What question did this study set out to answer?

The aim was to describe the outcomes related to arrhythmias and heart function in individuals with LMNA mutations.

June 18, 2026Open Access

Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers

SKSaurabh KumarElectrophysiology SBSamuel H. BaldingerUniversity of Bern EGEstelle GandjbakhchElectrophysiology

Key Points

The aim was to describe the outcomes related to arrhythmias and heart function in individuals with LMNA mutations.
Retrospective analysis of 122 LMNA mutation carriers across 5 centers for median follow-up of 7 years.
Assessment of incidence rates for various cardiac events such as AVB, AAs, and VAs.
Evaluation of predictors for development of VA and end-stage heart failure.
AVB prevalence rose from 46% to 57%, AAs from 39% to 63%, and VAs from 16% to 34% over the follow-up.
End-stage heart failure occurred in 19% of patients and the mortality rate was 13%.
Male sex, nonmissense mutations, and LVD at initial evaluation were significantly associated with the development of VA.

Abstract

BACKGROUND: Mutations in LMNA are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain. OBJECTIVES: This study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic significance of the index cardiac phenotype. METHODS: The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined. RESULTS: The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death. CONCLUSIONS: LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.

Ask AI

Helpful

Bookmark

View Full Paper