Cardiac Resynchronization Therapy
To the Editor:
We congratulate St John Sutton et al1 on their comprehensive study of the effects of cardiac resynchronization therapy (CRT) on left ventricular size and function. It is the first study to show a reverse remodeling effect of CRT in a randomized controlled study and confirms earlier reports from smaller trials that this effect is independent of, and thus complementary to, β-blocker treatment.2
The authors found beneficial long-term effects on left ventricular filling time, isovolumic contraction time, and myocardial performance index after 3 and 6 months of CRT. We noted that these long-term effects are similar in magnitude to the acute changes observed after 1 month of CRT.3 Thus, acute testing by Doppler echocardiography early after device implantation may predict a beneficial long-term response. The same applies to the reduction in mitral regurgitation, which may not only be caused by chronic reverse remodeling, as the authors imply in their discussion, but also by an acute increase in mitral valve closing force.4 We suggest that patients without acute Doppler echocardiographic improvement early after device implantation should be re-evaluated. In such acute nonresponders, improvements may be observed with individual optimization of the programmed atrioventricular and interventricular delay settings.5 However, it should be kept in mind that the correlation between clinical improvement achieved by CRT and the changes in echocardiographic parameters is weak.
Unfortunately, the authors missed the chance to elucidate in their large population whether preoperative markers can be identified that predict improvement in functional capacity and/or volumes. Such information would be extremely important in identifying the roughly 20% of patients who fulfill currently accepted implant criteria but do not show any long-term benefit.
St John Sutton MG, Plappert T, Abraham WT, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003; 107: 1985–1990.
Stellbrink C, Breithardt OA, Franke A, et al. Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances. J Am Coll Cardiol. 2001; 38: 1957–1965.
Sogaard P, Egeblad H, Pedersen AK, et al. Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation. 2002; 106: 2078–2084.
We thank Drs Breithardt and Stellbrink for their comments. The Multicenter InSync Randomized CLinical Evaluation (MIRACLE) trial was a prospective, double-blind trial designed to test the hypothesis that atrial-based biventricular pacing with optimized atrioventricular delay improved New York Heart Association symptom class, quality of life, and 6-minute hall-walk distance. The study design prevented us from “looking to see” which patients improved during the course of the trial so as to individually optimize the atrioventricular and interventricular delays, as suggested by Breithardt and Stellbrink. The secondary objective of MIRACLE was to determine whether changes in left ventricular (LV) structure or function accompanied the symptomatic benefit of cardiac resynchronization therapy (CRT) described in previous reports. Doppler echocardiography provided the infrastructure to explore possible mechanisms involved in remodeling in CRT patients who improved.
Breithardt and Stellbrink point out that in the MIRACLE trial, correlations between clinical improvement with CRT and changes in Doppler echocardiographic measurements were weak. We acknowledged this in our manuscript,1 and we bring to their attention the time-honored observation that measurements of LV size and function correlate notoriously poorly with measurements of exercise capacity in heart failure patients, although both measurements predict clinical outcome.
We have a strong interest in identifying baseline demographics and Doppler echocardiographic measurements that predict improvement in functional capacity and/or reverse remodeling, and for this reason we performed an extensive post hoc statistical analysis. No single measure emerged that predicted improvement. However, reversed remodeling in patients with heart failure of a nonischemic etiology was associated with greater changes in LV volumes and ejection fraction. Aortic pre-ejection period may identify patients likely to exhibit reversed remodeling and symptomatic benefit.2
We agree that patients without Doppler echocardiographic improvement should be re-evaluated early after device implantation, because improvement has been reported with individual optimization of the atrioventricular and interventricular delays.3
We believe that reverse remodeling is a major factor in the overall improvement in patient outcomes and that increased mitral valve closing force may be a contributing factor.
St John Sutton M, Plappert T, Abraham WT, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003; 107: 1985–1990.
St John Sutton M, Plappert T, Hilpisch KE, et al. Quartile analysis of the baseline aortic pre-ejection interval as a predictor of response to cardiac resynchronization therapy. J Am Coll Cardiol. 2003; 41: 187A.
Sogaard P, Eglablad H, Petersen AK, et al. Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation. 2002; 106: 2078–2084.