Heart failure patients frequently have intraventricular conduction delays. These contribute to asynchronous patterns of contraction and hemodynamic impairment. It is not clear what effect beta blockers might have on ventricular contractile synchrony. One hypothesis is beta blockers may improve left ventricular synchrony. This improvement might help explain the beneficial effect of beta blockers on left ventricular ejection fraction.

To evaluate this hypothesis, Dr. Dalle Mule and colleagues studied the effect of carvedilol on ventricular contractile synchrony in patients with left ventricular systolic dysfunction. This was a subanalysis of the Carvedilol Hibernation Reversible ISchaemia Trial; MArker of Success (CHRISTMAS).

The purpose of the CHRISTMAS trial was to determine whether presence or absence of hibernating myocardium predicts left ventricular ejection fraction improvement in patients who receive carvedilol. The patients had left ventricular systolic dysfunction and heart failure due to ischemic heart disease.

Investigators previously reported the main results of the CHRISTMAS study. Carvedilol was well tolerated, and increased left ventricular ejection fraction by 3.2% versus placebo (p=0.0001). This treatment benefit occurred regardless of presence or absence of hibernating myocardium. However, the effects were most favorable in patients with low left ventricular ejection fraction and a large volume of hibernating myocardium. Carvedilol also helped maintain myocardial perfusion and prevented loss of viability compared with placebo.

Here at ACC, Dr. Dalle Mule presented a substudy of intraventricular conduction delay for 164 patients in the CHRISTMAS study. Patients underwent radionuclide ventriculography at randomization and at the end of treatment with carvedilol or placebo. The mean age of the patients was 63 and 92% were men.

Interventricular dyssynchrony, or the difference between left and right ventricular mean phase angles, did not change from baseline to the final visit for patients in the placebo group. However, this measure improved in the carvedilol group. Interventricular dyssynchrony was significantly lower in the carvedilol group versus the placebo group at the final visit (p=0.015). Dr. Dalle Mule said this synchrony improvement translates into an improvement in contraction.

Investigators also looked at the degree of intraventricular dyssynchrony, or the standard deviation of the mean phase angle. They found a significant improvement in left ventricular intraventricular dyssynchrony, but no change in the placebo group. There was no change in right ventricular intraventricular dyssynchrony for either carvedilol or placebo.

Dr. Dalle Mule said that dyssynchrony of the ventricles occurs frequently in patients with ischemic heart disease. This study shows that carvedilol improves both interventricular dyssynchrony and intraventricular contraction synchrony of the left ventricle. This represents a newly discovered mechanism that helps explain why carvedilol has a beneficial effect on left ventricular function in these patients.