Review Articles

Treatment of cardiomyopathies has historically focused on symptom management. In this Review, Elliott and colleagues discuss how elucidation of the complex cellular and molecular pathways has led to the development of novel therapeutic agents that modify or mitigate the effects of causative genetic variants, enabling tailored treatment for cardiomyopathies.

In this Review, the authors focus on the tight interaction between cardiac mechanics and mitochondrial energetics, discuss how this mechano-energetic coupling is disturbed in various acquired and inherited forms of heart failure, and summarize the established and emerging treatments for heart failure that target this mechano-energetic uncoupling.

In this Review, the authors discuss the cellular and molecular mechanisms of immunometabolism in heart failure and highlight potential approaches for non-invasive monitoring and for the treatment of patients with heart failure.

Coronary and systemic vascular dysfunction contributes to the initiation and progression of heart failure (HF) with or without reduced ejection fraction and, vice versa, HF compromises vascular function. In this Review, Liberale and colleagues discuss vascular dysfunction in the pathogenesis of HF and how pharmacological, interventional and surgical management of HF can improve vascular function.

In this Review, Mericskay and colleagues discuss the role of cardiac intermediary metabolism in heart failure, describing the perturbations in cardiac energy metabolism that occur in heart failure with reduced ejection fraction and cardiometabolic heart failure with preserved ejection fraction, and highlighting potential treatments to target intermediary metabolism in these patients.

Glycogen has an important role in cardiac development and function. In this Review, Pinós and colleagues discuss the cardiovascular manifestations of glycogen storage diseases caused by rare inherited deficiencies of enzymes involved either in glycogen synthesis or breakdown, or in glycolysis. Interventions, including gene therapies, for these conditions are also summarized.

In this Review, Ackerman and colleagues describe the rationale for gene therapy to treat cardiac arrhythmias; discuss advantages and disadvantages of gene silencing, replacement and editing technologies; summarize vector modalities and delivery approaches; present examples of gene therapy strategies used for atrial and ventricular arrhythmias; and highlight the current challenges and limitations in the gene therapy field.

In this Review, the authors describe the metabolic programmes that control endothelial cell function in the cardiovascular system, discuss the role of endothelial cell metabolism in different cardiovascular diseases, and highlight the therapeutic potential and challenges of targeting endothelial cell metabolism to treat cardiovascular diseases.

Congestion is the predominant cause of heart failure symptoms and hospitalization. In this Review, Testani and colleagues discuss established and emerging medical and device strategies to treat congestion and improve outcomes in patients with heart failure.

In this Review, Liu, Yang and He explore the diverse mechanisms by which various post-translational protein acylations, and the dynamic interactions between them, contribute to cardiac hypertrophy. The authors also discuss the therapeutic potential of targeting acylations to modulate their effects on chromatin architecture, enzyme activity and metabolic pathways.

To regenerate the injured heart, cardiomyocytes must proliferate to replace lost myocardial tissue, but this capacity is largely absent in adult mammals. In this Review, Koopmans and van Rooij explore the key pathways that drive cardiomyocyte maturation after birth and how targeted manipulation might reactivate the cell cycle in adult cardiomyocytes.

In this Review, Schuermans and Honigberg highlight the involvement of clonal haematopoiesis of indeterminate potential (CHIP) in cardiovascular diseases, such as atherosclerosis and heart failure, and discuss the emerging role of CHIP as a potential prognostic marker and therapeutic target for these diseases.

Inhibition of factor XI has emerged as a promising strategy to mitigate bleeding while potentially preserving antithrombotic efficacy. In this Review, the authors comprehensively discuss the rationale, pharmacology, evidence and future directions for factor XI inhibitors across various clinical settings.

In this Review, Ravindran and Gustafsson describe the mechanisms involved in regulating mitochondrial quality control in cardiomyocytes, discuss how these pathways are altered in cardiovascular disease and ageing, and highlight the therapeutic potential of targeting mitochondrial quality control pathways in cardiovascular disease.

In this Review, Xiao and Sluijter describe the role of extracellular vesicles in cardiovascular physiology and pathology, and highlight their potential diagnostic and therapeutic utility for cardiovascular disease.

The brain–heart axis comprises the anatomical and functional interaction between the neural and cardiovascular systems that regulate physiological, cognitive and emotional states in both health and disease. In this Review, Valenza and colleagues explore the three primary pathways of the brain–heart axis — neural, mechanical and biochemical — discussing the regulatory mechanisms generated by each individual pathway and by interactions between the pathways.

In this Review, Mocumbi and colleagues provide an overview of the determinants and pathophysiology of endomyocardial fibrosis, describe the trends in epidemiology, and highlight the need for more cost-effective diagnostic and therapeutic strategies.

In this Review, Kirabo and colleagues discuss the mechanisms that underlie the sex-related differences in salt sensitivity of blood pressure and hypertension, highlighting the implications for research and clinical practice.

In this Review, Lee and colleagues describe the biosignal sensing principles of wearable blood pressure sensors and discuss blood pressure estimation methods, including the use of machine learning algorithms.

Hypertension is the leading cause of death globally but has low rates of diagnosis and treatment. In this Review, Dhaun and colleagues discuss the reasons for poor control of hypertension, such as therapeutic inertia and poor patient adherence, as well as novel pharmacological approaches to blood pressure lowering.