Impact of QRS Duration on Clinical Event Reduction With Cardiac Resynchronization Therapy: Meta-Analysis of Randomized Controlled Trials

Study Questions:

Is the clinical benefit of cardiac resynchronization therapy (CRT) similar for patients with moderately versus severely prolonged QRS intervals?


This was a meta-analysis of randomized trials of CRT in heart failure that reported clinical outcomes in relation to QRS duration. The QRS was considered severely prolonged if >150 ms, and moderately prolonged if 120-150 ms. The composite endpoint of “clinical events” was compared between QRS groups and is presented as relative risks (RRs) [95% confidence intervals]. All trials included “all-cause” mortality in the clinical event definition. Heart failure hospitalizations, heart failure events (hospitalization or outpatient intravenous diuretic therapy), or “major cardiovascular event” also contributed to the clinical events endpoint, but were not consistently defined or measured across trials.


Five clinical trials (COMPANION, CARE-HF, REVERSE, MADIT-CRT, and RAFT) encompassing 5,813 patients were included in the meta-analysis. Patients (n = 3,624) with a severely prolonged QRS had a 40% risk reduction in clinical events (RR, 0.60 [0.53-0.67]) with the application of CRT. However, patients (n = 2,189) with a moderately prolonged QRS gained no significant benefit (RR, 0.95 [0.82-1.10]) from CRT. Heterogeneity analysis showed a significant difference in outcome between the two QRS groups (p < 0.001). Overall, individuals with a longer QRS interval gained greater benefit from CRT (slope -0.06 [-0.10 to -0.04] for log RR vs. QRS duration). The above findings remained robust on sensitivity analysis and were not impacted by New York Heart Association class.


The authors concluded that CRT provides clinical benefit only to those patients with a QRS >150 ms.


While the response encountered by some heart failure patients to CRT can be dramatic, many still undergo the therapy without obvious benefit. Echocardiographic prediction of response remains poor. In this meta-analysis, Sipahi et al. provide strong support for applying CRT based on QRS duration. Clearly, they show that those with a QRS >150 ms achieve a clinically significant reduction in events with CRT. The authors were strong to say that CRT did not reduce events in patients with a QRS 120-150 ms. The overall RR would strongly suggest this, but the confidence interval is wide. In this moderately prolonged QRS group, can we tease out the noise and identify responders using other methods? A clinical trial seems warranted.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Heart Diseases, Risk, Defibrillators, Cardiac Pacing, Artificial, Risk Reduction Behavior, Cardiology, Diuretics, Heart Failure, New York, Echocardiography, Cardiac Resynchronization Therapy

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