Abstract and Introduction
Abstract
CRT and QRS Duration
Background: Cardiac resynchronization therapy (CRT) improves outcomes in patients with heart failure (HF) because of reduced left ventricular systolic function and a wide QRS complex. Whether this benefit is consistent across all degrees of QRS widening is unclear. We performed a meta-analysis of randomized clinical trials to evaluate the impact of QRS duration on the efficacy of CRT.
Methods and Results: We searched MEDLINE and EMBASE databases for studies evaluating the efficacy of CRT in patients with HF. Only trials that reported subgroup data according to QRS duration were included. Hazard ratios (HR) with 95% confidence interval (CI) were calculated using a random effects model. Five trials involving 6,501 patients (4,437 with QRS ≥ 150 ms and 2,064 with QRS < 150 ms) were included. Three trials, enrolling patients with mild to moderate HF, compared CRT-implantable cardioverter defibrillator with CRT, whereas CRT versus medical therapy was compared in the other 2 trials, which included patients with advanced HF. Based on the pooled estimate across the 5 studies, CRT significantly decreased the primary endpoint of death or hospitalization for HF in patients with QRS ≥ 150 ms (HR = 0.58, 95% CI: 0.50–0.68; P < 0.00001), but not in patients with QRS < 150 ms (HR = 0.95, 95% CI: 0.83–1.10; P = 0.51). These results were consistent across all degrees of HF severity.
Conclusions: The benefit of CRT seems to be dependent on QRS duration. Available data suggest a significant benefit associated with CRT in patients with QRS ≥ 150 ms, but not in patients with QRS < 150 ms. Further studies are needed to identify patients with QRS < 150 ms who might benefit from CRT.
Introduction
Heart failure (HF) is a significant cause of morbidity and mortality in the United States, with an estimated prevalence of 2.4% in adults. Although the survival after diagnosis of HF has improved over the past 2 decades, the rates of death and HF hospitalizations remain high, and approximately 50% of HF patients die within 5 years of diagnosis. Moreover, despite optimal pharmacologic treatment, many patients with HF remain symptomatic. In patients with advanced HF symptoms (New York Heart Association [NYHA] class-III or class-IV), despite optimal medical treatment, with a left ventricular ejection fraction (LVEF) of ≤35% and a wide QRS ≥ 120 ms, cardiac resynchronization therapy (CRT) has been shown to improve functional status and exercise capacity and to reduce hospitalizations and mortality. The beneficial effects of CRT are likely to be because of CRT-induced improvement of cardiac structure and function through reverse left ventricular (LV) remodeling. More recently, in patients with mild to moderate HF, CRT resulted in reverse LV remodeling and prevention of disease progression, as well as a reduction in HF hospitalizations and mortality. Based on these reports, CRT is being widely used in patients with HF because of reduced LV systolic function who have QRS duration of ≥120 ms. However, approximately 30% of the patients who are selected for therapy, according to the current criteria, do not benefit from CRT. Therefore, proper patient selection is crucial in assuring appropriate prescription of CRT.
A small previous study and 3 recent large trials suggested that QRS duration may influence the benefit derived from CRT, where the benefit was only evident in patients with QRS ≥ 150 ms. These findings differ from earlier studies, which reported no heterogeneity in the benefit of CRT among subgroups based on QRS duration. However, none of these trials were powered to detect subgroup effects of small to moderate magnitude. Therefore, whether the benefit from CRT is consistent across all degrees of QRS widening remains unclear. Moreover, a QRS threshold for clinical effectiveness in these patients with wide QRS (≥120 ms) has not been established. Given this uncertainty, we undertook a meta-analysis of subgroup data from published randomized clinical trials evaluating the efficacy of CRT with or without an implantable cardioverter defibrillator (ICD) to examine the impact of QRS duration on the efficacy of CRT.