Microplastics and nanoplastics (MNPs) are pervasive environmental pollutants that result from the degradation of plastic materials and the use of plastic-containing products. Although the accumulation of MNPs in the gast...Microplastics and nanoplastics (MNPs) are pervasive environmental pollutants that result from the degradation of plastic materials and the use of plastic-containing products. Although the accumulation of MNPs in the gastrointestinal and respiratory systems is well documented, growing evidence suggests that MNPs can translocate into the bloodstream and accumulate in cardiovascular tissue, raising concerns about their potential role in the development of cardiovascular disease. In this Review, we synthesize the current knowledge on MNP exposure routes, tissue distribution and biological effects relevant to cardiovascular health. We examine the latest clinical and experimental studies on the presence of MNPs in the blood, atherosclerotic plaques, thrombi and myocardial tissue, and critically evaluate the mechanistic evidence linking MNPs to endothelial dysfunction, atherosclerosis progression, myocardial injury and arrhythmogenesis. In vitro and in vivo data highlight plausible pathophysiological pathways linking MNPs to cardiovascular disease, including oxidative stress, mitochondrial dysfunction, inflammation and fibrotic remodelling. However, causal associations remain unproven in humans, and major methodological challenges persist, including inconsistent detection methods, limited epidemiological data and inadequate modelling of real-world exposure. We conclude by outlining research priorities and proposing a framework for how to integrate MNPs into environmental cardiology practice. As the global issue of plastic pollution intensifies, elucidating the cardiovascular risks posed by MNPs represents an urgent interdisciplinary challenge with substantial public health implications.
Diabetes mellitus and the associated increased risk of cardiovascular disease is a major health-care issue worldwide. Diabetic cardiomyopathy, a complication of diabetes mellitus, is driven primarily by hyperglycaemia an...Diabetes mellitus and the associated increased risk of cardiovascular disease is a major health-care issue worldwide. Diabetic cardiomyopathy, a complication of diabetes mellitus, is driven primarily by hyperglycaemia and hyperlipidaemia, which promote cardiac oxidative stress, mitochondrial dysfunction and pathological cardiac remodelling, leading to impaired cardiac function and eventual heart failure. Over the past 30 years, research on diabetic cardiomyopathy and other diabetes-associated cardiovascular diseases has focused on the role of chronic inflammation. Inflammation is a complex process involving pro-inflammatory cytokines, chemokines, activation of resident immune cells, and recruitment of immune cells to sites of injury, processes that are exacerbated in the setting of diabetes. Evidence now suggests that the inflammatory processes caused by persistent hyperglycaemia and hyperlipidaemia in diabetes contribute to the impairment of cardiac function. Importantly, no treatment options are available to reverse diabetic cardiomyopathy, with clinicians relying on strategies to delay or halt the progression of the disease. In this Review, we describe the inflammatory signalling pathways involved in diabetic cardiomyopathy and discuss strategies that can potentially be used to target these inflammatory pathways for the treatment of diabetic cardiomyopathy.
The field of cardiac lymphatic research has expanded considerably over the past decade. Clinical studies have uncovered lymphatic remodelling in a wide range of cardiovascular diseases, and experimental research has demo...The field of cardiac lymphatic research has expanded considerably over the past decade. Clinical studies have uncovered lymphatic remodelling in a wide range of cardiovascular diseases, and experimental research has demonstrated that these structural alterations often lead to dysfunction of lymphatic transport. Given the vital physiological role of lymphatics, insufficient lymphatic drainage can affect several aspects of cardiac pathophysiology, including myocardial fluid balance, the immune microenvironment, collagen turnover and lipid handling. In this Review, current knowledge on cardiac lymphatics is summarized, including the structural and molecular specializations underlying their diverse homeostatic functions, and how these features can be altered in cardiovascular diseases. The latest research on the effects of inflammation on lymphatics is presented, together with the mechanisms by which lymphatics modulate immunity. The regulation of cardiac lymphangiogenesis is discussed, including accumulating evidence of immune cell-lymphatic crosstalk in the heart, the role of metabolic and biomechanical stimulation of lymphangiogenesis, and examples of experimental approaches to therapeutic lymphangiogenesis and their current limitations. Finally, areas for future research are highlighted, including the translation of lymphatic imaging and lymphangiogenic therapies to the clinic for patients with cardiovascular disease.
Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β-glycoprotein 1, cardiolipin and oth...Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β-glycoprotein 1, cardiolipin and other molecules, as well as functional assays for lupus anticoagulant. The presence of aPL can lead to endothelial dysfunction or a hypercoagulable state through prothrombotic and antifibrinolytic mechanisms. These processes, often in conjunction with a 'second hit', such as trauma, surgery, or other causes of hypercoagulability or stasis, can lead to venous or arterial thrombosis. The thrombotic risk associated with aPL is best recognized in thrombotic antiphospholipid syndrome, characterized by a persistently positive test for lupus anticoagulant or seropositivity for aPL associated with venous, arterial or microvascular thrombosis. However, aPL seropositivity and its clinical effect on thrombotic events have been increasingly recognized in a broader group of individuals who do not meet traditional research criteria for thrombotic antiphospholipid syndrome. In this Review, we provide an overview of the evidence related to aPL seropositivity in individuals with or without previous thrombosis and the clinical relevance of aPL seropositivity in predicting the risk of thrombotic cardiovascular events. We discuss potential management strategies and identify key knowledge gaps that warrant further research.
Atrial failure is an emerging clinical syndrome that results from an underlying atrial cardiomyopathy and is characterized by impaired atrial haemodynamic and/or electrical function that is sufficient to cause symptoms,...Atrial failure is an emerging clinical syndrome that results from an underlying atrial cardiomyopathy and is characterized by impaired atrial haemodynamic and/or electrical function that is sufficient to cause symptoms, adverse clinical outcomes or both. Similar to ventricular cardiomyopathy, atrial cardiomyopathy refers to a structural, functional and/or electrophysiological tissue abnormality, whereas atrial failure denotes the stage at which it manifests clinically. Atrial failure can be classified as primary, when driven by intrinsic atrial pathology, or secondary, when atrial dysfunction arises from sustained haemodynamic or electrical stress imposed by ventricular, valvular or systemic disease. Increasing evidence indicates that atrial failure might not be merely a bystander, but a key determinant of symptoms and prognosis in cardiovascular conditions. Atrial failure can act as a primary driver of heart failure with preserved ejection fraction, promote atrial arrhythmias through adverse electrical remodelling, and potentially increase thromboembolic risk independently of atrial fibrillation. In this Review, we detail the pathophysiological mechanisms and clinical phenotypes of atrial failure and highlight the role of multimodality imaging in diagnosing and phenotyping atrial cardiomyopathy and clinical atrial failure. Finally, we summarize emerging therapeutic strategies aimed at potentially reversing atrial adverse remodelling and discuss future directions for integrating atrial failure into clinical practice.
Capone F, Häseli SP, Liu L
… +13 more, Strocchi S, Langenberg C, Lusis AJ, Pietzner M, Muoio DM, Rider OJ, Raman B, Fudim M, Romeo S, Wang Y, Völkers M, Shah SH, Schiattarella GG
Heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasingly prevalent, interrelated conditions driven by the global rise in obesity and met...Heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasingly prevalent, interrelated conditions driven by the global rise in obesity and metabolic syndrome. Once viewed in isolation, HFpEF and MASLD are now recognized as organ-specific manifestations of shared systemic metabolic dysfunction. Evidence from the past decade highlights not only overlapping risk factors but also a dynamic, bidirectional inter-organ crosstalk between the liver and the heart that shapes their natural history. In this Review, we explore the epidemiological and mechanistic basis of the MASLD-HFpEF connection, focusing on shared metabolic drivers such as lipotoxicity, meta-inflammation and oxidative stress. We also discuss emerging liver-derived mediators, including hepatokines, metabolites and extracellular vesicles, that influence cardiac structure and function. Finally, we highlight diagnostic and therapeutic strategies relevant to both conditions and propose a multiorgan framework to improve their clinical recognition and management. Understanding the liver-heart axis is key to rethinking cardiometabolic disease beyond organ silos and towards more integrated, mechanism-based approaches.
Raddatz MA, Stein-Merlob AF, Mahmood SS
… +5 more, Ganatra S, Addison D, Lin TL, Larson SM, Yang EH
Nat Rev Cardiol
· 2026 Feb · PMID 41730987
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T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour...T cell immunotherapies offer a new approach to cancer therapy. Chimeric antigen receptor (CAR) T cell therapy is the most prolific of these treatments, leveraging genetically engineered T cells to augment the antitumour response. Bispecific antibodies, T cell receptor-engineered T cells and tumour-infiltrating lymphocytes have also emerged as novel T cell therapies with therapeutic benefit. As the variety of T cell therapies and indications for their use expand, a nuanced understanding of potential haemodynamic sequelae and cardiovascular toxicities is required. T cell activation can lead to massive cytokine release and excessive inflammation, termed cytokine release syndrome (CRS). Like other inflammatory syndromes, CRS can lead to cardiovascular complications, including arrhythmias, myocardial infarction and heart failure, with an incidence of cardiovascular events as high as 20% among patients who develop high-grade CRS. In this Review, we summarize the mechanisms, epidemiology and management of T cell therapy-associated CRS and subsequent cardiotoxicity. We also explore how an improved understanding of CAR T cell therapy, and other emerging T cell-based treatments, will inform the prevention and management of adverse cardiovascular events.
Over the past two decades, approaches to managing patients with coronary artery disease have improved substantially with advances in percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery,...Over the past two decades, approaches to managing patients with coronary artery disease have improved substantially with advances in percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, pharmacological secondary prevention, anti-anginal agents and lifestyle interventions. Accordingly, clinical management choices in non-acute myocardial ischaemic syndromes (NAMIS) remain a timely and important topic. The risks and benefits of an invasive strategy combined with optimal medical therapy (OMT) versus a conservative strategy of OMT alone should be discussed with patients to facilitate shared clinical decision making. The findings from high-quality, randomized, controlled trials in the era of modern OMT form an essential platform for these informed conversations. In totality, the evidence from randomized, controlled trials supports OMT as the first-line therapeutic approach in patients with NAMIS, whereas selected patients at high anatomical risk or those with persistent anginal symptoms despite initial OMT often derive further symptom relief from invasive therapy with PCI. In patients with high-risk NAMIS, including those with multivessel disease and diabetes mellitus, CABG surgery improves survival, whereas the benefit is less clear for PCI. In this Review, we discuss the findings from contemporary trials evaluating outcomes in patients with NAMIS treated invasively or conservatively with OMT alone, and we conclude with proposed management pathways.
The global rise in life expectancy underscores the urgent need to extend healthspan and prevent age-related diseases. Cardiovascular disease is the leading cause of death worldwide, with ageing as a major non-modifiable...The global rise in life expectancy underscores the urgent need to extend healthspan and prevent age-related diseases. Cardiovascular disease is the leading cause of death worldwide, with ageing as a major non-modifiable risk factor. Ageing drives progressive vascular dysfunction and cardiac decline, including heart failure with preserved or reduced ejection fraction. Vascular cells are particularly vulnerable to ageing, resulting in structural and functional deterioration of the microvasculature and macrovasculature. Emerging evidence highlights that ageing also disrupts the neurovascular interface - an intricate axis between the nervous and vascular systems that governs cardiac function. Alterations to the neurovascular unit in the heart contribute to impaired autonomic regulation, increasing the risk of arrhythmias and heart failure. In this Review, we examine how neurovascular ageing shapes cardiac dysfunction and explore the therapeutic potential of targeting the cardiac neurovascular unit to mitigate cardiovascular ageing and promote resilience in ageing populations.
Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality globally, despite advances in preventative medicine. An individual's family history of premature coronary artery disease (CAD) cap...Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality globally, despite advances in preventative medicine. An individual's family history of premature coronary artery disease (CAD) captures the complex interplay among shared genetic, environmental and lifestyle factors within families and is a well-established, independent risk factor for CAD. Although family history has high predictive value, it is inconsistently defined, variably applied and under-recorded in routine cardiovascular risk assessment. Advances in cardiac imaging and genomic medicine offer an opportunity to redefine cardiovascular risk assessment, laying the foundation for a precise approach to prevention in families at high risk of CAD. In this Review, we synthesize the pathogenic mechanisms underlying the inherited risk of CAD, highlight limitations of using family history in current risk stratification models and explore the evolving role of cardiac imaging and polygenic risk scores in risk assessment. We discuss the implications of these methods for lifestyle modifications and therapeutic interventions, and how integrating traditional and emerging tools can enable a precision approach to prevention throughout life. Finally, we examine the limitations of current cardiovascular disease prevention guidelines and highlight the need for studies that will improve equity, evaluate cost-effectiveness and address barriers to integrating novel tools into preventative care.
Organ-on-a-chip platforms have revolutionized the modelling of cardiovascular pathophysiology, enabling researchers to elucidate underlying mechanisms and drug responses for a variety of inherited and acquired diseases....Organ-on-a-chip platforms have revolutionized the modelling of cardiovascular pathophysiology, enabling researchers to elucidate underlying mechanisms and drug responses for a variety of inherited and acquired diseases. This emerging technology can overcome the limitations of traditional in vitro culture systems and animal models such as poor biological relevance and species-specific differences. Heart-on-a-chip and vasculature-on-a-chip models consist of 3D structures incorporating relevant cell populations (often derived from pluripotent stem cell sources) with precisely controlled electromechanical conditions and biochemical stimuli to form functional biomimetic microenvironments. These tunable platforms hold great promise in establishing patient-specific disease models and accelerating drug discovery and development, an important step in the direction of personalized cardiovascular medicine. In this Review, we highlight organ-on-a-chip models that have successfully mimicked cardiovascular disease phenotypes and contributed to the development of novel therapeutics, and summarize the technical and biological barriers to the widespread utilization of this technology.