Biomedical subjects
Publications and source records attributed to E R Passamani.
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To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy.
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Given the many thrombolytic agents and the number of ways in which they can be combined with mechanical revascularization, the treatment of acute myocardial infarction has been the subject of active study and lively debate, which are likely to continue for some time. Several studies, including TIMI IIA (2,3,10,22), have suggested that immediate catheterization and angioplasty offer no clinical benefit and have a greater complication rate than a more delayed invasive strategy, but TIMI II (1) and SWIFT (16) trials have suggested that an even more conservative strategy of reserving catheterization and coronary angioplasty after thrombolytic therapy for patients with recurrent spontaneous or exercise-induced ischemia may be the most desirable approach for the majority of patients similar to those entered into these trials.
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Coronary heart disease (CHD) remains the leading cause of death in the United States--in women as well as men. In 1987, CHD was responsible for 512,138 deaths, of which 253,542 deaths were attributed to acute myocardial infarction (AMI) and accounted for over $43 billion in direct and indirect costs. The disease spares no one. Primary prevention is clearly important, but for those in whom primary prevention has not been applied or has failed, acting to minimize the effect of a heart attack is of paramount importance. Many of its victims do not obtain appropriate medical care, or obtain it too late for the latest lifesaving technologies to be effective. The goal of treatment is to prevent death and to salvage as much heart tissue as possible. To achieve this goal, it is essential to minimize the time from the first symptoms and signs to treatment. Opportunities exist at each phase of an evolving AMI to intervene promptly and appropriately to prevent sudden death and to preserve cardiac muscle and thereby reduce CHD morbidity and mortality. Yet, formidable problems also exist. These and other issues are presently being studied by the National Heart, Lung, and Blood Institute staff and advisors in consideration of whether to establish a national educational program aimed at reducing CHD morbidity and mortality through the rapid identification and treatment of those with AMI.
Before commencing the randomized Thrombolysis in Myocardial Infarction phase II (TIMI II) study, 370 patients were administered intravenous recombinant tissue plasminogen activator (rt-PA) within 4 hours of onset of acute myocardial infarction (AMI) and assigned to 2-hour (immediate) percutaneous transluminal angioplasty (n = 33), 18- to 48-hour (delayed) angioplasty (n = 288) or no angioplasty (n = 49) in a nonrandomized, observational pilot study. Left ventricular ejection fraction at rest and during exercise was assessed by gated equilibrium radionuclide ventriculography at hospital discharge and again at 6 weeks. At hospital discharge, ejection fraction averaged 50% at rest and 56% at peak exercise. At 6-week follow-up, ejection fraction averaged 50% at rest and 53% at peak exercise. At 6-week follow-up, resting ejection fraction average 49% in the 2-hour angioplasty group, 49% in the 18- to 48-hour angioplasty group and 55% in the no-angioplasty group. Variables independently predicting "good functional outcome" at 6-week follow-up (survival with resting ejection fraction greater than equal to 50% and no decrease with exercise) in the 18- to 48-hour angioplasty group were fewer leads with ST-segment elevation greater than or equal to 0.1 mV, younger age, rapid normalization during rt-PA infusion of ST segments or dramatic relief of chest pain, absence of arrhythmias within the first 24 hours of treatment initiation, no prior infarction and not a cigarette smoker at entry. Thus, the TIMI II pilot study demonstrates that most patients with AMI of less than or equal to 4-hour duration treated with rt-PA have good ventricular function after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)
Between September 1977 and September 1981, 1587 consecutive patients underwent a first coronary angioplasty (PTCA) at 16 clinical centres. After excluding patients with prior coronary bypass surgery (CABG) and left main or minimal vessel disease, 1390 were available for in-hospital and long-term follow-up. Mean duration of follow-up was 5.9 years (range 0-9.0 years). PTCA was successful (all attempted lesions reduced greater than or equal to 20%) in 882 patients (63.4%) and, overall, 624 patients (44.9%) had complete (COREV) and 766 (55.1%) incomplete (INCOREV) revascularization or a failed PtCA. In-hospital events included death in 0.7%, myocardial infarction (MI) in 5.0% and CABG in 24.0% of patients. Patients with COREV had significantly lower rates of these events than the INCOREV group. At 6 years, mortality in all registry patients was 6.5% and MI rate 15.0%; CABG was performed after the initial hospitalization in 15.5% of patients and repeat PTCA in 19.1%. All events, except repeated PTCA, were less frequent in the COREV than the INCOREV group. Among patients with a successful first PTCA, cumulative 6-year mortality was 5.8% and incidence of MI 10.8%; 16.9% underwent CABG and 24.7% repeat PTCA during follow-up. CABG was slightly more frequent in INCOREV than COREV patients with successful PTCA, but all other events were similar in the two groups, suggesting that INCOREV 'by intent' has a good prognosis. In patients with INCOREV, mortality and incidence of MI were higher during follow-up for patients with multivessel rather than single vessel disease. However, the incidence of CABG and repeat PTCA was similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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The Thrombolysis in Myocardial Infarction (TIMI) trial Phase I was designed to compare the efficacy and side effects of intravenous recombinant tissue-type plasminogen activator (rt-PA) and intravenous streptokinase (SK) in patients with acute myocardial infarction (AMI). As previously reported, rt-PA led to a reperfusion rate of 62% of totally occluded coronary arteries compared with 31% for SK (p less than 0.001). This study was not designed to determine if intravenous thrombolytic therapy decreases the mortality of AMI; however, the findings in these patients after 1 year of follow-up do permit certain insights into the impact of early reperfusion and reocclusion on the clinical course of patients with AMI. The mortality rate at 6 and 12 months was not significantly different in patients treated with rt-PA compared with SK (7.7% and 10.5% rt-PA vs 9.5% and 11.6% for SK). The frequency of recurrent AMI, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) was similar in the 2 treatment groups. There was no significant difference in 6- and 12-month mortality or in the rate of recurrent AMI in patients who received thrombolytic therapy before compared with after 4 hours of the onset of AMI symptoms. When the results were analyzed on the basis of the patency of the infarct-related artery, irrespective of thrombolytic agent used, for those patients with patent arteries 90 minutes after the initiation of therapy, there was a trend toward a lower 6-month (5.6% vs 12.5%) and 12-month mortality (8.1% vs 14.8%) (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)
A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propranolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the overall population. Because spontaneous reperfusion was more common in patients with early peaking of plasma creatine kinase MB or non-transmural electrocardiographic changes or both, the results were reanalysed for two subgroups: those in whom plasma creatine kinase peaked less than 15 hours after the onset of symptoms (early peak, n = 184) and those with a peak greater than 15 h after the onset of symptoms (late peak, n = 546). The distribution of time to peak activity of creatine kinase MB was similar in the hyaluronidase and placebo groups. In the early peak patients who were given hyaluronidase (groups A and B) total mortality and cardiac-specific four year mortality were significantly lower. This was most pronounced in group B in which the total mortality was 45% and cardiovascular mortality was 47% less than in the placebo group. Similarly, mortality from cardiovascular disease in patients (groups A and B) with nontransmural ischaemia (ST-T changes) given hyaluronidase was significantly lower, with group B showing a 50% reduction. In the subsets of patients with late peaking of creatine kinase MB or those presenting with transmural electrocardiographic changes there was no difference in total mortality or deaths from cardiac disease between those given hyaluronidase and those given placebo. Hyaluronidase was associated with improved survival in patients with early peaking of plasma creatine kinase MB, suggesting the possibility of salvage of myocardium in patients who have early spontaneous reperfusion and possibly after therapeutic reperfusion.
From July 1974 to May 1979, 573 black persons in the Coronary Artery Surgery Study (CASS) underwent coronary angiography. Compared with 23,008 white persons, larger percentages of black men and women were current smokers and reported a history of systemic hypertension. Despite the presence of chest pain, larger percentages of blacks had normal coronary arteries by angiography than did whites. The 5-year age- and sex-adjusted survival rate was 88% for whites and 82% for blacks (p less than 0.0001). Cox analysis indicated that black race was related to poorer survival in the medical group (p = 0.0006) but not in the surgical group (p = 0.28). For blacks, surgical therapy was related to a better survival rate (p = 0.009). These results raise questions concerning the effects of excess cigarette smoking and systemic hypertension and the role of coronary artery bypass surgery on survival of black persons.
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