Prognostic impact of prolonged QRS duration on cardiovascular outcomes in chronic heart failure without ventricular pacing or cardiac resynchronization therapy: a systematic review and meta-analysis

Introduction Prolonged QRS duration is a surface electrocardiographic marker of left ventricular dyssynchrony and has been associated with adverse outcomes in chronic heart failure (CHF). However, much of the available evidence derives from historical cohorts predating contemporary guideline-directed medical therapy and is largely restricted to heart failure with reduced ejection fraction (HFrEF). Data on the prognostic impact of prolonged QRS duration across the broader spectrum of heart failure phenotypes, including mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) remain limited. Whether native QRS prolongation independently identifies high-risk patients in contemporary, device-free CHF populations therefore remains uncertain. Purpose To perform a meta-analysis assessing the prognostic impact of prolonged QRS duration on cardiovascular outcomes in patients with CHF without ventricular pacing or cardiac resynchronization therapy (CRT). Methods We conducted a systematic search of PubMed, Embase, and the Cochrane Library to identify studies comparing prolonged versus narrow QRS duration (≥ 120 ms vs <120 ms) in patients with CHF without ventricular pacing or CRT. Outcomes were all-cause mortality, heart failure hospitalization, cardiovascular death, and sudden cardiac death. Multivariable-adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were extracted and pooled using random-effects models. Heterogeneity was quantified using the I² statistic. A two-sided P value < 0.05 was considered statistically significant. Results We included eight studies with a total of 81,979 patients, of whom 19,022 (23%) had prolonged QRS duration, and 37,642 (46%) had HFrEF. Mean age ranged from 62 to 80 years, and median follow-up ranged from 23 to 60 months across studies. Compared with patients with narrow QRS duration, those with prolonged QRS duration had a significantly higher risk of all-cause mortality (HR, 1.21; 95% CI, 1.13–1.29; I² =58%; P < 0.01), cardiovascular death (HR, 1.31; 95% CI, 1.19–1.44; I² = 16%; P < 0.01), heart failure hospitalization (HR, 1.42; 95% CI, 1.33–1.51; I² = 29%; P < 0.01), and sudden death (HR, 1.38; 95% CI, 1.20–1.59; I² = 0%; P < 0.01). In subgroup analyses by heart failure phenotype, prolonged QRS duration remained significantly associated with higher risk of all-cause mortality in patients with HFrEF (HR 1.20; 95% CI, 1.15–1.26; P<0.01), HFmEF (HR 1.14; 95% CI, 1.00–1.30; P<0.01), and HFpEF (HR 1.16; 95% CI, 1.04–1.31; P<0.01), with no significant differences between subgroups (P for interaction = 0.73). Conclusions In patients with CHF without ventricular pacing or CRT, prolonged QRS duration is associated with a significantly increased risk of all-cause mortality, cardiovascular death, heart failure hospitalization, and sudden death, with no with no evidence of effect modification by heart failure phenotype.