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Acute and long-term response to enalapril in congestive failure
Insights
Enalapril, an angiotensin converting enzyme (ACE) inhibitor, improved heart failure symptoms in patients. While cardiac output benefits were temporary, it significantly reduced filling pressures and improved clinical well-being.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic heart failure (CHF) presents significant challenges in managing patients with reduced cardiac function.
- Angiotensin converting enzyme (ACE) inhibitors have emerged as a key therapeutic class for cardiovascular diseases.
Purpose of the Study:
- To evaluate the efficacy and hemodynamic effects of enalapril in patients with severe chronic heart failure (NYHA functional class III and IV).
- To determine the optimal once-daily oral dosage of enalapril for this patient population.
Main Methods:
- Oral administration of enalapril to 12 patients with CHF and cardiomegaly.
- Monitoring of hemodynamic parameters including heart rate, blood pressure, pulmonary and cardiac pressures, and cardiac index during dose titration.
- Recatheterization at 3 months to assess long-term effects.
Main Results:
- Enalapril acutely increased cardiac index by 34% and reduced left ventricular filling pressure by 36%.
- At 12 weeks, left ventricular filling pressure was reduced by 41%, while cardiac index returned to baseline.
- Significant reductions in heart rate, systemic arterial pressure, right atrial pressure, and aldosterone levels were observed.
- ACE activity was markedly inhibited, with a corresponding elevation in renin levels.
- Patients experienced sustained clinical improvement and subjective well-being.
Conclusions:
- Enalapril demonstrates significant acute hemodynamic benefits in severe heart failure, primarily through reducing cardiac filling pressures.
- While acute cardiac output improvements may not be sustained, enalapril provides sustained reduction in filling pressures and leads to marked clinical improvement.
- Enalapril effectively inhibits ACE activity, leading to hormonal changes that correlate with positive clinical outcomes in heart failure patients.
Abstract:
Enalapril, a novel long acting angiotensin converting enzyme (ACE) inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and IV) and cardiomegaly. The optimal dose averaged 17 mg given once-daily. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. Eleven patients were recatheterised 3 months later. After stabilisation of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 20 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at 3 months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. ACE activity was inhibited at the time of peak haemodynamic effect from 25.3 +/- 9.8 to 4.9 +/- 3.4 U/ml (P less than 0.01). Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.