Ivonescimab is a first-in-class tetravalent, fragment crystallizable (Fc)-silenced bispecific antibody that binds programmed cell death protein 1 (PD-1) and vascular endothelial growth factor-A (VEGF-A) with mutually cooperative avidity. It is the lead molecule of a rapidly expanding PD-(L)1/VEGF bispecific class, has demonstrated superiority over both pembrolizumab and tislelizumab-based regimens in randomized phase III trials, and is under regulatory review in the United States. Its design combines two distinct cardiovascular liabilities in a single agent: the vascular toxicity of VEGF signaling pathway inhibition and the immune-mediated toxicity of PD-1 blockade. Cardio-oncology currently has no framework that addresses both at once. This narrative review aims to characterize the VEGF-A-axis and PD-1-axis cardiovascular toxicities of ivonescimab at the level of mechanism and clinical evidence, to appraise whether the molecular architecture of the antibody attenuates either of them, and to translate that appraisal into a bedside surveillance framework and a research agenda. Throughout, findings observed in ivonescimab-treated patients are distinguished from extrapolations drawn from the VEGF signaling pathway inhibitor and immune checkpoint inhibitor classes, and from hypotheses generated by this review. The VEGF-A arm appears to reproduce the class toxicity of VEGF signaling pathway inhibitors: hypertension and proteinuria as on-target endothelial and glomerular effects, thromboembolism and left-ventricular strain as downstream consequences, and hemorrhage as a renewed concern now that a survival benefit has been shown in squamous non-small cell lung cancer. The PD-1 arm carries a low-probability, high-lethality myocarditis hazard together with pericardial disease, vasculitis, and accelerated atherosclerosis. Cooperative binding chiefly supports tumor-enriched efficacy and offers limited protection to the systemic vasculature, since circulating VEGF-A is measurably suppressed and proteinuria occurs in roughly one in five patients. Fc silencing is a coherent but weakly supported rationale for reduced immune toxicity, and intermittent VEGF-A suppression remains an untested basis for vascular sparing. Ivonescimab’s cardiovascular profile appears favorable within the populations studied, but its mechanisms make it unlikely to be free of cardiovascular risk, and the trials conducted to date were not designed to measure the endpoints most relevant to cardio-oncology. We propose a risk-stratified surveillance framework, a set of falsifiable predictions, and a cardiovascular core outcome set for the PD-(L)1/VEGF bispecific class while registrational datasets are still open.
With improved cancer survivorship, cardiovascular disease (CVD)-related mortality in cancer survivors has risen. Cardio-oncology is an established subspecialty dedicated to the prevention and treatment of the adverse cardiac effects of cancer therapies, facilitating the continuation of cancer treatment, improving quality of life and long-term care. This review explores recent evidence and challenges in understanding and managing cardiotoxicity in respect of five cancers commonly encountered by the general physician. We focus on long-term cardiovascular risks of treatments, the bidirectional relationship between cancer and CVD and cardiotoxic mechanisms. We critique current methods of risk assessment and stratification of cardiotoxicity and future directions for prevention and management. Finally, emerging evidence for the role of lifestyle measures in cardioprotection is recognised.
To describe cardiovascular risk factors, cardiac biomarkers, and conventional echocardiographic findings in long-term childhood cancer survivors exposed to anthracyclines and to explore associations with treatment-related exposures. This retrospective cross-sectional single-center study included 97 long-term childhood cancer survivors exposed to anthracyclines, with or without thoracic radiotherapy. Cardiovascular risk factors and biomarkers were assessed during 2024–2025. Echocardiographic data were obtained retrospectively from the most recent examination performed during routine follow-up and were not contemporaneous with biomarker assessment. Anthracycline exposure was converted to doxorubicin-equivalent dose. Median time since completion of cancer treatment was 13.7 years. Overweight/obesity was present in 29.9
Radiation therapy (RT) is associated with cardiovascular complications, such as atrial fibrillation (AF). The prevalence of AF in patients with cancer receiving RT remains poorly characterized. This study describes the stratified prevalence of AF in patients with cancer receiving RT and explores the sources of variability across studies. A comprehensive literature search was performed using PubMed, Scopus, Cochrane Library, and Google Scholar from the inception to April 2026 to identify studies reporting AF prevalence among patients receiving RT. Pooled prevalence estimates with 95
