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Review
. 2025 Sep 1:434:133350.
doi: 10.1016/j.ijcard.2025.133350. Epub 2025 May 6.

High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: A multicenter cohort study and review of the literature

Martijn Tukker  1 , Wouter P Te Rijdt  2 , Ahmad S Amin  3 , Deborah J Morris-Rosendahl  4 , Alexander Hirsch  5 , Yael Ben-Haim  6 , Arjan C Houweling  7 , Amanda Varnava  8 , Elijah R Behr  6 , Matthew Edwards  9 , Alexander Vanmaele  1 , Aida Hajdarpasic  10 , Jan von der Thusen  11 , Michelle Michels  1 , Rudolf A de Boer  1 , Marjon A van Slegtenhorst  2 , Kadir Caliskan  12
Affiliations
Free article
Review

High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: A multicenter cohort study and review of the literature

Martijn Tukker et al. Int J Cardiol. .
Free article

Abstract

Background: Patients with RBM20 cardiomyopathy present with an aggressive phenotype, associated with premature malignant arrhythmias, sudden cardiac death, and progressive heart failure (HF). This study aimed to investigate genotype-phenotype correlations, clinical outcomes, and causes of death in patients with RBM20-associated cardiomyopathy and review the current literature.

Methods: The cohort included patients with cardiomyopathy harboring pathogenic (P) or likely pathogenic (LP) RBM20 variants. For survival and regression analysis, a control group matched for sex, age, and presence of left ventricular dysfunction was included. Additionally, a comprehensive literature search was conducted.

Results: Sixty-two patients (45 % male, 42 ± 15 years at presentation) were included. We found 11 truncating variants. Patients with truncating variants diagnosed with HF were older compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p = 0.01). Over a median follow-up duration of 5.0 [1.0-10.5] years, 21 (34 %) patients reached the composite endpoint, with 19 (31 %) patients experiencing malignant ventricular arrhythmia (VA) (mean age 45 ± 15 years, 63 % males). Males exhibited higher risk for the composite endpoint (log-rank p = 0.02), particularly for VA (log-rank p = 0.007). The literature review analyzed 34 studies comprising 678 patients (53 % male). In these studies, 123 (24 %) patients experienced a VA, 58 (12 %) underwent a heart transplant or were treated with LVAD, and 52 (11 %) died.

Conclusion: This multicenter study highlights the severe phenotype associated with LP/P RBM20 variants, with a high incidence of VA, particularly in males. Additionally, this study presents 11 truncating variants mainly observed in older individuals.

Keywords: Cardiomyopathy; Heart failure; RBM20 variants; Sudden cardiac death; Truncating variants; Ventricular arrhythmias.

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Conflict of interest statement

Declaration of competing interest A. Hirsch received a research grant and consultancy fees from GE Healthcare and speaker fees from GE Healthcare, Bayer, and Bristol Myers Squibb. He is also a member of the medical advisory board of Medis Medical Imaging Systems and was MRI corelab supervisor of Cardialysis BV until 2022. The institution of Dr. De Boer has received research grants and/or fees from Alnylam, AstraZeneca, Abbott, Bristol-Myers Squibb, NovoNordisk, and Roche; Dr. de Boer has had speaker engagements with and/or received fees from and/or served on an advisory board for Abbott, AstraZeneca, Bristol Myers Squibb, NovoNordisk, Roche, and Zoll; Dr. de Boer received travel support from Abbott and NovoNordisk. A Manohar acknowledges support from the American Heart Association (AHA 24POST1187968). A. Owens reports consulting for Alexion, Avidity, Bayer, Bristol Myers Squibb, Cytokinetics, Edgewise, Imbria, Corvista, BioMarin, Lexeo, Tenaya, Stealth and research grant to the institution from BMS.

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