000			04195nam a22003977a 4500
008			240807s20242024 xxu||||| |||| 00| 0 eng d
024			_aPMC11177901 [pmc]
040			_aOvid MEDLINE(R)
099			_a38883792
245			_aPredictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.
251			_aMedRxiv : the Preprint Server for Health Sciences. 2024 Jun 03
252			_amedRxiv. 2024 Jun 03
253			_amedRxiv : the preprint server for health sciences
260			_c2024
260			_fFY2024
260			_p2024 Jun 03
265			_sepublish
265			_tPubMed-not-MEDLINE
266			_d2024-08-07
266			_z2024/06/17 06:12
520			_aBackground: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking.
520			_aConclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
520			_aMethods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
520			_aResults: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for <=0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score>=4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
520			_aTrial registration number: NCT04294771 and NCT05454527.
546			_aEnglish
650			_zAutomated
651			_aMedStar Washington Hospital Center
656			_aCardiac Oncology Fellowship
657			_aJournal Article
657			_aPreprint
700			_aKassaian, Seyed Ebrahim _bMWHC _cCardiac Oncology Fellowship _dMD
790			_aPower JR, Dolladille C, Ozbay B, Procureur AM, Ederhy S, Palaskas NL, Lehmann LH, Cautela J, Courand PY, Hayek SS, Zhu H, Zaha VG, Cheng RK, Alexandre J, Roubille F, Baldassarre LA, Chen YC, Baik AH, Laufer-Perl M, Tamura Y, Asnani A, Francis S, Gaughan EM, Rainer PP, Bailly G, Flint D, Arangalage D, Cariou E, Florido R, Narezkina A, Liu Y, Sandhu S, Leong D, Issa N, Piriou N, Heinzerling L, Peretto G, Crusz SM, Akhter N, Levenson JE, Turker I, Eslami A, Fenioux C, Moliner P, Obeid M, Chan WT, Ewer SM, Kassaian SE, Johnson DB, Nohria A, Zadok OIB, Moslehi JJ, Salem JE
856			_uhttps://dx.doi.org/10.1101/2024.06.02.24308336 _zhttps://dx.doi.org/10.1101/2024.06.02.24308336
942			_cART _dArticle
999			_c14475 _d14475