Acute Myocarditis Associated With Desmosomal Gene Variants

Enrico Ammirati, Francesca Raimondi, Nicolas Piriou, Loren Sardo Infirri, Saidi A. Mohiddin, Andrea Mazzanti, Chetan Shenoy, Ugo A. Cavallari, Massimo Imazio, Giovanni Donato Aquaro, Iacopo Olivotto, Patrizia Pedrotti, Neha Sekhri, Caroline M. Van de Heyning, Glenn Broeckx, Giovanni Peretto, Oliver Guttmann, Santo Dellegrottaglie, Alessandra Scatteia, Piero GentileMarco Merlo, Randal I. Goldberg, Alex Reyentovich, Christopher Sciamanna, Sabine Klaassen, Wolfgang Poller, Cory R. Trankle, Antonio Abbate, Andre Keren, Smadar Horowitz-Cederboim, Julia Cadrin-Tourigny, Rafik Tadros, Giuseppe A. Annoni, Emanuela Bonoldi, Claire Toquet, Lara Marteau, Vincent Probst, Jean Noël Trochu, Antheia Kissopoulou, Aurelia Grosu, Deni Kukavica, Alessandro Trancuccio, Cristina Gil, Giacomo Tini, Matteo Pedrazzini, Margherita Torchio, Gianfranco Sinagra, Juan Ramón Gimeno, Davide Bernasconi, Maria Grazia Valsecchi, Karin Klingel, Eric D. Adler, Paolo G. Camici, Leslie T. Cooper

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)714-727
Number of pages14
JournalJACC: Heart Failure
Issue number10
StatePublished - Oct 2022

Bibliographical note

Funding Information:
Dr Ammirati has received a grant from the Italian Ministry of Health (GR-2019-12368506) and is a consultant for Kiniksa and Cytokinetics. Dr Adler is a consultant for Abbott, Abiomed, AstraZeneca, Endotronix, Ionis, Medtronic, and Novartis; is on the board of directors of Genstem Therapeutics; and is a shareholder of Rocket Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2022 American College of Cardiology Foundation


  • acute myocarditis
  • cardiac magnetic resonance
  • desmoplakin
  • desmosomal gene variants
  • prognosis
  • Myocarditis/genetics
  • Ventricular Function, Left
  • Humans
  • Gadolinium
  • Stroke Volume
  • Young Adult
  • Troponin
  • Heart Failure
  • Retrospective Studies

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article


Dive into the research topics of 'Acute Myocarditis Associated With Desmosomal Gene Variants'. Together they form a unique fingerprint.

Cite this