Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction

Enrico Ammirati, Giacomo Veronese, Michela Brambatti, M. Merlo, Manlio Cipriani, Luciano Potena, P. Sormani, Tatsuo Aoki, Koichiro Sugimura, Akinori Sawamura, Takahiro Okumura, Sean Pinney, Kimberly Hong, P. Shah, Öscar Braun, Caroline M. Van de Heyning, Santiago Montero, Duccio Petrella, Florent Huang, Matthieu SchmidtClaudia Raineri, Anuradha Lala, Marisa Varrenti, Alberto Foà, Ornella Leone, P. Gentile, Jessica Artico, Valentina Agostini, R. Patel, Andrea Garascia, Emeline M. Van Craenenbroeck, K. Hirose, Akihiro Isotani, Toyoaki Murohara, Yoh Arita, Alessandro Sionis, Enrico Fabris, Sherin Hashem, Victor Garcia-Hernando, Fabrizio Oliva, B. Greenberg, Hiroaki Shimokawa, Gianfranco Sinagra, Eric D. Adler, M. Frigerio, Paolo G. Camici

Research output: Contribution to journalArticle

Abstract

Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Original languageEnglish
Pages (from-to)299-311
Number of pages13
JournalJournal of the American College of Cardiology
Volume74
Issue number3
DOIs
Publication statusPublished - Jul 23 2019

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Myocarditis
Left Ventricular Dysfunction
Heart Transplantation
Registries
Giant Cells
Tertiary Care Centers

Keywords

  • acute myocarditis
  • endomyocardial biopsy
  • eosinophilic myocarditis
  • fulminant myocarditis
  • giant cell myocarditis
  • outcome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction. / Ammirati, Enrico; Veronese, Giacomo; Brambatti, Michela; Merlo, M.; Cipriani, Manlio; Potena, Luciano; Sormani, P.; Aoki, Tatsuo; Sugimura, Koichiro; Sawamura, Akinori; Okumura, Takahiro; Pinney, Sean; Hong, Kimberly; Shah, P.; Braun, Öscar; Van de Heyning, Caroline M.; Montero, Santiago; Petrella, Duccio; Huang, Florent; Schmidt, Matthieu; Raineri, Claudia; Lala, Anuradha; Varrenti, Marisa; Foà, Alberto; Leone, Ornella; Gentile, P.; Artico, Jessica; Agostini, Valentina; Patel, R.; Garascia, Andrea; Van Craenenbroeck, Emeline M.; Hirose, K.; Isotani, Akihiro; Murohara, Toyoaki; Arita, Yoh; Sionis, Alessandro; Fabris, Enrico; Hashem, Sherin; Garcia-Hernando, Victor; Oliva, Fabrizio; Greenberg, B.; Shimokawa, Hiroaki; Sinagra, Gianfranco; Adler, Eric D.; Frigerio, M.; Camici, Paolo G.

In: Journal of the American College of Cardiology, Vol. 74, No. 3, 23.07.2019, p. 299-311.

Research output: Contribution to journalArticle

Ammirati, E, Veronese, G, Brambatti, M, Merlo, M, Cipriani, M, Potena, L, Sormani, P, Aoki, T, Sugimura, K, Sawamura, A, Okumura, T, Pinney, S, Hong, K, Shah, P, Braun, Ö, Van de Heyning, CM, Montero, S, Petrella, D, Huang, F, Schmidt, M, Raineri, C, Lala, A, Varrenti, M, Foà, A, Leone, O, Gentile, P, Artico, J, Agostini, V, Patel, R, Garascia, A, Van Craenenbroeck, EM, Hirose, K, Isotani, A, Murohara, T, Arita, Y, Sionis, A, Fabris, E, Hashem, S, Garcia-Hernando, V, Oliva, F, Greenberg, B, Shimokawa, H, Sinagra, G, Adler, ED, Frigerio, M & Camici, PG 2019, 'Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction', Journal of the American College of Cardiology, vol. 74, no. 3, pp. 299-311. https://doi.org/10.1016/j.jacc.2019.04.063
Ammirati, Enrico ; Veronese, Giacomo ; Brambatti, Michela ; Merlo, M. ; Cipriani, Manlio ; Potena, Luciano ; Sormani, P. ; Aoki, Tatsuo ; Sugimura, Koichiro ; Sawamura, Akinori ; Okumura, Takahiro ; Pinney, Sean ; Hong, Kimberly ; Shah, P. ; Braun, Öscar ; Van de Heyning, Caroline M. ; Montero, Santiago ; Petrella, Duccio ; Huang, Florent ; Schmidt, Matthieu ; Raineri, Claudia ; Lala, Anuradha ; Varrenti, Marisa ; Foà, Alberto ; Leone, Ornella ; Gentile, P. ; Artico, Jessica ; Agostini, Valentina ; Patel, R. ; Garascia, Andrea ; Van Craenenbroeck, Emeline M. ; Hirose, K. ; Isotani, Akihiro ; Murohara, Toyoaki ; Arita, Yoh ; Sionis, Alessandro ; Fabris, Enrico ; Hashem, Sherin ; Garcia-Hernando, Victor ; Oliva, Fabrizio ; Greenberg, B. ; Shimokawa, Hiroaki ; Sinagra, Gianfranco ; Adler, Eric D. ; Frigerio, M. ; Camici, Paolo G. / Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction. In: Journal of the American College of Cardiology. 2019 ; Vol. 74, No. 3. pp. 299-311.
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abstract = "Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3{\%} female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0{\%} vs. 1.8{\%}, p = 0.0001) and at 7-year follow-up (47.7{\%} vs. 10.4{\%}, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5{\%} vs. 0{\%}, p = 0.005) and at 7-year follow up (41.4{\%} vs. 3.1{\%}, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.",
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author = "Enrico Ammirati and Giacomo Veronese and Michela Brambatti and M. Merlo and Manlio Cipriani and Luciano Potena and P. Sormani and Tatsuo Aoki and Koichiro Sugimura and Akinori Sawamura and Takahiro Okumura and Sean Pinney and Kimberly Hong and P. Shah and {\"O}scar Braun and {Van de Heyning}, {Caroline M.} and Santiago Montero and Duccio Petrella and Florent Huang and Matthieu Schmidt and Claudia Raineri and Anuradha Lala and Marisa Varrenti and Alberto Fo{\`a} and Ornella Leone and P. Gentile and Jessica Artico and Valentina Agostini and R. Patel and Andrea Garascia and {Van Craenenbroeck}, {Emeline M.} and K. Hirose and Akihiro Isotani and Toyoaki Murohara and Yoh Arita and Alessandro Sionis and Enrico Fabris and Sherin Hashem and Victor Garcia-Hernando and Fabrizio Oliva and B. Greenberg and Hiroaki Shimokawa and Gianfranco Sinagra and Adler, {Eric D.} and M. Frigerio and Camici, {Paolo G.}",
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TY - JOUR

T1 - Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction

AU - Ammirati, Enrico

AU - Veronese, Giacomo

AU - Brambatti, Michela

AU - Merlo, M.

AU - Cipriani, Manlio

AU - Potena, Luciano

AU - Sormani, P.

AU - Aoki, Tatsuo

AU - Sugimura, Koichiro

AU - Sawamura, Akinori

AU - Okumura, Takahiro

AU - Pinney, Sean

AU - Hong, Kimberly

AU - Shah, P.

AU - Braun, Öscar

AU - Van de Heyning, Caroline M.

AU - Montero, Santiago

AU - Petrella, Duccio

AU - Huang, Florent

AU - Schmidt, Matthieu

AU - Raineri, Claudia

AU - Lala, Anuradha

AU - Varrenti, Marisa

AU - Foà, Alberto

AU - Leone, Ornella

AU - Gentile, P.

AU - Artico, Jessica

AU - Agostini, Valentina

AU - Patel, R.

AU - Garascia, Andrea

AU - Van Craenenbroeck, Emeline M.

AU - Hirose, K.

AU - Isotani, Akihiro

AU - Murohara, Toyoaki

AU - Arita, Yoh

AU - Sionis, Alessandro

AU - Fabris, Enrico

AU - Hashem, Sherin

AU - Garcia-Hernando, Victor

AU - Oliva, Fabrizio

AU - Greenberg, B.

AU - Shimokawa, Hiroaki

AU - Sinagra, Gianfranco

AU - Adler, Eric D.

AU - Frigerio, M.

AU - Camici, Paolo G.

PY - 2019/7/23

Y1 - 2019/7/23

N2 - Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

AB - Background: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. Objectives: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. Results: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). Conclusions: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

KW - acute myocarditis

KW - endomyocardial biopsy

KW - eosinophilic myocarditis

KW - fulminant myocarditis

KW - giant cell myocarditis

KW - outcome

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