Vein graft failure: Pathophysiology, detection, prevention and emerging therapeutic strategies

Coronary and peripheral artery bypass graft surgery remain cornerstones of cardiac and vascular surgery, respectively. They utilize the saphenous vein as the preferred conduit, although it suffers from poor midterm and long-term outcomes, with the grafted vein often becoming occluded. Current therapeutic approaches aim to manage complications rather than prevent graft failure directly, and despite progress, failure rates have remained unchanged in decades, meaning there remains an unmet clinical need for novel therapeutic approaches. As access to the grafted tissue is available at the time of surgery, coronary and peripheral artery bypass graft are particularly suited to perioperative therapeutic manipulation and intervention that can be delivered locally and directly to the tissue immediately before grafting. Ongoing research attempts to uncover novel genes driving bypass graft failure that can be targeted for such therapies. In addition to protein-coding genes, multiple examples of noncoding genes driving graft failure are now described, including microRNAs and long noncoding RNAs with cell type-specific roles. The increasing wealth of single cell, single nuclei and spatial transcriptomic data related to cardiovascular pathologies are revealing novel target loci that could facilitate greater specificity for target manipulation in specific pathogenic cell types. In parallel, extensive research continues to develop advanced imaging techniques that can be used to monitor the patency of grafts over time, and guide the effective design of advanced therapies. Here, we discuss the progress in these areas and highlight how harmony among these will accelerate therapeutic progress toward vein graft disease. SIGNIFICANCE STATEMENT: Coronary or peripheral artery bypass surgery using saphenous vein grafts are among the most commonly performed cardiovascular surgeries for advanced vascular occlusions. However, both suffer from poor long-term graft patency. The continued development of next-generation multiomics technologies and advanced therapies are illuminating new therapeutic targets that offer hope toward novel precision medicines for peripheral and coronary artery bypass graft failure.