Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

OBJECTIVES: This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown. METHODS: Patient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i.e., sudden death and pump failure death), and all-cause death in unadjusted and adjusted analyses. RESULTS: Of the 8,466 patients included, 682 patients (8%) had a pacemaker. Pacemaker patients were older and more often men and had lower body mass indexes, estimated glomerular filtration rates, and blood pressures but higher concentrations of N-terminal pro-B-type natriuretic peptide than those without a pacemaker. The rate of the primary composite outcome in pacemaker patients was almost twice that in patients without a pacemaker (13.6 vs. 7.6 per 100 patient-years of follow up, respectively), with a similar finding for HF hospitalizations (10.8 vs. 5.1 per 100 patient-years, respectively). This risk rate persisted after adjusting for other prognostic variables (hazard ratio [HR] for the composite outcome: 1.17; 95% confidence interval [CI]: 1.02 to 1.33; p = 0.026), driven mainly by HF hospitalization (HR: 1.37; 95% CI: 1.17 to 1.60; p < 0.001). The risk of death was not significantly higher in pacemaker patients in the adjusted analyses. CONCLUSIONS: These findings raise the possibility that right ventricular pacing-induced left ventricular dyssynchrony may be detrimental in HFpEF patients.