppl.1): P.24
          
    Sildenafil dilates epicardial coronary arteries, reduces platelet actrivation, and improves endothelial dysfunction in the coronary and peripheral circulations of CAD patients. Sildenafil had an intermediate effect on myocardial ischaemia compared to ISDN and placebo. Thus, PDE5 inhibitors may be of therapeutic value in atherosclerosis.    
         

  • Israel in stem cell breakthroughs
    Scrip No.2667, August 8, 2001, p.22
        
    Researchers in Israel have made advances in stem cell research which could have applications for heart attack and diabetes patients. They have succeeded in producing heart cells from stem cells (cardiomyocytes) and insulin producing islet cells both in the laboratory stage. If they succeed, there will be major changes in the treatment of heart disease and diabetes.
        

  • Aldo P Maggioni
    Secondary prevention: improving outcomes following myocardial infarction.
    Heart 2000; 84(Suppl.1):i5-i7
         
    Early treatment with ACE inhibitors reduces the expansion of infarct and ventricular enlargement. Most (80%) of the benefit is obvious in the first week of onset of symptoms. These benefits achieved during the first week are maintained for atleast 4 years. There is reduction of mortality in all patients.
        
    Therefore ACE inhibitors should be considered in every MI patients as a parallel benefit. The incidence of diabetes is reduced.
       

  • John G F Cleland
    Improving patient outcomes in heart failure: evidence and barriers
    Heart 2000: 84 (Suppl.1): i8-i10.
         
    In the treatment of heart failure, the most important step is initiation of ACE inhibitors. Higher doses are necessary to exert great benefits. There is now conclusive evidence of the benefit of ACE inhibitors with beta blockers for treatment of heart failure.
        

  • M Petrie, J McMurray
    Changes in notions about heart failure
    The Lancet, Vol.358: 11 August 2001, p.432.
       
    Chronic Heart Failure (CHF) has been traditionally thought of as a clinical syndrome of breathlessness, fatigue and salt and water retention. Until lately the focus has been on symptoms and left ventricular systolic dysfunction. 
       
    In large survey of 3960 patients, in person over 45 years, who were examined and investigated in great detail, it was found that approximately half the patients had no symptoms. Left ventricular ejection fraction was seen as diminished in 139 patients out of 3960. Ejection fraction was calculated by echocardiography and when followed up the 5-year mortality rate was 50-75%.
       
    In treatment, ACE inhibitors were the drugs of choice given in adequate doses. Combination with beta blockers further improved the prognosis.
        

  • Helen Frankish
    News -Researchers turn human stem cells into heart tissue
    The Lancet, vol358, August 11, 2001, p.475
       
    A case report is presented whereby injection of human stem cells taken from patient’s hip has been injected into the coronary circulation, which has lead to growth of new myocytes. The work is under progress in Israel. Human stem cells are being experimented with for manufacture of pancreatic beta cells for treatment of diabetes.
         

  • Yoshiki Sawa
    Therapeutic angiogenesis with gene transfection for ischaemic heart disease.
    Drugs of Today, 2001, 37(1), pg.67-71
          
    Genetic engineering studies conducted in the field of cardiovascular medicine have lead to the use of gene therapy as a means of treating ischaemic disease. Folkman et al have shown that tumour growth is facilitated by revascularisation and revascularization factors are involved in tumour growth. The first revascularisation factor used for therapeutic angiogenesis was basic fibroblast growth factor (bFGF). In a rabbit model of acute leg ischaemia, 14 day IM treatment with bFGF at a dose of 1 or 3 mg promoted the formation of collaterals in the legs. Possibility of treating myocardial infarction has also been reported. Intramyocardial injection of vascular endothelial growth factor (VEGF) on induction of myocardial revascularisation has been shown in dogs and pigs.
          
    Clinical trials of gene therapy using VEGF have started at Tufts University in U.S. This therapy is designed to treat severe ischemic disease with revascularisation. VEGF genes were injected locally into myocardium after small thoracotomy. More than 70 patients have undergone this therapy and revascularisation and improved regional blood flow as assessed by angiography and myocardial scintigraphy has been reported. Crystal and coworkers at Cornell University have administered VEGF cDNA on an adenovirus vector into the myocardia of about 30 patients, with or without coronary artery bypass grafting, and reported revascularising effect and safety of this therapy. 
         
    Revascularising effects of HGF:- Hepatocyte growth factor has been shown to be specific to vascular endothelium and does not affect proliferation of vascular smooth muscle.
        
    Studies in rats have shown that HGF increases the number of newly formed blood vessels. HGF is more potent than VEGF and clinically useful. Introduction of HGF gene, which is a revascularisation factor produced endogenously, may be a new means of treating severe ischaemic heart disease.
            

  • S.L. Udupa
    Indigenous drugs and atherosclerosis
    Drugs of Today 2001, 37(1), 37-47
         
    An encouraging field for the application of indigenous drugs is regression of atherosclerosis. Vitamins C and E, carotenoids, flavonoids, terpenoids present in indigenous drugs have been shown to slow down progression of experimental atherosclerosis. Potassium and magnesium found in herbals are also beneficial.
          
    This is a review of some of the Indian indigenous drugs, found to be antiatherogenic. 
         
    The drugs included are: 
    (1) Achyranthus aspera – contains triterpenoids. Hypocholesterolemic effect in rats. 
         
    (2) Allium cepa (onion) – therapeutic effects attributed to sulphur compounds.
         
    (3) Allium satiuum (garlic) – known to have hypoglycaemic, hypocholesterolemic and hypolipidemic effects and protects against the development of atherosclerosis. The inhibition of cholesterol synthesis by garlic may be due to a mixture of multiple compounds of sulfur containing thiosulfinates, ajoenes and dithienes.
         
    (4) Aloe barbedensis – Lipid lowering agent lowers VLDL and LDL and increases HDL.
        
    (5) Capsicum annum (Red pepper). Red pepper or its active principle capsaicin prevented increase in cholesterol levels in rats.
       
    (6) Cicer arientinum – Bengal gram. Hypolipidemic effect – due to its isoflavonic component – Biochanin A.
        
    (7) Commiphora mukul – Crude guggul or its oleoresin lowers serum cholesterol in rabbits. Similar effect shown in patients with hypercholesterolemia. Long-term combination treatment with fraction A guggul and cholestyramine resulted in decrease in serum cholesterol and triglyceride levels.
       
    (8) Dolicos lablab – seeds used as pulse in diet. Reduces serum cholesterol in rats.
        
    (9) Emblica officinalis – Its fruit (amla) is probably the richest known natural source of vitamin C. Dietary supplementation with raw amla in normal and hypercholesterolemic subjects resulted in a decrease in cholesterol levels.
        
    (10) Medicago sativa : (Alfalfa). Alfalfa meals prevent hypercholesterolemia, triglyceridemia and atherogenesis in cholesterol fed rabbits.
         
    (11) Plantago ovata – They are a class of gel-forming, nonabsorbable, soluble fibres derived from oat or psyllium seed husk which have been shown to produce cholesterol lowering effects when added as dietary supplements. Addition of psyllium hydrophilic mucilloid to cholestyramine therapy may improve patient compliance by reducing drug-associated GI side-effects.
         
    (12) Terminalia arjuna – Powdered bark is used. Constituent of many Ayurvedic preparations shown to decrease serum cholesterol and blood sugar levels in experimental animals after 3 months of treatment. It is also reported to have antihypertensive and antiarrhythmic properties.
        
    (13) Terminalia belerica – Alcoholic extract has dose-dependent hypotensive effect. It is present in Triphala (T.belerica, T.chebula and E.officinalis).
        
    (14) Terminalia chebula – Reduces cholesterol levels in experimental atherosclerosis in rabbits.
        
    (15) Trichosanthes dioica – Fruit used. Hypoglycemic and hypocholesterolemic effects in normal and mildly diabetic humans.
         
    (16) Trigonella foenum graecum – The seeds (fenugreek) – caused cholesterol levels to decrease in diabetic hypercholesterolemic dogs. Also reduces hyperglycemia. Ethanol extract from defatted fenugreek seeds contained saponins that inhibit absorption of taurocholate and deoxycholate.
          
    In type I diabetes, fenugreek diet significantly reduced fasting blood sugar and improved glucose tolerance test. Serum cholesterol, LDL and VLDL and TG were significantly reduced but HDL was unchanged.
          

  • Frank B Hu.
    The role of N-3 polyunsaturated fatty acids in the prevention and treatment of cardiovascular disease.
    Drugs of Today, 2001, 37(1): 49-56
        
    Several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing MI. Epidemiologic and clinical studies have suggested that alpha-linoleic acid (ALA), a short-chain n3-3 fatty acid from plant sources may have similar cardiac benefits as long chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. Reduction of TG levels, reduction of platelet aggregation also contribute. There is growing evidence that fish oil may improve endothelial dysfunction.
        
    Substantial evidence is there for beneficial effects of ALA on CVD. Flaxseed as well as other important dietary sources of ALA e.g. unhydrogenated canola, soyabean oil and walnuts can be incorporated into a healthy and balanced diet for prevention of CVD. This is especially important for persons who do not consume fish.
        

  • G Richardson, AR Moore, et al (Dept. of Cardiology, London)
    Copper generates Nitric oxide from S-Nitrosoglutathione to inhibit platelet function – a potential stent coating?
    Heart May 2001; 85(Suppl.1): P1
         
    Copper produces NO from GSNO to inhibit platelet function in vitro. Coverage of stainless steel with small quantities of copper may not induce significant inflammatory responses. Further re-evaluation of copper, as a stent coating to generate NO, is required.
         

  • J P J Halcox, G Zalos, et al (National Insitutes of Health, Bethesda, Maryland, USA)
    Sildenafil: Effects on Human Vascular Function, Platelet Activation and myocardial Ischaemia
    Heart May 2001; 85(Suppl.1): P.24
          
    Sildenafil dilates epicardial coronary arteries, reduces platelet actrivation, and improves endothelial dysfunction in the coronary and peripheral circulations of CAD patients. Sildenafil had an intermediate effect on myocardial ischaemia compared to ISDN and placebo. Thus, PDE5 inhibitors may be of therapeutic value in atherosclerosis.
        

  • Patrick Tounian, Yacine Aggoun, et al 
    Presence of Increased Stiffness of the Common Carotid Artery and Endothelial Dysfunction in Severely Obese Children: A Prospective Study 
    Lancet, Vol.358, October 27, 2001, Pg. 1400-04
         
    Summary: Epidemiological studies suggest that obesity induced atherosclerosis may start in childhood, but this process has never been demonstrated.
          
    The authors looked for arterial changes and investigated their relation to cardiovascular risk factors in obese children.
          
    Non-invasive ultrasonographic measurements were made in 48 severely obese children and 27 controls to investigate arterial mechanics and endothelial function. Plasma lipid concentrations, indices of insulin resistance, and body composition were assessed in obese children.
          
    Severe obesity in children is associated with arterial wall stiffness and endothelial dysfunction. Low plasma apolipoprotein-A-I, insulin resistance, and android fat distribution may be the main risk factors for these arterial changes, which are of considerable concern as possible early events in the genesis of atheroma.
         

  • Bruce Zuraw
    Commentary – Bradykinin In Protection Against Left-Ventricular Hypertrophy
    Lancet, Vol. 358, October 6, 2001, Pg. 1116-18
         
    Summary : Left-Ventricular hypertrophy substantially increases risk of sudden death and other cardiovascular complications even after adjustment for other known risk factors.
        
    On the basis of pressor and remodeling effects of angiotensin II, the reninangiotensin system is widely thought to play an important part in the development of LVH. Efficacy of ACE inhibitors in lessening progressive LV remodeling and rates of sudden death in patient with LV dysfunction further proves the importance of this system.
          
    ACE generates angiotensin II but also degrades bradykinin, and bradykinin is the preferred ACE substrate. Of the 2 angiotensin receptors that have been identified, AT1 receptors mediates the pressor effect whereas AT2 receptor mediates hypotensive effects.
         
    David Brull and colleagues have reported that individuals with the greatest increase in LV mass had the highest concentration of ACE and the lowest concentration of B2 bradykinin receptor. These results strongly support an important role for bradykinin in the ACE medicated effect on LVH.
         
    Bradykinin mediates important cardiovascular effects, such as increased vascular permeability, enhanced myocardial glucose uptake, negative intropism and inhibition of myocardial growth. Bradykinin has been shown to play an intergral part in protecting ischaemic myocardium. Genetically ablating B2 bradykinin receptors result in enhanced salt-induced hypertension and hypertropic cardiomyopathy.
         
    There is also evidence of interaction between bradykinin and rein-angiotesin system. It is now seems that bradykinin ia an important participant in the cardiac effects of the renin-angiotensis system and novel pharmaceutical approches to further increase bradykinin concentrations may be clinically beneficial.
        
    It is important to recognise that the ACE and B2 bradykinin-receptor polymorphisms account for only a fraction of the total variability in the expression of LVH.
         
    A complete understanding of LVH variability is certain to be extremely complex, involving multiple gene interactions as well as gene-environment interactions.
             

  • Franz-Josef Neumann, Adnan Kastrati et al 
    Treatment of Chlamydia pneumoniae Infection with Roxithromycin and Effect on Neointima Proliferation After Coronary Stent Placement (ISAR-3): A Randomised, Double-Blind, Placebo-Controlled Trial 
    Lancet, Vol.357, June 30, 2001, Pg. 2085-89
          
    Summary : Vascular infection with Chlamydia pneumoniae might boost inflammatory responses that play an important role in neointima formation, which is the main cause of restenosis after stenting.
          
    The aim of this study was to investigate whether or not treatment of Chlamydia pneumoniae infection with antibiotics prevents restenosis after stent placement. 
           
    The interpretation of this study was that non-selective use of roxithromycin is inadequate for prevention of restenosis after coronary stenting. There is a differential effect dependent on Chlamydia pneumoniae titres. In patients with high titres, roxithromycin reduced the rate of restenosis.
           

  • C. Varma and S J D Brecker 
    Predictors of Mortality in Acute Myocardial Infarction 
    Lancet, Vol.358, November 3, 2001, Pg. 1473-74
           
    Summary : Initial treatment of myocardial infarction is aimed at establishing coronary artery patency, but it is myocardial viability that determines prognosis. Flow in the related artery is not always associated with myocardial perfusion because of microvascular damage.
          
    Angioplasty is the most successful method of reperfusion, but it is restricted by logistical issues, and for most patients thrombolysis is the initial method of reperfusion. 
           
    The most reliable predictor of outcome after myocardial infarction is the concentration of troponin T. Troponin concentration may start to rise within 6 h of infarction, and takes only 20 min to measure. Other predictors are ST-segment elevation and increased concentrations of kinase. C reactive protein and myoglobin are also of prognostic value.
          
    ECG is still the most widely used diagnostic tool and according to GUSTO-IIb study the 30-day incidence of death or myocardial reinfarction was 10.5% among those with ST-segment depression and 12.4% among those with ST elevation and depression. ST depression is also the strongest predictor of 1-year mortality among patients with acute coronary syndromes.
         
    In a study reported by Klaus Schroder and colleagues, they found that mortality at 180 days was predicted by analysis of just 1 ECG lead (the one with maximum deviation at 90 min) and that the ST deviation (not resolution) in this single lead was a better predictor than sum STR.
           
    Although the investigators used a lens-intensified calliper for their measurements, most of the measures are large enough not to require any special equipment.
            
    Novel adjunctive therapies for reducing microvascular damage and improving myocardial perfusion (myocardium protective agents and vascular growth factors) are being investigated.
             

  • Klaus Schroder, Karl Wegscheider et al 
    Extent of ST-Segment Deviation in a Single Electrocardiogram Lead 90 Min After Thrombolysis as a Predictor of Medium-Term Mortality in Acute Myocardial Infarction 
    Lancet, Vol.358, November 3, 2001, Pg. 1479-86
             
    Summary : In evolving myocardial infarction, assessment of the sum of early resolution of ST-segment elevation (sumSTR) has become an established method to predict outcome. 
           
    Authors have found previously that mortality is predicted more accurately by the existing ST-segment deviation in the single ECG lead with maximum deviation (maxSTE) 90 min after start of thrombolysis. Authors compared the power to predict medium-term mortality by these 2 approaches.
          
    Interpretation of this study was that, maxSTE predicts early and medium-term mortality more accurately than does sumSTR. The prognosis for an individual patient can be accurately estimated simply by the ST-segment deviation present in one ECG lead recorded 90 min after thrombolysis.
           

  • Gusto V Investigators 
    Reperfusion Therapy for Acute Myocardial Infarction with Fibrinolytic Therapy or Combination Reduced Fibrinolytic Therapy and Platelet Glycoprotein IIb/IIIa Inhibition: The GUSTO V Randomised Trial 
    Lancet, Vol.357, June 16, 2001, Pg. 1905-14
          
    Summary : Plasminogen activator therapy for acute myocardial infarction is limited by lack of achievement of early, complete, and sustained reperfusion in a substantial proportion of patients. Many phase II trials have supported the potential of combined fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition for improving reperfusion.
         
    The authors’ did a randomised, open-label trial to compare the effect of reteplase alone with reteplase plus abciximab in patients with acute myocardial infarction.
          
    Interpretation: Although combined reteplase and abciximab was not superior to standard reteplase, the 0.3% absolute (5% relative) decrease in 30-day mortality fulfilled the criteria of non-inferiority. 
          
    Combination therapy led to a consistent reduction in key secondary complications of myocardial infarction including reinfarction, which was partly counterbalanced by increased non-intracranial bleeding complications.
          

  • Freek W A Verheugt
    Commentary: GUSTO V: The Bottom Line of Fibrinolytic Reperfusion Therapy 
    Lancet, Vol.357, June 16, 2001, Pg. 1898-99
           
    Summary: Several drugs that could provide additional benefit to thrombolytic therapy have been investigated. Addition of heparin has not improved early patency rates or prevented reocclusion and has increased frequency of bleeding especially cerebral bleeding.
          
    Hirudin, a direct inhibitor of thrombin was similar. Aspirin, in addition to streptokinase, decreased mortality and has shown benefit of inhibiting platelet aggregation.
          
    Antagonists to the glycoprotein IIb/IIIa receptor, such as abciximab, eptifibatide or tirofiban, block the final common pathway of platelet aggregation. These drugs given IV have improved outcome of fibrinolytic agent and a glycoprotein protein abciximab has been extensively evaluated.
        
    Addition of full-dose abciximab to half-dose alteplase or to half-dose reteplase resulted in nearly 80% of patients achieving complete reperfusion at 90 min without much increase in side-effects. Patency improved and ECG signs of tissue perfusion were also better with the combination.
         
    Results of GUSTO V has both good and bad news. The good news is the report of the lowest 30 day mortality (less than 6%) and bad news is that concept of an improvement in early patency rates leading to a decrease in mortality was not confirmed.
            
    Future management of MI with ST elevation may involve early medical treatment with a bolus of fibrinolytic or a combination of a fibrinolytic and a glycoprotein blocker- followed immediately by angioplasty.
          

  • The GUSTO IV-ACS Investigators 
    Effect of Glycoprotein IIb/IIIa Receptor Blocker Abciximab on Outocome in Patients with Acute Coronary Syndromes Without Early Coronary Revascularisation: The GUSTO IV-ACS Randomised Trial 
    Lancet, Vol.357, June 16, 2001, Pg. 1915-24
            
    Summary : Glycoprotein IIb/IIIa blockers reduce procedure-related thrombotic complications of percutaneous coronary intervention, and the risk of death and myocardial infarction in patients with acute coronary syndromes.
           
    The effect on risk of death and myocardial infarction is particularly apparent in patients undergoing early percutaneous coronary interventions.
          
    The authors did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early revascularisation.
          
    Interpretations : Although the explanations for the findings are unclear, this study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes.
        

  • McKenna CJ, Codd MB, McCann HA, et al (Mater Misericordiae Hosp, Dublin) 
    Alcohol Consumption and Idiopathic Dilated Cardiomyopathy: A Case Control Study
    Am Heart J 135: 833-837, 1998
            
    Alcohol is believed to be a risk factor for idiopathic dilated cardiomyopathy (IDCM). A case control study was made comparing consumption of alcohol in cases with IDCM with that of normal controls.
           
    Patients were 100 adults (73 men and 27 women, with mean age of 54 years) with IDCM. Controls were 211 adults (86 men and 125 women with mean age of 56 years) who were randomly selected from the population. 
            
    All participants filled up questionnaires that addressed the duration and quantity of alcohol intake and alcohol abuse. Additionally 200 first-degree relatives of 56 patients with IDCM were examined by echocardiography to identify any familial disease. 
            
    It was observed, significantly more of patients with IDCM (40 or 40%) exceeded recommended weekly intake of alcohol (21 units for men and 14 units for women) than did the controls. Also significantly more of the patients were alcohol abusers than controls (27% vs 16%).
           
    Of the 56 patients whose relatives were examined, 25 (45%) had a familial tendency to IDCM. These 25 were compared with 31 patients with non-familial tendency and both groups had similar risk factors for IDCM (i.e. viral illness, atopy and pregnancy) in alcohol consumption and alcohol abuse.
            
    Thus alcohol consumption was identified as a possible aetiologic agent in 40% of patients with IDCM. However, 60% of the patients with IDCM were not heavy drinkers and yet had IDCM. Alcohol consumption is one of the factors, among others, involved in the aetiology of IDCM.
            

  • Grunig E, Tasmasn JA, Kucherer H, et al (Univ of Heidelberg, Germany; Univ of Lubeck, Germany) 
    Frequency and Phenotypes of Familial Dilated Cardiomyopathy 
    J Am Coll Cardiol 31: 186-194, 1998
           
    Aetiology of dilated cardiomyopathy (DCM) is unknown and accurate diagnosis remains difficult. Up to 25% of patients were classified as having inherited disease in one recent study. A typical phenotype pattern may often be found in a single family.
         
    To construct pedigrees, 445 consecutive patients with proven DCM were studied together with 970 first and second-degree family members.
          
    In 48 of the 445 patients (10.8%) familial DCM was confirmed; it was suspected in 108 (24.2%). These 156 patients with suspected or confirmed DCM were younger and more often had EKG changes, compared with those with non-familial disease.
          
    Five phenotypes of familial DCM were also identified, namely: 
    DCM with sensoneural hearing loss, 
    DCM with conduction defects, 
    DCM with segmental hypokinesia of the left ventricle, 
    Juvenile DCM with rapid progressive course in male relatives without muscular dystrophy; and 
    DCM with muscular dystrophy.
          
    Thus an inherited disorder may be found in 35% of patients with DCM.
           

  • The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators
    Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes Without ST-Segment Elevation 
    The New England Journal of Medicine Vol.345 (7), August 16, 2001, Pg. 494-502
           
    Summary: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. The authors have evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients.
          
    Patients (12,562) who presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) or placebo in addition to aspirin for 3-12 months.
          
    The conclusion was that clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.
            

  • D. P. Wade and J. S. Owen 
    Regulation of the Cholesterol Efflux Gene, ABCA1
    Lancet Vol.357, January 20, 2001, Pg. 161-163
          
    Summary : The possibility of controlling serum LDL cholesterol concentrations with statins is a major advance. But statins are not very effective if dietary cholesterol intake is excessive and they do not rectify low HDL, a risk factor as important as raised LDL for coronary heart disease. So, drugs that raise HDL or impair dietary cholesterol uptake are needed.
           
    Recent discovery suggests that a single protein ABCA1 has key functions in HDL production and cholesterol absorption. The first breakthrough was identification of ABCA1 as the defective gene in Tangier disease, a rare disorder characterised by very low plasma HDL and an inability of cells to excrete cholesterol onto lipid-poor apoA-I, the main HDL precursor.
           
    ABCA1 protein belongs to a superfamily of membrane transporters that bind and hydrolyse ATP to drive diverse substrates across membranes. Cholesterol, and perhaps phospholipid are ABCA1 substrates and their efflux may be aided by binding of apoA-1 to ABCA1.
           
    This step, first stage in reverse cholesterol transport, enables peripheral cells to unload superfluous cholesterol onto HDL for transfer to liver.
           
    Can ABCA1 be upregulated, as a means of atheroprotection? ABCA1 activity can be increased by increasing transcription of the ABCA1 gene. Increase in ABCA1 expression is mediated by 2 members of nuclear receptor superfamily – LXR (liver X receptor) and RXR (retinol X receptor).
           
    Insights into potential benefits of upregulating ABCA1 expression will prompt increased efforts to uncover regulatory pathways that provide new targets for pharmacological intervention.
           

  • Walter W. Rosser 
    Aspirin for Primary Prevention of Cardiovascular Events 
    Lancet Vol.357, January 13, 2001, Pg. 84-85
            
    Summary : Whether general practitioners should recommend aspirin to their patients to reduce the risk of heart attack and other cardiovascular events has been confusing. The report on the Primary Prevention Project (PPP) in Lancet provides general practitioners with some evidence.
            
    The PPP study was stopped after about 3.5 years of follow-up because 2 other studies of low doses of aspirin showed a significant beneficial effect of drug. PPP results showed that 100 mg daily of enteric coated aspirin had a protective effect in people with one or more cardiovascular risk factors.
            
    All 3 studies highlight the fact that in hypertensive patients blood pressure must be well controlled because higher the blood pressure greater the risk of haemorrhagic strokes, and aspirin should be prescribed in low doses to avoid bleeding complications.
            
    The 2nd segment of PPP, that of the effect of vitamin E did not provide evidence that the vitamin reduces cardiovascular risk. General practitioners can advise their patients that any beneficial effect that vitamin E might have is weak and awaits discovery.
          

  • Collaborative Group of the Primary Prevention Project (PPP)
    Low-dose Aspirin and Vitamin E in People at Cardiovascular Risk: A Randomised Trial in General Practice 
    Lancet Vol.357, January 13, 2001, Pg. 89-95
              
    Summary : Authors aimed to investigate in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with one or more major cardiovascular risk factors.
               
    They did a randomised controlled open trial to investigate low-dose aspirin (100 mg/day) and vitamin E (300 mg/day) in people with one or more of the following: hypertension, hypercholesterolaemia, diabetes, obesity, family history of premature myocardial infarction, or individuals who were elderly.
              
    Interpretation of the study was that in women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile.
              
    Results on vitamin E’s cardiovascular primary preventive efficacy are not conclusive per se, and are consistent with the negative results of other large published trials on secondary prevention.
          

  • Luchsinger JA, Steinberg JS (Columbia Univ, New York)
    Resolution of Cardiomyopathy After Ablation of Atrial Flutter
    J Am Coll Cardiol 32: 205-210, 1998
              
    Tachycardia-induced cardiomyopathy can lead to congestive heart failure (CHF) and studies have shown that controlling tachycardia improves left ventricular (LV) function. Possible effect of atrial flutter (AFl) in causing cardiomyopathy with LV dysfunction was examined. 
           
    Eleven patients (all men, mean age, 59 years) with refractory AFl who were undergoing radiofrequency ablation (RFA) of AFl, had dilated cardiomyopathy and CHF.
            
    RFA was successful in all eleven patients. 2-dimension echocardiography performed before RFA and a median of 7 months after RFA, showed significant improvements in LV function and complete resolution of CHF. Six patients had normal LV ejection fraction (LVEF).
             
    Thus AFl appears to contribute to LV dysfunction and tachycardia-induced cardiomyopathy which reverse with RFA.
            

  • Corrado D, Basso C, Schiavon M, et al (Univ of Padua, Italy; Natl Health Service, Padua, Italy)
    Screening for Hypertrophic Cardiomyopathy in Young Athletes 
    N Engl J Med 339: 364-369, 1998 
            
    Cardiovascular disease is the most common cause of sudden death in athletes. For athletes over 35 years, atherosclerotic coronary artery disease is the most common cause of sudden death. In younger athletes, hypertrophic cardiomyopathy has been implicated as a cause of sudden death, in a third of competing athletes.
               
    In Italy it is required by law, for every athlete to be clinically examined before entering competitive sports. A consecutive group of 33,375 young athletes who underwent preparticipation screening were studied.
             
    In a group of 269 young people with sudden death, 49 (18.2%) were competitive athletes (mean age 23 years; 44 men and 5 women). Amongst the causes of death, cardiomyopathy accounted for 2% of deaths only. Thus preparticipation screening reduces the incidence of sudden deaths in young athletes due to cardiomyopathy.
              

  • Hunt SA (Stanford Univ, Calif)
    Current Status of Cardiac Transplantation 
    JAMA 280: 1692-1698, 1998 
            
    The article deals with 30 years of heart transplantation and future trends. Heart transplantation is still reserved for those in end stage heart disease. Approximately 2500 heart transplants are being performed in USA per year and the trend has continued for the past decade.
           
    Combination of cyclosporine, azathioprine and corticosteroids remains the main stay for immunosuppression.
            
    Overall 1-year survival rate has remained 80%. The main limitations to heart transplantation are infection, rejection, coronary artery disease and malignancy in the graft.
          
    Future may see discovery of better immunosuppressive drugs. Newer donor materials by way of nonbiologic and mechanical hearts may become available to overcome shortage of donor hearts. Left ventricular assist devices are being devised and used but need more developments.
          

  • The Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators
    Thrombin-Specific Anticoagulation with Bivalirudin Versus Heparin in Patients Receiving Fibrinolytic Therapy for Acute Myocardial Infarction: The HERO-2 Randomised Trial 
    Lancet, Vol. 358, December 2001, Pg. 1855-1863
          
    Summary : Bivalirudin (Angiomax, previously known as Hirulog) is a direct thrombin-specific anticoagulant. The authors therefore tested the effect on 30-day mortality of bivalirudin (in a dose selected as being the optimum on the basis of HERO-1 efficacy and safety data) versus unfractionated heparin started before streptokinase.
          
    Interpretation : Bivalirudin did not reduce mortality compared with unfractionated haparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin.
         
    Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.
          

  • Sheila A. Doggrell 
    Clinical Trials With Glycoprotein IIb/IIIa Antagonists No Benefit Without Bleeding?
    Drugs of Today Vol.37 (8), August 2001, Pg. 509-531
          
    As the glycoprotein GPIIb/IIIa receptor is the final common pathway in platelet aggregation, an antagonist of this receptor can cause profound inhibition of aggregation induced by any agonist.
         
    Abciximab is a chimeric human-mouse monoclonal antibody that is less immunogenic than murine 7E3 Fab. A major clinical trial with abciximab showed that it reduced ischaemic complications of coronary balloon angioplasty in high-risk patients, but increased the risk of bleeding. 
          
    Subsequent studies showed that using less concurrent heparin reduced bleeding. Further studies have shown that the benefits extend to all patients with unstable angina and acute myocardial infarction. Clinical trials with eptifibatide and tirofiban have not shown benefit at the doses used, in angioplasty.
           
    Orally active GPIIb/IIIa antagonists are being developed for use in myocardial infarction. Abciximab can cause thrombocytopenia and all the GPIIb/IIIa antagonists increase the incidence of bleeding but there is no excess intracranial hemorrhage.
           

  • Veli-Pekka Valkonen, Hannu Paiva, et al 
    Risk of Acute Coronary Events and Serum Concentration of Asymmetrical Dimethylarginine
    Lancet Vol.358, December 22/29, 2001, Pg. 2127-2128
           
    Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease.
           
    The authors investigated the association of ADMA concentration in serum with risk of acute coronary events. They did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (> 0.62 mmol/L) had a 3.9-fold (95% C1 1.25-12.3, p=0.02) increase in risk of acute coronary events compared with the other quartiles. Their findings suggest that ADMA is a predictor of acute coronary events.
           

  • Sudlow M, Thomson R, Thwaites B, et al (Univ of Newcastle upon Tyne, England; Wansbeck Gen Hosp, Ashington, England)
    Prevalence of Atrial Fibrillation and Eligibility for Anticoagulants in the Community
    Lancet 352: 1167-1171, 1998
          
    The risk of stroke in patients with atrial fibrillation (AF) can be reduced by anticoagulation.
            
    A group of 3,678 people, 65 years and older, were screened by an electrocardiogram (ECG). Those with AF were evaluated further to determine the risk for stroke. ECGs revealed AF in 207 (5.6%). 
          
    Based on different inclusion criteria 41% to 61% of these 207 would have benefited from anticoagulation but only 23% were receiving warfarin.
             
    Thus anticoagulation with warfarin is underused in elderly patients with AF to decrease the incidence of stroke.
            

  • Sudlow M, Thomson R, Rodgers H, et al (Univ of Newcastle upon Tyne, England)
    The Effect of Age and Quality of Life on Doctor’s Decisions to Anticoagulate Patients With Atrial Fibrillation
    Age Ageing 27: 285-289, 1998
           
    Many studies have shown that in selected patients who have atrial fibrillation (AF) anticoagulation reduces the risk of strokes.
           
    Inspite of this a large number of patients who meet medical criteria for anticoagulation, do not receive the same.
          
    A questionnaire was sent to a random 50% of 824 local practitioners and 207 local consultants, seeking their views on use of anticoagulants in patients with AF.
           
    Overall response rates for general practitioners was 56% and consultants 79%. A large proportion (43% to 46%) from both groups felt that patients above age 84 years, should not be treated; a small minority felt it inappropriate to treat patients between 65 and 74 years and above; the criteria for selection being quality of life.
            
    Thus non use of anticoagulants based on age is not justified and amounts to inadequate treatment of such patients. A substantial number of strokes can be prevented with appropriate use of anticoagulants even in elderly patients.
            

  • Teo KK, for the Clinical Quality Improvement Network (CQIN) Investigators (Univ of Alberta, Edmonton, Canada)
    Thromboembolic Prophylaxis in 3,575 Hospitalized Patients With Atrial Fibrillation
    Can J Cardiol 14: 695-702, 1998
          
    Atrial fibrillation (AF) becomes more prevalent as population gets older. AF is a major contributing factor in 15% of overall strokes and 36% of strokes in persons over age 80. 
           
    Anticoagulation therapy is under utilized particularly in elderly patients. One of the primary reasons for this is the risk of bleeding. 3,375 patients from 12 hospitals (2005 males and 1570 females) with mean age of 72 years were monitored for use of warfarin or aspirin. 
           
    Thirty three percent of patients did not receive any anticoagulants. Of those on anticoagulants, 24% received warfarin; 35% received aspirin and 8% received both. 
           
    13% of patients had contraindications to warfarin and 6% to aspirin. Warfarin use was less likely in patients over 70 years in age. Thus almost a third of all patients did not receive anticoagulants and another third received only aspirin and only about one third received warfarin which alone provides proper prophylaxis against strokes in such patients.
             

  • Beyth RJ, Quinn LM, Landefeld CS (Case Western Univ, Cleveland, Ohio; Cleveland Veterans Affairs Med Ctr, Ohio; Univ Hosp of Cleveland, Ohio)
    Prospective Evaluation of an Index for Predicting the Risk of Major Bleeding in Outpatients Treated With Warfarin
    Am J Med 105: 91-99, 1998
           
    Anticoagulant-related bleeding reduces the net benefit of therapy. The accuracy and efficacy of the Outpatient Bleeding Risk Index, and its ability to estimate probability of major bleeding, were assessed.
           
    Warfarin therapy was initiated in 264 outpatients; bleeding amounts, rate, frequency and consequences were recorded by physicians.
           
    The rate of major bleeding was 6.5% per year. Four independent risk factors for major bleeding were age 65 years or over, history of gastrointestinal bleeding, history of stroke and 1 or more of 4 specific co-morbid conditions.
            
    The index predicted major bleeding better than did the physicians. The rate of bleeding at 4 years was 3% in 80 patients at low risk, 12% in 166 patients at intermediate risk, and 53% in 18 patients at high risk. Seventeen of the 18 episodes of major bleeding were potentially preventable.
           
    Thus Outpatient Bleeding Risk Index was able to discriminate between patients who would have a major bleed from those who would not, better than the physicians.
          

  • Yetman AT, Hamilton RM, Benson LN, et al (Univ of Toronto)
    Long-term Outcome and Prognostic Determinants in Children With Hypertrophic Cardiomyopathy
    J Am Coll Cardiol 32: 1943-1950, 1998
      
    The outcomes and effects of treatment in children with hypertrophic cardiomyopathy (HCM) are not well characterized.
     
    Ninety-nine HCM patients (71 males, aged 1 day to 17 years) treated between 1958 and 1997 were studied. Diagnoses were made by echocardiography (n=83) and angiography (n=16).
       
    The median age at diagnosis was 5 years. Heart murmurs were present in 41 patients, a family history of HCM in 37 and only an abnormal ECG in 3. Symptoms varied from shortness of breath, chest pain, syncope, palpitations, failure to thrive and sudden death.
      
    Various types of arrhythmias were seen on ECG. Twelve patients had sudden death and 6 others had resuscitated sudden death but survived. Risk factors for sudden death were increased QT interval in ECG and ventricular tachycardia on ambulatory ECG. Thus ECG, ambulatory ECG and angiography data can identify HCM children who are at risk of sudden death.
       

  • Iribarren C, Tekawa IS, Sidney S, et al (Kaiser Permanente Med Care Program, Oakland, Calif)
    Effect of Cigar Smoking on the Risk of Cardiovascular Disease, Chronic Obstructive Pulmonary Disease, and Cancer in Man
    N Engl J Med 340: 1773-1780, 1999
      
    Cigar smoking has increased in recent times. Cigar smoking is known to increase risk of pulmonary disease, its effect on cardiovascular disease has not been studied.
      
    A cohort of 17,774 men (aged 30 to 85 years) enrolled in the study. At baseline 1,546 men reported smoking cigars and 16,228 did not. The two groups were followed up from 1971 to 1995.
      
    Relative risks for chronic obstructive pulmonary disease (COPD), coronary heart disease, upper digestive tract cancer and lung cancer were higher in cigar smokers as compared to non smokers.
     
    The increase in incidence of coronary heart disease in cigar smokers is moderate but significant.        

  • Ling LH, Oh JK, Schaff HV, et al (Mayo Clinic and Mayo Found, Rochester, Minn)
    Constrictive Pericarditis in the Modern Era: Evolving Clinical Spectrum and Impact on Outcome After Pericardiectomy
    Circulation 100: 1380-1386, 1999
                                              

    There has been changes in the spectrum of constrictive pericarditis (CP) in the United States. There is a decline in the incidence of tuberculous pericarditis and an increase in the frequency of CP after cardiac surgery and mediastinal radiation. The effect of pericardiectomy in such cases was studied.
                                                                
    Files of Mayo Clinic presented 135 patients (67% men) with CP between January 1985 through June 1995. The follow-up was done by mailed questionnaires, hospital records, and calls to patients and physicians. The results of this cohort of patients were compared with another historic cohort from the years 1938 through 1982 at the Mayo Clinic.
                                                                      
    The recent cohort showed increasing incidence of CP following cardiac surgery and mediastinal radiotherapy. Also the patients in the present study reported at a later median age (61 years) as compared with the historic cohort (45 years). There was a decline in mortality from the historic cohort (14%) to the recent cohort (6%).
                                                                           
    Radiation-induced CP had poorer alleviation of symptoms compared to the others.                                   

  • Calkins H, for the Atakr Multicenter Investigators Group (John Hopkins Univ, Baltimore, Md; Stanford Univ, Calif)
    Catheter Ablation of Accessory Pathways, Atrio-ventricular Nodal Reentrant Tachycardia, and the Atrio-ventricular Junction: Final Results of a Prospective, Multicenter Clinical Trial
    Circulation 99: 262-270, 1999
                                                        

    There is growing interest in the use of radiofrequency (RF) catheter ablation procedures for patients with atrio-ventricular node reentrant tachycardia (AVNRT) or arrythmias involving an accessory pathway (AP) or the atrio-ventricular junction (AVJ). 
                                                         
    The study included 1050 patients undergoing 1136 AF ablation procedures at 18 centers. The mean age was 37 years with 31% of the patients being 20 years or younger. Each patient was treated for AVNRT (n=373) or arrythmias related to AP (n=500) or the AVJ (n=121); another 56 patients were treated for more than 1 type of target. Follow-up evaluations were performed at 1 to 24 months after ablation. 
                                                                 
    The acute success rate of ablation was 95% with a median application of 6 RF applications. Success rates by site were 100% for AVJ, 97% for AVNRT, and 93% for AP.
                                                                     
    Major complication rate was 3%, including 3 deaths and 2 strokes, 1 myocardial infarction and 10 cases of complete atrio-ventricular block requiring permanent pacemaker implantation. The recurrence rate was 6%, factors predictive of reentrant arrythmia was right free wall, posterolateral, septal and multiple AP ablations. 
                                                                            
    This prospective multicenter trial confirms that RF catheter ablation is a safe and effective treatment for children and adults with supraventricular tachycardias. The study identifies factors associated with probability of success, major complications, and recurrent arrhythmias.                                       
        

  • Jordan J, Shannon JR, Black BK, et al (Franz Volhard Clinic, Berlin; Vanderbilt Univ, Nashville, Tenn)
    The Pressor Response to Water Drinking in Humans: A Sympathetic Reflex?
    Circulation 101: 504-509, 2000
                                                   

    The short-term effect of water drinking on blood pressure was investigated in patients with orthostatic hypotension caused by autonomic failure. 
                                                               
    The subjects were 47 patients with disabling orthostatic hypotension caused by multiple system atrophy (20 men and 8 women; mean age 66 years), or pure autonomic failure (8 men and 11 women; mean age 72 years). Eleven older (mean age 57 years) and 8 younger (mean age 25 years) control subjects were also studied. Participants drank 480 mL of tap water while sitting and their systolic (SBP) and diastolic (DBP) blood pressures, and heart rate (HR) were measured for 60 minutes.
                                                                 
    Drinking water significantly increased SBP and DBP in patients with multiple system atrophy and pure autonomic failure, within 5 minutes of water ingestion and the effect continued up to 60 minutes. Heart rate also decreased significantly in both groups of patients. Similarly older controls showed significant increase in SBP and decrease in heart rate but younger controls showed no pressor response.
                                                         
    Drinking water did not affect plasma renin activity, vasopressin levels or blood volume of patients but it significantly increased plasma norepinephrine levels in both control groups. The mechanism of action of drinking water is not clear.          
                                 

  • Owen I Miller, Swee Fong Tang et al  
    Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a    randomised double-blind study. 
    Lancet, vol.356, 28 Oct.2000, pg.1464.    
                                   
    Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. A randomised double-blind study was carried out to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk.
                          
    Authors enrolled 124 infants with large ventricular and atrioventricular septal defects who had high pulmonary flow, pressure or both and were undergoing corrective surgery for congenital heart disease.
                                
    Interpretation of the study was that, in infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course with no toxic effects.                             
                                   

  • Maheshwari S, Bruckheimer E, Fahey JT, et al (Yale Univ, New Haven, Conn) 
    Balloon Angioplasty of Postsurgical Recoarctation in Infants: The Risk of Restenosis and Long-term Follow-up 
    J Am Coll Cardiol 35: 209-213, 2000
                
    The immediate results of balloon angioplasty (BA) for coarctation of the aorta are encouraging. Concerns remain regarding its use in children, particularly infants who are at higher risk for complications because of their small size, smaller vessels, and the potential for restenosis with growth. The long-term results of BA for postsurgical recoarctation were examined in 22 infants. 
                   
    Angioplasty was performed under conscious sedation with local anesthesia. Cardiology charts, recent echocardiogram or MRI, and repeat catheterization (when available) were reviewed retrospectively for the year 1986 through 1996. A successful result was defined as a post BA gradient of 20 mm Hg or less.
                
    Twenty of 22 (91%) infants achieved a successful result, with a decrease in systolic peak pressure gradient from 38 mm Hg to 9 mm Hg and an increase in the coarctation diameter from 2.7 mm to 5.2 mm. At long-term follow-up of 0.6 to 12 years (median 56 months), the restenosis rate after an initial optimal result was 16%. Five (24%) infants needed reintervention (2 initially unsuccessful and 3 recoarctation). The success rate was 95% after 2 procedures. Lower infant weight was associated with a sub-optimal long-term outcome. 
                          
    Infants can undergo BA with good long-term outcome. The risk of restenosis is low in infants who had undergone BA and can be successfully managed with a lower infant weight.                                     
                                                            

  • Zosia Kmietowicz            
    Statins are the new aspirin, Oxford researchers say     
    BMJ, 17 Nov.01, 323, 1145               
                                                 
    Results of the world’s largest trial on statins drug show that in addition to lowering cholesterol, the statins reduce the risk of vascular disease and especially heart attacks and strokes, even in people whose cholesterol concentration is normal. The statins stabilize atherosclerotic plaques by making them firm (less fragile) and causing a capping of the plaques.         
                                   

  • Ralf Koster, Dieter Vieluf, et al   
    Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis.   
    The Lancet, vol.356, Dec.2, 2000, pg.1895   
                                             
    Coronary in-stent restenosis might be triggered by contact allergy to nickel, chromate, or molybdenum ions released from stainless-steel stents. Authors investigated the association between allergic reactions to stent components and the occurrence of in-stent restenosis.            
                                                          
    Patients with allergic patch-test reactions to nickel and molybdenum had a higher frequency of in-stent restenoses than patients without hypersensitivity. Allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent restenosis.        
                                                                      

  • The CAPRICORN Investigators    
    Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction.
    The Lancet, vol.357 (9266), 5 May 2001, pg.1385   
    The beneficial effects of
    ß-blockers on long-term outcome after acute myocardial infarction were shown before the introduction of thrombolysis and angiotensin-converting-enzyme (ACE) inhibitors. Generally, the patients recruited to these trials were at low risk: few had heart failure, and none had measurements of left-ventricular function taken. The long-term efficacy of carvedilol on morbidity and mortality was investigated in patients with left-ventricular dysfunction after acute myocardial infarction treated according to current evidence-based practice.     
                                               
    In a multicentre, randomised placebo-controlled trial, 1959 patients with a proven acute myocardial infarction and a left-ventricular ejection fraction of > 40% were randomly assigned 6.25mg carvedilol (n=975) or placebo (n=984). Study medication was progressively increased to a maximum of 25mg twice daily during the next 4-6 weeks, and patients were followed up until the requisite number of primary endpoints had occurred. The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems. Analysis was by intention to treat.   
                                                                
    In patients treated long-term after an acute myocardial infarction complicated by left-ventricular systolic dysfunction, carvedilol reduced the frequency of all-cause and cardiovascular mortality, and recurrent, non-fatal myocardial infarctions. These beneficial effects are additional to those of evidence-based treatments for acute myocardial infarction including ACE inhibitors.    

 

By |2022-07-20T16:42:45+00:00July 20, 2022|Uncategorized|Comments Off on Cardiology

About the Author: