Aggarwal B, Gao Y, Alfini A
… +24 more, Azarbarzin A, Anafi RC, Glazer Baron K, Bautch VL, Bowles N, Broussard JL, Brown M, Cheng P, Cook SH, Cortese R, Fernandez FX, Galis Z, Johnson DA, Jelic S, Lipton JO, Lutsey PL, Miao Q, Ordovas JM, Prather AA, Swirski FK, Tasali E, Vargas I, Grandner MA, Lloyd-Jones D
Nat Rev Cardiol
· 2026 Feb · PMID 40968347
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The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate...The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular resilience as a dynamic and multifaceted concept spanning molecular, cellular and systemic levels across an individual's lifespan. The workshop emphasized the need to expand the focus from solely understanding whether and how sleep and circadian rhythm disturbances contribute to disease, to also exploring how healthy sleep and aligned circadian rhythms can increase cardiovascular resilience. To develop a Roadmap towards this goal, workshop participants identified key knowledge gaps and research opportunities, including the need to integrate biological, behavioural, environmental and societal factors in sleep and circadian health with cardiovascular research to identify therapeutic targets. Proposed interventions encompass behavioural therapies, chronotherapy, lifestyle changes, organizational policies and public health initiatives aimed at improving sleep and circadian health for better cardiovascular outcomes. Future cross-disciplinary research and translation of discoveries into public health strategies and clinical practices could improve cardiovascular resilience across the lifespan in all populations.
Arrhythmias and heart failure (HF) are common causes of morbidity and premature death worldwide, and patients who present with both conditions have particularly poor outcomes. Arrhythmia-induced cardiomyopathy (AIC) is a...Arrhythmias and heart failure (HF) are common causes of morbidity and premature death worldwide, and patients who present with both conditions have particularly poor outcomes. Arrhythmia-induced cardiomyopathy (AIC) is a condition in which arrhythmias, often atrial fibrillation (AF), but also frequent atrial or ventricular ectopic beats, cause or aggravate HF. The hallmark of this condition is partial or complete reversibility of left ventricular systolic dysfunction after restoration of normal sinus rhythm. Differentiation between HF that causes arrhythmias and arrhythmias that cause HF remains challenging, leads to the underuse of rhythm-control therapy and, consequently, to the under-diagnosis of AIC. In this Review, we describe the various pathophysiological mechanisms of AIC, with a focus on AF as the underlying arrhythmia. We then discuss the epidemiology, clinical presentation and assessment of patients with AIC, with consideration of the complex interactions between AF and left ventricular dysfunction. We also present the therapeutic approach taken in patients presenting with suspected AIC, including restoration of sinus rhythm to unmask a diagnosis of AIC and treatment of HF. We conclude with a discussion of priorities for future research and the observation that there is an urgent need for objective, easily quantifiable parameters to identify patients with AIC.
Growing evidence from the past seven decades indicates that atherosclerosis begins in youth and progresses in response to exposure to cardiovascular risk factors, which contribute to the development of cardiovascular dis...Growing evidence from the past seven decades indicates that atherosclerosis begins in youth and progresses in response to exposure to cardiovascular risk factors, which contribute to the development of cardiovascular disease in later life. A long-term randomized clinical trial lasting at least 50 years and involving screening and follow-up of children across their lifespan would provide the highest level of evidence to determine the lifelong influence of cardiovascular risk factors on cardiovascular disease risk but such an approach is not feasible. However, much can be learned from observing patients with familial hypercholesterolaemia. Those patients who were treated at a young age remained event-free into adulthood, beyond the ages at which their affected parent, who initiated treatment at a much later age, experienced their first cardiovascular event. The evidence is less certain for other types of dyslipidaemia and other cardiovascular risk factors, including high blood pressure. Nonetheless, the strategy of waiting until later in adulthood to screen and intervene, often after a non-fatal cardiovascular disease event has already occurred, might no longer seem prudent. In this Review, we summarize the growing body of evidence supporting intensified efforts to identify cardiovascular risk factors in children and young adults, and to identify knowledge gaps among this cohort such as the optimal timing and strategy for blood lipid screening.
A central paradigm in cardiac biology is the reactivation of the fetal gene programme in the adult heart in response to stress. This so-called 'fetal gene hypothesis' was first proposed almost 40 years ago following the...A central paradigm in cardiac biology is the reactivation of the fetal gene programme in the adult heart in response to stress. This so-called 'fetal gene hypothesis' was first proposed almost 40 years ago following the observation that certain fetal contractile protein isoforms were re-expressed in hypertrophied ventricles in the rodent heart in response to haemodynamic overload. Consequently, this concept was broadly adopted, and activation of the fetal gene programme became synonymous in the literature with the cardiac stress response. Transcriptomic and epigenomic profiling studies from the past 20 years have revealed the extent to which the diseased heart redeploys fetal gene programmes in response to stress. In this Review, we describe the historical origins of the fetal gene hypothesis and re-evaluate the general principles of fetal gene regulation in heart development, disease and regeneration.
Glazer AM, Tabet DR, Parikh VN
… +13 more, Kroncke BM, Cote AG, Yamamoto Y, Wang Q, Muhammad A, Lancaster MC, O'Neill MJ, Weile J, Yang T, Macrae CA, Ashley EA, Roth FP, Roden DM
Nat Rev Cardiol
· 2026 Mar · PMID 40890511
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Cardiovascular diseases are leading global causes of death and disability, often presenting as interrelated phenotypes of atherosclerotic vascular disease, heart failure and arrhythmias. Cardiovascular diseases arise fro...Cardiovascular diseases are leading global causes of death and disability, often presenting as interrelated phenotypes of atherosclerotic vascular disease, heart failure and arrhythmias. Cardiovascular diseases arise from interactions between environmental factors and predisposing genotypes and include common Mendelian lipid disorders, cardiomyopathies and arrhythmia syndromes. The identification of a pathogenic variant through genetic testing can inform disease diagnosis, risk prediction, treatment and family screening. However, a major roadblock in genomic medicine is that for many variants, especially missense variants, we lack sufficient evidence to enable a definitive classification, and therefore these variants are deemed as 'variants of uncertain significance'. In this Review, we describe how multiplexed assays of variant effects can enable the functional assessment of nearly all coding variants in a target sequence, potentially offering a proactive approach to identifying the functional significance of gene variants that are observed later in a patient. We discuss validation, including the role of in silico variant effect predictors, and how multiplexed experimental methods are informing cardiovascular disease biology and ultimately resolving the problem of variants of uncertain significance at scale.