Paaladinesh Thavendiranathan1, Lili Zhang2, Amna Zafar3, Zsofia D Drobni4, Syed S Mahmood5, Marcella Cabral6, Magid Awadalla7, Anju Nohria8, Daniel A Zlotoff7, Franck Thuny9, Lucie M Heinzerling10, Ana Barac11, Ryan J Sullivan12, Carol L Chen13, Dipti Gupta13, Michael C Kirchberger14, Sarah E Hartmann3, Jonathan W Weinsaft15, Hannah K Gilman3, Muhammad A Rizvi16, Bojan Kovacina6, Caroline Michel6, Gagan Sahni17, Ana González-Mansilla18, Antonio Calles18, Francisco Fernández-Avilés18, Michael Mahmoudi19, Kerry L Reynolds12, Sarju Ganatra20, Juan José Gavira21, Nahikari Salterain González21, Manuel García de Yébenes Castro21, Raymond Y Kwong22, Michael Jerosch-Herold22, Otavio R Coelho-Filho23, Jonathan Afilalo6, Eduardo Zataraín-Nicolás18, A John Baksi24, Bernd J Wintersperger25, Oscar Calvillo-Arguelles26, Stephane Ederhy27, Eric H Yang28, Alexander R Lyon29, Michael G Fradley30, Tomas G Neilan31. 1. Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: dinesh.thavendiranathan@uhn.ca. 2. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. 3. Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA. 4. Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA; Heart and Vascular Center, Semmelweis University, Budapest, Hungary. 5. Cardiology Division, NewYork-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USA. 6. Department of Cardiology or Diagnostic Radiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 7. Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. 8. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. 9. University Mediterranean Center of Cardio-Oncology, Nord Hospital, Aix-Marseille University, Marseille, France; Groupe Méditerranéen de Cardio-Oncologie, Marseille, France; Center for CardioVascular and Nutrition Research, INRA 1260, INSERM 1263, Aix-Marseille University, Marseille, France. 10. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany. 11. Cardio-Oncology Program, MedStar Heart and Vascular Institute, Georgetown University, Washington, DC, USA. 12. Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. 13. Cardiology Division, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA. 14. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. 15. Cardiology Division, NewYork-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USA; Cardiology Division, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA. 16. Division of Oncology and Hematology, Department of Medicine, Lehigh Valley Hospital, Allentown, Pennsylvania, USA. 17. Cardiovascular Institute, Mount Sinai Hospital, New York, New York, USA. 18. Hospital General Universitario Gregorio Marañón, CIBERCV, Instituto de Salud Carlos III, Universidad Complutense de Madrid, Madrid, Spain. 19. Faculty of Medicine, University of Southampton, Southampton, United Kingdom. 20. Cardio-Oncology Program, Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA. 21. Cardio-Oncology Program, Department of Cardiology, Clínica Universidad de Navarra, Pamplona and Madrid, Spain. 22. Cardiovascular Imaging Program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA. 23. Cardiology Division, State University of Campinas, Campinas, Brazil. 24. Cardiovascular Research Centre and Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, United Kingdom. 25. Department of Medical Imaging, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. 26. Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 27. Cardio-Oncology Program, Division of Cardiology, Hôpitaux Universitaires Est Parisien, Paris, France. 28. UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA. 29. Cardio-Oncology Program, Royal Brompton Hospital, Imperial College London, London, United Kingdom. 30. Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 31. Cardiovascular Imaging Research Center, Division of Cardiology and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: tneilan@mgh.harvard.edu.
Abstract
BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.
BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.
Keywords:
Lake Louise Criteria; T1 mapping; T2 mapping; cardiovascular magnetic resonance; immune checkpoint inhibitor; major adverse cardiovascular event; myocarditis
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