Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing and ageing. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue biology. Clinical evidence and experimental studies

A new study shows that adult mouse cardiomyocytes can be reversibly dedifferentiated into fetal-like cardiomyocytes by forcing the transient expression of four pluripotency factors, which enables cardiomyocytes to re-enter the cell cycle and divide, thereby conferring regenerative capacity to the adult heart.

Valsartan is safe and effective in improving cardiac structure and function in patients with early-stage hypertrophic cardiomyopathy, according to results from the phase II VANISH trial.

Human genetic studies combined with biotechnological advances have guided and accelerated the development of PCSK9-targeting therapies. In this Clinical Outlook, we highlight present and future approaches for PCSK9 inhibition to reduce LDL-cholesterol levels and the risk of atherosclerotic cardiovascular disease.

A form of adenine base editing has been used in mouse embryos to correct a genetic variant associated with hypertrophic cardiomyopathy. This approach is potentially safer than other forms of germline gene editing, which carry a risk of off-target editing and the introduction of indels.

Precision medicine envisages a changed paradigm for health care through better understanding of individual disease susceptibility and prognosis, enabling more personalized treatment. Enabling technologies such as the health digital twin are rapidly evolving, presenting important challenges and opportunities to be tackled within local contexts.

Apolipoproteins are important structural components of plasma lipoproteins that influence vascular biology and atherosclerotic disease pathophysiology by regulating lipoprotein metabolism. Clinically important apolipoproteins related to lipid metabolism and atherogenesis include apolipoprotein B-100, apolipoprotein B-48, apolipoprotein A-I, apolipoprotein C-II, apolipoprotein C-III, apolipoprotein

Patients who have undergone coronary artery bypass graft (CABG) surgery are susceptible to bypass graft failure and progression of native coronary artery disease. Although the saphenous vein graft (SVG) was traditionally the most-used conduit, arterial grafts (including the left and right internal thoracic arteries and the radial artery) have improved patency rates. However, the need for secondary

Mice deficient in type 2 innate lymphoid cells have a greater accumulation of inflammatory macrophages and poorer cardiac function after myocardial infarction compared with control mice, indicating a role for this subset of lymphocytes in regulating inflammatory pathways in the injured heart.

The field of cardiac cell therapy is under siege. Legacies of excessive hype, scientific misconduct and dead ends have fuelled the prevailing scepticism. However, promising clinical data, along with more trenchant mechanistic understanding, together provide glimmers of hope for the future of cell therapy for the heart.

Cardiac rehabilitation is a complex intervention that seeks to improve the functional capacity, wellbeing and health-related quality of life of patients with heart disease. A substantive evidence base supports cardiac rehabilitation as a clinically effective and cost-effective intervention for patients with acute coronary syndrome or heart failure with reduced ejection fraction and after coronary revascularization

Two new studies show that pharmacological blood pressure (BP) reduction is effective in older individuals and that a more intensive treatment with a lower BP threshold reduces the incidence of cardiovascular events in older patients with hypertension.

In a clinical first, empagliflozin treatment cuts the risk of cardiovascular death and hospitalization compared with placebo in patients with heart failure with preserved ejection fraction.

Hypertrophic cardiomyopathy (HCM) was traditionally described as an autosomal dominant Mendelian disease but is now increasingly recognized as having a complex genetic aetiology. Although eight core genes encoding sarcomeric proteins account for >90% of the pathogenic variants in patients with HCM, variants in several additional genes (ACTN2, ALPK3, CSRP3, FHOD3, FLNC, JPH2, KLHL24, PLN and TRIM63)

The STROKESTOP trial and The LOOP study used different approaches to screen for atrial fibrillation, with the aim of initiating oral anticoagulation to prevent stroke and death.

In the SSaSS trial, substituting regular table salt (100% sodium chloride) with an alternative containing 25% potassium chloride reduced the rate of stroke, major cardiovascular events and all-cause death.

In the QUARTET trial, initial treatment with a single pill containing quarter doses of four antihypertensive drugs achieved and maintained a greater blood-pressure-lowering effect than initial monotherapy with full-dose irbesartan.

Delivery of automated external defibrillators with drones to the scene of an out-of-hospital cardiac arrest is feasible and can be faster than an ambulance, according to findings from a pilot clinical study.

Influenza vaccination shortly after a myocardial infarction or in high-risk coronary heart disease reduces the risk of future cardiovascular events, according to findings from the IAMI trial.

Ablation plus cardiac resynchronization therapy is superior to pharmacological therapy in reducing mortality in patients with atrial fibrillation and a narrow QRS complex who were hospitalized with heart failure.

Data from the MASTER DAPT trial indicate that the duration of dual antiplatelet therapy can be abbreviated in patients at high risk of bleeding undergoing implantation of a drug-eluting stent, resulting in a reduction in bleeding risk without an increase in ischaemic events.

This Review presents data describing the health burden of cardiovascular disease (CVD) within and across the WHO European Region. CVD remains the most common cause of death in the region. Deaths from CVD in those aged <70 years, commonly referred to as premature, are a particular concern, with >60 million potential years of life lost to CVD in Europe annually. Although more women than men die from

Left ventricular ejection fraction (EF) remains the major parameter for diagnosis, phenotyping, prognosis and treatment decisions in heart failure. The 2016 ESC heart failure guidelines introduced a third EF category for an EF of 40–49%, defined as heart failure with mid-range EF (HFmrEF). This category has been largely unexplored compared with heart failure with reduced EF (HFrEF; defined as EF <40%

Successfully engineering a functional, human, myocardial pump would represent a therapeutic alternative for the millions of patients with end-stage heart disease and provide an alternative to animal-based preclinical models. Although the field of cardiac tissue engineering has made tremendous advances, major challenges remain, which, if properly resolved, might allow the clinical implementation of

For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such

Dietary supplementation with NAD+ precursors or ketone esters has been shown to improve mitochondrial function in preclinical models of heart failure with either reduced or preserved ejection fraction. Both supplementation approaches hold promise but are in the early stages of development as clinical therapies for heart failure.

Atherosclerosis causes myocardial infarction, ischaemic cardiomyopathy, many ischaemic strokes and jeopardized limbs. Despite enormous progress, atherosclerosis has become the major cause of death worldwide. This Comment intertwines clinical and basic advances in atherosclerosis to illustrate their interdependence, which provides a template for a way forwards to conquer the scourge of atherosclerotic

The Human Genome Project marked a major milestone in the scientific community as it unravelled the ~3 billion bases that are central to crucial aspects of human life. Despite this achievement, it only scratched the surface of understanding how each nucleotide matters, both individually and as part of a larger unit. Beyond the coding genome, which comprises only ~2% of the whole genome, scientists have

Sexual health has a fundamental role in overall health and well-being, and a healthy and dynamic sex life can make an important contribution to a good quality of life. Sexual dysfunction, and especially erectile dysfunction (ED) in men, is highly prevalent in patients with cardiovascular disease (CVD). CVD and ED have shared risk factors and pathophysiological links, such as endothelial dysfunction

High levels of extracellular glucose induce trained immunity in macrophages, promoting a pro-atherosclerotic phenotype that persists even after normalization of glucose levels.

A new study now shows that basophils can influence cardiac remodelling after myocardial infarction. Despite their low number in the injured myocardium, basophils strongly affected other immune cells involved in cardiac repair and remodelling in mice, promoting cardiac healing by facilitating the polarization of reparative macrophages.

The application of next-generation sequencing to study congenital heart disease (CHD) is increasingly providing new insights into the causes and mechanisms of this prevalent birth anomaly. Whole-exome sequencing analysis identifies damaging gene variants altering single or contiguous nucleotides that are assigned pathogenicity based on statistical analyses of families and cohorts with CHD, high expression

Inflammation is intimately involved at all stages of atherosclerosis and remains a substantial residual cardiovascular risk factor in optimally treated patients. The proof of concept that targeting inflammation reduces cardiovascular events in patients with a history of myocardial infarction has highlighted the urgent need to identify new immunotherapies to treat patients with atherosclerotic cardiovascular

Nanotherapies are emerging rapidly as options to treat cardiovascular disease. However, insufficient and heterogeneous delivery remain critical issues. Novel strategies to boost targeted delivery of systemically administered nanoparticles by optimizing the particle physical properties or using immune cells as carriers promise to increase nanotherapeutic effectiveness in cardiovascular and other inflammatory

A new study shows that gene therapy to knock down endogenous Hippo signalling in cardiomyocytes induces cardiac tissue renewal and improves heart function after myocardial infarction in adult pigs.

T cells are among the most common cell types present in atherosclerotic plaques and are increasingly being recognized as a central mediator in atherosclerosis development and progression. At the same time, triglycerides and fatty acids have re-emerged as crucial risk factors for atherosclerosis. Triglycerides and fatty acids are important components of the milieu to which the T cell is exposed from

Myocardial ischaemia results from coronary macrovascular or microvascular dysfunction compromising the supply of oxygen and nutrients to the myocardium. The underlying pathophysiological processes are manifold and encompass atherosclerosis of epicardial coronary arteries, vasospasm of large or small vessels and microvascular dysfunction — the clinical relevance of which is increasingly being appreciated

Mounting evidence from the SPRINT trial and the Blood Pressure Lowering Treatment Trialists points towards the use of absolute cardiovascular risk assessment to guide blood-pressure management. But who will fall between the cracks? We need to be pragmatic in keeping blood-pressure targets, if only to serve the >1 billion people at risk of cardiovascular disease living in low-resource settings.

A single-cell RNA-sequencing study in mice shows that, after myocardial infarction, the activated epicardium contains heterogeneous cell populations with distinct gene-expression profiles and paracrine signalling potential, which contribute to the cardioprotective and regenerative responses to ischaemic injury.

Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease

Genomic data are increasingly being integrated into health care. We propose an outline for structured training in cardiovascular genomics, recognizing the growing need for a cardiovascular genomics subspecialty and cardiovascular subspecialists who incorporate genomics advances to optimize the management of heritable cardiovascular diseases.

Patients with cardiovascular disease who live with socioeconomic disadvantage face barriers to healthy living. A new study assessing social disadvantage burden reveals that this patient population has poor adherence to COVID-19 risk-mitigation recommendations.

A new study shows that inhibition of microRNA-132 can attenuate myocardial hypertrophy in a large-animal model of hypertrophic heart failure.

Surgical mitral valve repair produces exceptional long-term survival, durable relief from mitral regurgitation, and physiological valve performance. Percutaneous mitral valve repair might prohibit subsequent surgical reconstruction. This finding has important implications, including for patient consent and clinical trial design. The objectives of mitral valve intervention must focus on life expectancy

Treatment with atglistatin, an inhibitor of adipose triglyceride lipase (ATGL) activity, has cardioprotective effects against catecholamine-induced cardiac damage in mice, according to a new study. Atglistatin inhibited adipose ATGL activity but had no effect on cardiac ATGL, indicating that its cardioprotective effects are mediated by non-cardiac actions.

Peroxisome proliferator-activated receptor-α (PPARα), PPARδ and PPARγ are transcription factors that regulate gene expression following ligand activation. PPARα increases cellular fatty acid uptake, esterification and trafficking, and regulates lipoprotein metabolism genes. PPARδ stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast

A new study published in Cell shows that cardiac mesoderm has the capacity to self-organize and form into chamber-like structures known as cardioids.

The number of therapies for heart failure (HF) with reduced ejection fraction has nearly doubled in the past decade. In addition, new therapies for HF caused by hypertrophic and infiltrative disease are emerging rapidly. Indeed, we are on the verge of a new era in HF in which insights into the biology of myocardial disease can be matched to an understanding of the genetic predisposition in an individual

The homogeneity of cardiovascular clinical trial populations limits the generalizability of results and compounds health inequities faced by women, older adults and people of colour. This Comment highlights the importance of diversity in clinical trial populations and describes multifaceted interventions that might help to close the diversity gap in trial enrolment.

A new study has identified a novel microRNA present in the blood that could potentially be used as a diagnostic test to distinguish between acute myocarditis and myocardial infarction.

PCSK9 inhibitors are a class of cholesterol-lowering drugs that regulate LDL-receptor degradation. Three new studies show successful reduction of PCSK9 levels by different approaches that all resulted in the lowering of LDL-cholesterol levels.

Atrial fibrillation affects almost 60 million adults worldwide. Atrial fibrillation is associated with a high risk of cardiovascular morbidity and death as well as with social, psychological and economic burdens on patients and their families. Social determinants — such as race and ethnicity, financial resources, social support, access to health care, rurality and residential environment, local language

Mineralocorticoid-receptor antagonism with the novel drug finerenone reduces the risk of new-onset atrial fibrillation or flutter in patients with chronic kidney disease and type 2 diabetes mellitus, according to a secondary analysis of the FIDELIO-DKD trial.

High blood pressure is one of the most important risk factors for ischaemic heart disease, stroke, other cardiovascular diseases, chronic kidney disease and dementia. Mean blood pressure and the prevalence of raised blood pressure have declined substantially in high-income regions since at least the 1970s. By contrast, blood pressure has risen in East, South and Southeast Asia, Oceania and sub-Saharan

Surgical occlusion of the left atrial appendage reduces the risk of ischaemic stroke among patients with atrial fibrillation who had undergone cardiac surgery for another indication.