# Long-term mortality and treatment outcomes in pacemaker-associated heart failure: insights from a nationwide propensity-matched study

## TL;DR

This study finds that upgrading pacemakers with cardiac resynchronisation therapy significantly reduces mortality in patients with pacemaker-associated heart failure.

## Contribution

The study provides real-world evidence that CRT-upgrade improves survival in pacemaker-associated heart failure patients compared to medical therapy alone.

## Key findings

- CRT-upgrade was associated with a 64% reduction in all-cause mortality compared to medical therapy alone.
- Age, male sex, diabetes, and chronic kidney disease were identified as independent risk factors for mortality.
- Use of ARNI and beta-blockers was associated with improved survival in PaHF patients.

## Abstract

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.

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.

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.

Graphical AbstractAmong 4166 patients diagnosed with PaHF after de novo pacemaker implantation between 2008 and 2019, 330 received a CRT-upgrade, while 3836 were treated with standard HF medications alone. After 1:4 propensity score matching, 316 patients in the CRT-upgrade group were compared to 1139 matched controls without CRT-upgrade. The primary outcome was all-cause mortality, with a median follow-up duration of 1.9 years (interquartile range, 0.7–2.6 years). CRT-upgrade was associated with significantly improved survival in the matched cohorts (HR 0.36, 95% CI 0.26–0.50, P < 0.001). Multivariable analysis identified increasing age, male sex, diabetes, and CKD or ESRD as independent risk factors for mortality, whereas CRT-upgrade and use of ARNI or beta-blockers were protective. Abbreviations: ARNI, angiotensin receptor neprilysin inhibitor; CKD, chronic kidney disease; CRT, cardiac resynchronisation therapy; ESRD, end-stage renal disease; HF, heart failure; PaHF, pacemaker-associated heart failure; PPM, permanent pacemaker.For image description, please refer to the figure legend and surrounding text.

Among 4166 patients diagnosed with PaHF after de novo pacemaker implantation between 2008 and 2019, 330 received a CRT-upgrade, while 3836 were treated with standard HF medications alone. After 1:4 propensity score matching, 316 patients in the CRT-upgrade group were compared to 1139 matched controls without CRT-upgrade. The primary outcome was all-cause mortality, with a median follow-up duration of 1.9 years (interquartile range, 0.7–2.6 years). CRT-upgrade was associated with significantly improved survival in the matched cohorts (HR 0.36, 95% CI 0.26–0.50, P < 0.001). Multivariable analysis identified increasing age, male sex, diabetes, and CKD or ESRD as independent risk factors for mortality, whereas CRT-upgrade and use of ARNI or beta-blockers were protective. Abbreviations: ARNI, angiotensin receptor neprilysin inhibitor; CKD, chronic kidney disease; CRT, cardiac resynchronisation therapy; ESRD, end-stage renal disease; HF, heart failure; PaHF, pacemaker-associated heart failure; PPM, permanent pacemaker.