Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Introduction and objectives: According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and >= 2 risk factors: male sex, left ventricular ejection fraction (LVEF) < 45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. Methods: The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age >= 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. Results: We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF < 45% (P=.001) and NSVT (P<.001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF < 45% (P<.001). Conclusions: In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF < 45%. Therefore, female carriers of missense variants with either NSVT or LVEF < 45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Automated summary

This study aimed to describe the clinical characteristics of carriers of LMNA genetic variants in a Spanish cardiac-laminopathies cohort and assess risk criteria. The results showed that LVEF <45% and NSVT were associated with major arrhythmic events, while sex or type of genetic variant were not. Female carriers of missense variants with NSVT or LVEF <45% should not be considered a low-risk group. Individualized risk stratification is important for carriers of LMNA missense variants, as prognosis varies among individuals.