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Cited by 150Viral Infections and Immunology ResearchCardiomyopathy and Myosin StudiesCardiovascular Effects of Exercise

Acute Myocarditis Associated With Desmosomal Gene Variants

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Ammirati, Enrico, Raimondi, Francesca, Piriou, Nicolas, Sardo Infirri, Loren, Mohiddin, Saidi A., Mazzanti, Andrea, Shenoy, Chetan, Cavallari, Ugo A. +46 more·2022·JACC: Heart Failure
DOI 10.1016/j.jchf.2022.06.013
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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.

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  • DGV-positive patients with myocarditis-like phenotypes are at increased risk of major ventricular arrhythmias and heart failure compared to DGV-negative patients.

    “DGV-positive patients with myocarditis-like phenotypes are at increased risk of major VAs and heart failure, as compared to DGV-negative patients [56,57,58].”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [58]

    Table 3 reports five VT/VF events in DGV-positive acute-myocarditis patients and none in DGV-negative patients, supporting the ventricular-arrhythmia comparison. But it reports no acute heart-failure episodes in the DGV-positive group versus one in the DGV-negative group, so it does not support the claimed increase in heart failure. (LLM, conf=0.93)

    Experimental — accuracy not yet measured

  • The "hot phase" of desmosomal ACM occurs more frequently in young individuals and women and is characterized by chest pain, peaks in serum cTnT, and mildly reduced or preserved cardiac function.

    “The so-called “hot phase” of desmosomal ACM occurs more frequently in young individuals and women and is characterized by chest pain, peaks in serum cTnT, and mildly reduced or preserved cardiac function [56,57,58].”

    From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [58]

    Table 1 reports a higher proportion of patients under 30 and women in the desmosomal-variant myocarditis group than in the comparison groups, although the Baseline Characteristics section says median age did not differ. That section reports chest pain as the most common presenting symptom and a median LVEF of 59%; Table 1 reports elevated troponin. The paper does not specify that the elevations were peaks in serum cTnT, so that detail is not supported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In a retrospective study of 97 patients across 23 hospitals, DSP-predominated desmosomal gene variants were identified.

    “In another retrospective study of 97 patients across 23 hospitals, mutations in DSP -predominated desmosomal gene variants were identified”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [220]

  • This subset of patients had worse prognosis.

    “with this subset of patients having worse prognosis.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [220]

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Authors
Ammirati, E., Raimondi, F., Piriou, N., Sardo Infirri, L., Mohiddin, S. A., Mazzanti, A., Shenoy, C., Cavallari, U. A., Imazio, M., Aquaro, G. D., Olivotto, I., Pedrotti, P., Sekhri, N., Van de Heyning, C. M., Broeckx, G., Peretto, G., Guttmann, O., Dellegrottaglie, S., Scatteia, A., Gentile, P., Merlo, M., Goldberg, R. I., Reyentovich, A., Sciamanna, C., Klaassen, S., Poller, W., Trankle, C. R., Abbate, A., Keren, A., Horowitz-Cederboim, S., Cadrin-Tourigny, J., Tadros, R., Annoni, G. A., Bonoldi, E., Toquet, C., Marteau, L., Probst, V., Trochu, J. N., Kissopoulou, A., Grosu, A., Kukavica, D., Trancuccio, A., Gil, C., Tini, G., Pedrazzini, M., Torchio, M., Sinagra, G., Gimeno, J. R., Bernasconi, D., Valsecchi, M. G., Klingel, K., Adler, E. D., Camici, P. G., & Cooper, L. T.
Affiliations
  • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
  • Hôpital Necker-Enfants Malades (FR)
  • Centre National de la Recherche Scientifique (FR)
  • St Bartholomew's Hospital (GB)
  • University of Pavia (IT)
  • University of Minnesota (US)
  • Ospedale Santa Maria della Misericordia di Udine (IT)
  • Fondazione Toscana Gabriele Monasterio (IT)
  • Azienda Ospedaliero-Universitaria Careggi (IT)
  • Antwerp University Hospital (BE)
  • IRCCS Ospedale San Raffaele (IT)
  • University of Trieste (IT)
  • NYU Langone Health (US)
  • University of Illinois Chicago (US)
  • Max Delbrück Center (DE)
  • Humboldt-Universität zu Berlin (DE)
  • Virginia Commonwealth University (US)
  • Montreal Heart Institute (CA)
  • Linköping University (SE)
  • Ospedale Papa Giovanni XXIII (IT)
  • Hospital Universitario Virgen de la Arrixaca (ES)
  • Ospedale Policlinico San Martino (IT)
  • IRCCS Istituto Auxologico Italiano (IT)
  • University of Milano-Bicocca (IT)
  • Universitätsklinikum Tübingen (DE)
  • University of California San Diego (US)
  • Mayo Clinic in Florida (US)
Corresponding author
  • Ammirati, Enrico
  • Cooper, Leslie T.
ORCID
Venue
JACC: Heart Failure
Publisher
Elsevier BV
Published
2022-10
Volume
10
Issue
10
Pages
714-727
ISSN
2213-1779 (ISSN-L)
DOI
10.1016/j.jchf.2022.06.013
OpenAlex
W4294898335
Cited by
150
References
35
Citations by year
2026: 41 · 2025: 45 · 2024: 35 · 2023: 26 · 2022: 3
FWCI
18.98
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Heart Failure (publishedVersion)
  • PubMed (publishedVersion)
  • ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion)
  • Institutional Research Information System (University of Udine) (submittedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders
Ministero della Salute (GR-2019-12368506)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
Keywords
acute myocarditis, recurrent myocarditis, ventricular arrhythmias, heart failure, late gadolinium enhancement, risk stratification, genetic testing, cardiovascular adverse events
MeSH terms
Gadolinium, Heart Failure, Humans, Myocarditis, Retrospective Studies, Stroke Volume, Troponin, Ventricular Function, Left, Young Adult

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