RT Journal Article
SR Electronic
T1 Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 1704
OP 1710
DO 10.1136/heartjnl-2016-311017
VO 103
IS 21
A1 Matteo Dal Ferro
A1 Davide Stolfo
A1 Alessandro Altinier
A1 Marta Gigli
A1 Martina Perrieri
A1 Federica Ramani
A1 Giulia Barbati
A1 Alberto Pivetta
A1 Francesca Brun
A1 Lorenzo Monserrat
A1 Mauro Giacca
A1 Luisa Mestroni
A1 Marco Merlo
A1 Gianfranco Sinagra
YR 2017
UL http://heart.bmj.com/content/103/21/1704.abstract
AB Objective To explore the genetic landscape of a well selected dilated cardiomyopathy (DCM) cohort, assessing the possible relation between different genotypes and left ventricular reverse remodelling (LVRR).Methods A cohort of 152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been studied by next-generation sequencing (NGS). Patients were grouped into different ‘gene-clusters’ with functionally homogeneous genetic backgrounds. LVRR was defined by left ventricular ejection fraction normalisation or increase ≥10% associated with normalisation in indexed left ventricular end-diastolic diameter or relative decrease ≥10% at 24 months follow-up.Results A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%) LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011).Conclusions NGS confirmed a high genetic diagnostic yield in DCM. A specific ‘gene-clusters’ classification based on functional similarities in different genes might be helpful in the clinical management of genetically determined DCM. In this study, structural cytoskeleton Z-disk gene rare variants were independently associated with a lower rate of LVRR at follow-up.