Cardiotoxicity of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Pathophysiology, Clinical Implications, and Echocardiographic Assessment

Abstract

Contemporary anticancer immunotherapy with chimeric antigen receptor T-cell (CAR-T) therapy has dramatically changed the treatment of many hematologic malignancies previously associated with poor prognosis. The clinical improvement and the survival benefit unveiled the risk of cardiotoxicity, ranging from minimal effects to severe cardiac adverse events, including death. Immunotherapy should also be proposed even in patients with pre-existing cardiovascular risk factors, thereby increasing the potential harm of cardiotoxicity. CAR-T therapy frequently results in cytokine release syndrome (CRS), and inflammatory activation is sustained by circulating cytokines that foster a positive feedback mechanism. Prompt diagnosis and treatment of CAR-T cardiotoxicity might significantly improve outcomes and reduce the burden associated with cardiovascular complications. Clinical and echocardiographic examinations are crucial to perform a tailored evaluation and follow-up during CAR-T treatment. This review aims to summarize the pathophysiology, clinical implications, and echocardiographic assessment of CAR-T-related cardiotoxicity to enlighten new avenues for future research.

Cardiotoxicity, Cardioprotection, and Prognosis in Survivors of Anticancer Treatment Undergoing Cardiac Surgery: Unmet Needs

“…However, the more the treatment is used, the more reports highlight some cardiotoxicity effects, potentially related to cytokine release syndrome (CRS), and inflammatory activation is sustained by circulating cytokines, including myocardial injury, tachyarrhythmias, ventricular arrhythmias and atrial fibrillation, myocardial ischemia, and venous thromboembolism [ 50 , 51 ]. CV ultrasound imaging surveillance of subjects treated with CAR-T identified earlier and prevented clinically overt severe cardiotoxicity and cardiovascular complications [ 52 ], as cardiac toxicity related to CAR T-cell-associated CRS may be resolved spontaneously at day-28 post infusion [ 53 ].…”

Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies

“…Underlining the importance of prompt identification and management of CAR-T cell toxicity may greatly enhance results and lessen the burden brought on with associated complications. In addition, these tests could confirm whether early action will reduce toxicity without impacting efficacy [95].…”

Cancer treatment-related cardiotoxicity: a focus on sacubitril/valsartan

“…Protease inhibitor [37][38][39] Bortezomil/carfezomil CHF/myocardial ischemia/hypertension 1.8-7.2 Endocrinotherapy [40] Goserin/levoprorelin/flutamide/bicalutamide Myocardial infarction/CHF 0.1-5 CART cell therapy [41,42] Tisagenlecleucel/axicabtagene ciloleucel Tachycardia/hypotension/cardiac insufficiency Unclear Arsenic trioxide [43,44] Arsenic trioxide/all-trans retinoic acid Prolonged QT interval/tachycardia 16 Hematopoietic stem cell transplantation [45] Lenalidomide, bortezomib, Isazzomib Arrhythmia/myocardial ischemia/CHF 2-12…”

“…Patients who began taking sacubitril/valsartan in hospital had a lower risk profile for heart failure rehospitalization and cardiovascular death than patients with a delayed initiation of sacubitril/valsartan (8 weeks later) [39] . The clinical trials of sacubitril/valsartan in HFrEF were shown in Table 2 [37][38][39][40][41][42][43][44][45][46][47][48] . LV remodeling was crucial in progression to HFrEF [70] .…”