Review Articles in 2015

Atrial fibrillation (AF) and heart failure (HF) are evolving epidemics with increasing global prevalence. HF is known to promote AF, but how AF exacerbates or even causes HF is uncertain. In this Review, Ling and colleagues present the current understanding of the epidemiology and pathophysiology of AF–HF, and the roles of pharmacological and interventional therapies in the management of patients with this comorbidity.

The numerous physiological changes that occur during pregnancy can affect the pharmacokinetics of drugs that a woman is receiving, often warranting an alteration in dosage. The well-being of the fetus is a major concern among pregnant women who require treatment for their heart disease. In this Review, Pieper provides an overview of the pharmacokinetic changes in drugs for cardiovascular disease during pregnancy, and how these might affect the fetus.

Systems of care have been established to optimize treatment of ST-segment elevation myocardial infarction (STEMI) occurring out of hospital, but not for patients in hospital. Unfavourable clinical characteristics of patients, combined with suboptimal strategies for diagnosis and treatment, mean that inpatient STEMI is associated with high mortality. Eliminating system delays and increasing use of reperfusion therapy could improve outcomes for inpatient STEMI.

Regulatory T (T_REG) cells are important for the induction and maintenance of immune homeostasis and tolerance. Numerous experimental and clinical studies have suggested a role for T_REG cells in protection against cardiovascular diseases, particularly atherosclerosis and abdominal aortic aneurysms. In this Review, Meng and colleagues summarize the available evidence on the role of T_REGcells in several cardiovascular disorders, such as atherosclerosis, hypertension, Kawasaki disease, and myocardial infarction.

The structural and temporal characteristics of atherosclerotic plaques differ between native coronary artery disease, vein-graft atherosclerosis, and in-stent neoatherosclerosis. In this Review, Yahagi et al. compare the shared and divergent morphological features, giving insight into the pathogenesis of atheroma formation, and provide an updated classification scheme for atherosclerotic lesions.

Mitral valve disease is a common cause of heart failure and death. In this Review from members of the Leducq Transatlantic Network, Levine and colleagues extensively summarize the molecular and cellular mechanisms underlying the dynamic changes that occur during progression of mitral valve disease, and indicate how improved understanding of the pathophysiology might lead to the discovery of novel therapeutic options.

Exposure to air pollution and to metals in the environment contributes to the development and severity of cardiovascular disease. Cosselman et al. review the pathophysiological processes associated with long-term and short-term exposure to these pollutants, at levels above and below current regulatory standards, and discuss the need for further reductions in levels of environmental pollutants.

Bone morphogenetic proteins (BMPs) and their receptors are important for the development and modulation of cardiovascular structure and function. Morrell and colleagues discuss physiological roles and regulation of BMP signalling in cardiovascular health and disease, and based on this advancing knowledge, they suggest opportunities for therapeutic intervention for a range of cardiovascular diseases, such as atherosclerosis and pulmonary arterial hypertension.

Heart failure is a major global health problem with unmet therapeutic requirements despite the development of neurohormonal modulators for systolic heart failure. In this Review, the authors discuss the evidence resulting from clinical trials of novel pharmacological agents targeting contractility, neurohormonal signalling, vasodilatation, renal preservation, inflammation, and myocardial protection.

Acute heart failure (AHF) is a complex disease characterized by an acute worsening of heart failure symptoms, usually in patients with pre-existing heart failure. Clinical evaluation of patients with AHF involves the assessment of clinical history, a comprehensive physical examination, and laboratory and diagnostic testing. In this Review, Mentz and O'Connor highlight the literature on the clinical evaluation of AHF, in addition to summarizing the pathophysiological mechanisms underlying its development.

High-density lipoproteins (HDLs) have various antiatherosclerotic effects; however, inflammation can cause HDL to become dysfunctional, which impairs its protective properties. In this Review, Rosenson and colleagues discuss the mechanisms by which HDL and apolipoprotein A-I protect against atherosclerosis, and how diagnostic and therapeutic approaches might target these proteins when they become dysfunctional.

Antiplatelet therapy with oral P2Y₁₂-receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) is widely used in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. However, patients often need to switch between these drugs for a variety of clinical reasons. In this Review, Rollini et al. summarize the practical considerations when switching therapies, including discussion of the new intravenous P2Y₁₂-receptor inhibitor cangrelor.

Most idiopathic ventricular arrhythmias (including forms of premature ventricular contraction and ventricular tachycardia) originate from the right or left ventricular outflow tracts. In this Review, Lerman summarizes how these arrhythmias are triggered by cAMP-mediated mechanisms, addresses the differential diagnosis between these and other arrhythmias, and discusses optimal treatment strategies, usually involving catheter-based radiofrequency ablation.

Many patients with pericarditis experience recurrent episodes. In this Review, Imazio et al. emphasize the importance of identifying the aetiology of the disease, and summarize the available evidence for the various treatment options. First-line anti-inflammatory therapy involves aspirin, NSAIDs, and colchicine; additional and alternative options include corticosteroids, anakinra, azathioprine, and intravenous immunoglobulins.

Mast cells have many roles in the pathogenesis of cardiometabolic diseases. In this Review, Shi et al. explore the mechanistic role of mast cells in atherogenesis and its atherothrombotic complications, as well as in aortic aneurysm, valvular disease, obesity, and diabetes mellitus. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders.

Various cardiovascular and noncardiovascular drugs, including so-called antiarrhythmic drugs, can induce cardiac arrhythmias. In this Review, Frommeyer and Eckardt summarize important proarrhythmic risk factors (such as age, female sex, and structural heart disease) and the underlying electrophysiological mechanisms (such as spatial or temporal dispersion of repolarization, alterations in action-potential morphology, and development of early afterdepolarizations).

This Review explores the pathophysiology and natural history of viral myocarditis—a common cause of dilated cardiomyopathy and sudden cardiac death. Despite established standards, heterogeneity exists in the evaluation, diagnosis, and treatment of patients with myocarditis, and these aspects are also covered in detail by Pollack and colleagues. Investigational treatment options are highlighted.

Iron deficiency is very common worldwide, and has detrimental effects in individuals with cardiovascular disease. Correction of iron deficiency via intravenous iron supplementation results in symptomatic improvement in patients with heart failure, and improved exercise capacity in patients with pulmonary hypertension, but iron administration after cardiac transplantation surgery is contraindicated.

Percutaneous device-based intervention has received increasing attention over the past 10 years. Carotid baroreflex activation therapy holds promise as a device-based intervention to supplement, but not replace, drug therapy for patients with drug-resistant hypertension. In this Review, Victor provides an overview of the current body of evidence for the utility of this intervention in patients with drug-resistant hypertension, and discusses the promise and possible pitfalls of this technology, highlighting potential solutions.

Despite being anucleate, platelets contain RNA transcripts, including microRNAs, which are involved in regulating platelet function and which can also be transferred to other vascular cells. In this Review, McManus and Freedman summarize the mechanistic roles of platelet-derived miRNAs in acute atherogenic and thrombotic diseases, such as acute coronary syndromes and stroke. These miRNAs might also be used as biomarkers of cardiovascular disease susceptibility, prognosis, and treatment.