Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy

作者：Ashwin Bhaskaran, Rabah Ben Yaou, Adam Helms, Abdallah Fayssoil, Pascale Richard, Tanya Stojkovic, Frédéric Anselme, Fabien Labombarda, Cathy Chikhaoui, Annachiara De Sandre‐Giovannoli, Isabelle Jéru, France Leturcq, Corinne Vigouroux, M Dembélé, Perry Elliott, Konstantinos Savvatis, Katja Zeppenfeld, Hassina Bouguerra, Philippe Charron, Saurabh Kumar, Gisèle Bonne, Karim Wahbi, Neal K. Lakdawala · 发表于：JAMA Cardiology · 年份：2025 · DOI：10.1001/jamacardio.2025.2069 · 被引用次数：18 · 研究领域：Nuclear Structure and Function、Genomics and Rare Diseases、Cardiac electrophysiology and arrhythmias

Importance: Prior studies have suggested that patients with nonmissense (ie, truncating) variants causing LMNA cardiomyopathy have worse arrhythmic outcomes compared to those with missense variants. However, the effect of the spatial distribution of missense and truncating variants on clinical outcomes remains poorly understood. Objective: To determine the association of the spatial distribution of missense and truncating LMNA variants with cardiac outcomes. Design, Setting, and Participants: This multicenter, retrospective, observational cohort study used data from an international registry (from January 2013 on) and data derived from tertiary cardiomyopathy centers (January 2000 and June 2017). Patients with likely pathogenic/pathogenic LMNA variants and no prior malignant ventricular arrhythmia (VA) were eligible for inclusion. Data analysis was completed from March 2022 to March 2025. Main Outcomes and Measures: The primary outcome of time to VA was defined as sudden cardiac death, appropriate implantable cardioverter-defibrillator therapy, or other manifestations of hemodynamically unstable VA. The secondary composite outcome of advanced heart failure was defined as nonsudden cardiac death, implantation of a left ventricular assist device, or cardiac transplant. Outcomes were stratified by type of variant (missense or truncating), affected transcript position (head, rod, or tail), and location on the LMNA gene. Results: A total of 718 patients were included, among whom m...