Coronary Artery Disease
Lars Wallentin, Bo Lagerqvist, et al (Department of Cardiology and Thoracic Surgery, University Hospital, Uppsala, Sweden, University Hospital, Aarhus, Denmark)
Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: The FRISC II invasive randomized trial.
Lancet, vol.356, July 1, 2000,p.9-15.
Invasive procedures have become increasingly common early after an episode of unstable coronary-artery disease, even in patients who are clinically stabilised.
The 6 months results of FRISC II (Fast revascularisation during instability in coronary artery disease) invasive trial showed a reduction in death or myocardial infarction with an invasive strategy in patients with unstable coronary-artery disease and signs of ischemia. Similar results were not seen in 2 previous large-scale randomized trials.
After 1 year in 1000 patients, an invasive strategy saved 1.7 lives, prevented 2.0 non-fatal myocardial infarctions and 20 readmissions, and provided earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischemia on ECG or raised levels of biochemical markers of myocardial damage.
Van Belle E, Lablanche JM, Bauters C, et al [Hospital Cardiologique, Lille Cedex, France]
Coronary Angioscopic Findings in the Infarct-Related Vessel I Month After Acute Myocardial Infarction : Natural History and the Effect of Thrombolysis
Circulation 97: 26-33, 1998
Re- occlusion is a major risk in recent myocardial infarction [MI] related lesions. Coronary angioscopy has provided a great deal of useful information on the characteristics of the plaque and thrombi. However, it has been little used to study the natural history of infarct-related plaque after MI, or the effect of thrombolysis. This study used angioscopy to study the morphology and natural history of infarct -related plaque, including the effects of thrombolysis.
Coronary angioscopy was performed on 56 patients with recent MI [within one month]. Four patients had received thrombolytic therapy and the rest had been treated medically. The morphological findings of the infarct-related lesion wee analyzed.
The angioscopic picture was a complex lesion with ulceration in 54% of the patients. The plaque was mainly yellow in 79% of patients and white in 6%. Visible thrombus was seen in 77% of patients; but only 7% had angina. In those with thrombolytic therapy, the thrombi were smaller although the frequency of plaque containing thrombi was unchanged.
The angioscopic appearance of recent MI-related plaques showed that such lesions take longer than a month of heal; during this period many lesions show unstable yellow plaques with adherent thrombi. The findings could partially account for tendency to re-occlude. The effects of thrombolytic therapy on plaque stabilization are not so impressive as the clinical benefits.
Goodman SG, for the GUSTO-1 Angiographic Investigators [Univ of Toronto; Duke Univ Durham, NC; George Washington Univ, Washington DC; et al]
Non-Q-Wave Versus Q-Wave Myocardial Infarction After Thrombolytic Therapy : Angiographic and Prognostic Insights from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries -1 Angiographic Substudy
Circulation 97: 444-450, 1998
The appearance of abnormal new Q waves on ECG is a clinically and prognostically important factor in patients with acute myocardial infarction. However, there are few data on the effects of thrombolytic therapy and the subsequent development of Q waves or on the prognosis of non Q-wave infarction. Using data from the Global Utilization of Strepokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO-1] angiographic substudy, the investigators analyzed the impact of thrombolytic therapy on non-Q-wave and Q-wave myocardial infarctions.
The analysis included 2046 patients with ST-segment elevation infarction. The presence of Q-wave myocardial infarction was assessed from follow-up ECG performed 24 hours or longer after initiation of throbolytic therapy. The ECG, coronary anatomy, left ventricular function, and mortality data were analyzed to assess the pathophysiology and prognosis of Q-wave versus non-Q-wave infarction after thrombolytic therapy. The rate of non-Q-wave myocardial infarction was 20%; these patients had significantly lower maximal CK and CK-MB values than those with Q-wave infarctions as also ECG indicators of infarct severity. The infarct -related artery in these patients was more likely to be non-anterior and distally located. Further, these patients had greater early and complete infarct related vessel patency and better global and regional left ventricular function. The -in-hospital mortality in such patients was 1.5% versus 3%; after 2 years the difference in mortality was significant [6.4% versus 10.1%]. There was no significant difference in the use of in-hospital coronary revascularization in the two groups. Non-Q-wave infarction patients were less likely to have cardiogenic shock and congestive heart failure; but thee was no difference in the rate of reinfarction, recurrent ischemia or stroke.
Patients with non-Q-wave myocardial infarction have an excellent prognosis after thrombolytic therapy, with high rate of early, complete patency of infarct-related vessel leading to limited left ventricular infarction and dysfunction. Among these patients, however, mortality is not effected whether revascularization is performed or not.
Bech GJW, De Bruyne B, Bonnier HJRM, et al [ Catharine Hosp, Eindhoven, The Netherlands; Cardiovascular Ctr, Aalst, Belgium]
Long-Term Follow-up After Deferral of Percutaneous Angioplasty of Intermediate Stenosis on the Basis of Coronary Pressure Measurement
J Am Coll Cardiol 31: 841-847, 1998
Patients who have persistent typical or atypical chest pain with angiographically intermediate stenosis but without inducible ischemia pose a clinical challenge. Although these patients are at increased risk of a coronary event, the extent of risk is unknown. Some reliable technique of evaluating the functional significance of intermediate lesions would be useful in making decisions about the need for dilation.
The use of coronary pressure measurement and myocardial fractional flow reserve [FFR myo] in deciding the need for percutaneous transluminal coronary angioplasty [PTCA] in patients with intermediate stenosis was examined retrospectively.
During a 4-year period, guide wire-based coronary pressure measurements of FFRmyo were obtained in more than 600 patients. Of these, 100 patients were referred for PTCA of an intermediate stenosis in the middle or proximal part of native coronary artery but had the procedure deferred because of a pressure derived FFRmyo of 0.75 or greater. This level was regarded as showing that myocardial perfusion was adequate, and that the lesion could not be causing the patient’s chest pain. Subsequent management decisions were left to the referring physician. Follow-up clinical data were available in all patients; mean follow-up was 18 months.
Mean percent stenosis diameter in these patients was 47%. Two patients died of noncardiac causes during follow-up. Only 4 patients had an event related to the target vessel; one had a myocardial infarction related to the target vessel at 26 months. At 42 months, estimated survival was 97%, survival without target vessel-related events was 84%, and survival without any coronary event was 78%.
PTCA can be safely deferred in patients with intermediate stenosis if the FFRmyo is 0.75 or higher. The clinical event rate with deferral of PTCA is much lower than expected with PTCA.
Rupprecht HJ, Darius H, Borkowski U, et al [ Johannes Gutenberg Univ, Mainz, Germany]
Comparison of Antiplatelet Effect of Aspirin, Ticlopidine, or Their Combination After Stent Implantation
Circulation 97: 1046-1052, 1998
With combined antiplatelet therapy using ticlopidine and aspirin to prevent subacute stent thrombosis, stenting has become a widely used interventional cardiology technique. Given the side effects of ticlopidine and aspirin, particularly neutropenia and gastointestinal bleeding respectively, it may be questioned whether these two drugs, alone or in combination, are sufficient to counteract platelet activation and aggregation after stenting. The effect of aspirin and/or ticlopidine on platelet activation and aggregation parameters were compared after stent implantation.
A total of 61 patients with stent implantation were studied. They were randomly assigned to 1 of 3 groups: group A received aspirin, 300 mg/day plus ticlopidine, 2 x 250 mg/day; group B received ticlopidine only and group C received aspirin only. Measurements of platelet activation were assessed on day 1, 7 and 14. Platelet aggregation in response to adenosine 5′ – diphosphate [ADP] and collagen was also evaluated.
From day 1 to day 14, collagen-induced platelet aggregation decreased from 62% to 37% in group A and from 68% to 58% in group B, with no significant change in group C. Platelet aggregation induced by ADP also decreased significantly in groups A and B, but not in group C.
Thus in patients receiving stents, combination of aspirin and ticlopidine has synergistic platelet inhibitory effects, and the combination is clearly superior to monotherapy with either drug alone, and is the treatment of choice.
Sobel BE, Woodcock-Mitchell J, Schneider DJ, et al (Univ of Vermont, Burlington; Massachusetts Gen Hosp, Boston)
Increased Plasminogen Activator Inhibitor Type 1 in Coronary Artery Atherectomy Specimens from Type 2 Diabetic Compared with Non-Diabetic Patients: A Potential Factor Predisposing to Thrombosis and its Persistence
Circulation 97:2213-2221, 1998
Compared with non-diabetic individuals, patients with Type 2 diabetes have a fourfold greater prevalence of coronary artery disease and reduced survival after angioplasty. Researchers hypothesized that a factor contributing to the poorer outcome among patients with Type 2 diabetes is a disproportionate elevation of plasminogen activator inhibitor type 1 (PAI-1) in the vascular wall components and atheroma.
Two groups of patients, both with clinical indications for directional coronary atherectomy, were studied. Twenty-five had Type 2 diabetes and 18 others had no diabetes. Treatment was the same and the procedure was successful in all. Atherectomy samples were analyzed for urokinase plasminogen activator (u-PA) and PAI-1, and assayed for cellularity.
The two groups of patients were similar in demographical variables and severity of coronary artery disease. Tissue from diabetic patients showed significantly more PAI-1 and less u-PA than tissue from those with no diabetes.
These differences were consistent in patients with primary and restenotic lesions and regardless of the treatment for diabetes; and may contribute to accelerated or persistent thrombosis and could be modified by reducing insulin resistance and stringently controlling hyperglycemia.
Yamamoto N, Kohmoto T, Gu A, et al (Columbia Univ, New York)
Angiogenesis is Enhanced in Ischemic Canine Myocardium by Transmyocardial Laser Revascularization
J Am Coll Cardiol 31:1426-1433, 1998
There is growing interest in transmyocardial laser revascularization (TMLR) because of its ability to relieve angina and improve myocardial perfusion in patients with diffuse, otherwise untreatable coronary artery disease. The concept behind this procedure is to create new vascular channels through the myocardium to reduce reliance on the coronary supply.
However, experimental evidence on dogs suggests that this not the true mechanism for clinical benefit. The authors confirmed a four-fold increase in vascular proliferation in the area of TMLR treated myocardium after two months.
Thus TMLR may help by creation of more angiogenesis rather than creating new channels for blood flow to the myocardium directly from the ventricular chamber.
Hochman JS, for the SHOCK Investigators (Columbia Univ, New York)
Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock
N Engl J Med 341: 625-634, 1999
Cardiogenic shock is the leading cause of death and is a complication factor in 7% to 10% of hospitalized patients with acute myocardial infarction (MI). Primary results of early revascularization in patients with MI complicated by cardiogenic shock were reported.
Patients were randomized to treatment with initial medical stabilization (n=150) or early revascularization with coronary bypass grafting or angioplasty (n=152). Mortality from all causes and 6-month survival were compared.
Mean patient age was 66 years and 32% were females; 55% had been transferred from other hospitals.
Of patients assigned to revascularization, early coronary angiography was performed in 97% and 87% underwent revascularization. Of patients assigned to medical therapy, 2.7% crossed over to early revascularization without any clinical indication.
The mortality in both groups remained same at 30 days but at 6 months mortality in the revascularized group was 53.3% against 63.1% in the rest. Thus early revascularization is strongly recommended in patients with MI complicated by cardiogenic shock.
Heidenreich PA, McDonald KM, Hastie T, et al (Veterans Affairs Palo Alto Health Care System, Calif; Stansford Univ, Calif)
Meta-analysis of Trials Comparing b-Blockers, Calcium Antagonists, and Nitrates for Stable Angina
JAMA 281: 1927-1936, 1999
b-Blockers, calcium antagonists, long-acting nitrates, or their combinations have been used to prevent anginal symptoms among patients with stable angina. There is still controversy over which of these agents should be used as first-line therapy. A meta-analysis of trials with these agents was performed to determine their relative efficacy in controlling angina.
Ninety randomized studies compared these drugs used for at least 1 week; the outcome was cardiac death, myocardial infarction or withdrawal because of adverse events. Treatment with b-Blockers and calcium antagonists did not result in significantly different rates of myocardial infarcts or death. With b-Blockers there were significantly fewer episodes of angina per week compared with calcium antagonists; the latter also needed to be withdrawn due to adverse defects.
The data from the multiple trials supports the use of b-Blockers as first-line therapy for patients with stable angina.
Lee LY, OHara MF, Finnin EB, et al (Cornell Univ, New York)
Transmyocardial Laser Revascularization With Excimer Laser: Clinical Results at 1 Year
Ann Thorac Surg 70: 498-503, 2000
Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty cannot be used for patients with diffuse coronary artery disease (CAD). Transmyocardial laser reperfusion (TMR) involves the use of lasers to create transluminal channels in the region of the ischaemic myocardium to increase perfusion directly from the left ventricle. Results with excimer laser TMR for diffuse CAD were described.
The subjects were 15 (11 men and 4 women; mean age 63 years) who had this procedure. Symptom reports, radionuclide single photon emission CT, exercise tolerance testing and 24-hour Holter monitoring were used to assess ischaemia and myocardial viability before TMR and at intervals upto 12 months after the procedure.
Two patients died; one refused follow-up; the remaining 12 had mean follow-up for 540 days, without any complications or adverse effects. TMR significantly reduced anginal attacks, and the need for nitroglycerine. Exercise duration increased marginally. Myocardial viability did not change.
Thus TMP is safe and improves ischaemic symptoms. But objective evidence of increased perfusion is not evident upto 12 months postoperatively.
Hughes GC, Kypson AP, Annex BH, et al (Duke Univ, Durham, NC)
Induction of Angiogenesis After TMR: A Comparison of Holmium: YAG, CO2, and Excimer Lasers
Ann Thorac Surg 70: 504-509, 2000
Three lasers used in transmyocardial laser revascularization (TMR) for end-stage coronary artery disease include the holmium (holmium YAG) laser, the CO2 laser and the excimer laser. The 3 were compared to assess improvement in myocardial blood flow and function 6 months after TMR in animals in which chronic myocardial ischaemia had been induced.
At 6 months both the holmium and CO2 laser groups showed significantly improved blood flow to the ischaemic myocardium with no change in the excimer laser and control groups.
Thus the type of laser used for TMR is important for good outcomes. The holmium and CO2 lasers cause more extensive tissue damage compared to the excimer laser and this may be responsible for greater release of angiogenic growth factor and thus enhance angiogenesis.
Franga DL, Kratz JM, Crumbley AJ, et al (Med Univ of South Carolina, Charleston)
Early and Long-term Results of Coronary Artery Bypass Grafting in Dialysis Patients
Ann Thorac Surg 70: 813-819, 2000
Almost half (44%) of all patients on long-term dialysis die of cardiac disease; one and two-year survivals after myocardial infarction are 41% and 27% respectively. Whether coronary artery bypass grafting (CABG) can improve morbidity and mortality in such patients was examined.
Records of 44 patients (29 men and 15 women; mean age 59.3 years) receiving long-term dialysis (mean 2.7 years) who underwent CABG were reviewed.
Two complications that occurred more frequently in these patients as compared to the rest, were cerebrovascular accident (7% vs 1.7%) and postoperative cardiac arrest (7% vs 1.5%). Five patients died within 30 days of surgery (11.4%). Over-all survival at 5 years was 32.0%. Smoking had a dramatic effect on survival; no smokers survived to 5 years, compared with 83.6% of non-smokers.
Thus patients with chronic dialysis have more complications and mortality after CABG; smokers have poor outcomes.
Arom KV, Flavin TF, Emery RW, et al (Cardiac Surgical Associates, Minneapolis)
Is Low Ejection Fraction Safe for Off-Pump Coronary Bypass Operation?
Ann Thorac Surg 70: 1021-1025, 2000
Patients with severely impaired ventricular function (ejection fraction <30%) have poor outcomes with coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Off-pump coronary artery bypass grafting (OPCABG) requires displacement of the heart for grafting and it is not known how patients with low ejection fractions do with this alternative method of bypass without CPB. Complications and mortality rates in patients with severely impaired ventricular function were compared in the two groups of CABG with CPB and OPCABG.
The subjects were 177 patients with ejection fraction of less than 30%; 132 had CABG and 45 OPCABG.
As expected OPCABG cases had less blood loss. Operative mortality and postoperative complication rates were not significantly different in the two groups.
Thus OPCABG is safe in patients with low ejection fractions in the hands of experienced surgeon.
van Domberg RT, Meeter K, van Berkel DEM, et al (Univ Hosp Rotterdam Dijkzigt, The Netherlands)
Smoking Cessation Reduces Mortality After Coronary Artery Bypass Surgery: A 20-Year Follow-up Study
J Am Coll Cardiol 36: 878-883, 2000
Although the contribution of cigarette smoking to the risk of coronary artery disease is well known, its effects on the mortality rate after coronary artery bypass grafting (CABG) as well as its cessation after CABG are not known.
Preoperative and postoperative smoking habits of 985 patients after CABG were studied. Patients who ceased smoking had decreased risk of death and the need for coronary reintervention. The estimated benefit of smoking cessation with respect to survival rose from 3% at 5 years to 14% at 15 years. Both repeat CABG and percutaneous coronary angioplasty were less likely to be required after cessation of smoking.
Stafford RS (Harvard Med School, Boston)
Aspirin Use Is Low Among United States Outpatients With Coronary Artery Disease
Circulation 101: 1097-1101, 2000
The use of aspirin to reduce risk of death or recurrent cardiac events has been advocated for outpatients with coronary artery disease, but whether the populace is using aspirin as advocated, was studied.
Data from National Ambulatory Medical Care Surveys (1980 through 1996) were evaluated and reports for use of aspirin as new or continuing medication, by patients with coronary artery disease, were evaluated.
From 1980 to 1996, aspirin use increased from 5% to 26.2%. More males consumed aspirin than females (29% vs 21%); more patients younger than age 80 years consumed aspirin than those among age 80 (28% vs 17%); and more patients with hyperlipidemia used aspirin than the rest (45% vs 24%). The use of aspirin prescription was more with cardiologists (37%), than intermists (20%) and family physicians (8%) and general practitioners (11%).
Thus even with known benefits of aspirin, its use remained low (26.2% of patients with coronary artery disease). More patients need to take aspirin if personal, social and financial gains are to be achieved.
Muhlestein JB, Anderson JL, Carlquist JF, et al (Univ of Utah, Salt Lake City)
Randomized Secondary Prevention Trial of Azithromycin in Patients with Coronary Artery Disease: Primary Clinical Results of the ACADEMIC Study
Circulation 102: 1755-1760, 2000
The possibility of a pathologic role for local inflammation in atherosclerotic plaque and systemic inflammation in coronary artery disease (CAD) is being increasingly recognized. Some researchers have also speculated on the role of infectious agents in stimulating vascular inflammation. Cytomegalovirus and Chlamydia pneumoniae have been identified with atheromatous plaque, but whether the relationship is of cause and effect is not established. In one small study reduction of more than 50% in ischemic events was achieved in seropositive patients with CAD using azithromycin, which is effective against C. pneumoniae. These results were tested in a larger, randomized, double-blind study.
A group of CAD patients seropositive to C. pneumoniae, were randomly assigned to either placebo or azithromycin 500 mg/d for 3 days and 500 mg/wk for 3 months. The drug was generally well tolerated.
Forty seven first primary events occurred during the trial, including 9 cardiovascular deaths, 1 resuscitated cardiac arrest, 11 myocardial infarctions, 3 strokes, 4 incidents of unstable angina and 19 unplanned coronary revascularizations. Of these 47 events, 22 occurred in the azithromycin group and 25 in the placebo group.
The results suggest there is no benefit in the use of azithromycin in CAD patients.
Rogers WJ, for the Investigators in the National Registry of Myocardial Infarction 2 (Univ of Alabama, Birmingham, et al)
Treatment and Outcome of Myocardial Infarction in Hospitals With and Without Invasive Capability
J Am Coll Cardiol 35: 371-379, 2000
A wide range of procedures are now available for the treatment of acute myocardial infarction (AMI). All hospitals can provide immediate thrombolysis; but majority cannot perform advanced procedures such as immediate coronary arteriography, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG). The outcomes in patients with AMI in various types of hospitals were evaluated.
The study included 1506 patients from the National Registry of Myocardial Infarction 2. They were classified on the basis of hospitals’ ability to perform procedures: none (noninvasive), 28.1%; coronary arteriography, 25.2%; coronary angioplasty (PTCA-capable), 7.4% and coronary surgery (CABG-capable), 39.2%. The effects of invasive capability on treatment and in-hospital outcomes were assessed for 305,812 patients admitted for AMI. Ninety-day follow-up data were available in 30,402 patients.
Results showed invasive capability had little impact on the percentage of patients receiving initial reperfusion therapy. In all hospitals, the median “door to drug” time among patients receiving thrombolysis was 42 to 45 minutes. The rates of PTCA, CABG were also not very different. The transfer rate to other hospitals from non-invasive to other hospitals decreased with increasing facility availability. But despite all the practice differences 90-day mortality of AMI did not differ significantly.