Background Chimeric antigen receptor T‑cell (CAR T) therapy has been a breakthrough in the treatment of multiple hematologic malignancies, yet its expanding use has revealed a spectrum of cardiotoxic effects. Cardiotoxicity is primarily mediated via cytokine release syndrome, with clinical manifestations including arrhythmias, hypotension, and heart failure. Severe cardiovascular events, such as myocardial infarction and cardiogenic shock occur less commonly, but are associated with significant morbidity and mortality. The risk of cardiotoxicity is heightened in patients with high-grade cytokine release syndrome and those with pre-existing cardiovascular disease or those with a history of exposure to anthracyclines. The pathophysiology is multifactorial, involving both direct T cell-mediated injury and indirect cytokine-driven myocardial dysfunction. This narrative review evaluates the current states of knowledge regarding CAR T‑cell therapy, its cardiovascular toxicity, clinical manifestations, pathophysiology, and outcomes. Methods Eligible studies for this narrative review were included if they reported original data on cardiovascular events associated with CAR T therapy in patients with hematologic or solid malignancies. Eligible study designs included: randomized controlled trials, cohort studies, case–control studies, case series, systematic reviews, and meta-analyses. Editorials and commentaries were excluded unless they provided pooled data relevant to cardiotoxicity. Studies published in languages other than English were excluded. A comprehensive literature search was conducted across the following electronic databases: PubMed/MEDLINE, Embase, Web of Science Core Collection, the Cochrane Library, and Google Scholar. The search included studies published from January 1, 1990, through March 31, 2026. In addition, the reference lists of all included studies and relevant review articles were searched to identify additional eligible publications. No filters for age, sex, or geographic region were applied. The search was limited to human studies. ClinicalTrials.gov was also searched for completed or ongoing trials reporting cardiovascular safety data. Search terms involved keywords related to “chimeric antigen receptor T cell,” “CAR T,” “cardiotoxicity,” “cytokine release syndrome,” “arrhythmia,” and “cardiac dysfunction.” Extracted variables included study design, CAR T product, sample size, incidence and type of cardiovascular event, association with cytokine release syndrome, and biomarker data. The selection process was documented using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram adapted for narrative reviews. Titles and abstracts retrieved from the database searches were screened for relevance by one reviewer. Full-text articles of potentially eligible studies were then assessed against the predefined inclusion and exclusion criteria. Results Cardiotoxicity was strongly associated with higher grades of cytokine release syndrome. The most common cardiovascular events included: hypotension, arrhythmias, and heart failure. Elevated cardiac biomarkers, including troponin and pro-BNP were frequently observed and correlated with adverse outcomes. Subgroup analyses demonstrated increased risk of cardiotoxicity in patients with pre-existing cardiovascular conditions. Conclusion Early recognition of cardiotoxicity, with utilization of a multidisciplinary management approach, remains critical to improving long-term outcomes in patients undergoing CAR T therapy. While most events are nonfatal, severe complications can occur and are associated with increased mortality. Long-term cardiovascular sequelae remain poorly defined, underscoring the need for ongoing surveillance and further prospective studies.

Cardiotoxicity of chimeric antigen receptor T-cell therapy: narrative review

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2026年6月2日

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Jas Virk

摘要

Background

Chimeric antigen receptor T‑cell (CAR T) therapy has been a breakthrough in the treatment of multiple hematologic malignancies, yet its expanding use has revealed a spectrum of cardiotoxic effects. Cardiotoxicity is primarily mediated via cytokine release syndrome, with clinical manifestations including arrhythmias, hypotension, and heart failure. Severe cardiovascular events, such as myocardial infarction and cardiogenic shock occur less commonly, but are associated with significant morbidity and mortality. The risk of cardiotoxicity is heightened in patients with high-grade cytokine release syndrome and those with pre-existing cardiovascular disease or those with a history of exposure to anthracyclines. The pathophysiology is multifactorial, involving both direct T cell-mediated injury and indirect cytokine-driven myocardial dysfunction. This narrative review evaluates the current states of knowledge regarding CAR T‑cell therapy, its cardiovascular toxicity, clinical manifestations, pathophysiology, and outcomes.

Methods

Eligible studies for this narrative review were included if they reported original data on cardiovascular events associated with CAR T therapy in patients with hematologic or solid malignancies. Eligible study designs included: randomized controlled trials, cohort studies, case–control studies, case series, systematic reviews, and meta-analyses. Editorials and commentaries were excluded unless they provided pooled data relevant to cardiotoxicity. Studies published in languages other than English were excluded. A comprehensive literature search was conducted across the following electronic databases: PubMed/MEDLINE, Embase, Web of Science Core Collection, the Cochrane Library, and Google Scholar. The search included studies published from January 1, 1990, through March 31, 2026. In addition, the reference lists of all included studies and relevant review articles were searched to identify additional eligible publications. No filters for age, sex, or geographic region were applied. The search was limited to human studies. ClinicalTrials.gov was also searched for completed or ongoing trials reporting cardiovascular safety data. Search terms involved keywords related to “chimeric antigen receptor T cell,” “CAR T,” “cardiotoxicity,” “cytokine release syndrome,” “arrhythmia,” and “cardiac dysfunction.” Extracted variables included study design, CAR T product, sample size, incidence and type of cardiovascular event, association with cytokine release syndrome, and biomarker data. The selection process was documented using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram adapted for narrative reviews. Titles and abstracts retrieved from the database searches were screened for relevance by one reviewer. Full-text articles of potentially eligible studies were then assessed against the predefined inclusion and exclusion criteria.

Results

Cardiotoxicity was strongly associated with higher grades of cytokine release syndrome. The most common cardiovascular events included: hypotension, arrhythmias, and heart failure. Elevated cardiac biomarkers, including troponin and pro-BNP were frequently observed and correlated with adverse outcomes. Subgroup analyses demonstrated increased risk of cardiotoxicity in patients with pre-existing cardiovascular conditions.

Conclusion

Early recognition of cardiotoxicity, with utilization of a multidisciplinary management approach, remains critical to improving long-term outcomes in patients undergoing CAR T therapy. While most events are nonfatal, severe complications can occur and are associated with increased mortality. Long-term cardiovascular sequelae remain poorly defined, underscoring the need for ongoing surveillance and further prospective studies.