Familial risk of sinus node dysfunction indicating pacemaker implantation: A nation-wide cohort study.

Background and aims: We aimed to investigate the risk of sinus node dysfunction (SND) indicating cardiac pacing and mortality in first-degree relatives to patients with a pacemaker implanted on this indication and assess the effect of onset-age on disease risk.

Methods: In this nationwide register-based study we used the Danish civil registration registry to establish family structures and merged data with the Danish National Patient Registry and the Danish Pacemaker and ICD registry containing information on all pacemakers implanted due to SND in Denmark.

Results: We followed 6,027,090 individuals born after 1954 for 180,775,041 personyears between 1982-2022 among whom 2.477 pacemakers were implanted due to SND. The adjusted rate ratio (RR) of pacemaker-treated SND was 2.9 (2.4-3.6) for individuals having any father, mother or sibling with a pacemaker implanted on this indication compared with the general population (derived cumulative incidence at the age of 68 years: 0.79% and 0.27%, respectively). This risk was inversely proportional to implantation-age in the index person (≤60 years: RR=5.5 (3.4-9.0)). Overall, mortality was similar between individuals having a father, mother or sibling with SND and the general population, but higher for relatives to index-persons with an early onset (≤60 years: RR=1.22 (1.05-1.41)).

Conclusions: First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with implantation-age in the index person. Mortality in first-degree relatives was comparable to the general population, although subgroup findings suggest an increased mortality among individuals with a family history of earlyonset SND.