BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P =0.03 versus cTnT), and 43 of 57 ([75%] P <0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P <0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco–German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2–16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2–38.0]; P <0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients ( P <0.001), respectively. CONCLUSIONS: cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.

Background and Aims: 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. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis. Methods: A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular 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. Results: In 748 patients (67% male, age 23–94 years), 30-day 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 (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7–7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5–4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1–3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1–2.6]), and incremental troponin elevation (HR 1.8 [1.4–2.4], 2.9 [1.8–4.7], and 4.6 [2.3–9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (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 cardiomyotoxic events. Conclusions: ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well. Clinical trial registration: NCT04294771 and NCT05454527.

Non-bacterial thrombotic endocarditis (NBTE), formerly recognized as marantic endocarditis, represents a rare cardiovascular pathology intricately linked with hypercoagulable states, notably malignancy and autoimmune disorders. Characterized by the development of sterile vegetations comprised of fibrin and platelets on cardiac valves, NBTE poses a diagnostic challenge due to its resemblance to infective endocarditis. Therapeutic endeavours primarily revolve around addressing the underlying aetiology and instituting anticoagulant regimens to forestall embolic events, with surgical intervention seldom warranted. Non-bacterial thrombotic endocarditis frequently coexists with malignancies and autoimmune conditions, such as lupus and antiphospholipid antibody syndrome, and, more recently, has been associated with COVID-19. Its pathogenesis is underpinned by a complex interplay of endothelial dysfunction, hypercoagulability, hypoxia, and immune complex deposition. Clinical manifestations typically manifest as embolic phenomena, particularly cerebrovascular accidents, bearing substantial mortality rates. Diagnosis necessitates a high index of suspicion and meticulous exclusion of infective endocarditis, often facilitated by advanced cardiac imaging modalities. Anticoagulation, typically employing low molecular weight heparin or warfarin, constitutes the cornerstone of pharmacological intervention. Surgical recourse may be warranted in instances of refractory heart failure or recurrent embolic events. Given its multifaceted nature, the management of NBTE mandates a multidisciplinary approach, with prognosis contingent upon individual clinical intricacies. Future endeavours should prioritize further research to refine therapeutic strategies and enhance patient outcomes.