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Original research article
Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy
  1. Matteo Dal Ferro1,
  2. Davide Stolfo1,
  3. Alessandro Altinier1,
  4. Marta Gigli1,
  5. Martina Perrieri1,
  6. Federica Ramani1,
  7. Giulia Barbati1,
  8. Alberto Pivetta1,
  9. Francesca Brun1,
  10. Lorenzo Monserrat2,
  11. Mauro Giacca3,
  12. Luisa Mestroni4,
  13. Marco Merlo1,
  14. Gianfranco Sinagra1
  1. 1 Cardiovascular Department, Azienda Sanitaria-Universitaria Integrata of Trieste “ASUITS”, Trieste, Italy
  2. 2 Department of Cardiology, Health in Code, Coruña, Spain
  3. 3 Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
  4. 4 Cardiovascular Institute, University of Colorado Denver, Denver, USA
  1. Correspondence to Dr Davide Stolfo, Cardiovascular Department, Azienda Sanitaria-Universitaria Integrata Trieste “ASUITS”, Via Valdoni 1, Trieste 34149, Italy; davide.stolfo{at}


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.

  • Clinical Genetics
  • Echocardiography
  • Idiopathic Dilated Cardiomyopathy.

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  • Contributors All authors have contributed significantly to the paper and read and approved the submission of the manuscript. In particular: MDF and DS: conception and design of paper, final approval of the manuscript; DS, MDF, MM, AA, MG, MP, FR, AP, FB, GB (statistical expert): collection, analysis and interpretation of data; DS, MDF, MM: drafting of the manuscript; LMo, LMe, MG and GS: revising critically the manuscript for important intellectual content.

  • Funding This work was supported by Fondazione CRT Trieste, Centre for Translational Cardiology (CTC) Project funding. LM is supported by the NIH grants UL1 RR025780, UL1 TR001082, R01 HL69071, R01 11 6906. This work is also supported in part by a Trans-Atlantic Network of Excellence grant from the Leducq Foundation (14-CVD 03).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Local centre-specific Ethics Committee of the Azienda Sanitaria Universitaria Integrata of Trieste.

  • Provenance and peer review Not commissioned; externally peer reviewed.