Chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary treatment for hematologic malignancies and solid tumors. Multiple approved products and ongoing clinical trials have demonstrated its remarkable antitumor efficacy. However, its clinical application is severely limited by prominent cardiotoxicity, which is closely associated with high morbidity and mortality, posing an urgent clinical challenge. This review systematically elucidates the pathophysiological mechanisms underlying CAR-T cell therapy-induced cardiotoxicity, which can be primarily categorized into acute and long-term adverse effects. Acute cardiotoxicity is driven by cytokine release syndrome (CRS) through macrophage and monocyte activation, endothelial dysfunction, and subsequent myocardial injury, leading to hypotension, reduced left ventricular ejection fraction, and cardiac arrhythmias. Long-term cardiotoxicity is mainly caused by B-cell aplasia-induced immune deficiency and secondary hemophagocytic lymphohistiocytosis, which trigger infectious complications, myocardial ischemia, and apoptosis. We have further summarized clinical pharmacological interventions for such cardiotoxicity, including interleukin (IL)-6 receptor antagonists (tocilizumab), interferon-γ inhibitors (emapalumab), and Janus kinase inhibitors (ruxolitinib). However, none of these drugs can completely alleviate CRS or CAR-T cell therapy-induced cardiotoxicity in all patients. Preclinical agents targeting inflammatory cytokines (IL-1β, tumor necrosis factor-α) and signaling pathways have shown efficacy in ameliorating cardiotoxicity in various animal models. These findings provide novel directions and drug candidates for the treatment of CAR-T cell therapy-induced myocardial toxicity. This review provides a comprehensive theoretical basis for optimizing cardiovascular safety management and developing novel targeted interventions for CAR-T cell therapy.

The cardiac vasculature is characterized by high pressure, high blood flow, and dense vascular branching, which may increase its exposure to circulating tumor cells (CTCs). However, both primary cardiac tumors and metastases are remarkably rare. This mechanism has remained poorly understood. A recent report by Ciucci and co-workers show that mechanical load in the heart inhibits cancer cell proliferation. Their work proposes that physiological mechanical stimuli is not merely a regulator of cancer progression, but also an intrinsic anticancer mechanism.

Cardiac metastases are significantly more common than primary cardiac tumours. Their clinical presentation varies depending on tumour size, location, and degree of myocardial or pericardial infiltration. Common manifestations include pericardial effusion, valvular dysfunction due to inflow or outflow obstruction, and conduction disturbances. 2:1 atrioventricular (AV) block secondary to cardiac metastases is rare.

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic variants in the BCOR gene and is characterized by distinctive craniofacial, ocular, cardiac, and dental abnormalities. Although OFCD syndrome is a well-defined developmental disorder, its association with endocrine tumors has not been clearly established. We report a female patient with genetically confirmed OFCD syndrome harboring a novel heterozygous deletion in BCOR who developed metachronous multiple insulinomas. The patient presented with recurrent hypoglycemic episodes, and pancreatic neuroendocrine tumors were detected at different time points, necessitating repeated surgical interventions. Histopathological examination confirmed insulinoma in each resected lesion. Comprehensive clinical and pathological evaluations revealed no features suggestive of other known hereditary insulinoma-associated syndromes, including multiple endocrine neoplasia type 1. Previous reports have described either recurrent insulinoma without genetic confirmation of OFCD syndrome or multiple insulinomas without documented recurrence in genetically confirmed cases. In contrast, the present case uniquely demonstrates metachronous development of multiple insulinomas in association with a novel BCOR deletion. Given the role of BCOR in transcriptional repression and developmental regulation, this case suggests a potential contribution of BCOR dysfunction to pancreatic neuroendocrine tumorigenesis. Our findings expand the phenotypic and genotypic spectrum of OFCD syndrome and underscore the importance of long-term surveillance and further accumulation of cases to clarify tumor predisposition in this rare disorder.