Nature Reviews Cardiology最新文献

Genetic and acquired forms of heart disease are leading causes of death worldwide. The epigenome, which governs cellular identity by modulating the accessibility of genetic regulatory elements, is established during development by transcription factors and has a pivotal role in the execution of cellular programmes. The epigenetic layers include DNA methylation, histone modifications and chromatin accessibility, which are dynamically regulated during development and in response to stress. Advances in single-cell and cell type-resolved epigenome analyses have provided unprecedented insights into the heterocellular nature of organs such as the heart, via the identification of epigenetic mechanisms and disease-associated epigenetic alterations in cardiomyocytes and other cardiac cell types. Chromatin remodelling, driven by specific modifiers, transcription factors and chaperones, orchestrates cardiac gene expression and contributes to disease manifestation and progression. Understanding how to modulate these epigenetic pathways in a cell type-specific manner offers promising avenues for therapeutic intervention, including epigenome editing for targeted modulation of regulatory elements. In this Review, we highlight studies decoding the various layers of the cardiac epigenome, emphasizing the interplay between cell type-specific mechanisms, describe emerging methods to study the cardiac epigenome, and discuss the translational potential of targeting epigenetic mechanisms for the prevention and treatment of cardiac diseases.

Tricuspid regurgitation is associated with an increased risk of hospitalization and death. Many patients with severe tricuspid regurgitation are unable to undergo surgical intervention owing to prohibitive technical or clinical risk. The past two decades has seen an outburst of technological advances in the field of transcatheter tricuspid technologies, with numerous randomized, controlled trials assessing the safety and efficacy of various repair and replacement therapies for tricuspid regurgitation. However, crucial knowledge gaps persist, particularly in areas such as patient selection, anatomical eligibility and the haemodynamic effects of device implantation. In this Review, we outline the anatomical features of the tricuspid valve and the haemodynamic consequences of tricuspid regurgitation, and we summarize the imaging modalities used for diagnosis and management. Furthermore, we detail the current guideline-directed medical therapy for tricuspid regurgitation, as well as valve repair and replacement surgical procedures being tested in clinical trials. Finally, we highlight future technological innovations that promise to optimize diagnosis, patient selection and the device development process.

The cardiac conduction system (CCS) has a vital role in initiating and coordinating nearly 3 billion heartbeats throughout a person's lifetime. The CCS comprises two primary tissue types: the impulse-generating, slow-conducting nodes and the fast-conducting components of the ventricular conduction system. Dysfunction in this system can give rise to a spectrum of clinical symptoms, including palpitations, syncope, heart failure and even sudden cardiac death. Owing to the limited therapeutic options other than electronic pacemakers, substantial research efforts have been aimed at uncovering the root causes of conduction system disorders. A comprehensive investigative approach integrating genetics, transcriptomics and proteomics has been used to unravel the complex biology of these diseases. Advances in single-cell genomic and transcriptomic technologies, together with spatial transcriptomics, are offering new insights into the cellular microenvironments that govern conduction system function. In this Review, we examine the latest progress in understanding the biology of the CCS, situating new findings within both established and emerging scientific paradigms. Additionally, we discuss how these insights can be leveraged to improve clinical risk assessment, expand drug discovery efforts, accelerate technology aimed at promoting CCS regeneration and foster the development of innovative therapies, including biological pacemakers.

The prevalence of frailty and its effect on cardiovascular outcomes is increasing on a global scale. Pharmacotherapies for cardiovascular diseases in older people with frailty present unique challenges that require a comprehensive and individualized approach. In this Review, we provide a general overview of these challenges, followed by an in-depth discussion of the problems inherent in applying standard approaches to cardiovascular care in this population. Specifically, we consider blood pressure control, glucose lowering in patients with type 2 diabetes mellitus, lipid lowering, antiplatelet therapies, direct oral anticoagulants for stroke prevention in atrial fibrillation, and the treatment of heart failure. Although the reduction in cardiovascular events in older individuals with frailty is crucial, the potentially increased risk of adverse effects with the use of cardiovascular medications must be carefully considered. Treatment targets and the choice of drug for these patients should be based on their overall health status and personal goals of care.

The discovery of non-coding RNAs has expanded our understanding of how genetic features are linked to cellular function. The illumination of this so-called dark matter of the genome has revealed new categories of RNA with essential roles in the regulation of protein-coding genes and genome organization. In particular, microRNAs and long non-coding RNAs have emerged as important regulators of cardiovascular health and disease. In this Review, we summarize our current understanding of the mechanisms and functional roles of microRNAs and long non-coding RNAs in the regulation of lipid homeostasis, vascular biology and atherosclerosis. We discuss how interruption of non-coding RNA regulatory circuits influence lipoprotein metabolism in the liver and the circulation, as well as the effects of non-coding RNAs on inflammatory processes in the artery wall that contribute to atherosclerotic plaque formation. Finally, we highlight potential opportunities to harness non-coding RNAs as biomarkers and targeted therapeutics for atherosclerotic cardiovascular disease.

Heart injury after acute myocardial infarction requires adequate repair to prevent left ventricular remodelling and the development of chronic heart failure. The early immune response to myocardial injury and its tight interconnection to fibroblast activation have a crucial role in determining the outcome after myocardial infarction. Emerging therapies aim to exploit these targets, harnessing the subacute window after cardiac injury to prevent subsequent contractile dysfunction. Given the complexity of the tissue response to myocardial injury and the molecular specificity of targeted therapies, only a subgroup of individuals might benefit from these therapies, which emphasizes the need for personalized therapies and the identification of suitable biomarkers to classify patients. Radiotracer-based, non-invasive molecular imaging is rapidly evolving alongside targeted drug development, providing novel tools for the investigation of immune and profibrotic mechanisms. These molecular imaging techniques hold unique potential to guide the development and selection of reparative therapies based on precise information about the most suitable candidates and the timing after acute myocardial infarction. In this Review, we outline a roadmap for the clinical implementation of radiotracer-based molecular imaging of immune and fibrotic pathways to guide targeted therapies for heart repair. The long-term goal is to establish clinical algorithms for immune-targeted and fibrosis-targeted imaging-guided therapy for cardiac repair.

Uraemic cardiomyopathy is a term widely used to describe the severe myocardial disease characterized by left ventricular hypertrophy and diffuse interstitial fibrosis that occurs in kidney failure. The causative factors are multiple and include many of the haemodynamic and metabolic abnormalities that are present in patients with chronic kidney disease (CKD). These abnormalities start to cause left ventricular damage and dysfunction in the early stages of CKD, probably from an estimated glomerular filtration rate of approximately 60 ml/min/1.73 m². The term 'uraemic cardiomyopathy' is therefore misleading and inaccurate, and we suggest instead using the term 'CKD-associated cardiomyopathy'. In this Review, we describe the clinical manifestations and myocardial abnormalities seen on imaging in both CKD and kidney failure, discuss the multiple and interacting causative factors, and consider both established and prospective treatment options. A better understanding of the pathogenesis of CKD-associated cardiomyopathy is likely to lead to the introduction of effective preventive therapies, with success measured as a reduction in the proportion of patients reaching kidney failure with severe cardiomyopathy and ultimately in a reduction in the mortality from this condition.