Prognostic Role of Myocarditis-Like Episodes and Their Treatment in Patients With Pathogenic Desmoplakin Variants
Abstract
BACKGROUND: Inflammatory, myocarditis-like episodes precede and are associated with higher risk of sustained ventricular arrhythmias and heart failure in patients with pathogenic or likely pathogenic desmoplakin (DSP) variants. Whether the recurrence and treatment of myocarditis-like episodes influence the outcomes in this population is unknown. This study aimed to assess the prognostic impact of the recurrence and treatment of myocarditis-like episodes in patients with pathogenic or likely pathogenic DSP variants. METHODS: The study was designed as an observational cohort study using all patients with pathogenic or likely pathogenic DSP variants in the DSP -ERADOS Network ( Desmopakin Specific Effort for a Rare Disease Outcome Study) enrolled at 31 institutions up until April 30, 2024. Survival from ventricular arrhythmia and heart failure end points and recurrent myocarditis-like episodes was evaluated for both first and recurrent documented myocarditis-like episodes and the impact of immunosuppressive treatment on outcomes assessed. RESULTS: A total of 1014 patients with pathogenic or likely pathogenic DSP variants (62.4% female; mean age, 40.4±17.4 years; 47.1% probands) were included. Among them, 177 individuals (17.5%) experienced ≥1 documented myocarditis-like episode, with 63 of them (35.6%) receiving immunosuppressive treatment. Immunosuppressive treatment of the first documented myocarditis-like episode was associated with reduced risk of ventricular arrhythmia and heart failure outcomes (hazard ratio, 0.18 [95% CI, 0.07–0.45]; P <0.001; and hazard ratio, 0.09 [95% CI, 0.02–0.39; P =0.001, respectively) over a median follow-up of 6.4 years (95% CI, 4.0–10.5). This risk was comparable to that of patients with no history of myocarditis-like episode but did not correlate with a reduction in recurrent episodes after completion of initial immunosuppression (hazard ratio, 0.85 [95% CI, 0.47–1.54]; P =0.599). In contrast, nonsteroidal anti-inflammatory drugs or colchicine treatment did not influence outcomes. CONCLUSIONS: Immunosuppressive treatment of myocarditis-like episodes in DSP patients was associated with improved combined ventricular arrhythmia or heart failure outcomes, supporting future prospective evaluation in DSP cohorts.
Article Details
Authors (66)
Alessio Gasperetti
Steven A. Muller
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Giovanni Peretto
Multidisciplinary Disease Unit for Myocarditis and Arrhythmogenic Cardiomyopathies, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy (G.P.).
Babken Asatryan
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Alexandros Protonotarios
Institute of Cardiovascular Science, University College London, United Kingdom (A.P., I.H., P.S., P.M.E.).
Mikael Laredo
Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France (M.L., P.-Y.T., P.C., F.A., E.G.).
Pierre-Yves Tarlet
Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France (M.L., P.-Y.T., P.C., F.A., E.G.).
Petros Syrris
Institute of Cardiovascular Science, University College London, United Kingdom (A.P., I.H., P.S., P.M.E.).
Richard T. Carrick
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Brittney Murray
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Crystal Tichnell
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Paul Scheel
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (A.G., S.A.M., B.A., R.T.C., B.M., C. Tichnell, P.S., L.A., H.C., C.A.J., N.A.G.).
Marta Gigli
Cardiothoracovascular Department, Division of Cardiology, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Italy (M.G., G.S., M.M.).
Sing-Chien Yap
Erasmus MC, Rotterdam, Netherlands
Kalliopi Pilichou
Cristina Basso
Kristen Medo
University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora (K.M., M.J., L.M., M.T.).
Max Jason
University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora (K.M., M.J., L.M., M.T.).
Valentina A. Rossi
Ardan M. Saguner
Department of Cardiology, Arrhythmia Unit, University Heart Center, University Hospital Zurich, Switzerland (V.A.R.., A.M.S., F.D.).
Firat Duru
Dominic Abrams
Boston Children's Hospital, Boston, Massachusetts, United States
Julia Cadrin-Tourigny
Research Center (S.S., P.J., S.G., I.H.-C., A.F., N.E.I., N.B., M.A., K.D., P.G.G., P.K., L.M., B.M., A.M.P., L.R., D.R., B.T., J.-C.T., J.C.-T., A.R.-P., R.T.), Montreal Heart Institute, QC, Canada.
Mattia Targetti
University of Colorado Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora (K.M., M.J., L.M., M.T.).
Maurizio Pieroni
Department of Experimental and Clinical Medicine, University of Florence, Meyer Children Hospital and Careggi University Hospital, Italy (M.P.).
Maddalena Graziosi
Cardiac Thoracic and Vascular Department, Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy (M.G., E.B.).
Elena Biagini
Cardiac Thoracic and Vascular Department, Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy (M.G., E.B.).
Philippe Charron
Sorbonne Université, AP-HP, IHU-ICAN, INSERM 1166, Hôpital Universitaire Pitié-Salpêtrière, Paris, France
Moniek Cox
Department of Cardiology, University Medical Centre Groningen, the Netherlands (M. Cox).
Michela Casella
Claudio Tondo
James S. Ware
Sanjay K. Prasad
CMR Unit, Royal Brompton and Harefield Hospitals, Part of Guy’s and St Thomas’ NHS Foundation Trust, London, UK (S.K.P.).
Leonardo Calò
Department of Cardiology, Policlinico Casilino, Rome, Italy (L. Calò).
Eric Smith
Jodie Ingles
Harikrishna Tandri
Department of Medicine, Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN (H.T.).
Flavie Ader
Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France (M.L., P.-Y.T., P.C., F.A., E.G.).
Stacey Peters
Royal Melbourne Hospital, Melbourne, Victoria, Australia (S.P., D.Z., J.R.).
Dominica Zentner
Royal Melbourne Hospital, Melbourne, Victoria, Australia (S.P., D.Z., J.R.).
Jeremy Russo
Royal Melbourne Hospital, Melbourne, Victoria, Australia (S.P., D.Z., J.R.).
Silvia Ravaro
IRCCS, Istituto Auxologico Italiano, Department of Cardiology, Cardiomyopathy Unit, Milan, Italy (S.R., L. Crotti).
Lia Crotti
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy (L.C.).
Sven Dittmann
Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Germany (S.D., E.-S.B.).
Eric Schulze-Bahr
Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, Germany (S.D., E.-S.B.).
Eric D. Carruth
Department of Genomic Health, Geisinger, Danville, PA (E.D.C.).
Vikki A. Krysov
Department of Medicine, Division of Cardiovascular Medicine, Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, CA (V.A.K., V.N.P.).
Victoria N. Parikh
Stanford Center for Inherited Cardiovascular Disease, Department of Medicine, Division of Cardiovascular Medicine, (Y.Y., K.C., D.S., A.F., B.J.F., C.C., L.W., Q.W., J.E.G., Y.H., F.B., R.H.W., A.S., A.T., R.A., M.T.W., M.M., E.A.A., V.N.P.), Stanford School of Medicine, Palo Alto, CA.
Giulio Conte
Arthur Wilde
Amsterdam UMC location University of Amsterdam, Department of Cardiology, the Netherlands (A.W.).
J. Peter van Tintelen
Division of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., J.P.v.T., A.S.J.M.t.R.).
Anneline S.J.M. te Riele
Division of Cardiology, University Medical Center Utrecht, the Netherlands (S.A.M., J.P.v.T., A.S.J.M.t.R.).
Gianfranco Sinagra
Luisa Mestroni
Department of Medicine, Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Matthew Taylor
University of Colorado, Anschutz, Medical Center, Aurora
Marco Merlo
Luigi Adamo
Hugh Calkins
Johns Hopkins University, Baltimore
Barbara Bauce
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Italy (K.P., C.B., B.B.).
Elena Arbelo
Arrhythmia Section, Department of Cardiology, Institut Clínic Cardiovascular (ICCV), Hospital Clínic de Barcelona, Universitat de Barcelona & Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Catalunya, Spain (I.R.-L, P.G., S.V.-C., J.T.O-P, J.-B.G., M.R.-C., E.G., J.-M.T., E.A., P.S.-S., L.Q., R.B., R.D., M.N., J.B., L.M., A.P.-S.).
Perry M. Elliott
Institute of Cardiovascular Science, University College London, United Kingdom (A.P., I.H., P.S., P.M.E.).
Estelle Gandjbakhch
Sorbonne Université, AP-HP, IHU-ICAN, Groupe Hospitalier Pitié-Salpêtrière, Institut de Cardiologie, Paris, France (M.L., P.-Y.T., P.C., F.A., E.G.).
Neal Lakdawala
Brigham and Women's Hospital, Boston, Massachusetts, United States
Adam Helms
UNIVERSITY OF MICHIGAN, Ann Arbor, Michigan, United States
Cynthia A. James
Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (A.G., C.A.J., H.C., N.A.G.).
Nisha A. Gilotra
Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (A.G., C.A.J., H.C., N.A.G.).