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Notes: Coronary angioplasty is used to treat coronary atherosclerotic disease in many patients. One problem with coronary angioplasty is the phenomenon of restenosis. Restenosis appears to be a universal response to arterial wall injury. The biological events that underlie restenosis are characterized by: platelet adhesion and aggregation at sites of damaged endothelium, and within dissections into the medial layers, release of platelet derived growth-promoting substances, inflammation of the injured medial zone, transformation, migration, and proliferation of smooth muscle cells of the media following their activation by growth-promoting substances, secretion of copious amounts of extracellular matrix material; and finally, termination of the growth process following regrowth of endothelium over the damaged area. More than a decade of research work has helped identify clinical correlates of restenosis after coronary angioplasty. Patient-related correlates include male gender, unstable angina, diabetes, and continued smoking after angioplasty. Lesion-related correlates include multilesion and multivessel procedures, higher post-angioplasty residual stenosis, proximal vessel location, location in the left anterior descending coronary artery, location in a vein graft, long lesions, and total occlusions. How-ever, for the purposes of individual patient care, clinical correlates are not particularly helpful. No group of variables has predicted complete freedom from restenosis, and conversely no group of variables has reliably indicated its presence. All patients undergoing angioplasty will require some form of follow-up evaluation. Symptom status by itself has not been found to be useful for predicting restenosis. However, when symptom status is combined with exercise thallium-201 scintigraphy, performed 4–6 months after angioplasty, it is less than ideal, but has a negative predictive value of over 90%. This means that over 90% of patients who are asymptomatic and have no evidence of ischemia by thallium-201 scintigraphy, will not have angiographic restenosis. Numerous clinical trials have been performed in order to reduce or prevent restenosis. Almost all have been disappointing, while a few have been encouraging. Studies of antiplatelet agents such as aspirin, dipyridamoleR (Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA), and TiclopidineR (Syntex, Humgcao, Puerto Rico) have not shown efficacy, yet studies of an inhibitor of platelet-derived growth factor have been provocatively encouraging. No reduction in restenosis rates was found with the anticoagulants CoumadinR (Du Pont Pharmaceuticals. Wilmington, DE, USA) and HeparinR (Wyeth-Ayerst, Philadelphia, PA, USA). Fish oils (omega fatty acids) have been found in several clinical trials to provide modest, but encouraging, reductions in restenosis, but await further confirmation. Inhibitors of thromboxane, along with analogues of prostacyclin, have not been found to be effective. A variety of other agents, including angiotensin converting enzyme inhibitors, calcium channel antagonists, beta adrenergic receptor antagonists, lipid lowering agents, and the anti-mitotic colchicine, have all been found to be ineffective. A number of other mechanical revascularization strategies, such as atherectomy procedures and coronary stent devices, can achieve potentially better initial results than standard balloon angioplasty in some situations. Restenosis rates appear to be slightly lower in some groups after these procedures; further research with them is required. Restenosis remains a clinical challenge, but a better understanding of coronary artery disease, its development and treatment, will ultimately be derived from studies of the phenomenon of restenosis. (J Interven Cardiol 1993; 6:187–202).

Notes: Summary Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown that in patients with left ventricular dysfunction, several neurohormonal systems were activated, even in the absence of symptoms of congestive heart failure. This suggested that the cardiovascular system was not in a steady state and pointed out potential culprits for the progression of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an important prognostic value. Another value of neurohormonal studies obviously is the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of these neurohormonal systems, such as with the use of the angiotensin-converting enzyme (ACE) inhibitors, particularly captopril and enalapril, and to a lesser extent, with beta-blockers. It can therefore be expected that, in the future, most patients with severe ischemic dysfunction will be treated with an ACE inhibitor. Nonetheless, neurohormonal control is not complete with these drugs; powerful vasoconstrictor forces, such as endothelin-1, remain activated, and an escape of angiotensin II from the control of ACE inhibition may exist. Thus, morbidity (e.g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In the search for further improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action, coupled with powerful coronary vasodilation, might hypothetically delay the progression of ischemic LV dysfunction. In addition, the improved pharmacokinetic profile of these drugs avoiding wide peak and trough variations in plasma levels may avoid triggering some neurohormonal reflexes.