Intraventricular conduction delays occur frequently in patients with heart failure. These delays contribute to asynchronous contraction patterns. The QRS width is typically used as a marker of cardiac dyssynchrony. In the 6 published cardiac resynchronization trials to date, researchers used QRS width as both a marker of dyssynchrony and an inclusion criteria.

QRS Width as a Marker of Dyssynchrony Inclusion Criteria in Completed CRT Trials   QRS ms (mean) NYHA EF MUSTIC >150 (176) III <35% MUSTIC-AF >200 III <35% MIRACLE ≧130 III-IV ≦35% MIRACLE-ICD ≧120 II-IV ≦35% PATH-CHF II ≧120 II-III ≦30% COMPANION >120 + PR>150 III-IV ≦35%

The CHRISTMAS trial (Carvedilol Hibernation Reversible ISchaemia Trial; MArker of Success) evaluated patients with systolic dysfunction and heart failure due to ischemic heart disease treated with carvedilol. Investigators designed this trial to determine whether the presence or absence of hibernating myocardium would predict improvement in left ventricular ejection fraction.

Beta-blockade may have an effect on dyssynchrony in heart failure patients. Dr. Dalle Mule and colleagues hypothesized that improvement in left ventricular synchrony explained at least part of the benefit of carvedilol in CHRISTMAS.

To determine this, they analyzed QRS duration, left ventricular ejection fraction and intraventricular/interventricular conduction delay. The analysis included 164 patients from the CHRISTMAS study. All these patients underwent radionuclide ventriculography at randomization and again at the end of the maintenance phase of treatment with carvedilol or placebo.

The analysis included 81 patients in the carvedilol group and 83 patients in the placebo group. Most were males (mean age 63 years), and most were NYHA functional class II. More than 80% had a previous myocardial infarction and almost half had a previous revascularization procedure.

Patient Characteristics   Placebo (n = 83) Carvedilol (n = 81) Age (years) 63 63 Males (%) 92 93 NYHA class I (%) 12 10 NYHA class II (%) 59 63 NYHA class III (%) 29 27 Mean LVEF (%) 28 30 Previous MI (%) 88 84 Previous revascularization (%) 51 47 Diuretics (%) 86 74 ACE-inhibitors (%) 88 88 Hibernators (%) 64 59

Interventricular Dyssynchrony

In the carvedilol-treated patients, the degree of interventricular dyssynchrony significantly improved between baseline and the end of the study. Degree of dyssynchrony did not change in the placebo-treated patients. At the final examination, the degree of interventricular dyssynchrony was significantly less apparent in the carvedilol group compared with the placebo group.

Intraventricular Dyssynchrony

The degree of intraventricular dyssynchrony for the left ventricle improved significantly in carvedilol-treated patients, but did not change for placebo-treated patients. At the final visit, intraventricular dyssynchrony was less evident in the carvedilol group than in the placebo group.

This is an example of a patient who received carvedilol. The yellow color on the apex of the left ventricle is an area of dyssynchrony (left image). The bell-shaped histograms result from delayed contraction. After treatment the area of dyssynchrony is much less (right image).

By contrast, this is an area of dyssynchrony in a placebo-treated patient. Dyssynchrony is evident at entry and persists at the final exam.

QRS Duration

In the overall population, QRS duration was 107 ms at baseline and 110 ms at final examination (p=0.16) and was similar in carvedilol versus placebo-treated patients. There was no change in QRS duration from baseline to final examination in either the carvedilol or placebo groups. Both at baseline and final exam, there was no significant correlation between QRS duration and degree of interventricular/intraventricular dyssynchrony. This suggests even patients with a lesser degree of QRS prolongation may experience dyssynchrony, Dr. Dalle Mule said.

Change in Ejection Fraction

As expected, the left ventricular ejection fraction increased significantly in the carvedilol group, but not in the placebo group. There was a closer relationship between ejection fraction and left intraventricular dyssynchrony (right), rather than interventricular dyssynchrony (left).

Improvement in Mechanical Function

Most patients who had an improvement in left ventricular ejection fraction also had an improvement in left ventricular intraventricular dyssynchrony (36 of 43 patients, 84%). Investigators noted that there was a deterioration in those who did not have an improvement in ejection fraction.

This study shows that dyssynchrony of ventricle contraction is common in patients with ischemic cardiomyopathy. Moreover, treatment with carvedilol improves contractile synchrony. The beneficial effects of carvedilol were independent of baseline QRS duration. This improvement in synchrony translates into an improvement of contraction.

Based on these results, Dr. Dalle Mule said improvement in ventricle contraction synchrony is an additional mechanism by which carvedilol provides a benefit in patients with ischemic cardiomyopathy.