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 Gentile; Marco 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

doi:10.1016/j.jchf.2022.06.013

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

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	714-727
Number of pages	14
Journal	JACC: Heart Failure
Volume	10
Issue number	10
DOIs	https://doi.org/10.1016/j.jchf.2022.06.013
State	Published - 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

Keywords

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

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10.1016/j.jchf.2022.06.013

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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., ... Cooper, L. T. (2022). Acute Myocarditis Associated With Desmosomal Gene Variants. JACC: Heart Failure, 10(10), 714-727. https://doi.org/10.1016/j.jchf.2022.06.013

Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, SA, Mazzanti, A, Shenoy, C, Cavallari, UA, Imazio, M, Aquaro, GD, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, CM, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, RI, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, CR, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, GA, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, JN, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, JR, Bernasconi, D, Valsecchi, MG, Klingel, K, Adler, ED, Camici, PG & Cooper, LT 2022, 'Acute Myocarditis Associated With Desmosomal Gene Variants', JACC: Heart Failure, vol. 10, no. 10, pp. 714-727. https://doi.org/10.1016/j.jchf.2022.06.013

@article{865ea5abb79b40bb8fc37319bd2386fb,

title = "Acute Myocarditis Associated With Desmosomal Gene Variants",

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.",

keywords = "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",

author = "Enrico Ammirati and Francesca Raimondi and Nicolas Piriou and {Sardo Infirri}, Loren and Mohiddin, {Saidi A.} and Andrea Mazzanti and Chetan Shenoy and Cavallari, {Ugo A.} and Massimo Imazio and Aquaro, {Giovanni Donato} and Iacopo Olivotto and Patrizia Pedrotti and Neha Sekhri and {Van de Heyning}, {Caroline M.} and Glenn Broeckx and Giovanni Peretto and Oliver Guttmann and Santo Dellegrottaglie and Alessandra Scatteia and Piero Gentile and Marco Merlo and Goldberg, {Randal I.} and Alex Reyentovich and Christopher Sciamanna and Sabine Klaassen and Wolfgang Poller and Trankle, {Cory R.} and Antonio Abbate and Andre Keren and Smadar Horowitz-Cederboim and Julia Cadrin-Tourigny and Rafik Tadros and Annoni, {Giuseppe A.} and Emanuela Bonoldi and Claire Toquet and Lara Marteau and Vincent Probst and Trochu, {Jean No{\"e}l} and Antheia Kissopoulou and Aurelia Grosu and Deni Kukavica and Alessandro Trancuccio and Cristina Gil and Giacomo Tini and Matteo Pedrazzini and Margherita Torchio and Gianfranco Sinagra and Gimeno, {Juan Ram{\'o}n} and Davide Bernasconi and Valsecchi, {Maria Grazia} and Karin Klingel and Adler, {Eric D.} and Camici, {Paolo G.} and Cooper, {Leslie T.}",

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: {\textcopyright} 2022 American College of Cardiology Foundation",

year = "2022",

month = oct,

doi = "10.1016/j.jchf.2022.06.013",

language = "English (US)",

volume = "10",

pages = "714--727",

journal = "JACC: Heart Failure",

issn = "2213-1779",

publisher = "Elsevier BV",

number = "10",

}

TY - JOUR

T1 - Acute Myocarditis Associated With Desmosomal Gene Variants

AU - Ammirati, Enrico

AU - Raimondi, Francesca

AU - Piriou, Nicolas

AU - Sardo Infirri, Loren

AU - Mohiddin, Saidi A.

AU - Mazzanti, Andrea

AU - Shenoy, Chetan

AU - Cavallari, Ugo A.

AU - Imazio, Massimo

AU - Aquaro, Giovanni Donato

AU - Olivotto, Iacopo

AU - Pedrotti, Patrizia

AU - Sekhri, Neha

AU - Van de Heyning, Caroline M.

AU - Broeckx, Glenn

AU - Peretto, Giovanni

AU - Guttmann, Oliver

AU - Dellegrottaglie, Santo

AU - Scatteia, Alessandra

AU - Gentile, Piero

AU - Merlo, Marco

AU - Goldberg, Randal I.

AU - Reyentovich, Alex

AU - Sciamanna, Christopher

AU - Klaassen, Sabine

AU - Poller, Wolfgang

AU - Trankle, Cory R.

AU - Abbate, Antonio

AU - Keren, Andre

AU - Horowitz-Cederboim, Smadar

AU - Cadrin-Tourigny, Julia

AU - Tadros, Rafik

AU - Annoni, Giuseppe A.

AU - Bonoldi, Emanuela

AU - Toquet, Claire

AU - Marteau, Lara

AU - Probst, Vincent

AU - Trochu, Jean Noël

AU - Kissopoulou, Antheia

AU - Grosu, Aurelia

AU - Kukavica, Deni

AU - Trancuccio, Alessandro

AU - Gil, Cristina

AU - Tini, Giacomo

AU - Pedrazzini, Matteo

AU - Torchio, Margherita

AU - Sinagra, Gianfranco

AU - Gimeno, Juan Ramón

AU - Bernasconi, Davide

AU - Valsecchi, Maria Grazia

AU - Klingel, Karin

AU - Adler, Eric D.

AU - Camici, Paolo G.

AU - Cooper, Leslie T.

N1 - 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

PY - 2022/10

Y1 - 2022/10

N2 - 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.

AB - 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.

KW - acute myocarditis

KW - cardiac magnetic resonance

KW - desmoplakin

KW - desmosomal gene variants

KW - prognosis

KW - Myocarditis/genetics

KW - Ventricular Function, Left

KW - Humans

KW - Gadolinium

KW - Stroke Volume

KW - Young Adult

KW - Troponin

KW - Heart Failure

KW - Retrospective Studies

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U2 - 10.1016/j.jchf.2022.06.013

DO - 10.1016/j.jchf.2022.06.013

M3 - Article

C2 - 36175056

AN - SCOPUS:85138040624

SN - 2213-1779

VL - 10

SP - 714

EP - 727

JO - JACC: Heart Failure

JF - JACC: Heart Failure

IS - 10

ER -

Acute Myocarditis Associated With Desmosomal Gene Variants

Abstract

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