Clément Menuet,Alona Ben-Tal,Ambre Linossier,Andrew M Allen,Benedito H Machado,Davi J A Moraes,David G S Farmer,David J Paterson,David Mendelowitz,Edward G Lakatta,Edwin W Taylor,Gareth L Ackland,Irving H Zucker,James P Fisher,James S Schwaber,Julia Shanks,Julian F R Paton,Julie Buron,K Michael Spyer,Kalyanam Shivkumar,Mathias Dutschmann,Michael J Joyner,Neil Herring,Paul Grossman,Robin M McAllen,Rohit Ramchandra,Song T Yao,Thomas Ritz,Alexander V Gourine
{"title":"Redefining respiratory sinus arrhythmia as respiratory heart rate variability: an international Expert Recommendation for terminological clarity.","authors":"Clément Menuet,Alona Ben-Tal,Ambre Linossier,Andrew M Allen,Benedito H Machado,Davi J A Moraes,David G S Farmer,David J Paterson,David Mendelowitz,Edward G Lakatta,Edwin W Taylor,Gareth L Ackland,Irving H Zucker,James P Fisher,James S Schwaber,Julia Shanks,Julian F R Paton,Julie Buron,K Michael Spyer,Kalyanam Shivkumar,Mathias Dutschmann,Michael J Joyner,Neil Herring,Paul Grossman,Robin M McAllen,Rohit Ramchandra,Song T Yao,Thomas Ritz,Alexander V Gourine","doi":"10.1038/s41569-025-01160-z","DOIUrl":"https://doi.org/10.1038/s41569-025-01160-z","url":null,"abstract":"The variation of heart rate in phase with breathing, known as 'respiratory sinus arrhythmia' (RSA), is a physiological phenomenon present in all air-breathing vertebrates. RSA arises from the interaction of several physiological mechanisms but is primarily mediated by rhythmic changes in cardiac parasympathetic (vagal) activity, increasing heart rate during inspiration and decreasing heart rate during expiration. RSA amplitude is an indicator of autonomic and cardiac health; RSA is diminished or absent in common pathological conditions such as chronic heart failure and hypertension. In this Expert Recommendation, we argue that the term 'RSA', although historically important, is semantically inaccurate and carries misleading pathological connotations, contributing to misunderstanding and misinterpretation of the origin and the physiological importance of the phenomenon. We propose replacing 'RSA' with the term 'respiratory heart rate variability' (RespHRV), which avoids pathological connotations and emphasizes the specific respiratory contribution to heart rate variability. We clarify that RespHRV encompasses respiratory-related heart rate variations in both the low-frequency and high-frequency bands traditionally defined in heart rate variability analysis, and that its amplitude should not be misconstrued as a measure of vagal tone. Adopting the proposed term 'RespHRV' is expected to unify understanding and stimulate further experimental and clinical research into the physiological mechanisms and functional importance of this phenomenon.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"51 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915152","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}
{"title":"Cholesterol crystals in the pathogenesis of atherosclerosis.","authors":"Yvonne Baumer, Jason Irei, William A Boisvert","doi":"10.1038/s41569-024-01100-3","DOIUrl":"10.1038/s41569-024-01100-3","url":null,"abstract":"<p><p>The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. Although the underlying mechanisms and signalling pathways involved in CC formation are incompletely understood, numerous studies have highlighted the existence of CCs at various stages of atheroma progression. In this Review, we summarize the mechanisms underlying CC formation and the role of CCs in cardiovascular disease. In particular, we explore the established links between lipid metabolism across various cell types and the formation of CCs, with a focus on CC occurrence in the vasculature. We also discuss CC-induced inflammation as one of the pathogenic features of CCs in the atheroma. Finally, we summarize the therapeutic strategies aimed at reducing CC-mediated atherosclerotic burden, including approaches to inhibit CC formation in the vasculature or to mitigate the inflammatory response triggered by CCs. Addressing CC formation might emerge as a crucial component in our broader efforts to combat cardiovascular disease.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":"315-332"},"PeriodicalIF":41.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668251","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}
Jianyi Jay Zhang, Steven M Pogwizd, Keiichi Fukuda, Wolfram-Hubertus Zimmermann, Chengming Fan, Joshua M Hare, Roberto Bolli, Philippe Menasché
{"title":"Trials and tribulations of cell therapy for heart failure: an update on ongoing trials.","authors":"Jianyi Jay Zhang, Steven M Pogwizd, Keiichi Fukuda, Wolfram-Hubertus Zimmermann, Chengming Fan, Joshua M Hare, Roberto Bolli, Philippe Menasché","doi":"10.1038/s41569-024-01098-8","DOIUrl":"10.1038/s41569-024-01098-8","url":null,"abstract":"<p><p>Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":"372-385"},"PeriodicalIF":41.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639368","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}
{"title":"Decongestion in heart failure: medical and device therapies","authors":"Zachary L. Cox, Kevin Damman, Jeffrey M. Testani","doi":"10.1038/s41569-025-01152-z","DOIUrl":"https://doi.org/10.1038/s41569-025-01152-z","url":null,"abstract":"<p>Heart failure is a leading cause of hospitalization worldwide, and congestion is the predominant cause of heart failure symptoms and hospitalization. The primary therapy used to treat and prevent congestion has historically been loop diuretics. However, many patients are discharged from hospital with residual congestion, which is associated with persistent heart failure symptoms, adverse outcomes and hospital readmission. Multiple medical strategies and devices have been and are being investigated with the aim of improving decongestion and subsequent heart failure outcomes. Numerous questions exist about the design of clinical trials to test emerging medical and device therapies, including the magnitude of benefit on congestive, kidney and post-discharge outcomes relative to conventional decongestion practices, and how best to implement novel therapies. In this Review, we discuss emerging medical and device strategies targeting congestion in patients with heart failure.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"32 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880706","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}
{"title":"Sotatercept as add-on therapy for advanced PAH","authors":"Xiulin Köhler","doi":"10.1038/s41569-025-01161-y","DOIUrl":"https://doi.org/10.1038/s41569-025-01161-y","url":null,"abstract":"Sotatercept, an activin-signalling inhibitor, is a promising add-on treatment for patients with advanced pulmonary arterial hypertension and a high risk of death, according to data from the ZENITH trial.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"108 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857762","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}
{"title":"Pulsed field ablation non-inferior to cryoablation for paroxysmal AF","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-025-01159-6","DOIUrl":"https://doi.org/10.1038/s41569-025-01159-6","url":null,"abstract":"In patients with symptomatic paroxysmal atrial fibrillation, pulsed field ablation is non-inferior to cryoballoon ablation for preventing the recurrence of atrial tachyarrhythmia, according to findings from the SINGLE SHOT CHAMPION trial.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"7 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836689","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}
{"title":"Expanding cardiovascular indications for semaglutide: results from the SOUL and STRIDE trials","authors":"Karina Huynh","doi":"10.1038/s41569-025-01158-7","DOIUrl":"https://doi.org/10.1038/s41569-025-01158-7","url":null,"abstract":"Two clinical trials presented at the ACC.25 describe the expanding indications for the glucagon-like peptide 1 receptor agonist semaglutide in patients with type 2 diabetes mellitus.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"49 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831797","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}
{"title":"Post-translational acylation of proteins in cardiac hypertrophy","authors":"Ying-Qi Liu, Qin Yang, Guo-Wei He","doi":"10.1038/s41569-025-01150-1","DOIUrl":"https://doi.org/10.1038/s41569-025-01150-1","url":null,"abstract":"<p>Acylations are post-translational modifications in which functional groups are attached to amino acids on proteins. Most acylations (acetylation, butyrylation, crotonylation, lactylation, malonylation, propionylation and succinylation) involve lysine but cysteine (palmitoylation) and glycine (myristoylation) residues can also be altered. Acylations have important roles in physiological and pathophysiological processes, including cardiac hypertrophy and related cardiovascular diseases. These post-translational modifications influence chromatin architecture, transcriptional regulation and metabolic pathways, thereby affecting cardiomyocyte function and pathology. The dynamic interaction between these acylations and their regulatory enzymes, such as histone acetyltransferases, histone deacetylases and sirtuins, underscores the complexity of cellular homeostasis and pathological processes. Emerging evidence highlights the therapeutic potential of targeting acylations to modulate enzyme activity and metabolite levels, offering promising avenues for novel treatments. In this Review, we explore the diverse mechanisms through which acylations contribute to cardiac hypertrophy, highlighting the complexity and potential therapeutic targets in this regulatory network.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"183 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827315","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}
{"title":"No effect of cerebral embolic protection devices on stroke risk after TAVI","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-025-01156-9","DOIUrl":"https://doi.org/10.1038/s41569-025-01156-9","url":null,"abstract":"Findings from the BHF PROTECT-TAVI trial indicate that the routine use of cerebral embolic protection devices during transcatheter aortic valve implantation does not decrease the incidence of stroke within 72 h after the intervention.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"60 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819332","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}
{"title":"Development of a miniature, bioresorbable, light-activated pacemaker","authors":"Gregory B. Lim","doi":"10.1038/s41569-025-01157-8","DOIUrl":"https://doi.org/10.1038/s41569-025-01157-8","url":null,"abstract":"Researchers have engineered a millimetre-scale, bioresorbable, optoelectronic system that can be minimally invasively implanted into the heart and wirelessly controlled by a light source on the surface of the skin to provide temporary cardiac pacing.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"12 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819246","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}