Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy

Martina Setti; Marco Merlo; Marta Gigli; Laura Munaretto; Alessia Paldino; Davide Stolfo; Carola Pio Loco; Kristen Medo; Caterina Gregorio; Antonio De Luca; Sharon Graw; Matteo Castrichini; Antonio Cannatà; Flavio Luciano Ribichini; Matteo Dal Ferro; Matthew Taylor; Gianfranco Sinagra; Luisa Mestroni

doi:10.1002/ejhf.3168

Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy

Eur J Heart Fail. 2024 Feb 26. doi: 10.1002/ejhf.3168. Online ahead of print.

Authors

Martina Setti^#^{1

2}, Marco Merlo^#¹, Marta Gigli¹, Laura Munaretto¹, Alessia Paldino¹, Davide Stolfo^{1

3}, Carola Pio Loco¹, Kristen Medo⁴, Caterina Gregorio^{5

6}, Antonio De Luca¹, Sharon Graw⁴, Matteo Castrichini^{4

7}, Antonio Cannatà^{1

8}, Flavio Luciano Ribichini², Matteo Dal Ferro¹, Matthew Taylor⁴, Gianfranco Sinagra¹, Luisa Mestroni⁴

Affiliations

¹ Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy.
² Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy.
³ Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
⁴ Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Biostatistics Unit, University of Trieste, Trieste, Italy.
⁶ MOX-Modeling and Scientific Computing Laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy.
⁷ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
⁸ Department of Cardiovascular Sciences, King's College London, London, UK.

^# Contributed equally.

PMID: 38404225
DOI: 10.1002/ejhf.3168

Abstract

Aims: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients.

Methods and results: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present.

Conclusion: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.

Keywords: Arrhythmogenic cardiomyopathy; Arrhythmogenic genotype; Dilated cardiomyopathy; Dilated cardiomyopathy with arrhythmic phenotype; Non-sustained ventricular tachycardia; Unexplained syncope.