Abstract

Background The long-term risk of heart failure (HF) and mortality following permanent pacemaker (PPM) implantation remains controversial and underexplored.

Objectives This study evaluated these risks and assessed the survival benefits of upgrading to cardiac resynchronisation therapy (CRT) and the impact of standard HF medications.

Methods Using the Korean National Health Insurance Service database, we identified 32,216 patients who underwent PPM implantation without preexisting HF between 2008 and 2019.

Results During the median 3.8-year follow-up period, pacemaker-associated HF (PaHF) and all-cause death occurred in 4170 (12.9%) patients, and 6184 (19.2%) died. PaHF development was strongly associated with all-cause mortality, with a significantly higher risk in the PaHF group than in the non-PaHF group (hazard ratio [HR] 3.11, 95% confidence interval [CI] 2.93–3.32) after adjusting for immortal-time bias and confounders. PaHF incidence and associated mortality were highest within the first 6 months, however, persisted throughout follow-up, with a mortality risk resurgence approximately five years post-implantation. In a propensity score-matched cohort of PaHF patients (n=1,455), CRT-upgrade was associated with a significantly lower risk of mortality (HR 0.34, 95% CI 0.24– 0.47), as were angiotensin receptor-neprilysin inhibitor (ARNI) (HR 0.28, 95% CI 0.14–0.54) and beta-blockers (HR 0.75, 95% CI 0.61–0.93).

Conclusions PaHF development independently predicted mortality post-PPM implantation, while CRT-upgrade and the use of beta-blockers or ARNI were associated with improved survival. Therefore, for PaHF patients, an immediate switching into CRT or conduction system pacing combined with optimal HF medications, may be required to mitigate the ongoing mortality risk.

Competing Interest Statement

S.J.-P. received research grants from Boston Scientific, Biotronik, Abbott, and Medtronic. K.-P. received research grants from Boston Scientific. Y.K.-O. received research grants from Bayer AG, Daiichi Sankyo Company.

Clinical Trial

This cohort study was approved by the institutional IRB and Korea NHI.

Funding Statement

No funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Institutional Review Board of Samsung Medical Center (File-No. 2019-05-075).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

This is a study using Korean NHI data, and analysis is possible with government permission.

AbbreviationsACEiAngiotensin-converting-enzyme inhibitorsARBAngiotensin II receptor antagonistsARNIAngiotensin receptor neprilysin inhibitorAVBAtrioventricular blockCRTCardiac resynchronization therapyEFEjection fractionLVLeft ventricularMRAsMineralocorticoid receptor antagonistsPaHFPacemaker-associated heart failurePPMPermanent pacemakerSNDSinus node dysfunction