Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis

John R Power¹, Joachim Alexandre², Arrush Choudhary³, Benay Ozbay⁴, Salim S Hayek⁵, Aarti Asnani³, Yuichi Tamura⁶, Mandar Aras⁷, Jennifer Cautela⁸, Franck Thuny⁸, Lauren Gilstrap⁹, Dimitri Arangalage¹⁰, Steven Ewer¹¹, Shi Huang¹², Anita Deswal¹³, Nicolas L Palaskas¹³, Daniel Finke¹⁴, Lorenz H Lehmann¹⁴, Stephane Ederhy¹⁴, Javid Moslehi⁷, Joe-Elie Salem¹⁵; International ICI-Myocarditis Registry

Collaborators, Affiliations

Collaborators

International ICI-Myocarditis Registry:
Charlotte Fenioux¹⁶, Baptiste Abbar¹⁶, Yves Allenbach¹⁶, Shanthini M Crusz¹⁷, Arjun K Ghosh¹⁷, Tyler Moran¹⁸, Tyler Mehegan¹⁹, Lawrence Piro²⁰, Wei-Ting Chang²¹, Johnny Chahine²², Danette Flint²³, Ben Stringer²⁴, Valérie Gounant²⁵, Martin Nicol²⁶, Barouyr Baroudjian²⁷, Marie-Claire Zimmer²⁸, Elvire Mervoyer²⁹, Darryl Leong³⁰, Ryota Morimoto³¹, Nicolas Piriou³², Cecilia Monge³³, Amy Copeland³⁴, Kambiz Ghafourian³⁵, Avirup Guha³⁶, Sergey Brodsky³⁷, Osnat Itzhaki Ben Zadok³⁸, Manhal Habib³⁹, Grace Dy⁴⁰, Ellen Warner⁴¹, Michal Laufer-Perl⁴², Lily Koo Lin⁴³, Ana Narezkina⁴⁴, Alan Baik⁴⁵, Carrie Lenneman⁴⁶, Pankit Vachhani⁴⁶, Tariq U Azam⁴⁷, Daniel Perry⁴⁷, Pennelope Blakely⁴⁷, Kazuko Tajiri⁴⁸, Matthew Martini⁴⁹, Joseph Nowatzke³⁷, Olusola Ayodeji Orimoloye³⁷, Andrew Hughes³⁷, Lauren A Baldassarre⁵⁰, Milan Patel⁵⁰

Affiliations

¹ UC San Diego Health, San Diego, CA, 92103, USA.
² Université de Caen Normandie, 14000 Caen, France.
³ Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
⁴ Basaksehir Cam and Sakura State Hospital, 34480 Basaksehir, Istanbul, Turkey.
⁵ University of Michigan, Ann Arbor, MI, 48109, USA.
⁶ International University of Health and Welfare Mita Hospital, Tokyo, 108-8329, Japan.
⁷ UCSF Medical Center, San Francisco, CA, 94143, USA.
⁸ AP-HM, Aix-Marseille University, 13005 Marseille, France.
⁹ Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03766, USA.
¹⁰ Hôpital Bichat, 75018 Paris, France.
¹¹ University of Wisconsin Hospital, Madison, WI, 53792, USA.
¹² Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
¹³ University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁴ Heidelberg University Hospital, 69120 Heidelberg; DZHK (German Centre for Cardiovascular Research/Deutsches Krebsforschungszentrum) Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
¹⁵ AP-HP, Sorbonne University, 75013 Paris, France. Electronic address: joe-elie.salem@aphp.fr.
¹⁶ AP-HP, Sorbonne University, Paris, France; Allama Iqbal Medical College, Lahore, Pakistan; AP-HM, Aix-Marseille University, Marseille, France.
¹⁷ Barts Health NHS Trust, London, UK; Basaksehir Cam and Sakura State Hospital, Istanbul, Turkey.
¹⁸ Baylor College of Medicine, Houston, TX, USA.
¹⁹ Beth Israel Deaconess Medical Center, Boston, MA, USA; Brigham & Women's Hospital, Boston, USA.
²⁰ Cedars-Sinai Medical Center, Los Angeles, CA, USA; Chibaken Saiseikai Narashino Hospital, Funabashi, Japan.
²¹ Chi-Mei Medical Center, Tainam, Taiwan.
²² Cleveland Clinic, Cleveland, OH, USA.
²³ Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; Emory University Hospital, Atlanta, GA, USA; General Hospital of Chinese People's Liberation Army, Beijing, China; Georgetown University Medical Center, Washington, DC, USA.
²⁴ Hartford Hospital, Hartford, CT, USA; Heidelberg University Hospital, Heidelberg, Germany.
²⁵ Hôpital Bichat, Paris, France; Hôpital Europeen Georges Pompidou, Paris, France.
²⁶ Hôpital Lariboisière, Paris, France.
²⁷ Hôpital Saint-Louis, Paris, France.
²⁸ Institut Bergonié, Centre Régional de Lutte Contre le Cancer, Bordeaux, France.
²⁹ Institut de Cancérologie de l'Ouest, Saint Herblain, France; International University of Health and Welfare Mita Hospital, Tokyo, Japan.
³⁰ McMaster University, Hamilton, ON, Canada.
³¹ Nagoya University Graduate School of Medicine, Nagoya, Japan.
³² Nantes University Hospital, Nantes, France.
³³ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁴ National Institutes of Health, Bethesda, MD, USA.
³⁵ Northwestern Memorial Hospital, Chicago, IL, USA.
³⁶ Ohio State University, Wexner Medical Center, Columbus, OH, USA.
³⁷ Vanderbilt University Medical Center, Nashville, TN, USA.
³⁸ Rabin Medical Center, Petah Tikva, Israel.
³⁹ Rambam Medical Center, Haifa, Israel.
⁴⁰ Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁴¹ Sunnybrook Health Sciences Center, Toronto, ON, Canada.
⁴² Tel Aviv Sourasky Medical Center, affiliated to the Sackler School of Medicine, Tel Aviv, Israel.
⁴³ UC Davis Medical Center, Sacramento, CA, USA.
⁴⁴ UC San Diego Health, San Diego, CA, USA.
⁴⁵ UCSF Medical Center, San Francisco, CA, USA; Université de Caen Normandie, Caen, France.
⁴⁶ University Medical Center, University of Alabama, Birmingham, AL, USA.
⁴⁷ University of Michigan, Ann Arbor, MI, USA; University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴⁸ University of Tsukuba, Tsukuba, Japan; University of Washington, VA Puget Sound Health Care System, Seattle, USA.
⁴⁹ University of Wisconsin Hospital, Madison, WI, USA.
⁵⁰ Yale University School of Medicine, New Haven, CT, USA.

PMID: 35595646
DOI: 10.1016/j.acvd.2022.03.003

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis

John R Power et al. Arch Cardiovasc Dis. 2022 May.

. 2022 May;115(5):315-330.

doi: 10.1016/j.acvd.2022.03.003. Epub 2022 Apr 27.

Authors

Collaborators

International ICI-Myocarditis Registry:
Charlotte Fenioux¹⁶, Baptiste Abbar¹⁶, Yves Allenbach¹⁶, Shanthini M Crusz¹⁷, Arjun K Ghosh¹⁷, Tyler Moran¹⁸, Tyler Mehegan¹⁹, Lawrence Piro²⁰, Wei-Ting Chang²¹, Johnny Chahine²², Danette Flint²³, Ben Stringer²⁴, Valérie Gounant²⁵, Martin Nicol²⁶, Barouyr Baroudjian²⁷, Marie-Claire Zimmer²⁸, Elvire Mervoyer²⁹, Darryl Leong³⁰, Ryota Morimoto³¹, Nicolas Piriou³², Cecilia Monge³³, Amy Copeland³⁴, Kambiz Ghafourian³⁵, Avirup Guha³⁶, Sergey Brodsky³⁷, Osnat Itzhaki Ben Zadok³⁸, Manhal Habib³⁹, Grace Dy⁴⁰, Ellen Warner⁴¹, Michal Laufer-Perl⁴², Lily Koo Lin⁴³, Ana Narezkina⁴⁴, Alan Baik⁴⁵, Carrie Lenneman⁴⁶, Pankit Vachhani⁴⁶, Tariq U Azam⁴⁷, Daniel Perry⁴⁷, Pennelope Blakely⁴⁷, Kazuko Tajiri⁴⁸, Matthew Martini⁴⁹, Joseph Nowatzke³⁷, Olusola Ayodeji Orimoloye³⁷, Andrew Hughes³⁷, Lauren A Baldassarre⁵⁰, Milan Patel⁵⁰

Affiliations

¹ UC San Diego Health, San Diego, CA, 92103, USA.
² Université de Caen Normandie, 14000 Caen, France.
³ Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
⁴ Basaksehir Cam and Sakura State Hospital, 34480 Basaksehir, Istanbul, Turkey.
⁵ University of Michigan, Ann Arbor, MI, 48109, USA.
⁶ International University of Health and Welfare Mita Hospital, Tokyo, 108-8329, Japan.
⁷ UCSF Medical Center, San Francisco, CA, 94143, USA.
⁸ AP-HM, Aix-Marseille University, 13005 Marseille, France.
⁹ Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03766, USA.
¹⁰ Hôpital Bichat, 75018 Paris, France.
¹¹ University of Wisconsin Hospital, Madison, WI, 53792, USA.
¹² Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
¹³ University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁴ Heidelberg University Hospital, 69120 Heidelberg; DZHK (German Centre for Cardiovascular Research/Deutsches Krebsforschungszentrum) Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
¹⁵ AP-HP, Sorbonne University, 75013 Paris, France. Electronic address: joe-elie.salem@aphp.fr.
¹⁶ AP-HP, Sorbonne University, Paris, France; Allama Iqbal Medical College, Lahore, Pakistan; AP-HM, Aix-Marseille University, Marseille, France.
¹⁷ Barts Health NHS Trust, London, UK; Basaksehir Cam and Sakura State Hospital, Istanbul, Turkey.
¹⁸ Baylor College of Medicine, Houston, TX, USA.
¹⁹ Beth Israel Deaconess Medical Center, Boston, MA, USA; Brigham & Women's Hospital, Boston, USA.
²⁰ Cedars-Sinai Medical Center, Los Angeles, CA, USA; Chibaken Saiseikai Narashino Hospital, Funabashi, Japan.
²¹ Chi-Mei Medical Center, Tainam, Taiwan.
²² Cleveland Clinic, Cleveland, OH, USA.
²³ Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; Emory University Hospital, Atlanta, GA, USA; General Hospital of Chinese People's Liberation Army, Beijing, China; Georgetown University Medical Center, Washington, DC, USA.
²⁴ Hartford Hospital, Hartford, CT, USA; Heidelberg University Hospital, Heidelberg, Germany.
²⁵ Hôpital Bichat, Paris, France; Hôpital Europeen Georges Pompidou, Paris, France.
²⁶ Hôpital Lariboisière, Paris, France.
²⁷ Hôpital Saint-Louis, Paris, France.
²⁸ Institut Bergonié, Centre Régional de Lutte Contre le Cancer, Bordeaux, France.
²⁹ Institut de Cancérologie de l'Ouest, Saint Herblain, France; International University of Health and Welfare Mita Hospital, Tokyo, Japan.
³⁰ McMaster University, Hamilton, ON, Canada.
³¹ Nagoya University Graduate School of Medicine, Nagoya, Japan.
³² Nantes University Hospital, Nantes, France.
³³ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁴ National Institutes of Health, Bethesda, MD, USA.
³⁵ Northwestern Memorial Hospital, Chicago, IL, USA.
³⁶ Ohio State University, Wexner Medical Center, Columbus, OH, USA.
³⁷ Vanderbilt University Medical Center, Nashville, TN, USA.
³⁸ Rabin Medical Center, Petah Tikva, Israel.
³⁹ Rambam Medical Center, Haifa, Israel.
⁴⁰ Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁴¹ Sunnybrook Health Sciences Center, Toronto, ON, Canada.
⁴² Tel Aviv Sourasky Medical Center, affiliated to the Sackler School of Medicine, Tel Aviv, Israel.
⁴³ UC Davis Medical Center, Sacramento, CA, USA.
⁴⁴ UC San Diego Health, San Diego, CA, USA.
⁴⁵ UCSF Medical Center, San Francisco, CA, USA; Université de Caen Normandie, Caen, France.
⁴⁶ University Medical Center, University of Alabama, Birmingham, AL, USA.
⁴⁷ University of Michigan, Ann Arbor, MI, USA; University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴⁸ University of Tsukuba, Tsukuba, Japan; University of Washington, VA Puget Sound Health Care System, Seattle, USA.
⁴⁹ University of Wisconsin Hospital, Madison, WI, USA.
⁵⁰ Yale University School of Medicine, New Haven, CT, USA.

PMID: 35595646
DOI: 10.1016/j.acvd.2022.03.003

Abstract

Background: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown.

Objective: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia.

Methods: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated.

Results: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004).

Conclusions: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

Keywords: Cardio-oncologie; Cardio-oncology; Electrophysiology; Immunotherapy; Immunothérapie; Myocardite; Myocarditis; Électrophysiologie.

PubMed Disclaimer

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis

Collaborators

Affiliations

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis

Authors

Collaborators

Affiliations

Abstract

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Miscellaneous