Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis
Abstract
BACKGROUND: No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS: In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS: Median age at presentation was 48 years (first to third quartile, 34–59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%–48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis–associated form (13.1%) at 3 years ( P =0.15). CONCLUSIONS: Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06447935.
Article Details
Authors (88)
Enrico Ammirati
De Gasperis Cardio Center and Transplant Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy (E.A., G. Colombo, S.N., F.A., A.G., M.G.M.).
Matteo Palazzini
De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy (E.A., M.P., P.G., A.G.).
Jukka Lehtonen
Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland (J.L.).
Luciano Potena
Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy (L.P., A. Foà).
Mikko I. Mäyränpää
Department of Pathology, University of Helsinki, and Diagnostic Center, Helsinki University Hospital, Finland (M.I.M.).
Johanna Rågback
Internal Medicine, Helsinki University Hospital and University of Helsinki, Finland (J.R.).
Alberto Foà
Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy (L.P., A. Foà).
Aitor Uribarri
Cardiology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain (A.U., M.V.-B.).
Holger Thiele
Department of Internal Medicine–Cardiology, Heart Center at Leipzig University, Leipzig, Germany
María Vidal-Burdeus
Cardiology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain (A.U., M.V.-B.).
Anne Freund
Heart Center Leipzig at Leipzig University and Leipzig Heart Science, Germany (H.T., A. Freund).
Finn Gustafsson
Carsten Tschöpe
Department of Cardiology, Angiology, and Intensive Medicine (CVK), German Heart Center at Charité (DHZC); and German Center for Cardiovascular Research (DZHK), partner site Berlin, Germany (C.T.).
Ahmed Elsanhoury
Berlin Institute of Health at Charité (BIH), Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Germany (C.T., A.E.).
Joshua Ihle
Intensive Care Unit, Alfred Hospital, Melbourne, Australia (J.I., M.K.).
Wolf-Stephan Rudi
Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munchen, Germany (W.-S.R., U.G.).
Ulrich Grabmaier
Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-Universität, Munchen, Germany (W.-S.R., U.G.).
Marco Merlo
Vojtěch Melenovský
Ivana Weislova
Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic (V.M., I.W.).
Stefanie Jellinghaus
Department of Internal Medicine and Cardiology, Heart Centre Dresden, University Hospital, Technische Universität Germany (S.J., A.L.).
Axel Linke
University Hospital, Dresden, Germany
Chiara Baldovini
Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy (C.B.).
Rachele Adorisio
Heart Failure, Transplant and Mechanical Assist Device Unit, IRCCS Bambino Gesù Children’s Hospital, Roma, Italy (A.F., G.I., A.A., R.A.).
Petr Kuchynka
Second Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic (P.K., T.P.).
Tomáš Paleček
Second Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic (P.K., T.P.).
Jan Krejčí
Hana Poloczková
Anna Laura Caterino
Azienda ULSS Numero 2 Treviso, Italy (A.L.C.).
Nisha A. Gilotra
Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (A.G., C.A.J., H.C., N.A.G.).
Jana P. Lovell
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.G., J.P.L.).
Elaine P. Macomb
Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL (E.P.M., J.S., L.T.C.).
Jeffrey Shih
Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL (E.P.M., J.S., L.T.C.).
Kimberly Hong
Department of Cardiology, University of California San Diego, La Jolla (K.H., E.D.A.).
Valentina A. Rossi
Frank Ruschitzka
Claudio Cavallini
Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy (C.C., C.R.).
Clara Riccini
Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy (C.C., C.R.).
Mohamed Kamal
Intensive Care Unit, Alfred Hospital, Melbourne, Australia (J.I., M.K.).
Florent Huang
ACTION Study Group, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, La Pitié-Salpêtrière Hospital, Department of Cardiology, France (F.H.).
Matthieu Groh
Université de Versailles St-Quentin-en-Yvelines, Montigny-le-Bretonneux, France (M.G).
Piero Gentile
De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy (E.A., M.P., P.G., A.G.).
Andrea Garascia
De Gasperis Cardio Center and Transplant Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy (E.A., G. Colombo, S.N., F.A., A.G., M.G.M.).
Anuradha Lala
Hiroaki Shimokawa
Tohoku University Graduate School of Medicine, Sendai, Japan (H.S.).
Christophe Vandenbriele
Cardiology and Cardiac Intensive Care, Heart Center, OLV Hospital Aalst, Belgium (C.V.).
Alessandro Sionis
Cardiology Department, Hospital de la Santa Creu I Sant Pau, IIB-SantPau, Universidad Autónoma de Barcelona, Spain (A.S.).
Matthieu Schmidt
Sorbonne Université, UMRS 1166, Institute of Cardiometabolism and Nutrition, Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, France (M.S.).
Aurelia Grosu
Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy (A.G.).
Entela Bollano
Annalisa Turco
Maria G. Crespo-Leiro
Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain (A.S., M.G.C.-L., D.C.-M., M.M.-S., F.D.).
David Couto-Mallon
Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain (A.S., M.G.C.-L., D.C.-M., M.M.-S., F.D.).
Antonio Cannata
King’s College Hospital, London
Daniel I. Bromage
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King’s College London, UK (A.C., D.I.B.).
Maria Lucia Narducci
Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (M.L.N.).
Vincenzo Cicchitti
Intensive Cardiac Care unit and Cardiology Unit, Heart Department, SS. Annunziata Hospital, Chieti, Italy (V.C., U.I.).
Umberto Ianni
Intensive Cardiac Care unit and Cardiology Unit, Heart Department, SS. Annunziata Hospital, Chieti, Italy (V.C., U.I.).
Leonardo De Luca
Raffaella Mistrulli
Division of Cardiology, A.O. San Camillo-Forlanini, and Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy (R.M.).
Simone Frea
Division of Cardiology, Cardiovascular and Thoracic Department Città della Salute e della Scienza Hospital, Turin, Italy (S.F., C.R.).
Claudia Raineri
Division of Cardiology, Cardiovascular and Thoracic Department Città della Salute e della Scienza Hospital, Turin, Italy (S.F., C.R.).
Jan W. Schroeder
Unit of Allergology and Immunology, Niguarda Hospital, Milan, Italy (J.W.S.).
Anibal Martin Arias
Servicio de Cardiología, Hospital Italiano de Buenos Aires, Argentina (A.M.A.).
Michele Emdin
Marco Corda
Cardiology Division, Azienda di Rilievo Nazionale e Alta Specializzazione “G. Brotzu,” Cagliari, Italy (M.C., D.P.).
Daniele Pasqualucci
Cardiology Division, Azienda di Rilievo Nazionale e Alta Specializzazione “G. Brotzu,” Cagliari, Italy (M.C., D.P.).
Simon Greulich
Department of Cardiology and Angiology (S.G., M.G.), University Hospital Tübingen, Germany.
Meinrad Gawaz
Tatiana Manuylova
Cardiopathology, Institute for Pathology (T.M., K.K.), University Hospital Tübingen, Germany.
Manuel Martínez-Sellés
Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain (A.S., M.G.C.-L., D.C.-M., M.M.-S., F.D.).
Francisco José Hernández Pérez
Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain (F.J.H.P., A.M.C., F.D.).
Alba Martín Centellas
Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain (F.J.H.P., A.M.C., F.D.).
Fernando Dominguez
Antoine Gaillet
Medical Intensive Care Unit, Hôpitaux Universitaires Henri Mondor, Assistance Publique Hôpitaux de Paris, Créteil, France (A.G.).
Nicoletta D’Alessandris
Department of Woman and Child’s Health and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (N.D.).
Cory Trankle
Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA (C.T.).
Marc K. Halushka
Institute of Pathology and Laboratory Medicine, Cleveland Clinic, OH (M.K.H.).
Francesco Moroni
Antonio Abbate
Cristina Basso
Gianfranco Sinagra
Giacomo Veronese
Pediatric Intensive Care Unit, ASST Papa Giovanni XXIII, Bergamo, Italy (G.V., I.P., G.B.C., E.B.).
Paolo G. Camici
IRCCS San Raffaele Hospital, Milano, Italy (P.G.C.).
Eric D. Adler
Department of Cardiology, University of California San Diego, La Jolla (K.H., E.D.A.).
Davide P. Bernasconi
Bicocca Bioinformatics Biostatistics and Bioimaging (B4) Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy (D.P.B.).
Karin Klingel
Leslie T. Cooper
Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL (E.P.M., J.S., L.T.C.).