Acute myocarditis associated with desmosomal gene variants

Authors

Enrico Ammirati, De Gasperis Cardio Center, Niguarda Hospital, Milano, Italy. Electronic address: enrico.ammirati@ospedaleniguarda.it.
Francesca Raimondi, Centre de Référence Malformations Cardiaques Congénitales Complexes-M3C Hôpital Necker Enfants Malades, APHP Paris Cité, Paris, France.
Nicolas Piriou, Université Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.
Loren Sardo Infirri, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
Saidi A. Mohiddin, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom.
Andrea Mazzanti, Molecular Cardiology, ICS Maugeri, IRCCS, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Chetan Shenoy, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Ugo A. Cavallari, Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Hospital, Milano, Italy.
Massimo Imazio, Cardiology, Cardiothoracic Department, "Santa Maria della Misericordia," Udine, Italy.
Giovanni Donato Aquaro, Gabriele Monasterio Foundation, Pisa, Italy.Follow
Iacopo Olivotto, Cardiomyopathy Unit, Careggi University Hospital, Firenze, Italy.
Patrizia Pedrotti, De Gasperis Cardio Center, Niguarda Hospital, Milano, Italy.
Neha Sekhri, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom.
Caroline M. Van de Heyning, Antwerp University Hospital, Edegem, Belgium.
Glenn Broeckx, Antwerp University Hospital, Edegem, Belgium.
Giovanni Peretto, IRCCS San Raffaele Hospital and Vita Salute University, Milano, Italy.
Oliver Guttmann, Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom.
Santo Dellegrottaglie, Division of Cardiology, Clinica Villa dei Fiori, Acerra, Napoli, Italy.
Alessandra Scatteia, Division of Cardiology, Clinica Villa dei Fiori, Acerra, Napoli, Italy.
Piero Gentile, De Gasperis Cardio Center, Niguarda Hospital, Milano, Italy.
Marco Merlo, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy.
Randal I. Goldberg, The Leon H. Charney Division of Cardiology, NYU Langone Health, New York, New York, USA.
Alex Reyentovich, The Leon H. Charney Division of Cardiology, NYU Langone Health, New York, New York, USA.
Christopher Sciamanna, Advocate Aurora HealthFollow
Sabine Klaassen, Department of Paediatric Cardiology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
Wolfgang Poller, Department of Paediatric Cardiology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Centre for Cardiovascular Research, Berlin, Germany; Department of Cardiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany.
Cory R. Trankle, Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Antonio Abbate, Division of Cardiology, Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Andre Keren, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Smadar Horowitz-Cederboim, Hadassah Center for Cardiogenetics, Hadassah Medical Center, Jerusalem, Israel.
et al

Recommended Citation

Ammirati E, Raimondi F, Piriou N, et al. Acute Myocarditis Associated With Desmosomal Gene Variants. JACC Heart Fail. 2022;10(10):714-727. doi:10.1016/j.jchf.2022.06.013

Affiliations

Advocate Christ Medical Center Cardiothoracic and Vascular Surgical Associates

Abstract

Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.

Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.

Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.

Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM.

Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

Document Type

Article

PubMed ID

36175056