Reviews & Analysis

The ability to identify which patients with atherosclerosis are at higher risk of future cardiovascular events is important not only for decisions about medical therapy, but also for decisions about surgical or percutaneous intervention. Pathological findings of plaque features that predict cardiovascular events may point the way to noninvasive imaging approaches to identify high-risk plaques.

Although the majority of implanted valves used in aortic valve surgery are tissue valves (bioprostheses), the mechanisms by which they interact with the host are not well understood. A new study by Flameng et al. gives insight into the structural and functional changes that result from patient–bioprosthesis mismatch.

Kantor and colleagues from the Hospital for Sick Children in Toronto, Canada have reported that outcomes for medically treated pediatric patients with dilated cardiomyopathy (DCM) have not changed over a 30-year period, despite institution of neurohormonal inhibition therapy. These findings are placed in the context of the worldwide experience of pediatric DCM and the limited number of studies of neurohormonal inhibition therapy in children with heart failure.

The optimal reperfusion strategy for patients with ST-segment elevation myocardial infarction who are admitted to community hospitals without a catheterization laboratory is still a matter of debate. The long-term results of the DANAMI-2 study contribute to the evidence base for optimal reperfusion, but should be interpreted with caution and in the context of the wider literature on this subject.

The effectiveness of existing strategies for management of atrial fibrillation is limited, which has stimulated research into novel therapeutic approaches. A new meta-analysis of randomized controlled trials of inhibitors of the renin–angiotensin system highlights the clinical benefits of these agents and underscores their potential in the prevention and treatment of this disease.

Admissions for heart failure are associated with an unacceptably high rate of early readmission and mortality. An early postdischarge visit with targeted interventions in high-risk patients may decrease this high event rate. Determining who should be seen early postdischarge and what should be done during the visit remains to be established.

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.

CABG surgery has been considered the optimal revascularization strategy for patients with diabetes mellitus who have left main and/or multivessel coronary artery disease. The results of a new analysis of data from the SYNTAX trial challenge this conventional wisdom and highlight additional coronary revascularization options to physicians and patients.

The diagnosis of diabetes mellitus in clinical practice has been mainly based on the measurement of glucose levels in blood. Growing evidence, including results from a new large-scale population study, however, strongly suggests that the assessment of glycated hemoglobin levels has advantages over measurement of glucose levels in predicting the risk of developing diabetes or cardiovascular disease.

Whether thiazolidinediones should be used to treat patients with type 2 diabetes mellitus is controversial, as studies on the cardiovascular effects of these drugs have produced conflicting results. A trial in which rosiglitazone and glipizide were compared supports earlier findings that rosiglitazone does not have an adverse effect on the progression of coronary atherosclerosis.

The relationship between patent foramen ovale and migraine is a hotly debated issue. Conflicting data on the association or independence of these conditions have been reported by various study groups around the world. Now, a large-scale case–control study has shown no association between the two entities; however, there were a number of methodological flaws in this study and we are unlikely to see the end of the controversy in the near future.

The impact of overlap of drug-eluting stents on clinical and angiographic outcomes is controversial. Individuals with long coronary lesions requiring implantation of multiple stents are an important patient subgroup for whom careful evaluation and decision-making with optimal stent deployment is needed to ensure the best possible short-term and long-term results.

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.

Combination therapy is used to lower blood pressure in the majority of patients with hypertension, yet there has been little evidence as to which classes of antihypertensive agents are most effective. The publication of findings from the ACCOMPLISH trial provides an opportunity to explore the merits of various combination therapies, with a focus on renal risk reduction.