Eugene R. Passamani

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.

Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study.

In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.

A randomized trial of coronary artery bypass surgery: survival of patients with a low ejection fraction

The Coronary Artery Surgery Study (CASS) was designed to compare medical and surgical treatment of selected patients with chronic, stable coronary artery disease. This report concerns a subset of patients with reduced ventricular function. Of 780 patients randomly assigned to medical or surgical treatment, 160 had ejection fractions above 0.34 but below 0.50 at base line and have been followed for an average of seven years. Eighty-two patients were assigned to medical therapy, and 78 to surgery; the two groups were comparable at base line with regard to prognostically important variables. At seven years, 84 per cent of patients in the surgical group were alive, as compared with 70 per cent of the medical group (P = 0.01). Nearly half the patients with impaired ventricular function had triple-vessel disease at entry; at seven years, observed survival in this group was 88 and 65 per cent for those assigned to surgical and medical treatment, respectively (P = 0.009). Survival of patients with single-vessel or double-vessel disease was similar in the two treatment groups. We conclude that patients with triple-vessel disease and ejection fractions higher than 0.34 but lower than 0.50 appear to have improved seven-year survival with elective bypass surgery.

Effects of gender and race on prognosis after myocardial infarction: Adverse prognosis for women, particularly black women

Controversy has arisen concerning whether gender influences the prognosis after myocardial infarction. Although some studies have shown there to be no difference between the sexes, most have indicated a worse prognosis for women, attributing this to differences in baseline characteristics. It has been further suggested that black women have a particularly poor prognosis after infarction. To determine the contribution of gender and race to the course of infarction, 816 patients with confirmed myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) were analyzed. Of those patients, 226 were women and 590 were men, 142 were black and 674 were white. The cumulative mortality rate at 48 months was 36% for women versus 21% for men (p less than 0.001, mean follow-up 32 months). The cumulative mortality rate by race was 34% for blacks versus 24% for whites (p less than 0.005). Both women and blacks exhibited more baseline characteristics predictive of mortality than did their male or white counterparts. It was possible to account for the greater mortality rate of blacks by identifiable baseline variables; however, even after adjustment, the mortality rate for women remained significantly higher (p less than 0.002). The poorer prognosis for women was influenced by a particularly high mortality rate among black women (48%); the mortality rate for white women was 32%, for black men 23% and for white men 21%. The mortality for black women was significantly greater than that of the other subgroups. Thus, findings in the MILIS population indicate that the prognosis after myocardial infarction is worse for women, particularly black women.

Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study.

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.

The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial.

In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.

The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of NHLBI Type II Coronary Intervention Study.

The National Heart, Lung and Blood Institute Type II Coronary Intervention Study, a double-blind, placebo-controlled trial, evaluated the efficacy of reduction in cholesterol levels induced by cholestyramine on progression of coronary artery disease (CAD). The rate of CAD progression in patients treated with cholestyramine plus diet was compared with that of patients treated with placebo plus diet. CAD progression was defined angiographically. Significant decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDLc) and increases in high-density lipoprotein cholesterol (HDLc), as well as in HDLc/TC and HDLc/LDLc ratios, were observed with cholestyramine. HDLc change was due to increase in HDL2A and HDL2B. When the relationship between CAD progression and lipid changes was examined independent of specific treatment group, a significant inverse relationship was found between progression at 5 years and the combination of an increase in HDLc and a decrease in LDLc; changes in HDLc/TC and HDLc/LDLc were the best predictors of CAD change. While the testing of these relationships independent of treatment group was not part of the initial study design, the trends were observed in both the placebo-treated and cholestyramine-treated groups. Moreover, with multivariate analysis, the effect of cholestyramine treatment on CAD progression was eliminated by adding changes in HDLc/TC to the regression model. These findings support the hypothesis that increases in HDLc and decreases in TC (or LDLc) can prevent or delay CAD progression.

Sex differences in early and long-term results of coronary angioplasty in the NHLBI PTCA Registry.

To assess whether gender influenced the outcome of percutaneous transluminal coronary angioplasty (PTCA), we analyzed data from the NHLBI PTCA Registry. Early results were compared in 705 women and 2374 men. Women were older (p less than .01) and had more unstable angina (p less than .01), and class 3 or 4 angina (p less than .01). Men had more multivessel disease (p less than .01), prior bypass surgery (p less than .01), and abnormal left ventricular function (p less than .05). Women had a lower angiographic success rate (60.3 vs 66.2%; p less than .01) and had a lower clinical success rate (56.6% vs 62.2%; p less than .01). More women had complications (27.2% vs 19.4%; p less than .01), but overall frequency of major complications (death, myocardial infarction, emergency surgery) was not different (9.8% vs 9.3%). Women had a higher incidence of coronary dissection (p less than .05) and higher in-hospital mortality (1.8% vs 0.7%; p less than .01). PTCA-related mortality was nearly six times higher in women (1.7% vs 0.3%; p less than .001) and mortality with emergency surgery was more than five time higher (17.4% vs 3.2%; p less than .001). Multivariate analysis indicated that female gender was an independent predictor for lower success (p less than .05) and early mortality (p less than .05) and was the only baseline predictor for PTCA-related mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of location and type of myocardial infarction: Independent adverse outcome associated with anterior location

To determine the relative prognostic significance of location (anterior or inferior) and type (Q wave or non-Q wave) of infarction, the hospital course and follow-up outcome (mean duration 30.8 months) of 471 patients with a first infarction were analyzed. Analyses were performed grouping the patients according to infarct location (anterior, n = 253; inferior, n = 218), infarct type (Q wave, n = 323; non-Q wave, n = 148), and both location and type (inferior non-Q wave, n = 85; inferior Q wave, n = 133; anterior non-Q wave, n = 63; and anterior Q wave, n = 190). Patients with anterior infarction had a substantially worse in-hospital and follow-up clinical course compared with those with inferior infarction, evidenced by a larger infarct size (21.2 versus 14.9 g Eq/m2 creatine kinase, MB fraction [MB CK], p less than 0.001), lower admission left ventricular ejection fraction (38.1 versus 55.3%, p less than 0.001) and higher incidence of heart failure (40.7 versus 14.7%, p less than 0.001), serious ventricular ectopic activity (70.2 versus 58.9%, p less than 0.05), in-hospital death (11.9 versus 2.8%, p less than 0.001) and total cumulative cardiac mortality (27 versus 11%, p less than 0.001). Patients with Q wave infarction similarly experienced a worse in-hospital course compared with patients with non-Q wave infarction, evidenced by a larger infarct size (20.7 versus 12.7 MB CK g Eq/m2, p less than 0.001), lower admission left ventricular ejection fraction (43.7 versus 50.6%, p less than 0.001), and a higher incidence of heart failure (31.9 versus 21.6%, p less than 0.05) and in-hospital death (9.3 versus 4.1% p less than 0.05). However, there was no increased rate of reinfarction or mortality in hospital survivors with non-Q wave infarction compared with those with Q wave infarction, and total cardiac mortality was similar (16 versus 21%, p = NS). To evaluate the role of infarct location and type independent of infarct size, patients were grouped according to quartile of infarct size, and outcome was reanalyzed within each group. Patients with anterior infarction demonstrated a lower left ventricular ejection fraction on admission and after 10 days than did patients with inferior infarction, even after adjustment for infarct size, as well as a higher incidence of congestive heart failure and cumulative cardiac mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

Six- and twelve-month follow-up of the Phase I Thrombolysis in Myocardial Infarction (TIMI) trial

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)