Review Articles in 2010

Aging is accompanied by changes in vascular structure and function leading to arterial stiffness, which is an important predictor of cardiovascular disease. Hemodynamic changes associated with arterial aging include increased pulse pressure, pulse wave velocity, and wave reflection. In this Review, Michel Safar describes the features of arterial aging, and how blockade of the renin–angiotensin–aldosterone system may ameliorate the effects of this process.

Vascular calcification is associated with an increased risk of cardiovascular and all-cause mortality. In the past decade, the prevalence, significance, and regulatory mechanisms of vascular calcification have gained increasing recognition. In this Review, Drs. Sage, Tintut and Demer discuss our knowledge of the regulatory mechanisms for both atherosclerotic and medial calcification.

Pulmonary embolism (PE) is a frequently occurring, acute, and potentially fatal condition. Numerous risk factors for PE have been identified. The diagnostic work-up for PE should comprise safe, efficient and noninvasive methods. In this Review, Renée Douma and colleagues discuss the epidemiology of PE, its risk factors and clinical presentation, together with the latest advances in the diagnostic approach to this condition.

Epigenetic modifications, such as DNA methylation and histone acetylation, are crucial for homeostasis, and enable cells to respond quickly to environmental changes. However, epigenetic alterations are also associated with the development and progression of disease. The authors of this Review outline how epigenetics may contribute to cardiovascular disease, and highlight potential therapeutic agents that modify the epigenetic state, which could be used in the prevention or treatment of cardiovascular disease.

Antithrombotic therapy with ADP-receptor antagonists or anticoagulant agents improves outcomes in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention. However, the current standard-of-care ADP-receptor antagonist for dual antiplatelet therapy, clopidogrel, and the currently available oral anticoagulants, the coumarins, have several limitations. In this Review, the authors discuss the pharmacology and clinical potential of new antithrombotic drugs, with an emphasis on data from phase III clinical trials.

The Fontan palliation was introduced in 1968 for congenital heart defects with a single dominant ventricle. Although considerable technical improvements have meant that this procedure can be applied to a wide range of patients, the Fontan circulation has intrinsic limitations. Professors de Leval and Deanfield consider the past four decades of Fontan palliation and describe how developments have moved practice closer to the 'perfect' Fontan. Future challenges and possible solutions are also discussed.

The duration and frequency of episodes of atrial fibrillation (AF) and the longitudinal history of this arrhythmia can vary markedly across patients. The currently accepted scheme for AF classification is based on temporal rhythm-based patterns. In this Review, the authors discuss the advantages and limitations of this categorization, highlighting gaps in knowledge that are opportunities to re-examine the current scheme and may lead to future improvements in AF classification.

Although effective therapies for hypertension exist, the prevalence of elevated blood pressure and resistant hypertension is increasing and novel treatment strategies are needed. In this Review, Drs. Paulis and Unger discuss new targets for antihypertensive therapy, many of which, including renalase and the (pro)renin receptor, are based on modulation of the renin–angiotensin–aldosterone system. Invasive strategies, such as renal denervation, are also explored.

This Review highlights the often-overlooked role that nonadherence has in apparent 'resistance' to antiplatelet therapy. Emerging evidence indicates that the prevalence and clinical impact of nonadherence to therapy overshadow that of true biochemical nonresponsiveness in the chronic phases of antiplatelet treatment. Potential reasons for this nonadherence, which should be considered when trying to overcome apparent 'resistance' to this therapy, are discussed.

Diagnosis of hereditary transthyretin-related amyloidosis (ATTR) is challenging owing to its extremely heterogeneous phenotype. The existence of predominantly cardiac presentations should prompt cardiologists to consider ATTR in patients with otherwise unexplained left ventricular wall thickening. Orthotopic liver transplantation (or combined heart–liver transplantation) can potentially provide surgical 'gene therapy' in patients with ATTR, provided that diagnosis is timely.

To date, treatment strategies for heart failure have focused on the symptomatic stage of disease, often after irreversible remodeling and functional impairment have occurred. Early identification of cardiac dysfunction would allow implementation of early intervention strategies to delay the progression or to prevent the onset of heart failure altogether. This Review highlights the utility of a staged approach for patients with predisposing risk factors, which uses serological biomarkers followed by noninvasive imaging techniques.

Echocardiography is commonly used to assess hypertrophic myopathies. The authors of this Review outline imaging modalities that are more sensitive than standard echocardiography, which can be used to determine characteristic changes in regional deformation at an earlier stage, and provide more information about the underlying processes associated with different hypertrophic myopathies.

Current strategies for prevention of cardiovascular disease (CVD) are focused on identifying individuals at high risk by recognizing and managing established cardiovascular risk factors. Early detection of subclinical atherosclerosis is a promising opportunity for CVD prevention. In this article, the authors review the role of noninvasive imaging techniques in understanding the mechanisms of atherosclerosis and in identifying early stages of disease, and highlight their potential impact on CVD prevention.

In this Review, Drs Kullo and Cooper discuss the role of genomics and proteomics in cardiovascular risk assessment, using the specific example of atherosclerosis. The availability of good markers for risk stratification might enable the health-care system to become more proactive, moving the focus away from treatment of end-stage coronary heart disease and towards early detection of disease risk and prevention of adverse outcomes.

Detection of fetal conduction system abnormalities relies upon magnetocardiographic or electrocardiographic recording techniques. Appropriate fetal treatment requires awareness of arrhythmia characteristics, mechanisms, and their potential associations. This Review discusses current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Early management of this disorder using imaging, antiarrhythmia drugs and catheter ablation is necessary to prevent the progression of AF. In this Review, the authors discuss the current status of important facets of the early management of AF and emphasize the need for a greater understanding of the underlying etiology, which will lead to novel treatment approaches and amelioration of AF.

Sudden cardiac death (SCD) is a serious health concern worldwide. Despite the need for risk factors that can identify high-risk individuals, there are few available owing to the complex and often asymptomatic nature of SCD. In this Review, Sumeet Chugh outlines novel risk markers and predictors of SCD that will allow more effective prevention, and suggests a framework for studies in the future for the discovery and validation of these risk markers.

The number of patients undergoing implantation of a cardioverter-defibrillator (ICD) is increasing, as the indications for device therapy have broadened. Despite the mortality benefits associated with ICDs, they can also cause substantial complications. Drs. Wazni and Wilkoff explore the issues involved in managing patients with an ICD and discuss approaches for reducing these adverse effects, from prevention of infection, and the choice of lead and implantation technique, to strategies for programming and monitoring the device.

This Review discusses the effects of intensive glycemic control on cardiovascular disease in patients with diabetes, and examines key factors in recent intervention trials that might have contributed to their disparate findings. The authors suggest that care of these patients should focus on achieving current treatment goals, rather than on changes to glycemic targets.

The cardiovascular manifestations of Marfan syndrome are the main cause of morbidity and mortality in patients with this disease. In Part 1 of a 2-part Review on Marfan syndrome, Dr Cañadas and colleagues discuss the pathogenesis of Marfan syndrome, our idea of which has dramatically changed in the past decade, as well as the current strategy for diagnosis.