Review Articles in 2006

The cardiovascular benefits of statin therapy are well documented; however, no trial has identified a target level for LDL cholesterol below which no further benefit of treatment is seen. With the introduction of more-aggressive optional LDL-cholesterol targets in US guidelines, Antonio Gotto and John Farmer consider the rationale for combination therapy of statins with the cholesterol absorption inhibitor ezetimibe.

The loss of cardiomyocytes in failing or cardiomyopathic hearts is gradual and not accompanied by inflammation or major histomorphologic deformity. Apoptosis, therefore, seems to be the most logical mechanism of cell death. In this Review, Narula et al. discuss the role of apoptosis in systolic dysfunction and heart failure, and in the development of novel strategies for the management of heart failure.

The current treatment for patients receiving coronary stents is dual antiplatelet therapy. Approximately 5% of these patients, however, require long-term anticoagulation because of an underlying chronic medical therapy and, theoretically, should receive triple therapy, which increases bleeding risk. Here, Helft et al. critically appraise the available literature concerning antithrombotic therapy and make recommendations for antiplatelet therapy following revascularization in the small subset of patients already receiving anticoagulation.

Currently, the only proven treatment to re-establish cerebral blood flow in acute ischemic stroke is intravenous tissue plasminogen activator within 3 h of symptom onset. Few patients, however, qualify for this therapy. Here, Juttler et al. provide an integrated view of the current state of reperfusion therapy in acute stroke patients and discuss future treatment options to extend the therapeutic window for intervention.

Gestational glycemic disorders and hypertension in previously healthy women are thought to have a notable bearing on women's cardiovascular risk in later life. In this Review, Banerjee and Cruickshank discuss the opportunities for identification and prevention of early cardiovascular disease in women afforded by these disorders arising.

Claudication is a disabling complication of peripheral arterial disease. Therapy aims to minimize the risk of related cardiovascular events and to improve patients' walking ability by limiting the claudication symptoms. Judith Regensteiner and Kerry Stewart present information on the pharmacological and exercise therapy options currently available.

Enhanced external counterpulsation, a noninvasive treatment that involves the sequential inflation of three sets of lower-extremity cuffs during diastole, can reduce the severity and frequency of angina pectoris. Here, Michaels et al. review the experience from the International EECP Patient Registries to evaluate the therapy's safety and efficacy, and provide a practical guide to the selection of patients and application of enhanced external counterpulsation.

Outcomes after repair of tetralogy of Fallot have been remarkably improved and short-term survival is now excellent. As patients live longer, however, late complication rates and the need for reoperation are rising. In this Review, the major complications of this heterogeneous condition are outlined and the surgical options for management discussed.

Malignant cardiac tumors have a dismal prognosis left untreated but pose a therapeutic challenge to oncologists and cardiac surgeons. Extensive resection can be required and the positions of the tumors create technical difficulties. Primary malignant tumors can also represent aggressive disease. The clinical manifestations and therapeutic options are discussed in this Review.

Although apolipoprotein A-I has benefits in relation to atherosclerosis, this large protein can only be administered intravenously and is difficult and expensive to manufacture. Smaller peptides that mimic apolipoprotein A-I and yield the same beneficial effects have, therefore, been sought. The advances being made in this therapeutic area are described.

After becoming established as a therapy for various anemic states, wider uses—including cardiovascular therapy—are being explored for erythropoietin. The possible mechanisms for actions in the cardiovascular and renal systems are explored in this Review, showing that the therapeutic benefits of this cytokine seem much broader than initially anticipated.

Use of MRI to track cell migration to target tissue, such as after stem cell transplantation in heart failure, offers a potential new way to monitor treatment. Most data come from preclinical studies but suggest a role for this technique in humans. This Review discusses the suitability of various contrast agents and labelling methods.

A single definition for the metabolic syndrome is not forthcoming since discussion of its forms and causes is continuing. Genetic causes and onset of the syndrome in relation to triggering genetic–environment interactions have been suggested. In this Review, the currently available knowledge about the most common purported genetic causes is drawn together.

In healthy adult hearts approximately 70% of energy is obtained from fatty acids; the balance comes from lactate, pyruvate and ketones. The pattern of substrate use is altered in failing hearts. This Review discusses substrate use and the possible benefits of using metabolic agents to cause a shift away from fatty acids as the main substrate.

The severity of left ventricular dilatation and remodeling represents one of the strongest predictors of mortality. Prevention, reversal, or both of left ventricular remodeling therefore constitute crucial parts of therapy in many cases. Along with pharmacologic therapies various surgical procedures are available. In this Review, the most common surgical options for left ventricular remodeling are discussed.

In the no-reflow phenomenon, blood flow to an infarcted area can be markedly reduced by destruction of the microvasculature or blockage of vessels by microemboli, despite an open infarct-related artery. Minimization of the affected area is important to improve outcomes. Data are presented in this Review on causes and therapies.

Despite LDL-cholesterol targets being lowered several times in recent years, are they low enough? New data continue to be published showing that LDL lowering should be a primary target of therapy, with the possibility of simultaneously raising HDL cholesterol. Wiviott and Cannon bring together the extensive data to provide an update.

Many protein kinases are positioned proximal to critical proteins that mediate cell function. Since these functions can be altered by disease, attention has turned to protein kinases as therapeutic targets. In this Review, the role of protein kinases in myocardial disease, and the pharmacologic therapy possibilities they present are discussed.

In this Review, Amish Desai, Cindy Fuller, Jill Jesurum and Mark Reisman discuss the possible link between patent foramen ovale and cryptogenic stroke, treatment options for prevention of paradoxical embolism related to patent foramen ovale and the controversial association between patent foramen ovale and migraine headaches.

Although mechanical circulatory support has been used in children for many years, the development of implantable devices and improvements in extracorporeal support have provided viable options for bridging to transplantation or even to recovery. Hetzer and Stiller share their experience with the technology and techniques and discuss the decision-making processes.