Aims: Cardio-oncology has traditionally focused on cardiovascular complications of cancer and its treatment. Emerging evidence suggests the reverse relationship, whereby cardiovascular disease (CVD) may contribute to malignant evolution. We reviewed current evidence supporting reverse cardio-oncology in hematologic malignancies, focusing on mechanistic pathways linking cardiovascular pathology with hematopoietic transformation.
Methods: A structured narrative review was conducted using PubMed, Scopus, and Google Scholar (through January 2026). Literature examining cardiovascular disease, reverse cardio-oncology, clonal hematopoiesis, hematologic malignancies, heart failure, inflammation, hypoxia, and bone marrow biology was reviewed. Priority was given to epidemiologic studies, mechanistic investigations, and contemporary review articles.
Results: Current evidence consistently demonstrates an association between heart failure, myocardial infarction, and atrial fibrillation with an increased incidence of subsequent malignancy, including hematologic cancers, although residual confounding and surveillance bias limit causal inference. Mechanistic evidence identifies three interconnected biological pathways. Chronic hypoxia may remodel the bone marrow microenvironment and promote adaptive signaling through hypoxia-inducible pathways. Persistent inflammation, mediated by IL-1β, IL-6, TNF-α, and NLRP3 activation, may facilitate hematopoietic stem-cell activation, oxidative stress, and selection of premalignant clones. Clonal hematopoiesis of indeterminate potential (CHIP), particularly involving DNMT3A, TET2, and ASXL1, represents the strongest mechanistic bridge between cardiovascular disease and hematologic malignancy. Bone marrow–cardiovascular crosstalk, endothelial remodeling, neurohormonal activation, and oxidative stress further support a biologically plausible bidirectional relationship.
Conclusion: Reverse cardio-oncology provides a compelling framework linking cardiovascular disease with hematologic malignancy through shared inflammatory, hypoxic, and clonal mechanisms. Although current evidence supports biological plausibility, prospective longitudinal studies integrating cardiovascular phenotypes, inflammatory biomarkers, hematologic parameters, and somatic mutation profiling are required before these concepts can inform routine clinical practice.