Current interventional cardiology reports最新文献

This review examines methods for detecting the effects of angiogenic interventions on myocardial blood flow and left ventricular function. Animal-based methods of measuring myocardial blood flow are presented, as are other methods for detecting angiogenesis in animal models. Clinically feasible end points, including perfusion imaging with radionuclide techniques, positron emission tomography, myocardial contrast echocardiography, magnetic resonance perfusion imaging, and electron-beam computed tomography with iodinated contrast, are then discussed. The strengths and weaknesses of each technique in relation to measurement of the efficacy of angiogenic interventions are analyzed. Indirect methods for detecting enhanced blood flow by regional or global left ventricular function are discussed, with attention to the reproducibility of serial measurements obtained with these approaches. Specific recommendations for efficacy and effectiveness end points in angiogenic trials are provided.

For the well-being of our patients with coronary atherosclerosis, it is important that cardiologists become more familiar with the diagnosis and treatment of noncardiac atherosclerotic lesions commonly associated with coronary atherosclerosis. Cardiologists receive instruction in peripheral vascular disorders during fellowship training, and this includes training in the performance of noncardiac angiography. Interventional cardiologists possess the technical skills to perform peripheral vascular interventions and the clinical skills to care for patients who undergo these interventions, but they generally lack the fund of knowledge needed to provide comprehensive care. Newly revised criteria for the certification of cardiologists in peripheral vascular intervention were recently published by the Society of Cardiac Angiography and Intervention. A novel element of these revised guidelines is a tiered approach that includes limited certification for renal and iliac intervention, or unrestricted certification for physicians who meet more rigid criteria. The limited certification criteria are designed to facilitate entry into the field by practicing cardiologists who wish to expand their clinical skills for the benefit of patients with peripheral vascular disease.

Eptifibatide (Integrelin, Corr Therapeutics, South San Francisco, CA) is a cyclic heptapeptide competitive inhibitor of the platelet glycoprotein (GP) IIb/IIIa receptor that has a short half-life. The results of the initial dose-finding and phase III trials are reviewed and the ongoing Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial are described.

Blood vessels are essential for the supply of oxygen and nutrients to the heart. An imbalance between oxygen demand and supply (ischemia), as occurs when coronary arteries become obstructed by atherosclerotic plaques, triggers a response to improve myocardial perfusion by the formation of new capillaries (angiogenesis) and by the enlargement of preexisting collateral vessels (arteriogenesis). Recently, novel insights have been obtained in the molecular mechanisms of angiogenesis and in its control by hypoxia. This has lead to the design of strategies to improve myocardial perfusion. However, rational design of therapeutic angiogenesis mandates a better understanding of the molecular basis of angiogenesis. This review discusses the role of two prime classes of angiogenic molecules, namely of vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and addresses novel insights in the regulation of angiogenesis by hypoxia. In addition, a novel mouse model of ischemic cardiomyopathy with signs of hibernation is presented. Possible implications for therapeutic myocardial angiogenesis are discussed.

Inhibition of thrombin and platelets during percutaneous coronary intervention (PCI), using a combination of unfractionated heparin and aspirin, is designed primarily to minimize the rare but devastating potential acute thrombotic complications of the procedure. Direct thrombin inhibitors, such as bivalirudin (formerly Hirulog, The Medicines Company, Cambridge, MA), offer specific theoretic advantages over unfractionated heparin as antithrombin therapy. This review focuses on the pharmacologic promise and the clinical performance of bivalirudin in PCI, and in the pharmacologic management of acute coronary syndromes. Clinical experience with bivalirudin in PCI preceded recent dramatic advances in mechanical interventional techniques and the emergence of novel potent platelet inhibitors. The role of bivalirudin and other direct thrombin inhibitors in the modern era of coronary intervention therefore requires further elucidation.

New technology has given vascular surgeons novel treatment options for aortic diseases. Endovascular aortic aneurysm repair is a minimally invasive technique that uses a graft to reconstruct an aneurysmal segment without laparotomy, aortic incision, or cross-clamping. The procedure results in less pain and suffering for patients and requires fewer health care resources. Although still experimental in the United States, this operation has become routine in several centers in Australia and Europe. Collective experience with endovascular repair has yielded complication and mortality results that compare favorably with those from leading studies of conventional repair, despite significant medical comorbidity among its cohorts. The durability of contemporary endovascular repair approaches, but does not yet equal, that of conventional surgery. However, in conditions such as complicated aortic dissection, the new technique may be superior. In this review we describe endovascular devices and their selection and discuss results of the largest contemporary studies.

Five randomized trials have conclusively demonstrated that aspirin and ticlopidine are more effective than aspirin and Coumadin (DuPont Merck Pharmaceutical Co., Wilmington, DE), or aspirin alone, at preventing thrombosis and other ischemic complications after stent placement. However, side effects from ticlopidine are common, the most serious of which are neutropenia and thrombotic thrombocytopenic purpura. Another problem with ticlopidine is its slow onset of action. Recent observational data from several centers and data from a randomized trial indicate that clopidogrel, which can be administered with large loading doses that are well tolerated and speed the onset of action, is at least as effective as ticlopidine. Clopidogrel has far fewer side effects as well. Questions remain about the most appropriate loading dose of clopidogrel and duration of therapy after stent placement.

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.

Because angiogenesis appears to be a fundamental mechanism associated with direct myocardial revascularization (DMR) procedures, it seems natural to combine the overall field of DMR with angiogenesis therapy. Such myocardial treatment strategy can thus be termed "mechanical approach for myocardial angiogenesis." In this article, we review the myocardial response to various ablative energy sources in order to explore data indicative for angiogenesis in response to mechanical myocardial injury, or by using hybrid approaches, combining energy sources with proangiogenic pharmacotherapy.

The development of the heparin-coated (HC)-stent should be viewed against the backdrop of the early unfavorable results with noncoated stents in the pre-intravascular ultrasound and pre-ticlopidine era. Notwithstanding, results of pilot and randomized trials show a surprisingly low incidence of (sub)acute stent thrombosis under challenging circumstances, such as acute coronary syndromes. Considering the quite low incidence of early complications with noncoated second-generation stents, it may require large trials to prove the clinical efficacy of the heparin- coating against noncoated devices. However, even if the "added value" of the heparin-coating will never be clinically proven, it has helped to enhance the penetration of stent therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now disagree with the statement that stents contribute to the state-of-the-art treatment of patients with angina pectoris or acute myocardial infarction. A preliminary comparison of available trials also suggests that the heparin-coated Palmaz-Schatz stent (Cordis Corp., Waterloo, Belgium) is as effective as the noncoated stent plus abciximab treatment.