Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction
Yen-Chou Chen, Charles Dolladille, Anjali Rao, Nicolas L. Palaskas, Anita Deswal, Lorenz Lehmann, Jennifer Cautela, Pierre‐Yves Courand, Salim S. Hayek, Han Zhu, Richard K. Cheng, Joachim Alexandre, Lauren A. Baldassarre, François Roubille, Michal Laufer‐Perl, Aarti Asnani, Stephane Ederhy, Yuichi Tamura, Sanjeev Francis, Elizabeth M Gaughan, Douglas B. Johnson, Danette L. Flint, Peter P. Rainer, Guillaume Bailly, Steven M. Ewer, Mandar A. Aras, Dimitri Arangalage, Eve Cariou, Roberta Florido, Giovanni Peretto, Osnat Itzhaki Ben Zadok, Nausheen Akhter, Anna Narezkina, Joshua Levenson, Yan Liu, Shanthini Mary Crusz, Nahéma Issa, Nicolas Piriou, Darryl P. Leong, Shahneen Sandhu, Isik Turker, Pedro Moliner, Michel Obéid, Lucie Heinzerling, Wei‐Ting Chang, Andrew Stewart, Vishnu Venkatesh, Z Y Du, Anirudh Yadavalli, Do‐Hyeong Kim, Alvin Chandra, Kathleen W. Zhang, John R. Power, Javid J. Moslehi, Joe‐Elie Salem, Vlad G. Zaha
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood. OBJECTIVES: The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M. A secondary objective was to evaluate the relationship between LVEF and 30-day all-cause mortality. METHODS: The International ICI-Myocarditis Registry, a retrospective, international, multicenter database, included 757 patients hospitalized with ICI-M. Patients were stratified by LVEF as reduced LVEF (<50%) or preserved LVEF (≥50%) on admission. Cox proportional hazards models were used to assess the associations between LVEF and clinical events, and multivariable logistic regression was conducted to examine factors linked to LVEF. RESULTS: , and were more likely to have received chest radiation (24.2% vs 13.5%; P < 0.001). Multivariable analysis identified predictors of LVEF <50%, including exposure to v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated protein kinase inhibitors, pre-existing heart failure, dyspnea at presentation, and at least 40 days from ICI initiation to ICI-M onset. Conversely, myositis symptoms were associated with LVEF ≥50%. LVEF <50% was marginally associated with 30-day all-cause mortality (unadjusted log-rank P = 0.062; adjusted for age, cancer types, and ICI therapy, HR: 1.50; 95% CI: 1.02-2.20). CONCLUSIONS: Dyspnea, time from ICI initiation, a history of heart failure, and prior cardiotoxic therapy may be predictors of an initial LVEF <50% in patients with ICI-M.