Abstract
AIMS: Pacing-associated heart failure (PaHF) has emerged as a clinically significant complication in patients with pacemakers, yet its prognostic factors and optimal management remain underexplored. We aimed to assess mortality risk and the clinical impact of cardiac resynchronisation therapy (CRT)-upgrade and heart failure (HF) medications in patients with PaHF using a nationwide real-world cohort. METHODS AND RESULTS: We analysed 4166 patients who developed PaHF after de novo permanent pacemaker implantation using a nationwide real-world cohort from the Korean National Health Insurance Service. To address confounding and immortal-time bias, propensity score matching and time-dependent Cox regression models were applied. During a median follow-up of 1.9 years, 330 patients underwent CRT-upgrade in addition to standard HF medical therapy, while 3836 received guideline-directed HF medications alone. Increasing age (HR = 1.05 per year, 95% CI 1.04-1.06, P < 0.001), male sex (HR = 1.41, 95% CI 1.16-1.71, P < 0.001), diabetes (HR = 1.28, 95% CI 1.02-1.60, P = 0.035), and chronic kidney disease or end-stage renal disease (HR = 1.69, 95% CI 1.32-2.17, P < 0.001) were independently associated with increased all-cause mortality. In contrast, CRT-upgrade (HR = 0.36, 95% CI 0.26-0.50, P < 0.001), angiotensin receptor-neprilysin inhibitor (ARNI) use (HR = 0.37, 95% CI 0.19-0.68, P = 0.004), and beta-blockers (HR = 0.80, 95% CI 0.64-0.99, P = 0.042) were strongly associated with improved survival. CONCLUSION: In this nationwide real-world cohort, CRT-upgrade was associated with a significant reduction in all-cause mortality compared with medical therapy alone in patients with PaHF. These findings support the prognostic importance of device-based therapy in combination with contemporary HF medical treatment in real-world clinical practice.