Cardiovascular implications of CAR-T cell therapy: insights from a regional cardio-oncology program

Abstract Background Chimeric Antigen Receptor (CAR)-T cell therapy represents a major advancement in immuno-oncology, offering promising treatment options for leukemia and lymphoma. However, its potential cardiovascular complications remain insufficiently characterized. Proposed mechanisms include cytokine release syndrome (CRS)-induced myocardial dysfunction, takotsubo cardiomyopathy, and direct CAR-T cell-mediated toxicity. This study examines cardiovascular outcomes in patients undergoing CAR-T therapy at a regional referral center in collaboration with a specialized cardio-oncology team. Methods A prospective analysis was conducted on all consecutive patients referred for CAR-T therapy at our institution since the program’s inception. Eligible patients had refractory hematologic malignancies, had failed at least two lines of chemotherapy, and had prior anthracycline exposure. Baseline cardiac assessments included 12-lead ECG, echocardiography, and biomarker evaluation. Patients received autologous CAR-T cells (tisagenlecleucel) following conditioning. Cardiovascular follow-up was performed at hospital discharge and at six months post-therapy. Results A total of 21 patients (mean age 62±11 years; 11males) underwent CAR-T therapy after a median of two prior treatment lines (range 1-3). CRS occurred in 30% of patients, with a median onset of 12 days (range 7-40). Two patients developed Grade I CRS, managed conservatively. Three patients with Grade 2 CRS required cardioprotective therapy (ACE inhibitors and beta-blockers) for transient left ventricular dysfunction (mean lowest LVEF 44%). One patient experienced Grade IV CRS, leading to takotsubo syndrome and cardiogenic shock on day 4, necessitating vasopressor support and mechanical ventilation. Pre-treatment echocardiography revealed lower baseline left ventricular ejection fraction (LVEF) and right ventricular function in CRS patients compared to non-CRS patients (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, Figure 1). Baseline cardiac biomarkers did not predict adverse outcomes. All CRS patients experienced ventricular function recovery and survived to discharge. Six patients succumbed to oncologic progression unrelated to cardiac complications. Conclusions CAR-T therapy carries a notable risk of cardiovascular complications, with 30% of patients requiring specialized cardio-oncology management. Echocardiographic assessment before treatment may help identify high-risk individuals, facilitating early intervention and improved clinical outcomes.