AUTHOR=Grebur Kinga , Mester Balázs , Fekete Bálint András , Kiss Anna Réka , Gregor Zsófia , Horváth Márton , Farkas-Sütő Kristóf , Csonka Katalin , Bödör Csaba , Merkely Béla , Vágó Hajnalka , Szűcs Andrea TITLE=Genetic, clinical and imaging implications of a noncompaction phenotype population with preserved ejection fraction JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1337378 DOI=10.3389/fcvm.2024.1337378 ISSN=2297-055X ABSTRACT=Introduction

The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF.

Methods

We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered “red flags”.

Results

Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found.

Discussion

The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.