Seminars in interventional cardiology : SIIC最新文献

Angioplasty therapy for acute myocardial infarction (direct or primary coronary angioplasty) has been a hot issue of the medical literature since 1982. It was first presented as a rescue therapy in the case of failed intracoronary thrombolysis. Later it was described as a useful complement to thrombolysis before it emerged as a formidable alternative. For a number of years in the late 1980s, the advent of clot-specific intravenous thrombolysis swayed the spotlight from direct angioplasty on to the non-invasive active drug treatment. This was reversed by the appearance of several randomized studies demonstrating superiority of angioplasty in 1992. Later studies have put this advantage of angioplasty over thrombolysis in perspective again. It was found that the superior results of the randomized studies on selected patients could not be reproduced in everyday cases. Nonetheless, a small but significant advantage of primary angioplasty remains when all available literature is scrutinized carefully. Even if the results in terms of mortality and acute events during the initial hospital stay are quite comparable for thrombolysis and primary angioplasty, the latter removes the culprit clot, treats the underlying lesion, and informs about the general state of the coronary vasculature and the myocardium with unsurpassed details. Moreover, most patients with intravenous thrombolysis will undergo cardiac catheterization within the first year after their infarction. Thus, the facts that the initial savings of foregoing cardiac catheterization is lost and the cost of the thrombolytic drug can be spared with primary angioplasty may tilt the scale in favour of primary catheter intervention. As direct angioplasty establishes patency earlier and more completely than thrombolysis, a slightly better hospital course and markedly better long-term course with improved longevity, myocardial function, and fewer cardiac events can be achieved. This is not necessarily associated with a higher investment, because the initial surplus in cost of primary angioplasty tends to revert into savings over time. All patients amenable to direct angioplasty within 30-60 min after initial diagnosis should be offered the procedure. In the remaining cases, thrombolysis is the preferred treatment. The role of primary angioplasty is the more important the larger the infarction. However, in small infarctions but also in protracted cardiogenic shock it may be wasted, but so is any other aggressive treatment.

The treatment of acute myocardial infarction consists of pain and anxiety relief, anti-ischaemic treatment and antithrombotic therapy. Due to its bleeding complications and, in some cases, procoagulant effects, antithrombotic therapy has consequences for coronary procedures in the setting of acute myocardial infarction. Antiplatelet therapy has no procoagulant effects, and its bleeding complications can easily be managed. Antithrombin therapy has rebound effects, for which no clear solution is available. Thrombolytic therapy has also procoagulant effects, which may interfere with coronary procedures in the early hours of acute myocardial infarction. Heparin may counteract the thrombolysis-induced thrombin generation, but has an unpredictable effect. Postprocedural therapy after angioplasty in the setting of acute myocardial infarction should consist of antiplatelet therapy.

Although the benefits of primary angioplasty for acute myocardial infarction have been demonstrated, several areas for improvement remain. The initial results of randomized trials have shown that primary stenting for acute myocardial infarction is feasible and effective with a low complication rate. Primary stenting results in a reduction in recurrent infarction and in the need for subsequent re-intervention, when compared to balloon angioplasty. Whether long-term clinical and angiographic outcome is also favourable has yet to be confirmed in large-scale multicentre trials, before primary stenting can be adopted as routine approach for acute myocardial infarction.

In the last few years, radioactive stents has been proved to inhibit neointima formation. This paper describes the actual status of producing such radioactive stents. After a short discussion of the different radioisotopes suitable for radioactive stents, potential production methods are discussed. The ion beam implantation of P-32 applied at the Karlsruhe Research Centre shall be described in more detail.

A novel approach of cell seeding of stents using xenotransplanted endothelium is proposed. The advantages of this approach are that these doubly transgenic animals will provide a limitless supply of endothelial cells producing controllable levels of active compound. These foreign cells will act as Trojan horses, graciously accepted at face value by the host organism, but capable of modifying the pathophysiological response to vessel damage, typified by the process of restenosis. Once implanted, the production of the bioactive compound is under exogenous control by means of 'designer' genes coding for modified cell surface receptors, which are introduced with the transgene to provide controllable levels of compound. Interaction of an orally administered compound with the modified cell receptor will switch on the transgene, while in its absence the transgene remains dormant. We have been able to show the feasibility this type of approach has for other animal species, and it shows great potential for application to humans.

Restenosis remains the major problem in interventional cardiology today. The intracoronary stent is an indispensable part of the interventional coronary practice. Restenosis rates, using current third generation devices in straightforward lesions are now less than 10%. Advances in stenting have had a remarkable effect on the safety and efficacy of clinical practice. Now that stents are easily deployed, and have shown substantive clinical impact, questions arise about the future of stenting. Answers to this question centre on several remaining problems with current stent technology and interaction with the biology of coronary arteries. One method to accomplish this is to have the material of the stent interact directly with the vessel. This can be achieved by better stent materials, or by impregnating the stent with drugs or genes to modify the vessel wall. This chapter will describe several such approaches under consideration.

In an effort to overcome the limitations of local drug delivery associated with the use of catheters, drug-loaded stents have been developed. Loading of such stents is achieved through either drug absorption (incorporation into a matrix) or drug adsorption (surface layering). The type of drug binding determines the elution profile/release kinetics of the drug, while the therapeutic target determines both the choice of drug used and the manner in which it is bound, i.e. eluting or non-eluting. While non-eluting stents have clinically reduced thrombotic complications following stent implantation, current experimental work concentrates on the use of eluting stents to combat restenosis.

The potential beneficial effect of metal surface treatment using electrochemical polishing on stent thrombogenicity and neointimal hyperplasia was evaluated in a rat A-V model and a porcine coronary model. Thrombogenicity of polished stents (n=6) was compared to non-polished stents (n=5) in a rat A-V shunt model using 125I-fibrinogen and 51Cr-labelled platelets. Total clot weight after 30 min was significantly lower in the polished stents (32.1+/-2.8 vs 18.1+/-4.4: p<0.001). Also, 125I-fibrinogen deposition was significantly lower in the polished stents (1.30+/-0.07 vs 0.66+/-0.04: p<0.001). Platelet deposition was, however, not significantly reduced (12.7+/-3.4 vs 9.87+/-1.9, NS). Subsequently, the effect of electrochemical polishing on neointimal hyperplasia was evaluated in a porcine coronary model. Polished (n=10) and non-polished stents (n=10) were randomly implanted in the right coronary artery of healthy pigs. Neointimal hyperplasia was significantly decreased in the polished stents (0.56+/-0.28 vs 0.94+/-0.34 mm2: p<0.01).

The development of the end-point attached HC stent should be regarded against the early unfavourable results with uncoated stents in the pre-IVUS- and pre-ticlopidine era. Despite this, results of pilot- and randomized trials show a surprising low incidence of (sub)acute stent thrombosis under challenging circumstances like acute coronary events. Considering the quite low incidence of early complications of non-coated second generation stents it may require very large trials to test the clinical efficacy of the HC coating against non-coated devices. However, even if the 'added value' of the HC coating is never scientifically proven, it has helped to a large degree to enhance the penetration of stent-therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now oppose the statement that stents contribute to the state of the art treatment of patients with angina pectoris or acute myocardial infarction.