Review Articles in 2015

Measurement of biomarkers is a critical component of cardiovascular care, but sex-specific differences in these markers have not been fully integrated into clinical practice. In this Review, Daniels and Maisel assess the utility of sex-specific cut-off points when measuring cardiac troponins or natriuretic peptides in the diagnosis and prognosis of acute coronary syndrome and heart failure, respectively. They also discuss sex-specific differences in novel cardiovascular biomarkers, such as galectin-3, soluble ST2, and proneurotensin.

Although the harmful cardiovascular effects of alcoholism are well-known, the potentially beneficial effects of low-to-moderate alcohol intake are still debated. In this Review, Fernández-Solà considers the evidence for and against the cardioprotective properties of alcohol, and makes the case for the overall health benefits of reductions in alcohol consumption.

Cardiovascular disease (CVD) remains a leading cause of death worldwide, but age-standardized CVD death rates are decreasing steadily. In this Review, Ezzati and colleagues use the available epidemiological data to examine regional and global changes in CVD mortality, as well as trends in smoking, alcohol consumption, diet, physiological risk factors, and improvements in medical care that might underlie these changes.

Familial hypercholesterolaemia (FH) is a common genetic disorder that remains mostly undetected, and even high-intensity statin therapy—the standard treatment for FH—often fails to lower LDL-cholesterol levels below those recommended by guidelines. In this Review, Reiner describes the different therapeutic strategies available for patients with FH that have been used with some success, including statin combination therapy, bile acid sequestrants, ezetimibe, apheresis, repression of apolipoprotein B-100 expression, and PCSK9 inhibition.

Venous thromboembolism, including deep-vein thrombosis and pulmonary embolism, is a common, often-recurring condition that is occurring with increasing frequency, despite the availability of prophylactic treatments. The epidemiology of VTE involves interactions between predispositions to thrombosis and a range of risk factors, including hospitalization, cancer, and pregnancy.

In the presence of signs and symptoms of myocardial ischaemia, women are more likely than men to have no obstructive coronary artery disease, but might have a higher burden of coronary microvascular dysfunction. In this Review, Dean et al. discuss the prevalence, presentation, diagnosis, and treatment of coronary microvascular dysfunction, with a particular emphasis on sex-specific differences between women and men.

Patients with cancer often experience concomitant cardiovascular disease that results from the malignant process itself, or from anticancer treatment. Treatment-induced cardiotoxicity can be either transient or irreversible, and is associated with arrhythmia, ischaemia, and myocardial infarction. The authors discuss the mechanisms by which anticancer treatments damage the heart, and suggest potential strategies on how to protect patients with cancer from anticancer therapy-induced cardiotoxicity.

Cardiomyocyte function is regulated by epigenetic modifications (to cytosine residues on DNA, and post-translational acetylation or methylation of histones), as well as by noncoding RNAs (such as microRNAs and long noncoding RNAs). In this Review, Greco and Condorelli describe the complex roles of these two layers of gene-expression regulation in the pathogenesis of cardiac hypertrophy and failure.

Drug response and the development of adverse effects can vary between individuals. The use of pharmacogenomics should aid in the delivery of the right drug to the right patient, but clinical implementation of pharmacogenetic principles has been difficult, owing to a lack of randomized clinical trials that demonstrate benefit of this approach. This article reviews the use of pharmacogenetic markers in randomized clinical trials, highlighting studies related to cardiovascular disease.

Transthoracic echocardiography is a well-established imaging modality for the qualitative and quantitative evaluation of cardiac structure and function. In this Review, Boyd et al. describe the broad principles of traditional echocardiographic techniques, including two-dimensional, colour, and spectral Doppler echocardiography, as well as newer and more advanced techniques, including tissue Doppler, stress, contrast, and three-dimensional echocardiography.

Gene therapy for cardiac arrhythmias is now undergoing clinical testing. In this Review, Bongianino and Priori discuss the principles of gene therapy and how this approach can be tailored and targeted to the heart. They then summarize the preclinical and clinical experience of gene therapy applied to acquired and inherited arrhythmias of the atria or ventricles.

Implantable cardiac defibrillators (ICD) are effective in reducing mortality in patient populations at risk for sudden cardiac death, but transvenous ICDs are associated with complications such as infections, pneumothorax, venous thrombosis, lead dislodgement, lead malfunction, and haemopericardium. In this Review, Lewis and Gold describe a novel design of entirely subcutaneous ICDs that avoid some of the complications of transvenous systems, and explore the advantages and disadvantages of both ICD systems.

Takotsubo syndrome is an acute cardiac disorder first identified in Japan in 1990. The pathophysiology of Takotsubo syndrome is complex and involves the neuroendocrine system. Cardiovascular responses are often induced by a sudden surge in sympathetic activation and subsequent catecholamine concentration. In this Review, Akashi et al. discuss the epidemiology, diagnosis, and prognosis of the syndrome, as well as some of the proposed pathophysiological mechanisms underlying its development.

Long noncoding RNAs (lncRNAs) regulate cellular and tissue function by activating or repressing gene expression. In this Review, Devaux and colleagues summarize the mechanisms by which lncRNAs exert their epigenetic effects, and discuss their role in cardiac development and ageing, with emphasis on the importance of chromatin remodelling. The authors also discuss the potential of lncRNAs to be used as biomarkers and therapeutic agents.

The accumulation of lipid-laden macrophages in atherosclerotic lesions occurs preferentially at branching sites owing to poor adaptation of endothelial cells to disturbed blood flow. MicroRNAs (miRNAs) have been implicated in the pathogenic mechanisms of unresolved inflammation that precede and potentiate atherosclerosis. In this Review, Schober and colleagues provide an overview of the role of miRNAs in homeostasis and dysfunction of endothelial cells and macrophages in atherosclerosis, and explore the potential of novel miRNA-based diagnostics and therapeutic strategies.

In an increasingly digital world, widespread access to smartphones and mobile technology might be harnessed to improve cardiovascular disease prevention, management, and rehabilitation. In this Review, Neubeck et al. discuss the burgeoning market of health-related mobile apps, and question whether they are evidence-based and beneficial to individuals with cardiovascular disease, and what design features might encourage behavioural change.

Patients with sinus node disease (SND) and an implanted cardiac pacemaker have high prevalence of atrial tachyarrhythmias and atrial fibrillation (AF). In this Review, Boriani and Padeletti describe new developments in pacemaker technology that enable continuous monitoring of the atrial rhythm and allow detection of the burden of AF. These clinical advances could improve guidelines and management of AF and atrial tachyarrhythmias.

Stent thrombosis is a rare, but serious, complication of percutaneous coronary intervention and is associated with severe morbidity and mortality. In this Review, Ong and Jang discuss the use of intravascular imaging to study stent underexpansion, malapposition, uncovered struts, and neoatherosclerosis as risk factors for stent thrombosis. They also discuss the potential utility of intravascular imaging in the optimization of stent deployment and treatment of stent thrombosis events.

Risk-assessment models are important for the identification of individuals at high risk of developing cardiovascular diseases. Although several well-known models for risk assessment have been published in Europe and the USA, very few studies have discussed the development of risk-assessment models from a global perspective. In this Review, Zhao and colleagues discuss differences in risk-assessment recommendations from developed compared with developing countries, and consider their effects on clinical practice.

Cardiac sarcoidosis is a life-threatening condition characterized by the formation of granulomas in the heart, and can lead to heart failure, heart block, or rhythm disturbance. The diagnosis of cardiac sarcoidosis is complicated, as patients often remain asymptomatic, despite cardiac imaging results suggestive of heart disease. In this Review, Hamzeh et al. discuss the current screening and management protocols used to identify and treat patients with cardiac sarcoidosis.