High prevalence and distinctive clinical features of LMNA-associated atrioventricular block in young patients

Background and aims Atrioventricular block (AVB) is a degenerative disease and more commonly encountered in elderly patients, but unusual and often of unknown etiology in young patients. This study aimed to investigate the potential contributions of genetic variations to AVB of unknown reasons in young patients. Methods We enrolled 41 patients aged < 55 years with high-degree AVB of unknown etiology whose clinical and genetic data were collected. Results Genetic variants were identified in 20 (20/41, 48.8%) patients, 11 (11/20, 55%) of whom had LMNA variants including 3 pathogenic (c.961C > T, c.936+1G > T and c.646C > T), 4 likely pathogenic (c.1489 -1G > C, c.265C > A, c.1609 -2A > G and c.1129C > T) and 3 of uncertain significance (c.1158 -3C > G, c.776A > G and c.674G > T). Compared to those without LMNA variants, patients with LMNA variants demonstrated a later age at onset of AVB (41.45 +/- 9.89 years vs 32.93 +/- 12.07 years, P = .043), had more prevalent family history of cardiac events (81.8% vs 16.7%, P < .000), suffered more frequently atrial (81.8% vs 10.0%, P < .000) and ventricular (72.7% vs 10.0%, P < .000) arrhythmias, and were more significantly associated with enlargement of left atrium (39.91 +/- 7.83 mm vs 34.30 +/- 7.54 mm, P = .043) and left ventricle (53.27 +/- 8.53 mm vs 47.77 +/- 6.66 mm, P = .036). Conclusions Our findings provide insights into the genetic etiology of AVB in young patients. LMNA variants are predominant in genotype positive patients and relevant to distinctive phenotypic properties. (Am Heart J 2024;269:8-14.)