Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction.
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Chen Yen-Chou, Dolladille Charles, Rao Anjali, Palaskas Nicolas L, Deswal Anita, Lehmann Lorenz, Cautela Jennifer, Courand Pierre-Yves, Hayek Salim, Zhu Han, Cheng Richard K, Alexandre Joachim, Baldassarre Lauren A, Roubille François, Laufer-Perl Michal, Asnani Aarti, Ederhy Stephane, Tamura Yuichi, Francis Sanjeev, Gaughan Elizabeth M, Johnson Douglas B, Flint Danette L, Rainer Peter P, Bailly Guillaume, Ewer Steven M, Aras Mandar A, Arangalage Dimitri, Cariou Eve, Florido Roberta, Peretto Giovanni, Itzhaki Ben Zadok Osnat, Akhter Nausheen, Narezkina Anna, Levenson Joshua E, Liu Yan, Crusz Shanthini M, Issa Nahema, Piriou Nicolas, Leong Darryl, Sandhu Shahneen, Turker Isik, Moliner Pedro, Obeid Michel, Heinzerling Lucie, Chang Wei-Ting, Stewart Andrew, Venkatesh Vishnu, Du Zoe, Yadavalli Anirudh, Kim Dohyeong, Chandra Alvin, Zhang Kathleen W, Power John R, Moslehi Javid, Salem Joe-Elie, Zaha Vlad G, International ICI Myocarditis Registry
Аннотация
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: Of 757 patients, 707 had documented LVEFs on admission: 244 (35%) with LVEF <50% and 463 (65%) with LVEF ≥50%. Compared with patients with LVEF ≥50%, those with LVEF <50% were younger (<70 years), had a body mass index of <25 kg/m2, 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.