Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry

Joseph Nowatzke; Paul Guedeney; Nicholas Palaskas; Lorenz Lehmann; Stephane Ederhy; Han Zhu; Jennifer Cautela; Sanjeev Francis; Pierre-Yves Courand; Anita Deswal; Steven M Ewer; Mandar Aras; Dimitri Arangalage; Kambiz Ghafourian; Charlotte Fenioux; Daniel Finke; Giovanni Peretto; Vlad Zaha; Osnat Itzhaki Ben Zadok; Kazuko Tajiri; Nausheen Akhter; Joshua Levenson; Lauren Baldassarre; John Power; Shi Huang; Jean-Philippe Collet; Javid Moslehi; Joe-Elie Salem; International ICI-myocarditis registry contributors

doi:10.1016/j.ejca.2022.07.018

Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry

Eur J Cancer. 2022 Dec:177:197-205. doi: 10.1016/j.ejca.2022.07.018. Epub 2022 Aug 24.

Authors

Joseph Nowatzke¹, Paul Guedeney², Nicholas Palaskas³, Lorenz Lehmann⁴, Stephane Ederhy⁵, Han Zhu⁶, Jennifer Cautela⁷, Sanjeev Francis⁸, Pierre-Yves Courand⁹, Anita Deswal³, Steven M Ewer¹⁰, Mandar Aras¹¹, Dimitri Arangalage¹², Kambiz Ghafourian¹³, Charlotte Fenioux¹⁴, Daniel Finke⁴, Giovanni Peretto¹⁵, Vlad Zaha¹⁶, Osnat Itzhaki Ben Zadok¹⁷, Kazuko Tajiri¹⁸, Nausheen Akhter¹³, Joshua Levenson¹⁹, Lauren Baldassarre²⁰, John Power²¹, Shi Huang¹, Jean-Philippe Collet², Javid Moslehi²², Joe-Elie Salem²³; International ICI-myocarditis registry contributors

Collaborators

International ICI-myocarditis registry contributors:
Nazanin Aghel²⁴, Joachim Alexandre²⁵, Kazutaka Aonuma²⁶, Aarti H Asnani²⁷, Juliane Behling²⁸, Mehmet Bilen²⁹, Wendy Bottinor³⁰, Eve Cariou³¹, Johnny Chahine³², Weiting Chan³³, Aman Chauhan³⁴, Max Cohen³⁵, Shanthini Crusz³⁶, Suran Fernando³⁷, Roberta Florido³⁸, Mauro Frigeri³⁹, Satoshi Fukushima⁴⁰, Elizabeth Gaughan⁴¹, Benjamin P Geisler²⁷, Lauren Gilstrap⁴², Christian Grohe⁴³, Avirup Guha⁴⁴, Manhal Habib⁴⁵, Eva Haegler-Laube⁴⁶, Andrew Haydon⁴⁷, Salim Hayek⁴⁸, Andrew Hughes⁴⁹, Rysk Imai⁵⁰, Yumi Katsume⁵¹, Hideki Kimura⁵², Lily Koo Lin⁵³, Carrie Lenneman⁵⁴, Daryl Leong⁵⁵, Vicky Makker⁵⁶, Nicolas Martinez-Calle⁵⁷, Melissa Moey⁵⁸, Masahiro Mohri⁵⁹, Ryota Morimoto⁶⁰, Yoshinobu Moritoki⁶¹, Anna Narezkina⁶², Martin Nicol⁶³, Ajay Nooka²⁹, Olusola Orimoloye⁴⁹, Milan Patel⁶⁴, Michal Perl⁶⁵, Nicolas Piriou⁶⁶, Jayant K Raikhelkar⁶⁷, Yasmin Raza⁶⁸, Anjali Rao⁶⁹, Sunil Reddy⁷⁰, Nobuhiko Seki⁷¹, Karl Stangl⁴³, Andrew Stewart⁶⁹, Bryan Stringer⁷², Balaji K Tamarappoo⁷³, Yuichi Tamura⁷⁴, Frank Thuny⁷⁵, Sean Tierney⁷⁶, Romain Tresorier⁷⁷, Waqas Ullah⁷⁸, Jean-Jacques Von Hunolstein⁷⁹, Ellen Warner⁸⁰, Allison Weppler⁸¹

Affiliations

¹ Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
² Sorbonne Université, Department of Cardiology, INSERM UMRS_1166, Pitié Salpêtrière (AP-HP), Paris, France.
³ Department of Cardiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Cardiology, University Hospital of Heidelberg, 69120, Heidelberg, Germany; Institute of Experimental Cardiology, University Hospital of Heidelberg, 69120, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Heidelberg/Mannheim, Germany.
⁵ Department of Cardiology, UNICO Cardio-Oncology Program, INSERM U 856, Hôpital Saint-Antoine, AP-HP, Paris, France.
⁶ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁷ French Institute of Health and Medical Research 1263, National Institute of Agricultural Research, Centre for CardioVascular and Nutrition Research, Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, University Mediterranean Centre of Cardio-Oncology, Nord Hospital, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France.
⁸ Cardiovascular Disease Service Line, Maine Medical Center, Portland, ME, USA.
⁹ Fédération de Cardiologie, Hôpital de La Croix-Rousse et Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France; Université de Lyon, CREATIS, CNRS UMR5220, INSERM U1044, INSA-Lyon, Université Claude Bernard Lyon 1, France.
¹⁰ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
¹¹ Division of Cardiology, University of California-San Francisco, San Francisco, CA, USA.
¹² Department of Cardiology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, UMRS1148, INSERM, Paris, France; Université de Paris, Paris, France.
¹³ Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁴ Department of Pharmacology and Clinical Investigation Centre (CIC-1901), Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, INSERM, 75013, Paris, France.
¹⁵ Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Vita-Salute University and San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
¹⁶ Division of Cardiology, Department of Internal Medicine, Cardio-Oncology Program, Harold C. Simmons Comprehensive Cancer Center, Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁷ Heart Failure Unit, Cardiology Department, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁸ Department of Cardiology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
¹⁹ Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
²⁰ Yale School of Medicine, New Haven, CT, USA.
²¹ Division of Cardiovascular Medicine, University of California San Diego, San Diego, CA, USA.
²² Division of Cardiology, University of California-San Francisco, San Francisco, CA, USA. Electronic address: javid.moslehi@ucsf.edu.
²³ Department of Pharmacology and Clinical Investigation Centre (CIC-1901), Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, INSERM, 75013, Paris, France. Electronic address: joe-elie.salem@aphp.fr.
²⁴ Toronto General Hospital, Toronto, Canada.
²⁵ Caen University, Caen, France.
²⁶ Univerity of Tsukuba, Tsukuba, Japan.
²⁷ Harvard, Boston, MA, USA.
²⁸ University Hospital Mainz, Mainz, Germany.
²⁹ Emory University, Atlanta, GA, USA.
³⁰ Virginia Commonwealth University, Richmond, VA, USA.
³¹ CHU Toulouse, Toulouse, France.
³² Cleveland Clinic, Cleveland, OH, USA.
³³ Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
³⁴ University of Kentucky, Lexington, KY, USA.
³⁵ New York Institute of Technology, Old Westbury, NY, USA.
³⁶ Barts Health NHS, London, United Kingdom.
³⁷ Royal North Shore Hospital, Sydney Australia.
³⁸ Johns Hopkins University, Baltimore, MD, USA.
³⁹ Hopitaux Universitaire de Genève, Geneva, Switzerland.
⁴⁰ Kumamoto University, Kumamoto, Japan.
⁴¹ Univeristy of Viriginia, Charlottsville, VA, USA.
⁴² Dartmouth, Lebanon NH, USA.
⁴³ Charité Universitatsmedizin, Berlin, Germany.
⁴⁴ Case Western Reserve University, Cleveland, OH, USA.
⁴⁵ Rambam Health Care Campus, Haifa, Israel.
⁴⁶ Universitatsspital, Bern, Switzerland.
⁴⁷ Monash University, Clayton, Australia.
⁴⁸ University of Michigan, Ann Arbor, MI, USA.
⁴⁹ Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁰ St Luke's International Hospital, Tokyo, Japan.
⁵¹ Sendai Kousei Hospital, Sendai, Japan.
⁵² Chiba Cancer Center, Chiba, Japan.
⁵³ UC Davis, Sacramento, CA, USA.
⁵⁴ University of Alabama Birmingham, Birmingham, AL, USA.
⁵⁵ McMaster University, Hamilton, Canada.
⁵⁶ Memorial Sloan Kettering, New York, NY, USA.
⁵⁷ Clinica Universitaria de Navarra, Pamplona, Spain.
⁵⁸ Eastern Carolina University, Greenville, NC, USA.
⁵⁹ Japan Community HealthCare Organization Kyushu Hospital, Kyushu, Japan.
⁶⁰ Nagoya University, Nagoya, Japan.
⁶¹ Kyoto University, Kyoto, Japan.
⁶² UCSD, San Diego, CA, USA.
⁶³ Lariboisière, Paris, France.
⁶⁴ Yale University, New Haven, CT, USA.
⁶⁵ Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
⁶⁶ CHU de Nantes, Nantes, France.
⁶⁷ Columbia University, New York, NY, USA.
⁶⁸ Northwestern Univeristy, Chicago, IL, USA.
⁶⁹ The University of Texas Southwestern, Dallas, TX, USA.
⁷⁰ Stanford University, Stanford, CA, USA.
⁷¹ Teikyo University School of Medicine, Teikyo, Japan.
⁷² Uconn Health Center, Farmington, CT, USA.
⁷³ Cedars Sinai Medical Center, Los Angeles, CA, USA.
⁷⁴ International University of Health and Welfare, Narita, Japan.
⁷⁵ APHM, Marseille, France.
⁷⁶ Heart Care Centers of Illinois, Palos Park, IL, USA.
⁷⁷ CHU Clermont-Ferrand, Clermont-Ferrand, France.
⁷⁸ Jefferson Health, Philadelphia, PA, USA.
⁷⁹ CHU Strasbourg, Strasbourg, France.
⁸⁰ Sunny Brook Hospital, Toronto, Canada.
⁸¹ Peter MacCallum Cancer Center, East Melbourne, Australia.

Abstract

Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis.

Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram.

Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057).

Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.

Keywords: Acute coronary syndrome; Coronary revascularization; Immune checkpoint blockers; Immune-related adverse events; Myocarditis.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Coronary Artery Disease* / diagnostic imaging
Coronary Artery Disease* / therapy
Humans
Immune Checkpoint Inhibitors
Myocarditis* / drug therapy
Prognosis
Registries
Retrospective Studies
Risk Factors

Substances

Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding