Clinical outcomes according to QRS duration and morphology in the Irbesartan in Patients with Heart Failure and Preserved Systolic Function (I-PRESERVE) trial

Background: The aims of this study were to describe the prevalence of QRS prolongation and abnormal QRS morphology in patients with heart failure and preserved ejection fraction (HF-PEF) and to examine the relationship between these QRS abnormalities and clinical outcomes. Methods and results: We categorized patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-PRESERVE) according to QRS duration < 120 vs. ≥120 ms and QRS morphology: normal, left bundle branch block (LBBB), and right bundle branch block (RBBB) or other non-specific intra-ventricular conduction defect (IVCD). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization (and its components) and all-cause mortality. Of the 4128 patients enrolled in I-PRESERVE, 3754 were included in the present analyses. A total of 606 patients had a QRS duration ≥120 ms, 302 had LBBB and 742 had RBBB/IVCD. Patients with an abnormal QRS had evidence of more severe heart failure [lower left ventricular ejection fraction, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and worse clinical status (higher New York Heart Association functional class and greater use of diuretics). Both abnormalities of QRS duration and QRS morphology were associated with worse outcomes. The rates of the composite outcome were: 6.0 and 9.3 per 100 patient years in the < 120 ms and ≥120 ms groups, respectively [adjusted hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.11–1.57; P = 0.002) and 6.0, 7.7 and 8.7 per 100 patient years in the normal, non-LBBB and LBBB groups, respectively (adjusted HR 1.19, 95% CI 1.00–1.42, P = 0.046; and HR 1.31, 95% CI 1.03–1.66, P = 0.026, respectively, compared with normal). The heightened risk related to QRS abnormalities persisted after adjustment for other prognostic variables, including NT-proBNP. Conclusion: We found that both prolongation of QRS duration and abnormal QRS morphology were associated with a high risk of fatal and non-fatal adverse outcomes in heart failure with preserved ejection fraction.