Reviews & Analysis

The environmental exposome, which includes pollution, contamination, climate and social determinants of health, is intricately involved in the pathophysiology of heart failure. In this Review, Hahad and colleagues explore the complex relationship between environmental stressors and heart failure, advocating for their inclusion alongside traditional risk factors and highlighting the need for new strategies to address the effects of the exposome on public health.

In this Review, Galli and colleagues discuss the mechanisms and associated biomarkers of traditional and emerging factors responsible for the residual risk of recurrent adverse cardiovascular events in patients with coronary artery disease, with a focus on new pathophysiological insights and the therapeutic implications.

In this Review, Ferrucci and colleagues propose that inflammation is a resilience mechanism that resolves molecular and cellular damage driven by environmental stressors. With ageing, however, this protective response can become dysregulated and maladaptive, promoting collateral changes central to the pathophysiology of cardiovascular disease.

In this Review, Kaiser and Nicolai summarize our understanding of procoagulant platelets, describing the signalling pathways that control platelet procoagulant activation and discussing the role of procoagulant platelets in venous and arterial thrombosis, as well as potential therapeutic approaches to target these platelets in thrombotic and thromboinflammatory disorders, including cardiovascular disease, septic inflammation and immune complex-mediated diseases.

Frailty is common in older individuals, but can occur independently of advanced age, multimorbidity or disability. In this Review, Nguyen and colleagues draw on evidence from clinical guidelines and randomized controlled trials to provide an in-depth discussion of the unique challenges associated with cardiovascular pharmacotherapy in older patients with frailty.

In this Review, Laurette and Gilsbach summarize the current knowledge on the cardiac epigenome, including the dynamic changes in DNA methylation, histone modifications and chromatin accessibility in cardiomyocytes during development and disease. They also describe the interplay between cell type-specific mechanisms and discuss the translational potential of targeting epigenetic mechanisms for the prevention and treatment of cardiac diseases.

In this Review, Bengel and colleagues propose a roadmap for the clinical implementation of radiotracer-based molecular imaging of immune and fibrotic pathways to guide targeted therapies for heart repair after myocardial infarction.

In this Review, Grapsa and colleagues provide an overview of the imaging modalities used in the diagnosis and management of tricuspid regurgitation, describe the valve repair and replacement strategies undergoing clinical testing, and highlight the technological innovations that aim to optimize diagnosis, patient selection and the device development process.

In this Review, Moore and co-workers provide an overview of the mechanisms and functions of microRNAs and long non-coding RNAs in vascular biology and the regulation of lipid metabolism, as well as the effects of non-coding RNAs on atherosclerotic plaque formation and progression.

In this Review, Park and Fishman summarize the biology, function and disease of the cardiac conduction system and discuss how this knowledge could help to improve clinical risk assessment and the development of therapies, including biological pacemakers and interventions to promote cardiac conduction system regeneration.

Chronic kidney disease (CKD)-associated cardiomyopathy, also known as uraemic cardiomyopathy, describes the myocardial abnormalities that occur in patients with CKD or kidney failure. In this Review, Edwards and colleagues discuss the pathophysiological mechanisms of this condition, as well as the imaging, prevention and treatment options.

In this Review, Zhao and colleagues summarize the major challenges in the implementation of preventative strategies for cardiovascular disease in China and discuss the potential value of digital health-care and artificial intelligence technologies in overcoming these challenges.

In this Review, Nicholas Chew and colleagues use epidemiological data on the cardiovascular–liver–metabolic disease syndemic to illustrate current and future projections on the burden of these diseases and their risk factors, and propose a unified framework for integrating and implementing effective multisystem interventions to tackle key components of this syndemic.

In this Review, Omerovic and Redfors discuss the historical background, clinical presentation and current best practices for the diagnosis and management of Takotsubo syndrome. They also summarize the current understanding of the complex pathophysiology of Takotsubo syndrome, highlighting ongoing and potential future research directions.

In this Review, Paterson and colleagues describe how bioelectronic approaches involving site-specific targeting of the autonomic nervous circuit could be used to treat cardiovascular disease, and reflect on current bioelectronic modalities, their limitations and future ways to improve therapeutic efficiency.

Arrhythmia-induced cardiomyopathy (AIC) refers to heart failure caused or exacerbated by arrhythmias, which resolves completely after restoration of sinus rhythm. In this Review, Fabritz and colleagues focus on atrial fibrillation as the cause of AIC, describing its pathophysiology, epidemiology and clinical presentation, and the various approaches to the diagnostic–therapeutic strategy of rhythm restoration.

In this Review, Khoury and colleagues examine the growing body of evidence demonstrating the benefits of screening for cardiovascular risk factors, including dyslipidaemia and high blood pressure, starting in childhood to reduce the lifetime burden of cardiovascular disease.

In this Review, Porrello and colleagues describe the origins of the fetal gene hypothesis and discuss the evolution of this hypothesis by considering more recent evidence from genome-wide sequencing studies.

In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to improve variant annotation for cardiovascular-related genes and to resolve the problem of classification as variants of uncertain significance. They also discuss how variant effect predictors can be integrated with multiplexed methods to inform cardiovascular genomic medicine.

In this Review, the authors explore the state of artificial intelligence (AI) applications in echocardiography, discussing the integration of AI throughout the echocardiographic workflow and highlighting the clinical implementation, challenges and future directions of AI-supported echocardiography.