Magid Awadalla1, Syed S Mahmood2, John D Groarke3, Malek Z O Hassan4, Anju Nohria3, Adam Rokicki4, Sean P Murphy4, Nathaniel D Mercaldo4, Lili Zhang1, Daniel A Zlotoff5, Kerry L Reynolds6, Raza M Alvi4, Dahlia Banerji4, Shiying Liu7, Lucie M Heinzerling8, Maeve Jones-O'Connor4, Rula B Bakar4, Justine V Cohen6, Michael C Kirchberger8, Ryan J Sullivan6, Dipti Gupta9, Connor P Mulligan4, Sachin P Shah10, Sarju Ganatra10, Muhammad A Rizvi11, Gagan Sahni12, Carlo G Tocchetti13, Donald P Lawrence6, Michael Mahmoudi14, Richard B Devereux2, Brian J Forrestal15, Anant Mandawat16, Alexander R Lyon17, Carol L Chen9, Ana Barac15, Judy Hung7, Paaladinesh Thavendiranathan18, Michael H Picard7, Franck Thuny19, Stephane Ederhy20, Michael G Fradley21, Tomas G Neilan22. 1. Cardiovascular Imaging Research Center (CIRC), Department of Radiology, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 2. Cardiology Division, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, New York. 3. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 4. Cardiovascular Imaging Research Center (CIRC), Department of Radiology, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. 5. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 6. Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 7. Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. 8. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Erlangen and Nurnberg, Germany. 9. Cardiology Division, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York. 10. Cardiology Division, Lahey Hospital & Medical Center, Burlington, Massachusetts. 11. Division of Oncology and Hematology, Department of Medicine, Lehigh Valley Hospital, Allentown, Pennsylvania. 12. Cardiovascular Institute, School of Medicine, The Mount Sinai Hospital, New York, New York. 13. Department of Translational Medical Sciences and Interdepartmental Center for Clinical and Translational Sciences (CIRCET), Federico II University, Naples, Italy. 14. Faculty of Medicine, University of Southampton, Southampton, United Kingdom. 15. Cardio-Oncology Program, Department of Cardiology, Medstar Washington Hospital Center, Medstar Heart and Vascular institute, Washington, DC. 16. Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. 17. Cardio-Oncology Program, Royal Brompton Hospital and Imperial College, London, United Kingdom. 18. Ted Rogers Program in Cardiotoxicity Prevention, Peter Munk Cardiac Center, Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 19. Cardiology Division, Cardiovascular Division, Department of Medicine, Aix-Marseille Universite, Marseille, France. 20. UNICO-GRECO, Cardio-Oncology Program, Department of Cardiology, Assistance Publique-Hopitaux de Paris, Saint-Antoine Hospital, Paris, France. 21. Cardio-Oncology Program, H. Lee Moffitt Cancer Center & Research Institute and University of South Florida Division of Cardiovascular Medicine, Tampa, Florida. 22. Cardiovascular Imaging Research Center (CIRC), Department of Radiology, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: tneilan@mgh.harvard.edu.
Abstract
BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF. Crown
BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF. Crown
Authors: Daniel Lenihan; Joseph Carver; Charles Porter; Jennifer E Liu; Susan Dent; Paaladinesh Thavendiranathan; Joshua D Mitchell; Anju Nohria; Michael G Fradley; Iskra Pusic; Keith Stockerl-Goldstein; Anne Blaes; Alexander R Lyon; Sarju Ganatra; Teresa López-Fernández; Rupal O'Quinn; Giorgio Minotti; Sebastian Szmit; Daniela Cardinale; Jose Alvarez-Cardona; Giuseppe Curigliano; Tomas G Neilan; Joerg Herrmann Journal: CA Cancer J Clin Date: 2020-09-10 Impact factor: 508.702
Authors: José Luis Zamorano; Christer Gottfridsson; Riccardo Asteggiano; Dan Atar; Lina Badimon; Jeroen J Bax; Daniela Cardinale; Antonella Cardone; Elizabeth A M Feijen; Péter Ferdinandy; Teresa López-Fernández; Chris P Gale; John H Maduro; Javid Moslehi; Torbjørn Omland; Juan Carlos Plana Gomez; Jessica Scott; Thomas M Suter; Giorgio Minotti Journal: Eur J Heart Fail Date: 2020-10-02 Impact factor: 15.534
Authors: Lili Zhang; Daniel A Zlotoff; Magid Awadalla; Syed S Mahmood; Anju Nohria; Malek Z O Hassan; Franck Thuny; Leyre Zubiri; Carol L Chen; Ryan J Sullivan; Raza M Alvi; Adam Rokicki; Sean P Murphy; Maeve Jones-O'Connor; Lucie M Heinzerling; Ana Barac; Brian J Forrestal; Eric H Yang; Dipti Gupta; Michael C Kirchberger; Sachin P Shah; Muhammad A Rizvi; Gagan Sahni; Anant Mandawat; Michael Mahmoudi; Sarju Ganatra; Stephane Ederhy; Eduardo Zatarain-Nicolas; John D Groarke; Carlo G Tocchetti; Alexander R Lyon; Paaladinesh Thavendiranathan; Justine V Cohen; Kerry L Reynolds; Michael G Fradley; Tomas G Neilan Journal: Circulation Date: 2020-06-15 Impact factor: 29.690
Authors: Paaladinesh Thavendiranathan; Lili Zhang; Amna Zafar; Zsofia D Drobni; Syed S Mahmood; Marcella Cabral; Magid Awadalla; Anju Nohria; Daniel A Zlotoff; Franck Thuny; Lucie M Heinzerling; Ana Barac; Ryan J Sullivan; Carol L Chen; Dipti Gupta; Michael C Kirchberger; Sarah E Hartmann; Jonathan W Weinsaft; Hannah K Gilman; Muhammad A Rizvi; Bojan Kovacina; Caroline Michel; Gagan Sahni; Ana González-Mansilla; Antonio Calles; Francisco Fernández-Avilés; Michael Mahmoudi; Kerry L Reynolds; Sarju Ganatra; Juan José Gavira; Nahikari Salterain González; Manuel García de Yébenes Castro; Raymond Y Kwong; Michael Jerosch-Herold; Otavio R Coelho-Filho; Jonathan Afilalo; Eduardo Zataraín-Nicolás; A John Baksi; Bernd J Wintersperger; Oscar Calvillo-Arguelles; Stephane Ederhy; Eric H Yang; Alexander R Lyon; Michael G Fradley; Tomas G Neilan Journal: J Am Coll Cardiol Date: 2021-03-30 Impact factor: 24.094
Authors: Gabriel E Molina; Leyre Zubiri; Justine V Cohen; Sienna M Durbin; Laura Petrillo; Ian M Allen; Yonina R Murciano-Goroff; Michael Dougan; Molly F Thomas; Alexander T Faje; Michelle Rengarajan; Amanda C Guidon; Steven T Chen; Daniel Okin; Benjamin D Medoff; Mazen Nasrallah; Minna J Kohler; Sara R Schoenfeld; Rebecca S Karp Leaf; Meghan E Sise; Tomas G Neilan; Daniel A Zlotoff; Jocelyn R Farmer; Meghan J Mooradian; Aditya Bardia; Minh Mai; Ryan J Sullivan; Yevgeniy R Semenov; Alexandra Chloé Villani; Kerry L Reynolds Journal: Oncologist Date: 2021-03-31
Authors: Udo Hoffmann; Tomas G Neilan; Zsofia D Drobni; Raza M Alvi; Jana Taron; Amna Zafar; Sean P Murphy; Paula K Rambarat; Rayma C Mosarla; Charlotte Lee; Daniel A Zlotoff; Vineet K Raghu; Sarah E Hartmann; Hannah K Gilman; Jingyi Gong; Leyre Zubiri; Ryan J Sullivan; Kerry L Reynolds; Thomas Mayrhofer; Lili Zhang Journal: Circulation Date: 2020-10-02 Impact factor: 29.690