Enalapril Reduces QTc Dispersion in Mild Congestive Heart Failure Secondary to Coronary Artery Disease

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Abstract

This study was designed to investigate the possible mechanisms whereby enalapril improves cardiac function and mortality in chronic heart failure. We explored potential mechanisms by following 41 patients with early heart failure over the course of 1 year. These patients were randomized in a prospective triple-blind manner to receive either enalapril or placebo. Over the 1 year, repeated measurements were obtained of echocardiographic parameters, glomerular filtration rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion. Echocardiographic parameters improved with enalapril but deteriorated with placebo (cardiac output 4.6 ± 1.6 to 3.7 ± 1.5 L/min with placebo, and 4.5 ± 1.3 to 5.8 ± 2.0 L/min with enalapril; p <0.01). In contrast, there were no significant changes in renal blood flow (518 ± 185 to 509 ± 180 ml/min/1.73 m2 with placebo, and 541 ± 142 to 504 ± 162 ml/min/1.73 m2 with enalapril). Glomerular filtration rate changed from 79 ± 20 to 78 ± 19 ml/min/1.73 m2 with placebo, and from 85 ± 21 to 73 ± 27 ml/min/1.73 m2 with enalapril (p = 0.051). Enalapril reduced hematocrit (0.414 ± 0.041 to 0.377 ± 0.040%) significantly more than placebo (0.420 ± 0.029 to 0.411 ± 0.023 l/l; p <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93 ± 36 to 88 ± 28 ms with placebo and 93 ± 35 to 60 ± 22 ms with enalapril; p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc dispersion in early heart failure. Both of these effects, but especially the latter, could be an important mechanism for the reduced mortality seen with angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal hemodynamics did not parallel either the placebo-induced deterioration in cardiac function or the enalapril-induced improvements in cardiac function.

Section snippets

Methods

Forty-one patients (38 men and 3 women, mean [± SD] age 66 ± 8 years) with New York Heart Association class I to II CHF (few or no symptoms), and with echocardiographic evidence of left ventricular systolic dysfunction and left ventricular ejection fraction >35%, were identified from the heart failure clinic of our institution. All patients had evidence of coronary artery disease.

Patients were consecutive eligible patients attending the cardiac failure clinic of our institute with left

Results

Patient's demographic and baseline echocardiographic, renal, and laboratory characteristics are listed in Table 1, Table 2. There were no significant differences between the groups with respect to these measures.

Study medication was well tolerated by most patients. All but 2 patients tolerated dose titration. One patient withdrew during this period and one patient tolerated only the initial dose, both having orthostatic hypotension (enalapril-treated group). No serious drug-related adverse

Discussion

The most significant findings of this study relate to QTc dispersion. In our cohort of patients with early CHF, QTc dispersion was variable at baseline, with some patients already having markedly prolonged QTc dispersion even at this early stage of the disease. No obvious factor appeared to account for this marked variability. There is increasing evidence that prolonged QTc dispersion is a marker for sudden death in a number of conditions including CHF, peripheral vascular disease, and

Acknowledgements

This study was supported by Merck, Sharp & Dohme Hoddesdon, Herts, United Kingdom.

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