Integrated role of cardiac magnetic resonance and genetics in predicting left ventricular reverse remodelling in dilated and non-dilated cardiomyopathy

Martina Setti; Manuela Iseppi; Job A J Verdonschot; Jacopo G Rizzi; Alessia Paldino; Carola Pio Loco Detto Gava; Giulia Barbati; Matteo Dal Ferro; Max F G H M Venner; Anne G Raafs; Marta Gigli; Davide Stolfo; Antonio De Luca; Giulia De Angelis; Teresa M Capovilla; Sharon Graw; Flavio L Ribichini; Matthew Taylor; Luisa Mestroni; Stephane R B Heymans; Gianfranco Sinagra; Marco Merlo

doi:10.1002/ejhf.3671

Integrated role of cardiac magnetic resonance and genetics in predicting left ventricular reverse remodelling in dilated and non-dilated cardiomyopathy

Eur J Heart Fail. 2025 Apr 29. doi: 10.1002/ejhf.3671. Online ahead of print.

Authors

Martina Setti^#^{1

2

3}, Manuela Iseppi^#^{1

2

4}, Job A J Verdonschot^{2

5

6}, Jacopo G Rizzi^{1

2}, Alessia Paldino^{1

2}, Carola Pio Loco Detto Gava^{1

2}, Giulia Barbati⁷, Matteo Dal Ferro^{1

2}, Max F G H M Venner^{2

5}, Anne G Raafs^{2

5

8}, Marta Gigli^{1

2}, Davide Stolfo^{1

2

9

10}, Antonio De Luca^{1

2}, Giulia De Angelis^{1

2

10}, Teresa M Capovilla^{1

2}, Sharon Graw¹¹, Flavio L Ribichini³, Matthew Taylor¹¹, Luisa Mestroni¹¹, Stephane R B Heymans^{2

5

12}, Gianfranco Sinagra^#^{1

2}, Marco Merlo^#^{1

2}

Affiliations

¹ Center for Diagnosis and Treatment of Cardiomyopathies, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy.
² European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart).
³ Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy.
⁴ Division of Cardiology, Ospedale Santa Chiara, Azienda Provinciale per i Servizi Sanitari della Provincia Autonoma di Trento, Trento, Italy.
⁵ Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
⁶ Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
⁷ Biostatistics Unit, University of Trieste, Trieste, Italy.
⁸ Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands.
⁹ Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Cardiothoracic Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), University Hospital of Udine, Udine, Italy.
¹¹ Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹² Center of Cardiovascular Research, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.

^# Contributed equally.

PMID: 40296583
DOI: 10.1002/ejhf.3671

Abstract

Aims: Left ventricular reverse remodelling (LVRR) is a prognostic marker in patients with dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). The utility of combining late gadolinium enhancement (LGE) and genetic testing in predicting LVRR in DCM/NDLVC remains a knowledge gap. This study aimed to assess an integrated approach including LGE data and genetics to predict LVRR in DCM/NDLVC patients.

Methods and results: This multicentre observational study included DCM/NDLVC patients with: (i) baseline echocardiographic left ventricular ejection fraction (LVEF) <50%; (ii) genetic testing; (iii) baseline cardiac magnetic resonance (CMR); (iv) 12-month follow-up echocardiographic data. LVRR was defined as LVEF increase ≥10% or LVEF ≥50% (if baseline LVEF <45%) at 12 months. Outcome measures were: (i) all-cause mortality, heart transplant, or left ventricular assist device implantation (D/HT/LVAD); (ii) sudden cardiac death or major ventricular arrhythmias (SCD/MVA). Arrhythmogenic genes studied were LMNA, DSP, FLNC, and RBM20. Among 1757 DCM/NDLVC with genetic data, 616 met eligibility (462 DCM, 154 NDLVC; age 51 ± 14 years, 34% female). LVRR occurred in 314 patients (51%): 251 (54%) in DCM and 63 (41%) in NDLVC (p = 0.004). Independent predictors of LVRR within 1 year included titin truncating variants, absence of arrhythmogenic genes, and absence of LGE ring-like pattern. In patients with LVEF <35%, only the presence of LGE ring-like pattern and arrhythmogenic genes remained independently related to a lower rate of LVRR and increased SCD/MVA risk.

Conclusion: In a large genetically and CMR characterized DCM/NDLVC cohort, arrhythmogenic genotypes and LGE ring-like pattern were inversely related to LVRR, particularly in patients with LVEF <35%.

Keywords: Arrhythmogenic genes; Cardiac magnetic resonance; Dilated cardiomyopathy; Left ventricular reverse remodelling; Non dilated left ventricular cardiomyopathy; Ring‐like late gadolinium enhancement.