A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p<0.05) in anaerobic threshold at 1 month with enoximone (2.7±0.8 ml OJkg/min) compared with placebo (-0.8±1.2 ml OJkg/min). This improvement was not sustained at 4 months (0.5±1.7 ml OJkg/min with enoximone and 0.2± 1.5 ml OJkg/min with placebo). The dropout rate was significantly higher (p<0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p <0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p<0.05). All five enoximone-and three placebo-treated patients who died after therapy was discontinued died from terminal myocardial failure. This study does not demonstrate improvement in exercise capacity or symptoms with 16 weeks of enoximone therapy compared with placebo in patients with congestive heart failure receiving digoxin and diuretics without vasodilators and does not provide evidence that enoximone is beneficial in the long-term therapy of chronic heart failure. The unexpectedly worse survival rate with enoximone therapy raises concerns about a possible detrimental effect of enoximone in the dose range given in this study. (Circulation 1990;82: 774-780) A pplication of inotropic therapy is the most direct approach of counteracting the myocardial systolic dysfunction that is often the underlying abnormality in the development of chronic congestive heart failure. Nevertheless, proof of the efficacy of this approach remains incomplete.

Amrinone, a new bipyridine derivative, exerts a positive inotropic action in experimental preparations and is effective when administered orally to dogs. To assess its immediate effects in man, we studied by cardiac catheterization the hemodynamic responses to amrinone (1.85 to 3.5 mg per kilogram given intravenously) in eight patients with congestive heart failure already receiving full doses of digitalis. the following statistically significant (P less than 0.01) effects were noted: cardiac index increased from a mean +/- 1 S.D. of 1.8 +/- 0.3 to 2.6 +/- 0.3 liters per minute per square meter; peak rate of left ventricular pressure rise rose from 849 +/- 233 to 1206 +/- 456 mm Hg per second; left ventricular end-diastolic pressure fell from 25 +/- 9 to 14 +/- 7 mm Hg; pulmonary-capillary pressure fell from 28 +/- 8 to 15 +/- 4 mm Hg; and right atrial pressure fell from 12 +/- 6 to 7 +/- 5 mm Hg. Mean heart rate was unchanged, and aortic mean pressure declined slightly (86 +/- 10 to 80 +/- 7 mm Hg, P less than 0.025). No toxicity was observed. Amrinone, whose mechanism of action has not yet ben defined, warrants further study as a possible treatment for heart failure.

No abstract

A method is presented for determination of total iodine in biologic material. The procedure requires a minimum number of reagents, eliminating the possibility of reagent iodine contamination. The actual cost of equipment for this method is less than for others, and the method offers good replication and excellent recovery of added iodine.

Severe obesity is associated with abnormalities of cardiac structure and function. These include an increased cardiac workload and ventricular hypertrophy. Hypertension in combination with severe obesity seriously burdens the heart because the increased preload and afterload compound cardiac work. Weight reduction induced by gastric operations for severe obesity is associated with resolution of hypertension, reduction in ventricular wall thickness and cardiac chamber size, as well as improved systolic function. Additional data are needed to predict when in the course of development of obese cardiomyopathy the changes in contractile function become irreversible. Additionally, the impact of coronary artery disease on the progression of obese cardiomyopathy and the effects of surgical weight reduction on cardiac structure and function need to be further clarified. Studies of the association between obesity, its treatment, and modification of cardiovascular risk are a major focus of preventive cardiology today.