Key result
RBM20 cardiomyopathy carries severe risk, with ~34% reaching major adverse events over 5 years.
Why the study?
Patients with RBM20-associated cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death, and progressive heart failure, but genotype-phenotype correlations and clinical outcomes require further investigation.
Does the presence of a pathogenic or likely pathogenic RBM20 variant increase the risk of malignant arrhythmias and heart failure in patients with cardiomyopathy compared to matched DCM controls?
Cohort (n=62)
Yes
Does the presence of a pathogenic or likely pathogenic RBM20 variant increase the risk of malignant arrhythmias and heart failure in patients with cardiomyopathy compared to matched DCM controls?
Patients with RBM20-associated cardiomyopathy exhibit a severe phenotype with a high incidence of ventricular arrhythmias, particularly in males, highlighting the need for careful risk stratification.
May support intensified surveillance in RBM20 cardiomyopathy, especially males; leaves open whether genotype-specific interventions improve outcomes.
Background Patients with RBM20 cardiomyopathy commonly experience malignant arrhythmias, sudden cardiac death (SCD), and progressive heart failure (HF). Objective The aim of this study is to investigate genotype-phenotype correlations, clinical outcomes and causes of death in patients with RBM20-associated cardiomyopathy in a multicenter cohort, combined with an overview of the current literature. Methods This international, multicenter cohort included all patients with cardiomyopathy who had a pathogenic (P) or likely pathogenic (LP) RBM20 variant. For survival and regression analysis, we matched a control group based on sex, age, and presence of left ventricular dysfunction. Additionally, we conducted a literature search on studies investigating RBM20-associated cardiomyopathy. Results Sixty-two patients (45% male) were included in the study, with a mean age of 42 ± 15 years at presentation. Of the LP/P RBM20 variants identified, 9 were novel. Eleven variants were truncating, while the remaining variants consisted of missense and splice-site variants. Patients with a truncating variant who developed HF were on average older at the time of diagnosis compared to patients with missense variants (mean age 62 ± 9 vs. 45 ± 14; p=0.01). After a median follow-up duration of 5.0 [1.0 – 10.5] years, 21 (34%) patients reached the composite endpoint of ventricular arrhythmias (VA), implantable cardioverter-defibrillator therapy, heart transplantation (HTx), left ventricular assist device (LVAD) implantation, or cardiovascular death. Of these, 19 (31%) patients experienced malignant VA (mean age 45 ± 15 years, 63% males). Males were at 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 with a total of 678 patients, of whom 53% were male. In these studies, 123 (24%) patients experienced a VA, 58 (12%) underwent HTx or were treated with LVAD, and 52 (11%) died. Conclusion In this multicenter study the patients carrying a LP/P variant in RBM20 variants had a severe phenotype, with a high incidence of VA, particularly in males. Additionally, this study presents 9 novel DNA variants, of which 8 were truncating, and were mainly observed in older individuals. Finally, we report a lower mortality rate compared to the literature, possibly due to a higher number of heart transplantations performed in our patient cohort.
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Tukker et al. (2024) conducted a cohort in RBM20-associated cardiomyopathy (n=62). Pathogenic or likely pathogenic RBM20 variants vs. Matched DCM patients without genetic variants (for survival analysis) / Unexposed reference was evaluated on Composite of sustained ventricular arrhythmia, appropriate ICD therapy, heart transplantation, and cardiovascular death. Patients with RBM20-associated cardiomyopathy exhibited a severe phenotype, with 34% reaching the composite endpoint of malignant arrhythmias, heart failure, or death over 5 years, and males at significantly higher risk.
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