Reverse Electrical Remodeling by Cardiac Resynchronization Therapy: Prevalence and Clinical Impact

Intrinsic QRS Narrowing with CRT . Background: Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown. Objective: We sought to determine (1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), (2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT, and (3) to identify predictors of iQRS width shortening. Methods: We prospectively included 85 consecutive patients with left bundle‐branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF, and left ventricular volumes were assessed before and 1 year after CRT implantation. Clinical and echocardiographic CRT responders were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 ms. Results: Baseline and 1‐year follow‐up mean iQRS durations were, respectively, 168.0 ± 19.7 ms and 149.6 ± 31.6 ms (P < 0.0001). Electrocardiographic response, observed in 43/85 patients (51%), was associated with a greater rate of clinical (P = 0.035) and echocardiographic (P = 0.023) response. Younger age, male gender, and longer baseline QRS width were independent predictors of electrocardiographic response. Conclusion: CRT decreases iQRS duration. A reduction of at least 20 ms in iQRS duration is associated with better clinical and echocardiographic response. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1219–1227, November 2012)     

ON THE RELATIONSHIP BETWEEN RESPONSE TO TREATMENT AND SURVIVAL TIME

In this paper we review several approaches which have been used to investigate the relationship between survival time and response to treatment. We show that the approaches based on summary data are subjected to various types of biases (publication bias, confounding by prognostic features, ecologic bias) and are therefore of doubtful value. We also discuss several approaches based on individual patient data. Comparisons of survival by response are generally subject to length-biased sampling, and are therefore inadequate. The landmark method is adequate when responses occur soon after starting treatment, but not when responses may appear later in the course of the disease. For responses which can occur over extended periods of time, response must be considered as a time-dependent covariate. Using data from randomized trials in advanced colorectal cancer, we show that response is a potent and independent prognostic factor for survival in this disease. Analyses using the landmark method yield results essentially equivalent to those in which response is considered as a time-dependent covariate. The hazard rate of responders is about half that of non-responders, after taking the patient's performance status into account. The issue of response as a surrogate marker for survival is taken up further in a separate paper.