Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results

Patients not amenable to complete myocardial revascularization by conventional methods present a difficult clinical problem. Here we present the early results and technical considerations of the administration of basic fibroblast growth factor for the induction of collateral growth using heparin-alginate slow-release devices in patients undergoing coronary artery bypass grafting.

Eight patients were enrolled. Patients were candidates if they had at least one graftable obstructed coronary artery and at least one major arterial distribution not amenable to revascularization, a serum creatinine level less than 3 mg/dL, ejection fraction greater than 0.20, and estimated operative mortality of less than 25%. During conventional coronary artery bypass grafting, 10 heparin-alginate devices, each containing either 1 microg or 10 microg of basic fibroblast growth factor, were implanted in the epicardial fat in multiple regions of the unrevascularizable territory and also in the distal distribution of a grafted or patent artery.

There was no mortality and no evidence of renal, hematologic, or hepatic toxicity during follow-up. Three months after the operation, all patients remain free of angina. Seven patients were examined with stress perfusion scans. Three patients had clear enhancement of perfusion to the unrevascularized myocardium, 1 patient had a new fixed defect, and 3 had minimal overall change but had evidence of new small, fixed perfusion defects. Seven patients had improved or similar myocardial contractile function (ejection fraction at 3-month follow-up = 0.53 +/- 0.22 versus 0.47 +/- 0.14 preoperatively). One patient suffered a perioperative myocardial infarction in the area of basic fibroblast growth factor administration.

This preliminary study demonstrates the safety and technical feasibility of therapeutic angiogenesis with basic fibroblast growth factor delivered by heparin-alginate slow-release devices. Further studies examining the safety, clinical efficacy, and long-term results are ongoing.