Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate.

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)

Inadvertent administration of streptokinase to patients with pericarditis.

Two patients with acute pericarditis who received intravenous streptokinase for presumed acute myocardial infarction are described. Although the administration of streptokinase did not cause an immediate increase in pericardial effusion, delayed nonhemorrhagic pericardial tamponade developed in both. Since pericarditis and other disease entities may mimic the pain and early electrocardiographic manifestations of acute myocardial infarction, precautions should be taken if thrombolytic therapy is given when there are no angiographic data to confirm the myocardial infarction. Pericarditis should be included in the differential diagnosis of patients with chest pain and ST segment elevation for the sake of diagnostic accuracy to avoid inappropriate therapy that may have some inherent risk.

Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.

To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.

Left ventricular performance after coronary artery bypass surgery. Prediction of functional benefit.

Global left ventricular performance (ejection fraction) and regional function were studied by rest-exercise radionuclide ventriculography in 36 patients before and after (23 +/- 8.5 wk) they had coronary artery bypass surgery for stable angina pectoris. The exercise ejection fraction was less than the resting ejection fraction before surgery (n = 36,p = 0.006), but not after surgery. The degree of postoperative improvement correlated with the degree of preoperative dysfunction (r = 0.55, n = 36, p less than 0.001). Improvement was most likely to occur if exercise-induced dysfunction was present preoperatively (n = 15,p = 0.001), even with old myocardial infarction. Regional dysfunction during preoperative exercise was also likely to improve postoperatively (n = 18, p = 0.001). Protocol design is important in determining the results and their interpretation. Matching postoperative exercise loads to preoperative loads and using regional analysis with two imaging projections improved judgment of the results. Regional dysfunction was commoner than global dysfunction and was less sensitive to workloads than was ejection fraction. This study shows that coronary artery bypass surgery can improve left ventricular performance on exercise if preoperative tests indicate the presence of ischemia-induced dysfunction.

Variability of response to beta receptor blockade for angina pectoris in clinical trials: a study of pindolol.

In a randomized, controlled study we found a significant decrease in pressure-rate (double) product and an improvement in exercise tolerance in patients with angina pectoris treated with pindolol. However, when patients were observed in a long-term double-blind crossover study, pindolol treatment did not produce a significant improvement in angina pectoris or exercise tolerance over placebo. Patients treated with placebo had a gradual improvement in exercise tolerance, possibly because of the training effect of multiple treadmill tests and increased daily walking. The individual patient response to pindolol varied, with some patients showing clinical improvement and decreased double product with exercise and some having no clinical improvement despite a similar decrease in double product. Angina occurred at a lower double product with exercise, suggesting that beta receptor blockade adversely affected other variables of myocardial oxygen demand or decreased coronary blood supply. This study illustrates the difficulties with patient variability and study design that are encountered in studies of beta blocker agents for angina pectoris.

Randomized double-blind study of pindolol in patients with stable angina pectoris.

Twelve patients with documented coronary arteriosclerosis and severe stable angina pectoris were treated with the beta blocker pindolol, 5 mg four times a day, utilizing a double-blind crossover protocol. Following 4 weeks of baseline observation with no active treatment, pindolol and placebo were given for 4 weeks each. End points evaluated were episodes of angina pectoris/week, number of nitroglycerin tablets used per week, time on treadmill test until onset of angina pectoris, double product of heart rate and blood pressure at onset of angina pectoris, and amount of ST depression during the treadmill exercise test. Episodes of angina pectoris and nitroglycerin consumption were reduced by 18% on placebo and 32% on pindolol (not significant). All of the improvement occurred in the third and fourth weeks of pindolol treatment. Less difference between pindolol and placebo was noted when the placebo period came after the pindolol period, suggesting a carry-over effect of pindolol. With pindolol, treatment exercise tolerance was increased 13% (33 seconds) over baseline levels but only 2% over the levels achieved with placebo treatment (not significant). ST depression with exercise was 6% less when patients were on pindolol than when they were on placebo (not significant). There was a marked decrease in myocardial oxygen demand as measured by the double product of blood pressure and pulse during exercise (23% reduction when on pindolol and no change when on placebo, p less than 0.01). This study shows that there was an important placebo effect when treatment of angina pectoris was evaluated and that pindolol significantly reduced myocardial oxygen demand but evidence of ischemia was not significantly reduced. Possible mechanisms to explain the disparity between reduction in estimated myocardial oxygen demand (double product) and objective improvement in ischemia include coronary spasm and altered regional flow resulting from beta blockade. Alternative explanations may be the relatively small fixed dose of pindolol and the small number of patients studied.

Histoplasma capsulatum endocarditis cured by amphotericin B combined with surgery.

A patient is reported who had Histoplasma capsulatum endocarditis, a rare form of disseminated histoplasmosis. He also had disseminated intravascular coagulopathy and defects in cell-mediated immune responses to Histoplasma antigens. Prompt etiologic diagnosis was made by stain of tissue from a mouth ulcer and confirmed by culture of the organism from blood. An echocardiogram compared to a previous normal echocardiogram indicated changes consistent with a vegetation. Histologic examination of the resected valve demonstrated organisms. Amphotericin B administration (3.4 g) plus an aortic valve replacement resulted in cure.

Echocardiographic evaluation of porcine heterograft valves in the mitral and aortic positions.

We evaluated 15 porcine heterograft valves in the mitral position and seven in the aortic position by echocardiography. Combining our quantitative description of valve stent and leaflet motion with 31 previously reported cases, we suggest echocardiographic criteria for the range of normal porcine heterograft valve motion in the mitral position. Quantitative evaluation of valve leaflet and stent motion for valves in the aortic position is described for the first time. Correlative hemodynamic and echocardiographic data is provided for three patients who underwent postoperative catheterization. The use of echocardiography in following the function of porcine heterograft valves is discussed.