Lili Zhang1,2, Magid Awadalla1,2, Syed S Mahmood3, Anju Nohria4, Malek Z O Hassan1, Franck Thuny5,6,7, Daniel A Zlotoff2, Sean P Murphy1, James R Stone8, Doll Lauren Alexandra Golden1, Raza M Alvi1, Adam Rokicki1,2, Maeve Jones-O'Connor1, Justine V Cohen9, Lucie M Heinzerling10, Connor Mulligan1, Merna Armanious11, Ana Barac12, Brian J Forrestal12, Ryan J Sullivan9, Raymond Y Kwong13, Eric H Yang14, Rongras Damrongwatanasuk11, Carol L Chen15, Dipti Gupta15, Michael C Kirchberger10, Javid J Moslehi16, Otavio R Coelho-Filho17, Sarju Ganatra18, Muhammad A Rizvi19, Gagan Sahni20, Carlo G Tocchetti21, Valentina Mercurio21, Michael Mahmoudi22, Donald P Lawrence9, Kerry L Reynolds9, Jonathan W Weinsaft3,15, A John Baksi23,24, Stephane Ederhy25, John D Groarke4, Alexander R Lyon26,27, Michael G Fradley11, Paaladinesh Thavendiranathan28, Tomas G Neilan1,2. 1. Cardiovascular Imaging Research Center (CIRC), Division of Cardiology, Department of Radiology, Massachusetts General Hospital, 165 Cambridge Street, Suite 400, Boston, MA 02114, USA. 2. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, 165 Cambridge Street, Suite 400, Boston, MA 02114, USA. 3. Cardiology Division, Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical Center, 1300 York Avenue, New York, NY 10065, USA. 4. Cardio-Oncology Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. 5. Department of Cardiology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Mediterranean university, Cardio-Oncology center (MEDI-CO center), Unit of Heart Failure and Valvular Heart Diseases, Hôpital Nord, Jardin du Pharo, 58 Boulevard Charles Livon 13007, Marseille, France. 6. Groupe Méditerranéen de Cardio-Oncologie (gMEDICO), AP-HM, Chemin des Bourrely, 13015, Marseille, France. 7. Aix-Marseille University, Center for CardioVascular and Nutrition research (C2VN), Inserm 1263, Inra 1260, 13385 Marseille, France. 8. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA. 9. Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA. 10. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany. 11. Cardio-Oncology Program, Division of Cardiovascular Medicine, H. Lee Moffitt Cancer Center & Research Institute and University of South Florida, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. 12. Cardio-Oncology program, MedStar Heart and Vascular Institute, Georgetown University, 110 Irving St NW, Washington, DC 20010, USA. 13. Noninvasive Cardiovascular Imaging Section, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. 14. UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, 757 Westwood Plaza, Los Angeles, CA 90095, USA. 15. Cardiology Division, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 1275 York Avenue, New York, NY 10065, USA. 16. Cardio-Oncology Program, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN 37232, USA. 17. Cardiology Division, State University of Campinas, Cidade Universitária Zeferino Vaz - Barão Geraldo, Campinas, São Paulo 13083-970, Brazil. 18. Cardio-Oncology Program, Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA 01805, USA. 19. Division of Oncology and Hematology, Department of Medicine, Lehigh Valley Hospital, 1200 S Cedar Crest Blvd, Allentown, PA 18103, USA. 20. Cardiology Division, The Mount Sinai Hospital, 1468 Madison Ave, New York, NY 10029, USA. 21. Department of Translational Medical Sciences, Federico II University, via S. Pansini 5, 80131 Naples, NA, Italy. 22. Faculty of Medicine, University of Southampton, University Road Southampton SO17 1BJ, UK. 23. Cardiovascular Research Centre and Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, Sydney St, Chelsea, London SW3 6NP, UK. 24. National Heart and Lung Institute, Imperial College London, Kensington, London SW7 2DD, UK. 25. UNICO-GRECO cardio-oncology program, sorbonne universite, Hopital Saint Antoine, 27 Rue de Chaligny, 75012 Paris, France. 26. Cardio-Oncology Program, Royal Brompton Hospital, Sydney St, Chelsea, London SW3 6NP, UK. 27. National Heart and Lung Institute, Imperial College London, Cale Street, Chelsea, London, SW3 6LY, United Kingdom. 28. Ted Rogers Program in Cardiotoxicity Prevention, Division of Cardiology, Toronto General Hospital, Peter Munk Cardiac Center, University of Toronto, Toronto, ON, Canada.
Abstract
AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis. Published on behalf of the European Society of Cardiology. All rights reserved.
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