Therapeutic Angiogenesis Using Endocardial Approach to Administration: Techniques and Results

The availability of various angiogenic growth factors and gene therapy vectors, and the demonstration of their angiogenic potential in animal models of chronic myocardial ischemia, has propelled their investigation in clinical trials of therapeutic angiogenesis in patients with ischemic heart disease. Although most preclinical studies have employed methods of prolonged drug delivery and local therapy, the need for repeated administration and invasive access has limited the clinical usefulness of these delivery strategies. Intracoronary and intravenous delivery, with their potential widespread applicability, has fueled their use in most clinical trials of therapeutic angiogenesis; however, the significant systemic recirculation, limited myocardial retention, and potential for serious systemic adverse events are major limitations to their clinical use. Epicardial delivery using surgical access has been used in several clinical studies, but the need for surgical access and general anesthesia may limit the usefulness of this technique. The development of percutaneous endocardial delivery catheters using fluoroscopic guidance or Biosense NOGA (Biosense Laboratories, Haifa, Israel) electromagnetic three- dimensional navigation system has generated significant interest in the use of this delivery strategy in therapeutic myocardial angiogenesis studies. These strategies are being intensively investigated in preclinical studies with clinical studies soon to follow. We describe the limited experience with these drug delivery devices.