Cardiovascular complications of chimeric antigen receptor (CAR)-t cell therapy: insights from a regional cardio-oncology program

Abstract Background Chimeric Antigen Receptor (CAR)-T cell therapy, a breakthrough in immuno-oncology, is increasingly utilized for treating leukemia and lymphoma. However, its association with cardiovascular complications remains poorly understood. Potential mechanisms include cytokine release syndrome (CRS)-induced myocardial depression, takotsubo cardiomyopathy, and direct CAR-T cell toxicity. This study evaluates the cardiovascular outcomes of patients undergoing CAR-T therapy at a regional referral center, in collaboration with a dedicated cardio-oncology team. Methods We prospectively enrolled all consecutive patients referred for CAR-T therapy at our institution, starting from the program’s initiation. All participants had refractory hematological malignancies, failed at least two lines of chemotherapy, and had previously received anthracyclines. Pre-treatment cardiac evaluations included a 12-lead ECG, echocardiography, and cardiac biomarkers. Patients received autologous CAR-T cells (tisagenlecleucel) after conditioning. Follow-up evaluations were performed at discharge and at six months. Results Twenty patients (mean age 63±11 years; 8 males) were treated with CAR-T after a median of two lines of treatment (range 1-3). 30% developed CRS, with a median onset of 12 days (range 7-40). Two patients presented with Grade I CRS and was managed with supportive care. Three patients with Grade 2 CRS required cardioprotective therapy (ACE inhibitors and beta-blockers) due to transient left ventricular dysfunction (mean lowest LVEF 44%). One patient experienced Grade IV CRS complicated by takotsubo syndrome and cardiogenic shock on day 4, requiring vasopressor support and mechanical ventilation. Pre-treatment echocardiography showed lower baseline left ventricular ejection fraction (LVEF) and right ventricular systolic function in CRS patients compared to others (LVEF 53.6±5.9% vs. 63.2±7.7%; p=0.03; TAPSE 25±4 mm vs. 20±3 mm; p=0.02; S' 0.09±0.01 m/s vs. 0.12±0.02 m/s; p=0.03). Baseline cardiac biomarkers did not predict adverse outcomes. All CRS patients showed recovery of ventricular function and survived to discharge. Six patients died from oncological progression unrelated to cardiac complications. Conclusions CAR-T therapy is associated with significant cardiovascular risks, with 30% of patients requiring cardio-oncology management. Echocardiographic assessments prior to treatment may help identify individuals at higher risk for cardiac events, aiding in early intervention and better outcomes.LVEF trend during CRS