Reviews & Analysis

Current medical therapies for chronic stable angina pectoris do not always render patients free of symptoms and may not be well tolerated. Xanthine oxidase inhibition with drugs such as allopurinol might be a promising new approach to treat these patients.

Patients with diabetes mellitus and hypertension are at high cardiovascular risk and treatment guidelines recommend aggressive blood pressure (BP) control. However, a reanalysis of data from the previously published INVEST trial indicates that achieving systolic BPs <130 mmHg in patients with diabetes and coronary artery disease increases mortality, although this finding might reflect the speculative conclusions produced by post-hoc analyses.

The hope that a simple, affordable, and safe homocysteine-lowering intervention with folic acid and vitamin B₁₂ would improve outcomes for patients with established cardiovascular or renal disease has been crushed by the null results from large B-vitamin treatment trials completed to date.

Induced pluripotent stem (iPS) cells are somatic cells that have been reprogrammed to an embryonic stem-cell-like state. This technology enables us to study the molecular mechanisms of development and disease processes, and provides a strategy for individualized diagnostics and therapy. In this Review, Timothy Nelson and colleagues describe the steps involved in bioengineering somatic cells to achieve pluripotency, allowing their differentiation into cardiomyocytes or any other cell type. Clinical applications of iPS cells, including treatment of cardiovascular conditions, are also discussed.

Pulmonary hypertension is frequently associated with left-sided heart disease. Patients with this condition have a poor outcome, and few therapeutic strategies are available. In this Review, Drs. Guazzi and Arena describe the consequences and clinical features of this form of pulmonary hypertension, from reversible injury to permanent remodeling. Current and emerging therapeutic approaches are also examined.

Obstructive sleep apnea syndrome is known to cause hypertension and might also be an independent risk factor for stroke and myocardial ischemia. In this Review, Dr. Malcolm Kohler and Professor John Stradling discuss the biological mechanisms thought to underpin the association of obstructive sleep apnea with endothelial dysfunction and arterial disease.

The best strategy for management of patients with non-ST-segment elevation acute coronary syndrome is still a matter of debate. A meta-analysis, in which results from three large-scale studies were pooled, shows that a routine invasive approach is associated with better 5-year outcomes than a selectively invasive approach.

Transvenous leads are the most common source of complications associated with the use of implantable cardioverter-defibrillators (ICDs). A preliminary experience with an entirely subcutaneous ICD system, which avoids the need for transvenous leads, has been reported. We discuss these results and the importance of investigations in this new field.

T2-weighted cardiovascular magnetic resonance imaging (T2W-CMR) has been championed as the best noninvasive method to determine the myocardial area at risk and to quantify myocardial salvage in patients with acute coronary syndromes. However, several unresolved issues warrant discussion and we urge caution when utilizing T2W-CMR for this purpose.

Determining the appropriate dose of warfarin that should be used in each patient is challenging, and the rate of adverse events at the beginning of therapy remains high. Testing for genetic variability related to warfarin sensitivity at the start of treatment is a promising strategy to guide dosing in clinical practice.

Cardiac magnetic resonance imaging (CMR) is an established diagnostic tool that provides accurate information on the myocardium. The authors of this Review suggest how CMR can be used in the acute setting to manage treatment and improve prognosis in patients with acute coronary syndromes. Current and emerging CMR techniques are discussed, as well as challenges facing CMR applications in clinical practice.

In the second part of their Review on pulmonary embolism (PE), van Es and colleagues discuss risk stratification of patients with this condition, the short-term and long-term treatment options, and introduce some of the novel therapeutic agents under investigation for PE.

Mechanical reperfusion in acute myocardial infarction does not always result in desirable optimal microvascular perfusion. Failure to achieve a normal myocardial blush in the infarcted region by contrast injection immediately after percutaneous coronary intervention—the 'no-reflow' phenomenon—is an ominous sign whose prognostic importance may go beyond its intimate association with infarct size.

The optimum strategy to treat patients with coronary artery disease (CAD) has been under debate. New data show that revascularization guided by fractional flow measurements leads to better outcomes than revascularization guided by arteriography. We call for a paradigm shift in CAD care, with coronary flow measurements by PET as key to diagnosis and clinical decision-making.

The association between periodontitis and other chronic diseases, such as cardiovascular disease (CVD) and type 2 diabetes mellitus, could be related to systemic inflammation initiated by a local inflammatory challenge. Oliveira et al. have added lack of oral hygiene, and its link with systemic inflammation, to the spectrum of risk factors for CVD.

Percutaneous coronary intervention can be performed successfully in most lesions; however, some specific types of lesion continue to present unique technical challenges. In this Review, stenting of bifurcations, fibrocalcific and undilatable lesions, chronic total occlusions, unprotected left main coronary artery stenoses, thrombotic lesions, and saphenous vein grafts are discussed in detail.

Animal models have generated much evidence to implicate the activation of Rho family proteins in the pathogenesis of hypertension. Pharmacological and genetic studies have indicated that Rho-protein signaling pathways also have a role in the generation of high blood pressure in humans. In this article, Drs. Loirand and Pacaud discuss our current knowledge of Rho-protein signaling in hypertension.

Cancer therapies can have a profound, and often permanent, effect on the cardiovascular system. Patients at high risk of cardiotoxicity should be identified before treatment, closely monitored, and given cardioprotective agents to reduce adverse events. The authors of this Review discuss the complications that can occur as a result of cancer therapy, and emphasize the importance of assessing both the cardiotoxicity and benefits of cancer treatment.

Excess dietary salt is associated with insulin resistance and hypertension, and may lead to type 2 diabetes, cardiovascular disease and chronic kidney disease. The mechanisms underlying the pathogenic effects of salt on the cardiovascular system include impaired glucose homeostasis and activation of the sympathetic nervous system and renin–angiotensin–aldosterone system. Mineralocorticoid receptor blockers are promising therapies to counteract the adverse metabolic and cardiovascular effects of salt.

The morphology, structure and position of the right ventricle differ substantially from those of the left ventricle and have posed difficulties in the assessment of right ventricular function. Imaging techniques, notably echocardiography and MRI, have enabled a better understanding of right ventricular performance. Mertens and Friedberg discuss the advantages and disadvantages of established and new methods of right ventricular imaging and their potential in the clinical setting.