PT  - JOURNAL ARTICLE
AU  - Matteo Dal Ferro
AU  - Davide Stolfo
AU  - Alessandro Altinier
AU  - Marta Gigli
AU  - Martina Perrieri
AU  - Federica Ramani
AU  - Giulia Barbati
AU  - Alberto Pivetta
AU  - Francesca Brun
AU  - Lorenzo Monserrat
AU  - Mauro Giacca
AU  - Luisa Mestroni
AU  - Marco Merlo
AU  - Gianfranco Sinagra
TI  - Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy
AID  - 10.1136/heartjnl-2016-311017
DP  - 2017 Nov 01
TA  - Heart
PG  - 1704--1710
VI  - 103
IP  - 21
4099  - http://heart.bmj.com/content/103/21/1704.short
4100  - http://heart.bmj.com/content/103/21/1704.full
SO  - Heart2017 Nov 01; 103
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.