No abstract

No abstract

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.

No abstract

No abstract

No abstract

SUMMARY In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2-39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 ± 1.3 (SEM) to 20.3 ± 1.4 mm Hg (P < 0.001), CO rose from 3.94 ± 0.23 to 4.75 ± 0.31 1/min (P < 0.001), MAP fell from 87.5 ± 3.8 to 77.9 ± 4.1 mm Hg (P < 0.001) and SVR from 1619 ± 148 to 1252 ± 137 dyne-sec-cm-5 (P < 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 ± 3.4 to 37.9 + 7.7 ng/ml/hr, P < 0.05) but plasma norepinephrine fell (619.1 ± 103.6 to 449.7 ± 75.7, P < 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach. IN PATIENTS WITH LOW cardiac output (CO)due to heart failure, arterial pressure usually is supported by a rise in systemic vascular resistance. Several mechanisms could contribute to this systemic vasoconstriction, including neural, hormonal and structural factors. An understanding of the mechanism of the vasoconstriction of heart failure has taken on particular importance because of the recent interest in using vasodilator drugs in the treatment of left ventricular failure.'Increased activity of the renin-angiotensin (R-A) system has been demonstrated in clinical and experimental heart failure.2 9 Since angiotensin is a potent vasoconstrictor substance,10 enhanced renin activity in patients with heart failure could be an important factor in the systemic vasoconstriction.The introduction of a competitive inhibitor of angiotensin II (saralasen)" and of a converting en- zyme inhibitor (teprotide) which blocks the conversion of angiotensin I to angiotensin II12 has provided fairly specific means of studying the activity of the R-A system. Johnson and Davis13 found that normal dogs had no significant change in blood pressure after infusion of saralasen, whereas sodium-depleted dogs and those with low CO secondary to thoracic caval obstruction had significant lowering of blood pressure. Watkins et al.'4 used teprotide in a dog model of rightsided heart failure and found that the R-A system was important in maintaining arterial pressure early in the course of heart failure but not later, after plasma volume had re-equilibrated. Gavras et al.'1 described a patient with hypertensive heart failure in whom saralasen exerted a marked vasodilator effect. Since saralasen has angiotensin-like agonist properties,16 the hemodynamic response to thi...

Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy.