Abstract 4142400: Clinical implication and potential role of immunosuppression for myocarditis episodes in patients with desmoplakin cardiomyopathy: hope from the DSP-ERADOS Network?

Introduction: Variants in the desmoplakin (DSP) gene are associated with a form of arrhythmogenic cardiomyopathy (ACM) characterized by high risk of ventricular arrhythmias (VAs), heart failure (HF), and recurrent myocarditis. The clinical implications and management of myocarditis episodes in DSP-ACM have been scarcely investigated and are a major unmet clinical challenge. Research Question: what is the clinical impact of myocarditis episodes in DSP-ACM? Is there any role for immunosuppression? Methods: Patients (pts) with DSP-ACM in the worldwide DSP-ERADOS Network (26 institutions across 9 countries in 3 continents) were enrolled. Pts were classified as myocarditis-positive (Myo+) if they had a diagnosis of myocarditis at any time as per ESC criteria and otherwise as negative (Myo-). A multi-state model was used to compare the time-dependent risk of the outcome of interest (combined occurrence of VAs or HF hospitalization) at follow up. Hazard ratios (HR) were reported for quantifying the impact of single or repeated myocarditis on combined outcome occurrences, as well as the impact of immunosuppression. Results: A total of 801 pts (38.8±17.3 yo, 63.9% female; LVEF 49.7±14.7%; RVEF 50.1±13.2%) were enrolled. Over 3.5 [1.2–6.7] years, 153 (19.1%) patients (Myo+) experienced 260 myocarditis episodes (1.7 episode/pt; n=54 pts with 2+ episodes), 79 of which were treated with immunosuppression. A total of 193 (24.1%; 6.7%/year) pts experienced the combined end-point (n=120/648 (18.5%) Myo-; n=73/153 (47.7%) Myo+; log rank p <0.001). Occurrence of myocarditis was associated with increased risk in the composite outcome, with repeated myocarditis having a non-significant trend towards a higher risk than single events (Panel A). However, when adjusting for treatment with immunosuppressants in the Myo+ cohort, there were no differences in endpoint compared to pts in the Myo- cohort (Panel B) (Relative HR to Myo- pt: for treated Myo+ episodes: 0.76 [0.33–1.72], p=0.503; for untreated Myo+ episodes: 2.89 [2.11–3.95], p <0.001). Application: Myocarditis episodes in pts with DSP-ACM are associated with increased risk in VA/HF hospitalizations. This analysis suggests a potential benefit of immunosuppression therapy for myocarditis episodes in DSP cardiomyopathy and warrants further study. Next Steps/Future: A randomized controlled trial is needed to test the role of immunotherapy in this patient population.

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Publication Details

Journal
Circulation
Published
2024-11-12
DOI
https://doi.org/10.1161/circ.150.suppl_1.4142400
Citations
3
Primary Topic
Viral Infections and Immunology Research
Type
article
Field-Weighted Citation Impact
1.21
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article

Abstract 4142400: Clinical implication and potential role of immunosuppression for myocarditis episodes in patients with desmoplakin cardiomyopathy: hope from the DSP-ERADOS Network?

Perry Elliott, Nisha A. Gilotra, Kristen Medo, Philippe Charron et al.
3 citations
Circulation
Viral Infections and Immunology Research
1.21
article

Abstract 4142400: Clinical implication and potential role of immunosuppression for myocarditis episodes in patients with desmoplakin cardiomyopathy: hope from the DSP-ERADOS Network?

Perry Elliott, Nisha A. Gilotra, Kristen Medo, Philippe Charron, Flavie Ader, Jeremy Russo, Petros Syrris, James S. Ware, Kalliopi Pilichou, Alessio Gasperetti, Giovanni Peretto, Ardan M. Saguner, Gianfranco Sinagra, Hugh G Calkins, Iacopo Olivotto, Mikaël Laredo, Stacey Peters, Alexandros Protonotarios, Brittney Murray, Robyn J. Hylind, Matthew Taylor, Eric Carruth, Valentina A. Rossi, Dominica Zentner, Neal K. Lakdawala, Victoria Nicole Parikh, Eric D. Smith, Steven A. Muller, Barbara Bauce, Anneline Te Riele, Marco Merlo, Babken Asatryan, Luisa Mestroni, Julia Cadrin‐Tourigny, Eric Schulze Bahr, Jodie Ingles, Dominic James Abrams, Adam S. Helms, Elena Biagini, Paul J. Scheel, Richard Carrick, Luigi Adamo, J. Peter van Tintelen, Moniek G.P.J. Cox, L. A. Cal, Chris Haggerty, Cynthia A James, Arthur A. Wilde, Max Jason, Estelle Gandjbakhch
article en
3 citations

Abstract

Introduction: Variants in the desmoplakin (DSP) gene are associated with a form of arrhythmogenic cardiomyopathy (ACM) characterized by high risk of ventricular arrhythmias (VAs), heart failure (HF), and recurrent myocarditis. The clinical implications and management of myocarditis episodes in DSP-ACM have been scarcely investigated and are a major unmet clinical challenge. Research Question: what is the clinical impact of myocarditis episodes in DSP-ACM? Is there any role for immunosuppression? Methods: Patients (pts) with DSP-ACM in the worldwide DSP-ERADOS Network (26 institutions across 9 countries in 3 continents) were enrolled. Pts were classified as myocarditis-positive (Myo+) if they had a diagnosis of myocarditis at any time as per ESC criteria and otherwise as negative (Myo-). A multi-state model was used to compare the time-dependent risk of the outcome of interest (combined occurrence of VAs or HF hospitalization) at follow up. Hazard ratios (HR) were reported for quantifying the impact of single or repeated myocarditis on combined outcome occurrences, as well as the impact of immunosuppression. Results: A total of 801 pts (38.8±17.3 yo, 63.9% female; LVEF 49.7±14.7%; RVEF 50.1±13.2%) were enrolled. Over 3.5 [1.2–6.7] years, 153 (19.1%) patients (Myo+) experienced 260 myocarditis episodes (1.7 episode/pt; n=54 pts with 2+ episodes), 79 of which were treated with immunosuppression. A total of 193 (24.1%; 6.7%/year) pts experienced the combined end-point (n=120/648 (18.5%) Myo-; n=73/153 (47.7%) Myo+; log rank p <0.001). Occurrence of myocarditis was associated with increased risk in the composite outcome, with repeated myocarditis having a non-significant trend towards a higher risk than single events (Panel A). However, when adjusting for treatment with immunosuppressants in the Myo+ cohort, there were no differences in endpoint compared to pts in the Myo- cohort (Panel B) (Relative HR to Myo- pt: for treated Myo+ episodes: 0.76 [0.33–1.72], p=0.503; for untreated Myo+ episodes: 2.89 [2.11–3.95], p <0.001). Application: Myocarditis episodes in pts with DSP-ACM are associated with increased risk in VA/HF hospitalizations. This analysis suggests a potential benefit of immunosuppression therapy for myocarditis episodes in DSP cardiomyopathy and warrants further study. Next Steps/Future: A randomized controlled trial is needed to test the role of immunotherapy in this patient population.

CirculationVol. 150(Suppl_1)
Brigham and Women's Hospital (US), Boston Children's Hospital (US), Geisinger Medical Center (US), The Royal Melbourne Hospital (AU), Garvan Institute of Medical Research (AU), University of Padua (IT), Johns Hopkins University (US), Vita-Salute San Raffaele University (IT), Johns Hopkins Medicine (US), Montreal Heart Institute (CA), Amsterdam UMC Location University of Amsterdam (NL), University Medical Center Utrecht (NL), Sorbonne Université (FR), University Hospital of Zurich (CH), University Hospital Münster (DE), Azienda Ospedaliero Universitaria Ospedali Riuniti (IT), Michigan United (US), Pitié-Salpêtrière Hospital (FR), Policlinico Casilino (IT), Univé (Netherlands) (NL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Florence (IT), University College London (GB), Imperial College London (GB), University of Colorado Anschutz Medical Campus (US), Stanford University (US)
Openalex Percentile: Top 18%
Viral Infections and Immunology Research
1.21
DOISourceOpenAlex
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