Conventional therapy with an ACE inhibitor diminishes left ventricular dyssynchrony during the progression of heart failure

Abstract

Purpose: Left ventricular (LV) mechanical dyssynchrony is an important codeterminant of cardiac dysfunction in heart failure (HF) patients exhibiting either a narrow or a wide QRS complex. We hypothesized that an angiotensin converting enzyme (ACE) inhibitor would prevent LV dyssynchrony during the progression of pacing-induced HF through its beneficial effects on hemodynamic change and myocardial fibrosis.

Methods: Twenty-eight dogs were assigned to the following treatment groups; rapid ventricular pacing (HF group; n=10), concomitant ACE inhibitor and rapid pacing (enalapril 1.9 mg/kg/day: ACEI group; n=8), or sham-operated control (control group; n=10). After 4 weeks of pacing, cardiac function was evaluated using micromanometers and conductance catheters. We used indexes to quantify the temporal and spatial aspects of mechanical dyssynchrony derived from online segmental conductance catheter signals. At each time point, a segmental signal was defined as dyssynchronous if its change was opposite to the simultaneous change in the total LV volume. Mechanical dyssynchrony was calculated as the mean of the segmental dyssynchronies during systole, diastole, and throughout the cardiac cycle.

Results: In the ACEI group, the LV ejection fraction was preserved, and total systemic resistance and end-diastolic volume were significantly decreased, while stroke volume was significantly increased compared to the HF group. The mechanical dyssynchrony index in the HF group was significantly higher compared to that of the control group, while it was significantly lower in the ACEI group. Thus, conventional therapy with an ACE inhibitor diminished LV dyssynchrony during the progression of pacing-induced HF.