Review Articles

Adult cardiac hypertrophy initially develops as an adaptive response to an increased workload, but this physiological growth can ultimately lead to pathological hypertrophy and disease. In this Review, Nakamura and Sadoshima summarize the characteristics and underlying mechanisms of physiological and pathological hypertrophy, and discuss possible therapeutic strategies targeting these pathways to prevent or reverse pathological hypertrophy.

This Review describes the relationship between urban and transport planning and the city environment, the main cardiovascular risk factors (including physical activity, hypertension, and obesity), and cardiovascular disease and mortality. Improved city planning that promotes physical activity, reduces levels of air pollution and noise, and increases green space could decrease the burden of cardiovascular disease.

In this Review, Katritsis and colleagues discuss the major factors underlying the clinical decision to perform revascularization in patients with stable coronary artery disease and examine the use and limitations of existing evidence on the choice for, and preferred methods of, revascularization, namely, CABG surgery versus percutaneous coronary intervention.

In this Review, Serruys and colleagues describe the pathophysiology of unprotected left main coronary artery disease, discuss novel diagnostic approaches in light of new imaging techniques, and describe risk stratification models to help in the decision-making process for determining the best revascularization strategy in these patients.

Novel antisense oligonucleotide and small interfering RNA technology can be used to reduce levels of lipoproteins that cause cardiovascular disease. In this Review, Nordestgaard and colleagues describe the principles of these gene-silencing approaches and summarize the trials that have tested the efficacy of these approaches in patients at risk of cardiovascular disease.

Nitric oxide (NO) signalling has pleiotropic roles in biology and a crucial function in cardiovascular homeostasis. In this Review, Balligand and colleagues summarize the updated paradigms on NO synthase regulation, NO interaction with reactive oxidant species in specific subcellular compartments, and downstream effects of NO in target cardiovascular tissues under both physiological and pathological conditions.

Heart failure has emerged as the most common cardiovascular complication among patients with type 2 diabetes mellitus. In this Review, Nassif and Kosiborod describe the detrimental, neutral, or even beneficial effects of different classes of glucose-lowering medications on heart failure outcomes.

The non-vitamin K antagonist oral anticoagulants (NOACs) include direct inhibitors of factor Xa or thrombin. In this Review, Levy and colleagues describe the mechanism of action of the NOAC-reversal strategies, provide guidance on potential indications for reversal, and offer a management approach for patients treated with NOACs who present with serious bleeding or require urgent surgery.

Antiplatelet drugs are routinely used for the prevention and treatment of thrombosis, but also carry an inherent increased risk of bleeding. In this Review, McFadyen and colleagues assess the differences between thrombosis and haemostasis in the context of currently available antiplatelet drugs as well as novel antiplatelet agents that are entering preclinical and early-phase clinical testing.

The most common genetic predisposition to dilated cardiomyopathy (DCM) is truncating variation in the giant sarcomeric protein, titin. Ware and Cook review the molecular mechanisms ofTTNgene variation in the pathogenesis of DCM, strategies for clinical interpretation of genetic variants for diagnosis, and the role of genetic stratification as a predictor of outcome and treatment response.

In this Review, Kivimäki and Steptoe assess the current evidence on the association between stress and cardiovascular disease, covering the multiple roles of stress in the development and triggering of disease and as a determinant of prognosis and outcome. In addition, they discuss the clinical and public health importance of major stressors and the implications for prevention and treatment of cardiovascular disease.

Ischaemic injury during an acute myocardial infarction (AMI) event is followed by an intense inflammatory response that occurs after reperfusion. The inflammasome is a protein complex involved in the regulation of this inflammatory response. In this Review, Toldo and Abbate summarize evidence supporting the therapeutic value of inflammasome-targeted strategies in the context of AMI.

Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. Current pacemakers, although effective, have limitations including lead malfunction, lack of autonomic responsiveness, and device-related infections. In this Review, Marbán and colleagues discuss next-generation electronic devices designed to address current limitations, as well as biological pacemakers as alternatives to implantable hardware.

The effects of microgravity and cosmic rays on the cardiovascular system are major health concerns for astronauts in space. In this Review, Hughson and colleagues summarize the current evidence on risk estimation and dysfunction of the cardiovascular system in space, and discuss potential countermeasures, including physical exercise, antioxidants, nutraceuticals, and radiation shielding.

Increased arterial stiffness influences pulse pressure, wave reflections, kidney function, and cardiovascular risk. In this Review, Safar describes the importance of arterial stiffness in the diagnosis and management of hypertension, using historical perspectives to emphasize the need for new treatment approaches in patients with essential hypertension.

In the past 2 decades, an increasing prevalence of risk factors for cardiovascular disease, such as obesity, physical inactivity, and diabetes mellitus, has been observed among young adults (aged 18–45 years) living in developed countries. In their Review, Andersson and Vasan discuss the evolving risk factor burden and available epidemiological data on cardiovascular disease in young adults.

Cardiovascular mortality among the almost 600 million people living in the Eastern Mediterranean region (EMR) has been proposed to increase more dramatically in the next decade than in any other region except Africa. Turk-Adawi and colleagues summarize the available data on cardiovascular disease burden, risk factors, and treatment modalities for the EMR population.

This Review summarizes the latest findings on heart reverse remodelling, which demonstrate that despite apparent normalization of function, the molecular changes associated with heart failure persist in the reverse-remodelled heart. This myocardial remission is distinct from true recovery, in which both function and molecular makeup are normalized. These findings have implications for developing therapies to repair the failing heart.

Over the past decade, marijuana has been legalized for medicinal purposes or recreational use in many countries, and the potency of marijuana and synthetic cannabinoids has substantially increased. In this Review, Pacher and colleagues summarize the role of the endocannabinoid system in cardiovascular health and disease, and critically discuss the beneficial and detrimental cardiovascular effects of marijuana and synthetic cannabinoid use.

Sudden infant death syndrome (SIDS) is the leading cause of infant mortality in developed countries. In this Review, Behr and colleagues provide an update on the spectrum and prevalence of the subset of SIDS mediated by cardiogenetic factors, and the clinical implications of SIDS in the surviving family and general population.