Pub Date : 2025-07-21DOI: 10.1038/s41569-025-01196-1
Irene Fernández-Ruiz
Immune cells contribute to pathological remodelling in hypertrophic cardiomyopathy but regulatory T cells in particular can attenuate cardiac fibrosis and systolic dysfunction through their immunosuppressive properties, according to a new study.
{"title":"Regulatory T cells protect the heart in hypertrophic cardiomyopathy","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-025-01196-1","DOIUrl":"10.1038/s41569-025-01196-1","url":null,"abstract":"Immune cells contribute to pathological remodelling in hypertrophic cardiomyopathy but regulatory T cells in particular can attenuate cardiac fibrosis and systolic dysfunction through their immunosuppressive properties, according to a new study.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 9","pages":"609-609"},"PeriodicalIF":44.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1038/s41569-025-01193-4
Seyed Soheil Saeedi Saravi
Seyed Soheil Saeedi Saravi discusses the seminal study that linked a gut microbial metabolite to atherosclerotic cardiovascular disease and opened the way to mechanistic studies assessing how the gut microbiota influences host cardiovascular health.
{"title":"Metabolites matter for gut microbiota as a modifiable risk factor in cardiovascular diseases","authors":"Seyed Soheil Saeedi Saravi","doi":"10.1038/s41569-025-01193-4","DOIUrl":"10.1038/s41569-025-01193-4","url":null,"abstract":"Seyed Soheil Saeedi Saravi discusses the seminal study that linked a gut microbial metabolite to atherosclerotic cardiovascular disease and opened the way to mechanistic studies assessing how the gut microbiota influences host cardiovascular health.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 9","pages":"610-610"},"PeriodicalIF":44.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1038/s41569-025-01186-3
Luca Saba, Peter Libby
A misconception persisting among the scientific and clinical communities relates to the correlation between arterial stenosis and acute ischaemic events, including myocardial infarction and cerebral stroke. This Perspective article challenges the approach that most of the current guidelines codify, which is based on the concept that occlusive arterial stenosis generally provokes ischaemic events. We highlight the mechanistic differences between chronic or inducible ischaemia caused by flow-limiting stenoses and acute thrombotic events and question the traditional reliance on stenosis grading as a biomarker for therapeutic decision-making that many guidelines enshrine. Furthermore, we review the latest evidence highlighting the lack of a correlation between stenosis severity and the occurrence of acute thrombotic complications of atherosclerosis, in the light of a major clinical trial that included a large contemporary population and showed that only one-third of major adverse cardiovascular events occur in individuals with obstructive coronary artery disease. These considerations aim to foster a shift, grounded in contemporary evidence, towards treatment approaches that address modifying plaque biology rather than stenoses per se, using pharmacological treatment as a fundamental factor in risk mitigation and moving away from sole reliance on stenosis grading as a primary determinant of therapeutic decisions. In this Perspective article, Saba and Libby review the latest evidence highlighting the lack of a correlation between stenosis severity and the risk of atherosclerosis-induced thrombotic complications and question the overreliance on stenosis grading for therapeutic decision-making.
{"title":"Myocardial infarction, stroke and arterial stenosis: time to reassess a major misunderstanding","authors":"Luca Saba, Peter Libby","doi":"10.1038/s41569-025-01186-3","DOIUrl":"10.1038/s41569-025-01186-3","url":null,"abstract":"A misconception persisting among the scientific and clinical communities relates to the correlation between arterial stenosis and acute ischaemic events, including myocardial infarction and cerebral stroke. This Perspective article challenges the approach that most of the current guidelines codify, which is based on the concept that occlusive arterial stenosis generally provokes ischaemic events. We highlight the mechanistic differences between chronic or inducible ischaemia caused by flow-limiting stenoses and acute thrombotic events and question the traditional reliance on stenosis grading as a biomarker for therapeutic decision-making that many guidelines enshrine. Furthermore, we review the latest evidence highlighting the lack of a correlation between stenosis severity and the occurrence of acute thrombotic complications of atherosclerosis, in the light of a major clinical trial that included a large contemporary population and showed that only one-third of major adverse cardiovascular events occur in individuals with obstructive coronary artery disease. These considerations aim to foster a shift, grounded in contemporary evidence, towards treatment approaches that address modifying plaque biology rather than stenoses per se, using pharmacological treatment as a fundamental factor in risk mitigation and moving away from sole reliance on stenosis grading as a primary determinant of therapeutic decisions. In this Perspective article, Saba and Libby review the latest evidence highlighting the lack of a correlation between stenosis severity and the risk of atherosclerosis-induced thrombotic complications and question the overreliance on stenosis grading for therapeutic decision-making.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"23 2","pages":"131-142"},"PeriodicalIF":44.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-17DOI: 10.1038/s41569-025-01194-3
Jae Hyun Byun, Stella S. Daskalopoulou
Jae Hyun Byun and Stella S. Daskalopoulou describe the study that identified lipoprotein(a) as a genetically determined contributor to coronary artery disease.
Jae Hyun Byun和Stella S. Daskalopoulou描述了将脂蛋白(a)确定为冠状动脉疾病遗传因素的研究。
{"title":"Lipoprotein(a) in coronary artery disease","authors":"Jae Hyun Byun, Stella S. Daskalopoulou","doi":"10.1038/s41569-025-01194-3","DOIUrl":"10.1038/s41569-025-01194-3","url":null,"abstract":"Jae Hyun Byun and Stella S. Daskalopoulou describe the study that identified lipoprotein(a) as a genetically determined contributor to coronary artery disease.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 10","pages":"702-702"},"PeriodicalIF":44.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-16DOI: 10.1038/s41569-025-01184-5
Sanjiv M. Narayan, Mina K. Chung, Demilade Adedinsewo, Luisa C. C. Brant, Leslie L. Davis, David Duncker, Jennifer L. Hall, Janet K. Han, Carolyn S. P. Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F. Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A. Armoundas
The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to enable broad access to DHT and to benefit diverse and under-represented communities. Doing so will fill gaps in the clinical evidence base and avoid perpetuating historical biases. In this Review, we propose a personalized framework to improve access to DHT, addressing determinants of access at the individual, interpersonal, community, society, government and industry levels. We frame these issues globally, highlighting how the challenges to DHT access and potential solutions might differ between continents while also emphasizing common themes. We provide perspectives from partners across the spectrum of health care, including clinicians, clinical trialists, and experts from digital health and industry. In this Review, Narayan and colleagues discuss global disparities in access to digital health technologies, with a focus on cardiovascular medicine. The authors summarize the factors that affect access at various levels of society and present solutions that target each of these levels, culminating in a personalized framework to improve access to digital health technologies.
{"title":"Access to digital health technologies: personalized framework and global perspectives","authors":"Sanjiv M. Narayan, Mina K. Chung, Demilade Adedinsewo, Luisa C. C. Brant, Leslie L. Davis, David Duncker, Jennifer L. Hall, Janet K. Han, Carolyn S. P. Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F. Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A. Armoundas","doi":"10.1038/s41569-025-01184-5","DOIUrl":"10.1038/s41569-025-01184-5","url":null,"abstract":"The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to enable broad access to DHT and to benefit diverse and under-represented communities. Doing so will fill gaps in the clinical evidence base and avoid perpetuating historical biases. In this Review, we propose a personalized framework to improve access to DHT, addressing determinants of access at the individual, interpersonal, community, society, government and industry levels. We frame these issues globally, highlighting how the challenges to DHT access and potential solutions might differ between continents while also emphasizing common themes. We provide perspectives from partners across the spectrum of health care, including clinicians, clinical trialists, and experts from digital health and industry. In this Review, Narayan and colleagues discuss global disparities in access to digital health technologies, with a focus on cardiovascular medicine. The authors summarize the factors that affect access at various levels of society and present solutions that target each of these levels, culminating in a personalized framework to improve access to digital health technologies.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"23 1","pages":"9-22"},"PeriodicalIF":44.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-04DOI: 10.1038/s41569-025-01189-0
Seongwook Min, Jaehun An, Jae Hee Lee, Ji Hoon Kim, Daniel J. Joe, Soo Hwan Eom, Chang D. Yoo, Hyo-Suk Ahn, Jin-Young Hwang, Sheng Xu, John A. Rogers, Keon Jae Lee
{"title":"Publisher Correction: Wearable blood pressure sensors for cardiovascular monitoring and machine learning algorithms for blood pressure estimation","authors":"Seongwook Min, Jaehun An, Jae Hee Lee, Ji Hoon Kim, Daniel J. Joe, Soo Hwan Eom, Chang D. Yoo, Hyo-Suk Ahn, Jin-Young Hwang, Sheng Xu, John A. Rogers, Keon Jae Lee","doi":"10.1038/s41569-025-01189-0","DOIUrl":"10.1038/s41569-025-01189-0","url":null,"abstract":"","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 9","pages":"693-693"},"PeriodicalIF":44.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41569-025-01189-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-27DOI: 10.1038/s41569-025-01183-6
Athanasios Bakalakos, Emanuele Monda, Perry Mark Elliott
The term cardiomyopathy is used to describe a large family of complex heart muscle disorders of diverse aetiology and pathophysiology. For decades, the management of individual cardiomyopathy subtypes has focused primarily on the management of symptoms and the prevention of disease-related complications, such as heart failure and sudden cardiac death. Treatment of progressive myocardial dysfunction has relied on conventional evidence-based heart failure therapies, with variable success. In contrast to other areas of medicine, cardiology is characterized by few aetiology-targeted therapies, but cardiomyopathies offer an ideal model for innovation because, in many individuals, the disorder has a monogenic cause, the expression of which is modified by complex genetic mechanisms, comorbidities and lifestyle. Elucidation of the complex cellular and molecular pathways that result in downstream tissue phenotypes has led to the investigation of new or repurposed pharmacological agents and, in parallel, therapies that modify or mitigate the effects of causative genetic variants, offering the prospect of targeting the disease at its source. In this Review, we describe some of the most promising therapeutic approaches in cardiomyopathy and discuss their potential effect on the lives of patients and relatives. 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.
{"title":"Tailored therapeutics for cardiomyopathies","authors":"Athanasios Bakalakos, Emanuele Monda, Perry Mark Elliott","doi":"10.1038/s41569-025-01183-6","DOIUrl":"10.1038/s41569-025-01183-6","url":null,"abstract":"The term cardiomyopathy is used to describe a large family of complex heart muscle disorders of diverse aetiology and pathophysiology. For decades, the management of individual cardiomyopathy subtypes has focused primarily on the management of symptoms and the prevention of disease-related complications, such as heart failure and sudden cardiac death. Treatment of progressive myocardial dysfunction has relied on conventional evidence-based heart failure therapies, with variable success. In contrast to other areas of medicine, cardiology is characterized by few aetiology-targeted therapies, but cardiomyopathies offer an ideal model for innovation because, in many individuals, the disorder has a monogenic cause, the expression of which is modified by complex genetic mechanisms, comorbidities and lifestyle. Elucidation of the complex cellular and molecular pathways that result in downstream tissue phenotypes has led to the investigation of new or repurposed pharmacological agents and, in parallel, therapies that modify or mitigate the effects of causative genetic variants, offering the prospect of targeting the disease at its source. In this Review, we describe some of the most promising therapeutic approaches in cardiomyopathy and discuss their potential effect on the lives of patients and relatives. 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.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 10","pages":"814-831"},"PeriodicalIF":44.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-25DOI: 10.1038/s41569-025-01180-9
Attila Kovács, Harry Magunia, Alina Nicoara, David Oxborough, Marius Keller, Daniel X. Augustine, Dick Thijssen, Arie van Dijk, Andre Denault, Francois Haddad, Elena Surkova
Given its crucial role in determining patient symptoms and outcomes in various cardiopulmonary diseases, the thorough and accurate assessment of right ventricular function is essential for both diagnosis and ongoing patient monitoring. In the era of precision medicine, a more detailed characterization of patients with cardiopulmonary diseases is needed, especially with the emergence of novel pharmacological and device-based therapies, such as transcatheter tricuspid valve intervention, gene therapy in patients with cardiomyopathy and anti-obesity interventions for patients with heart failure. Precise and reproducible quantification of right ventricular morphology and function are crucial for risk stratification, the selection of different therapies for the appropriate patients and the evaluation of treatment outcomes. As our understanding of right ventricular pathophysiology expands, the need for sensitive markers of functional deterioration, reliable prognostic indicators and more precise surrogates for clinical trials becomes increasingly important. In this Roadmap, we address current challenges in the standardization of image acquisition, analysis and interpretation across different modalities. We explore the factors limiting the clinical adoption of more advanced approaches and provide expert recommendations to overcome these barriers. Additionally, we outline potential next steps for incorporating parameters of right ventricular function as surrogate end points in multicentre clinical trials of new drugs or devices, and highlight new research opportunities, including the integration of artificial intelligence technologies. Finally, we issue a call for international collaboration on selected priority areas. In this Roadmap, Kovács and colleagues review the imaging techniques used for evaluating the right ventricle, highlight challenges related to standardization, data analysis and clinical implementation, outline research opportunities, including the integration of artificial intelligence technologies, and call for international collaboration to drive advances in the assessment of the right ventricle.
{"title":"Challenges and opportunities in assessing right ventricular structure and function: a Roadmap for standardization, clinical implementation and research","authors":"Attila Kovács, Harry Magunia, Alina Nicoara, David Oxborough, Marius Keller, Daniel X. Augustine, Dick Thijssen, Arie van Dijk, Andre Denault, Francois Haddad, Elena Surkova","doi":"10.1038/s41569-025-01180-9","DOIUrl":"10.1038/s41569-025-01180-9","url":null,"abstract":"Given its crucial role in determining patient symptoms and outcomes in various cardiopulmonary diseases, the thorough and accurate assessment of right ventricular function is essential for both diagnosis and ongoing patient monitoring. In the era of precision medicine, a more detailed characterization of patients with cardiopulmonary diseases is needed, especially with the emergence of novel pharmacological and device-based therapies, such as transcatheter tricuspid valve intervention, gene therapy in patients with cardiomyopathy and anti-obesity interventions for patients with heart failure. Precise and reproducible quantification of right ventricular morphology and function are crucial for risk stratification, the selection of different therapies for the appropriate patients and the evaluation of treatment outcomes. As our understanding of right ventricular pathophysiology expands, the need for sensitive markers of functional deterioration, reliable prognostic indicators and more precise surrogates for clinical trials becomes increasingly important. In this Roadmap, we address current challenges in the standardization of image acquisition, analysis and interpretation across different modalities. We explore the factors limiting the clinical adoption of more advanced approaches and provide expert recommendations to overcome these barriers. Additionally, we outline potential next steps for incorporating parameters of right ventricular function as surrogate end points in multicentre clinical trials of new drugs or devices, and highlight new research opportunities, including the integration of artificial intelligence technologies. Finally, we issue a call for international collaboration on selected priority areas. In this Roadmap, Kovács and colleagues review the imaging techniques used for evaluating the right ventricle, highlight challenges related to standardization, data analysis and clinical implementation, outline research opportunities, including the integration of artificial intelligence technologies, and call for international collaboration to drive advances in the assessment of the right ventricle.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"23 1","pages":"60-77"},"PeriodicalIF":44.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-23DOI: 10.1038/s41569-025-01185-4
Gregory B. Lim
Endothelial cells in ischaemic microvessels undergo necroptosis, which is linked to haemolysis and the deposition of haemolysed red blood cell membranes at the sites of endothelial cell death. This process might be a haemostatic mechanism to prevent interstitial bleeding; however, excessive aggregation can cause microvascular obstruction and microangiopathy.
{"title":"Endothelial cell necroptosis induces haemolysis and microangiopathy","authors":"Gregory B. Lim","doi":"10.1038/s41569-025-01185-4","DOIUrl":"10.1038/s41569-025-01185-4","url":null,"abstract":"Endothelial cells in ischaemic microvessels undergo necroptosis, which is linked to haemolysis and the deposition of haemolysed red blood cell membranes at the sites of endothelial cell death. This process might be a haemostatic mechanism to prevent interstitial bleeding; however, excessive aggregation can cause microvascular obstruction and microangiopathy.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 8","pages":"534-534"},"PeriodicalIF":44.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-22DOI: 10.1038/s41569-025-01167-6
Dunja Aksentijevic, Simon Sedej, Jeremy Fauconnier, Melanie Paillard, Mahmoud Abdellatif, Katrin Streckfuss-Bömeke, Renée Ventura-Clapier, Jolanda van der Velden, Rudolf A. de Boer, Edoardo Bertero, Jan Dudek, Vasco Sequeira, Christoph Maack
Heart failure (HF) is a major global and life-threatening disease. Despite advances in therapies, the prevalence of HF is increasing owing to an ageing population and the pervasive pandemic of obesity and metabolic disorders, which have transformed the pathophysiology of HF. Changes in cardiac energy metabolism and the related energy deficit crucially contribute to the severity and type of HF. Furthermore, perturbations in excitation–contraction coupling, mitochondrial function and oxidative stress are characteristic features of HF. In this Review, we focus on the close interaction between cardiac mechanics and mitochondrial energetics, and decipher how this mechano-energetic coupling is disturbed in various acquired and hereditary forms of HF. In HF with reduced ejection fraction, defects in excitation–contraction coupling are key drivers of mechano-energetic uncoupling, whereas in HF with preserved ejection fraction, increased preload and afterload imposed by obesity, hypertension and age-dependent vascular stiffness increase mechanical workload, which is insufficiently matched by mitochondrial tricarboxylic acid cycle activity and ATP supply. In both scenarios, oxidative stress results from depletion of the antioxidative capacity and contributes to maladaptive cardiac remodelling and dysfunction. Several established and emerging treatments for HF target this mechano-energetic uncoupling, and a greater understanding of the underlying mechanisms will open new therapeutic opportunities to alleviate the burden of HF. 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.
{"title":"Mechano-energetic uncoupling in heart failure","authors":"Dunja Aksentijevic, Simon Sedej, Jeremy Fauconnier, Melanie Paillard, Mahmoud Abdellatif, Katrin Streckfuss-Bömeke, Renée Ventura-Clapier, Jolanda van der Velden, Rudolf A. de Boer, Edoardo Bertero, Jan Dudek, Vasco Sequeira, Christoph Maack","doi":"10.1038/s41569-025-01167-6","DOIUrl":"10.1038/s41569-025-01167-6","url":null,"abstract":"Heart failure (HF) is a major global and life-threatening disease. Despite advances in therapies, the prevalence of HF is increasing owing to an ageing population and the pervasive pandemic of obesity and metabolic disorders, which have transformed the pathophysiology of HF. Changes in cardiac energy metabolism and the related energy deficit crucially contribute to the severity and type of HF. Furthermore, perturbations in excitation–contraction coupling, mitochondrial function and oxidative stress are characteristic features of HF. In this Review, we focus on the close interaction between cardiac mechanics and mitochondrial energetics, and decipher how this mechano-energetic coupling is disturbed in various acquired and hereditary forms of HF. In HF with reduced ejection fraction, defects in excitation–contraction coupling are key drivers of mechano-energetic uncoupling, whereas in HF with preserved ejection fraction, increased preload and afterload imposed by obesity, hypertension and age-dependent vascular stiffness increase mechanical workload, which is insufficiently matched by mitochondrial tricarboxylic acid cycle activity and ATP supply. In both scenarios, oxidative stress results from depletion of the antioxidative capacity and contributes to maladaptive cardiac remodelling and dysfunction. Several established and emerging treatments for HF target this mechano-energetic uncoupling, and a greater understanding of the underlying mechanisms will open new therapeutic opportunities to alleviate the burden of HF. 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.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 10","pages":"773-797"},"PeriodicalIF":44.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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