Reviews & Analysis

The pathophysiology of heart failure is complex, but mitochondrial dysfunction is an emerging therapeutic target to improve cardiac function. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.

The dual-acting angiotensin-receptor–neprilysin inhibitor (ARNI) LCZ696, approved for treatment of heart failure with reduced ejection fraction, is the first approval for chronic neprilysin inhibition. Neprilysin metabolizes many peptides, suggesting many potential consequences of chronic neprilysin inhibition, both beneficial and adverse. This Review summarizes current knowledge on neprilysin inhibitor therapy, and the possible consequences of chronic inhibition.

Atherosclerosis is a disease of ageing, and the most common cause of death in the industrialized world. Cell senescence and the therapeutic removal of senescent cells using 'senolytics' are topical areas of science and translational medicine. A new study reports surprising findings on cell senescence and atherosclerosis with important therapeutic implications.

Ischaemic cardiomyopathy leads to destruction of cardiomyocytes beyond the regenerative potential of the adult human heart. The murine heart can regenerate in utero and shortly after birth, but oxidative stress eventually arrests cardiomyocyte division. Chronic hypoxia in mice has now been shown to induce the cell cycle in cardiomyocytes, resulting in cardiac regeneration.

Microorganisms that populate the human body have been shown to be involved in metabolic and cardiovascular disorders, but the precise mechanisms are not completely understood. In this Review, Lindskog Jonsson and Bäckhed describe the different pathways by which the gut microbiota might affect the development of atherosclerosis.

Inflammatory processes are central to the development and complications of atherosclerosis and acute myocardial infarction. In this Review, Ruparelia et al. summarize the inflammatory pathways involved in these cardiovascular diseases, highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments.

Depression is a highly prevalent risk factor for incident coronary heart disease (CHD) and for cardiovascular morbidity and mortality in patients with established CHD. In this Review, Carney and Freedland consider the evidence for depression as a cardiac risk factor, and summarize the biological and behavioural mechanisms that might link depression to CHD. They also consider whether treatment of depression can prevent cardiac morbidity and mortality in patients with CHD.

Peripheral artery disease (PAD) is undergoing a major epidemiological transition, with a rapid shift from high-income to low-income and middle-income countries. In this Review, Fowkes et al. describe the measurement of PAD in populations, as well as the worldwide prevalence, risk factors, and burden of the disease.

The association between exercise and increased risk of atrial fibrillation among athletes is well established. In this Review, Guasch and Mont discuss the evidence supporting the existence of exercise-induced arrhythmias and describe the special considerations for management of these patients.

Genetic cardiomyopathies are complex diseases with heterogeneous clinical presentations and phenotypes, and mild pathology can overlap with physiological variation, particularly in athletes. In this Review, three of the most common and controversial areas are discussed, including left ventricular hypertrophy; left ventricular dilatation, noncompaction, and fibrosis; and arrhythmias originating from the right ventricle.

Thyroid hormones have an important role in maintaining cardiovascular homeostasis, and subtle changes in thyroid hormone concentrations adversely influence the cardiovascular system. In this Review, Jabbar et al. discuss the role of thyroid hormones in the pathogenesis and management of cardiovascular diseases such as heart failure and acute myocardial infarction, and outline the utility of therapy with thyroid hormones for the management of these conditions.

When administered in the setting of an acute myocardial infarction, β-blockers decrease myocardial ischaemia, reduce the rates of reinfarction and serious ventricular tachyarrhythmias, and have substantial early benefits. However, the benefits of prolonged β-blockade after acute myocardial infarction are unproven and are discussed.

Women with atrial fibrillation (AF) generally experience worse symptoms, poorer quality of life, and have higher risk of stroke and death than men with AF. In this Review, Ko et al. summarize the evidence on sex-specific differences in the utilization and outcomes of treatments for AF, including rate-control and rhythm-control strategies, and stroke-prevention therapy.

3D printing applications for cardiovascular care range from models for education to planning and simulation of interventions and the generation of implantable devices. This Review summarizes the current cardiovascular 3D printing strategies and applications, including the workflow from image acquisition to the generation of a hand-held model, and highlights the future perspectives of cardiovascular 3D printing.

The cardiovascular benefits of weight loss in patients with obesity are well documented. Bariatric surgery is an effective and long-lasting strategy for weight loss, and can improve many cardiovascular risk factors such as hypertension and dyslipidaemia. In this Review, Beamish and colleagues highlight the effects of bariatric surgery on cardiovascular risk factors and outcomes.

Unstable plaques have been used as a target for imaging and drug discovery, and as a model of atherosclerosis in preclinical experiments. In this Review, Pasterkamp and colleagues describe the temporal shift in the characteristics of plaques in patients with acute coronary syndrome, and argue that the 'vulnerable plaque' concept might no longer be relevant to current practice.

Blood-pressure lowering has undisputable benefits, but the optimal values to which blood pressure should be lowered are debated. Interpretation of recent trials is controversial, and post-hoc analyses to investigate the inflection point of the curve relating events to blood pressure are disputed. Meta-analyses of randomized trials and prospective, cohort studies might guide decision-making.

The ANTARCTIC trial does not provide sufficient evidence to refute the utility of platelet function monitoring in patients with high risk of coronary artery disease. Future trials on personalized antiplatelet therapy should try to address the limitations of previous studies.

In this Perspectives article, Captur et al. explain the fundamental principles of fractal geometry, and summarize cardiovascular studies in which fractal methods have been used to investigate disease mechanisms. The authors propose that clinical researchers can deploy innovative fractal solutions to common cardiac problems, which might ultimately translate into advancements in patient care.

Chronic activation of neurohormonal systems, such as the sympathetic nervous system and the renin–angiotensin–aldosterone system can lead to deleterious effects on the heart. In this Review, Hartupee and Mann describe the effects of neurohormonal activation in patients with heart failure with reduced ejection fraction, and the implications for disease progression.