Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.

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  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 101714113 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2574-8300 (Electronic) Linking ISSN: 25748300 NLM ISO Abbreviation: Circ Genom Precis Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Baltimore, MD] : Lippincott Williams & Wilkins, [2018]-
    • Subject Terms:
      Heart Failure*/genetics ; Ventricular Dysfunction, Left*/genetics; Adult ; Female ; Humans ; Male ; Arrhythmias, Cardiac ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left
    • Abstract:
      Background: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes.
      Methods: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction ( RBM20 LVSD ) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction.
      Results: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P =0.07 and P =0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P <0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20 LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P <0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point.
      Conclusions: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.
      Competing Interests: Disclosures Dr Sengupta reports speakers fees from Pfizer. Dr Elliott reports consultancies for Pfizer, Sarepta, Bristol Myers Squibb, Biomarin, Leal, and Novo Nordisk. The other authors report no conflict.
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    • Grant Information:
      K23 HL067915 United States HL NHLBI NIH HHS; R01 HL069071 United States HL NHLBI NIH HHS; R01 HL147064 United States HL NHLBI NIH HHS; R01 HL116906 United States HL NHLBI NIH HHS; R01 HL109209 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: dilated cardiomyopathy; heart failure; sudden cardiac death
    • Accession Number:
      0 (ribonucleic acid binding motif protein 20, human)
    • Publication Date:
      Date Created: 20230818 Date Completed: 20231030 Latest Revision: 20240102
    • Publication Date:
      20240102
    • Accession Number:
      PMC10581410
    • Accession Number:
      10.1161/CIRCGEN.123.004059
    • Accession Number:
      37593875