Risks and long-term prognosis of new-onset heart failure after de novo permanent pacemaker implantation: nationwide cohort study

BackgroundPrevious studies on pacemaker-associated heart failure (PaHF) have predominantly analyzed relatively small, single-center datasets, mainly focusing on incidence and predictors. However, the clinical implications of PaHF on mortality, particularly in relation to standard HF medications or upgrading to cardiac resynchronization therapy (CRT), has been underexplored. MethodsUtilizing nationwide real-world data from the Korean National Health Insurance Service database, we analyzed 32,216 patients undergoing permanent pacemaker (PPM) implantation without preexisting HF between 2008 and 2019. The incidence, predictors, and mortality risk of PaFH were evaluated. To address potential immortal-time bias due to the time-dependent occurrence of PaHF, the time from the PPM implantation to the first diagnosis of PaHF was analyzed as a time-dependent covariate. For patients with PaHF, a propensity score-matched analysis was conducted based on CRT-upgrade status to explore the effect of CRT-upgrade on the risk of all-cause mortality. ResultsDuring the median 3.8-year follow-up period, PaHF and all-cause death occurred in 4170 (12.9%) and 6184 (19.2%) of the 32,216 PPM patients (42.3% male, mean age 70.6 years), respectively. PaHF development was closely associated with all-cause mortality, with a significantly higher mortality risk in the PaHF than in the non-PaHF group (hazard ratio [HR]=3.11, 95% confidence interval [CI]=2.93-3.32, P<0.001) after adjusting for immortal-time bias. The PaHF incidence and PaHF-associated mortality risk, although highest for the first six months post-PPM, did not disappear and increased again with follow-up time. In both the entire cohort (n=4170) and the propensity score-matched cohort (n=1685) of PaHF patients, CRT upgrade (HR=0.34, 95% CI=0.24-0.47, P<0.001), the use of beta-blockers (HR=0.75, 95% CI=0.61-0.93, P=0.010), and angiotensin receptor neprilysin inhibitor (ARNI) use (HR=0.28, 95% CI=0.14-0.54, P<0.001) were identified as potent protective factors against post-PaHF all-cause mortality. ConclusionsPaHF development independently predicted post-PPM mortality, while upgrading to CRT and the use of beta-blockers or ARNI were identified as favorable prognostic factors for post-PaHF overall survival. Therefore, for PaHF patients, an immediate change into CRT or conduction system pacing, may be required along with optimal HF medications owing to the ongoing mortality risk.