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Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure
A Mehra1, E Ostrzega, A Shotan
1Department of Medicine, Los Angeles County-University of Southern California Medical Center 90033.
Insights
Organic nitrates, like isosorbide dinitrate, effectively reduce heart pressures in chronic heart failure patients already on angiotensin-converting enzyme (ACE) inhibitors. This combination therapy shows therapeutic potential for managing congestive heart failure (CHF).
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic congestive heart failure (CHF) management often involves multiple drug classes.
- Angiotensin-converting enzyme (ACE) inhibitors are a cornerstone therapy for CHF.
- The combined effect of organic nitrates and ACE inhibitors in CHF requires further elucidation.
Purpose of the Study:
- To assess the hemodynamic impact of oral isosorbide dinitrate in patients with chronic CHF already receiving captopril (an ACE inhibitor).
- To determine if organic nitrates retain their vasodilatory effects when co-administered with ACE inhibitors.
Main Methods:
- 11 patients with chronic CHF who responded to nitrates were enrolled.
- Patients received oral isosorbide dinitrate (40-120 mg every 6 hours) in addition to their existing captopril therapy.
- Hemodynamic parameters including right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and systemic blood pressure were monitored over 24 hours.
Main Results:
- Isosorbide dinitrate significantly reduced mean right atrial pressure, pulmonary artery pressure, and pulmonary artery wedge pressure.
- These reductions were observed within 1 hour of administration and persisted for 20-24 hours.
- A transient, asymptomatic decrease in systemic blood pressure was noted for 2 hours post-initiation.
Conclusions:
- Organic nitrates demonstrate preserved vasodilatory effects in patients with chronic CHF treated with ACE inhibitors.
- Nitrate therapy improves ventricular filling pressures and reduces pulmonary hypertension, supporting combined use with ACE inhibitors.
- Long-term evaluation of combined nitrate and ACE inhibitor therapy in CHF patients is warranted.
Abstract:
To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin-converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/- 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long-term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors.