Sustained Hemodynamic Efficacy of Therapy Tailored to Reduce Filling Pressures in Survivors With Advanced Heart Failure

Background During therapy to relieve congestion in advanced heart failure, cardiac filling pressures can frequently be reduced to near-normal levels with improved cardiac output. It is not known whether the early hemodynamic improvement and drug response can be maintained long term. Methods and Results After referral for cardiac transplantation with initially severe hemodynamic decompensation, 25 patients survived without transplantation to undergo hemodynamic reassessment after 8±6 months of treatment tailored to early hemodynamic response. Initial changes included net diuresis, increased ACE inhibitor doses, and frequent addition of nitrates. After 8 months of therapy, early reductions were sustained for pulmonary wedge pressure (24±9 to 15±5 mm Hg early; 12±6 mm Hg late) and systemic vascular resistance (1651±369 to 1207±281 dynes·s −1 ·cm −5 early; 1003±193 dynes·s −1 ·cm −5 late). Acute response to doses persisted at reevaluation. Sustained reduction in filling pressures was accompanied by a progressive increase in stroke volume (42±10 to 56±13 mL early; 79±20 mL late), improved functional class, and freedom from resting symptoms. Study design did not control for amiodarone, which was initiated for arrhythmias in 12 patients and associated with greater improvement in cardiac index (1.8 to 3.2 L·min −1 ·m −2 late on amiodarone versus 2.0 to 2.6 L·min −1 ·m −2 , P &lt;.05). Conclusions During chronic therapy tailored to early hemodynamic response in advanced heart failure, acute vasodilator response persists, and near-normal filling pressures can be maintained in patients who survive without transplantation. Stroke volumes at low filling pressures increase further over time. Chronic hemodynamic improvement was accompanied by symptomatic improvement, but the contributions of the monitored hemodynamic approach, increased vasodilator doses, and comprehensive outpatient management have not yet been established. </jats:p

Effect of direct vasodilation with hydralazine versus angiotensin-converting enzyme inhibition with captopril on mortality in advanced heart failure: The Hy-C trial

AbstractTo compare the benefit of angiotensin-converting enzyme inhibition and direct vasodilation on the prognosis of advanced heart failure, 117 patients evaluated for cardiac transplantation who had severe symptoms and abnormal hemodynamic status at rest were randomized to treatment with either captopril or hydralazine plus isosorbide dinitrate (Hy-C Trial). Comparable hemodynamic effects of the two regimens were sought by titrating vasodilator doses to match the hemodynamic status achieved with nitroprusside and diuretic agents, attempting to achieve a pulmonary capillary wedge pressure of 15 mm Hg and a systemic vascular resistance of 1,200 dynes · s · cm−5. Treatment with the alternate vasodilator was started because of poor hemodynamic response or side effects (40% of patients in the captopril group and 22% in the hydralazine group). Adequate hemodynamic response in patients with a serum sodium level <135 mg/dl was more likely with hydralazine than with captopril (71% vs. 33%, p = 0.04). Isosorbide dinitrate was prescribed in 88% of the hydralazine-treated patients and 84% of the captopril-treated patients. The hemodynamic improvements from each regimen were equivalent. After 8 ± 7 months of follow-up, the actuarial 1-year survival rate was 81% in the captopril-treated patients and 51% in the hydralazine-treated patients (p = 0.05). The improved survival with captopril resulted from a lower rate of sudden death, which occurred in only 3 of 44 captopril-treated patients compared with 17 of 60 hydralazine-treated patients (p = 0.01). In the subset of patients who continued treatment with the initial vasodilator, results were similar to those for the entire treatment group. Cox multivariate analysis revealed that therapy with captopril, low pulmonary capillary wedge pressure during therapy and serum sodium were each an independent predictor of survival.This study demonstrates that angiotensin-converting enzyme inhibition with captopril confers an additional benefit over that achieved by direct vasodilation with hydralazine when doses are titrated to achieve the same hemodynamic goals and nitrates are included in both regimens. This differential effect on mortality results primarily from a decrease in sudden death