From unidirectional toxicity to bidirectional systemic interplay in Cardio-Oncology

<p>Cardio-oncology has expanded beyond the traditional focus on cancer therapy-related cardiovascular toxicity (CTR-CVT) to encompass the broader and increasingly recognized interplay between cancer and the cardiovascular system. Although advances in anticancer therapy have markedly improved survival, cardiovascular complications have become a major determinant of long-term morbidity and mortality in patients with cancer. At the same time, emerging evidence suggests that the relationship between cancer and cardiovascular disease is bidirectional: malignancy itself may impair cardiac structure and function, whereas pre-existing cardiovascular disease may contribute to tumor progression through immune, metabolic, neuroendocrine, and secretory mechanisms. In this review, we summarize the evolving clinical spectrum of CTR-CVT, discuss its pathophysiological basis within a multi-hit framework linking baseline cardiovascular vulnerability, tumor-derived signals, treatment-related injury, and review recent advances in multi-modal imaging, biomarker surveillance, artificial intelligence-assisted risk assessment, and real-world data integration. We further propose a multi-dimensional stewardship framework spanning pre-therapy risk stratification, intra-therapy surveillance and cardio protection, and long-term survivorship care. Finally, we highlight the emerging concept of reverse cardio-oncology, in which the diseased cardiovascular system may act as a systemic driver of malignancy, thereby reinforcing a reciprocal relationship between cancer and the heart. Together, these advances support a shift from a unidirectional toxicity model toward a systems-based framework for precision surveillance, mechanism-informed intervention, and integrated cardio-oncology care.</p>