Scientific Sessions 2024  /  Cutting Edge Clinical Cardiomyopathies Research  /  The Impact of Genotype in Dilated and Arrhythmogenic Cardiomyopathy: Insights from the SHaRE Registry
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Final ID: 4137272

The Impact of Genotype in Dilated and Arrhythmogenic Cardiomyopathy: Insights from the SHaRE Registry

Abstract Body (Do not enter title and authors here): Background:
The impact of genotype on the risk of arrhythmia and heart failure in dilated and arrhythmogenic cardiomyopathy (DCM/ACM) is not well defined. Better understanding of genetic risk factors is needed to improve patient risk stratification, management, and outcomes.

Methods:
In this observational study, we leveraged the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) to analyze the effect of arrhythmic gene variants on clinical events in patients with DCM/ACM (excluding arrhythmogenic right ventricular cardiomyopathy). Patients were stratified by the presence of pathogenic variants in 8 genes most commonly associated with ACM (AR(+): LMNA, DSP, FLNC, RBM20, PLN, SCN5A, DES, and TMEM43). We assessed for risk of clinical events including ventricular arrhythmia (VA), atrial fibrillation (AF), heart failure (HF), death, and the overall composite of any of these events. Analyses were adjusted for age at diagnosis, sex, and baseline left ventricular ejection fraction (EF). Patients were also stratified by EF ≥50% in subgroup analyses.

Results:
A total of 1373 genotyped adults with DCM/ACM from 6 centers were included with median follow-up of 5.5 (IQR 2.4-10.4) years. Mean diagnosis age was 48 (± 15) years, and 39.5% were female. The cohort included 185 (13.5%) AR(+) patients. AR(+) compared to genotype-negative patients (N=486, 35.4%) had increased risk of VA (HR 5.02, 95% CI 3.46-7.29) and AF (HR 3.02, 95% CI 2.20-4.10). Risk of HF (HR 2.32, 95% CI 1.55-3.49) and the overall composite (HR 2.12, 95% CI 1.68-2.67) were also increased (Figure). Risk of each event remained significant after adjusting for age, sex, and baseline EF (Table). AR(+) patients with EF ≥50% also had increased risk of VA (HR 4.56, 95% CI 2.16-9.63), AF (HR 2.94, 95% CI 1.72-5.03), and the overall composite (HR 2.15, 95% CI 1.41-3.28).

Conclusions:
Genetic testing enables powerful risk stratification for both arrhythmias and heart failure in DCM/ACM independent of age, sex, or EF.
  • Padalia, Kishan  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Khan, Sadiya  ( Northwestern University , Oak Park , Illinois , United States )
  • Lakdawala, Neal  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Olivotto, Iacopo  ( Careggi University Hospital , Florence , Italy )
  • Owens, Anjali  ( UNIVERSITY OF PENN , Walliford , Pennsylvania , United States )
  • Prasad, Sanjay  ( ROYAL BROMPTON HOSPITAL , London , United Kingdom )
  • Axelsson, Anna  ( Rigshospitalet , Copenhagen , Denmark )
  • Reza, Nosheen  ( Perelman School of Medicine at the University of Pennsylvania , Philadelphia , Pennsylvania , United States )
  • Shore, Supriya  ( UNIVERSITY OF MICHIGAN , Ann Arbor , Michigan , United States )
  • Sinagra, Gianfranco  ( University of Trieste , Trieste , Italy )
  • Tayal, Upasana  ( Royal Brompton Hospital , London , United Kingdom )
  • Slaven, Sarah  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Verdonschot, Job  ( Maastricht University Medical Centr , Maastricht , Netherlands )
  • Wheeler, Matthew  ( Stanford University , Palo Alto , California , United States )
  • Taylor, Matthew  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Merlo, Marco  ( University of Trieste , Trieste , Italy )
  • Fornaro, Alessandra  ( Careggi University Hospital , Florence , Italy )
  • Parikh, Victoria  ( Stanford University , San Francisco , California , United States )
  • Wilsbacher, Lisa  ( NORTHWESTERN UNIVERSITY , Chicago , Illinois , United States )
  • Mestroni, Luisa  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Medo, Kristen  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Graw, Sharon  ( University of Colorado Anschutz , Aurora , United States Minor Outlying Islands )
  • Claggett, Brian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Bundgaard, Henning  ( NATIONAL UNIVERSITY HOSPITAL , Copenhagen , Denmark )
  • Helms, Adam  ( UNIVERSITY OF MICHIGAN , Ann Arbor , Michigan , United States )
  • Heymans, Stephane  ( Maastricht University Medical Centr , Maastricht , Netherlands )
  • Ho, Carolyn  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
    • Author Disclosures:
    Kishan Padalia: DO NOT have relevant financial relationships | Sadiya Khan: DO NOT have relevant financial relationships | Neal Lakdawala: DO have relevant financial relationships ; Research Funding (PI or named investigator):BMS:Active (exists now) ; Consultant:Lexeo:Past (completed) ; Consultant:Solid Biosciences:Past (completed) ; Consultant:Alexion:Active (exists now) ; Consultant:Nuevocore:Active (exists now) ; Consultant:Akros:Active (exists now) ; Consultant:Tenaya:Active (exists now) ; Consultant:Cytokinetics:Active (exists now) ; Consultant:Pfizer:Active (exists now) ; Consultant:BMS:Active (exists now) ; Research Funding (PI or named investigator):Pfizer:Active (exists now) | Iacopo Olivotto: No Answer | Anjali Owens: DO have relevant financial relationships ; Consultant:BMS:Active (exists now) ; Consultant:corvista:Active (exists now) ; Consultant:stealth:Active (exists now) ; Consultant:Edgewise:Active (exists now) ; Consultant:Alexion:Active (exists now) ; Consultant:Lexicon:Active (exists now) ; Consultant:Lexeo:Active (exists now) ; Consultant:Tenaya:Active (exists now) ; Consultant:biomarin:Active (exists now) ; Consultant:Cytokinetics:Active (exists now) | Sanjay Prasad: No Answer | Anna Axelsson: DO NOT have relevant financial relationships | Nosheen Reza: DO have relevant financial relationships ; Advisor:American Regent:Past (completed) ; Advisor:Bristol Myers Squibb:Past (completed) ; Research Funding (PI or named investigator):Bristol Myers Squibb:Active (exists now) ; Advisor:Roche Diagnostics:Past (completed) ; Speaker:Zoll:Past (completed) | Supriya Shore: DO NOT have relevant financial relationships | Gianfranco sinagra: DO NOT have relevant financial relationships | Upasana Tayal: DO NOT have relevant financial relationships | Sarah Slaven: DO NOT have relevant financial relationships | Job Verdonschot: DO NOT have relevant financial relationships | Matthew Wheeler: DO have relevant financial relationships ; Research Funding (PI or named investigator):BMS:Active (exists now) ; Research Funding (PI or named investigator):Astra Zeneca:Active (exists now) ; Consultant:Leal Tx:Past (completed) ; Research Funding (PI or named investigator):Salubris Bio:Active (exists now) ; Research Funding (PI or named investigator):Cytokinetics:Active (exists now) | Matthew Taylor: DO NOT have relevant financial relationships | Marco Merlo: No Answer | Alessandra Fornaro: No Answer | Victoria Parikh: DO have relevant financial relationships ; Consultant:BioMarin:Active (exists now) ; Advisor:Constantiam Biosciences:Active (exists now) ; Consultant:Nuevocor:Active (exists now) ; Consultant:Viz.ai:Active (exists now) ; Consultant:Lexeo Therapeutics:Active (exists now) | Lisa Wilsbacher: DO NOT have relevant financial relationships | Luisa Mestroni: No Answer | Kristen Medo: DO NOT have relevant financial relationships | Sharon Graw: No Answer | Brian Claggett: DO have relevant financial relationships ; Consultant:Cardior:Active (exists now) ; Consultant:Eli Lilly:Active (exists now) ; Consultant:CVRx:Past (completed) ; Consultant:Intellia:Active (exists now) ; Consultant:Cytokinetics:Past (completed) ; Consultant:Cardurion:Active (exists now) | Henning Bundgaard: DO NOT have relevant financial relationships | Adam Helms: DO have relevant financial relationships ; Consultant:Tenaya Therapeutics:Active (exists now) ; Consultant:Bristol Myers Squibb:Active (exists now) ; Consultant:Lexeo Therapeutics:Active (exists now) ; Research Funding (PI or named investigator):Tenaya Therapeutics:Active (exists now) | Stephane Heymans: No Answer | Carolyn Ho: DO have relevant financial relationships ; Consultant:Bristol Myers Squib:Active (exists now) ; Consultant:viz.ai:Active (exists now) ; Consultant:Lexicon:Active (exists now) ; Research Funding (PI or named investigator):Tenaya:Active (exists now) ; Consultant:Tenaya:Active (exists now) ; Research Funding (PI or named investigator):Biomarin:Active (exists now) ; Consultant:Biomarin:Active (exists now) ; Research Funding (PI or named investigator):Cytokinetics:Active (exists now) ; Consultant:Cytokinetics:Active (exists now) ; Research Funding (PI or named investigator):Bristol Myers Squib:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Cutting Edge Clinical Cardiomyopathies Research

Sunday, 11/17/2024 , 08:00AM - 09:15AM

Abstract Oral Session

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