Circulation最新文献

{"title":"Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction.","authors":"Nigopan Gopalasingam, Kristoffer Berg-Hansen, Kristian Hylleberg Christensen, Bertil T Ladefoged, Steen Hvitfeldt Poulsen, Mads Jønsson Andersen, Barry A Borlaug, Roni Nielsen, Niels Møller, Henrik Wiggers","doi":"10.1161/CIRCULATIONAHA.124.069732","DOIUrl":"10.1161/CIRCULATIONAHA.124.069732","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2D). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2D with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2D and HFpEF remain unknown.</p><p><strong>Methods: </strong>A total of 24 patients with T2D and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period.</p><p><strong>Results: </strong>During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; <i>P</i><0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (<i>P</i><0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs.</p><p><strong>Conclusions: </strong>In patients with T2D and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2D and HFpEF.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1570-1583"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003749","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":"Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.","authors":"Xiongjing Jiang, Felix Mahfoud, Wei Li, Hui Dong, Jing Yu, Shuhua Yu, Xiaoping Chen, Peijian Wang, Zhiqiang Li, Lucas Lauder, Zhifang Wang, Zheng Ji, Yifei Dong, Bing Han, Zhiming Zhu, Yulin Chen, Jianzhong Xu, Xingsheng Zhao, Weidong Fan, Wen Xie, Brad Hubbard, Xi Hu, Kazuomi Kario, Runlin Gao","doi":"10.1161/CIRCULATIONAHA.124.069215","DOIUrl":"10.1161/CIRCULATIONAHA.124.069215","url":null,"abstract":"<p><strong>Background: </strong>Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is a sham-controlled trial investigating the safety and efficacy of RDN in China.</p><p><strong>Methods: </strong>This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; Shanghai Angiocare Medical Technology, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months.</p><p><strong>Results: </strong>Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; <i>P</i><0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; <i>P</i><0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; <i>P</i>=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; <i>P</i>=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up.</p><p><strong>Conclusions: </strong>In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02901704.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1588-1598"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125027","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}

{"title":"Identifying Atypical Interatrial Block.","authors":"Amin Meghdadi, Cengiz Burak, Adrian Baranchuk","doi":"10.1161/CIRCULATIONAHA.124.071620","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071620","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 20","pages":"1645-1647"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615978","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":"A Tale of Two Maladies: Interplay of Mendelian Principles.","authors":"Reynaldo H Sanchez, Veena Rajaram, Nicholas S Hendren","doi":"10.1161/CIRCULATIONAHA.123.067135","DOIUrl":"10.1161/CIRCULATIONAHA.123.067135","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1640-1644"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478721","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":"From the Literature.","authors":"Tracy Hampton","doi":"10.1161/CIRCULATIONAHA.124.072368","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072368","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 20","pages":"1638-1639"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615974","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":"Endothelial-to-Mesenchymal Transition Contributes to Accelerated Atherosclerosis in Hutchinson-Gilford Progeria Syndrome.","authors":"Magda R Hamczyk, Rosa M Nevado, Pilar Gonzalo, María J Andrés-Manzano, Paula Nogales, Víctor Quesada, Aránzazu Rosado, Carlos Torroja, Fátima Sánchez-Cabo, Ana Dopazo, Jacob F Bentzon, Carlos López-Otín, Vicente Andrés","doi":"10.1161/CIRCULATIONAHA.123.065768","DOIUrl":"10.1161/CIRCULATIONAHA.123.065768","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is the main medical problem in Hutchinson-Gilford progeria syndrome, a rare premature aging disorder caused by the mutant lamin-A protein progerin. Recently, we found that limiting progerin expression to vascular smooth muscle cells (VSMCs) is sufficient to hasten atherosclerosis and death in <i>Apoe</i>-deficient mice. However, the impact of progerin-driven VSMC defects on endothelial cells (ECs) remained unclear.</p><p><strong>Methods: </strong><i>Apoe</i>- or <i>Ldlr</i>-deficient C57BL/6J mice with ubiquitous, VSMC-, EC- or myeloid-specific progerin expression fed a normal or high-fat diet were used to study endothelial phenotype during Hutchinson-Gilford progeria syndrome-associated atherosclerosis. Endothelial permeability to low-density lipoproteins was assessed by intravenous injection of fluorescently labeled human low-density lipoprotein and confocal microscopy analysis of the aorta. Leukocyte recruitment to the aortic wall was evaluated by en face immunofluorescence. Endothelial-to-mesenchymal transition (EndMT) was assessed by quantitative polymerase chain reaction and RNA sequencing in the aortic intima and by immunofluorescence in aortic root sections. TGFβ (transforming growth factor β) signaling was analyzed by multiplex immunoassay in serum, by Western blot in the aorta, and by immunofluorescence in aortic root sections. The therapeutic benefit of TGFβ1/SMAD3 pathway inhibition was evaluated in mice by intraperitoneal injection of SIS3 (specific inhibitor of SMAD3), and vascular phenotype was assessed by Oil Red O staining, histology, and immunofluorescence in the aorta and the aortic root.</p><p><strong>Results: </strong>Both ubiquitous and VSMC-specific progerin expression in <i>Apoe</i>-null mice provoked alterations in aortic ECs, including increased permeability to low-density lipoprotein and leukocyte recruitment. Atherosclerotic lesions in these progeroid mouse models, but not in EC- and myeloid-specific progeria models, contained abundant cells combining endothelial and mesenchymal features, indicating extensive EndMT triggered by dysfunctional VSMCs. Accordingly, the intima of ubiquitous and VSMC-specific progeroid models at the onset of atherosclerosis presented increased expression of EndMT-linked genes, especially those specific to fibroblasts and extracellular matrix. Aorta in both models showed activation of the TGFβ1/SMAD3 pathway, a major trigger of EndMT, and treatment of VSMC-specific progeroid mice with SIS3 alleviated the aortic phenotype.</p><p><strong>Conclusions: </strong>Progerin-induced VSMC alterations promote EC dysfunction and EndMT through TGFβ1/SMAD3, identifying this process as a candidate target for Hutchinson-Gilford progeria syndrome treatment. These findings also provide insight into the complex role of EndMT during atherogenesis.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1612-1630"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104925","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":"Letter by Y. Liang and B. Liang Regarding Article, \"Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial\".","authors":"Yi Liang, Bo Liang","doi":"10.1161/CIRCULATIONAHA.124.069679","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069679","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 20","pages":"e443"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616000","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":"Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.","authors":"Davor Vukadinović, Lucas Lauder, David E Kandzari, Deepak L Bhatt, Ajay J Kirtane, Elazer R Edelman, Roland E Schmieder, Michel Azizi, Michael Böhm, Felix Mahfoud","doi":"10.1161/CIRCULATIONAHA.124.069709","DOIUrl":"10.1161/CIRCULATIONAHA.124.069709","url":null,"abstract":"<p><strong>Background: </strong>Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.</p><p><strong>Methods: </strong>We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data.</p><p><strong>Results: </strong>Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; <i>P</i><0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; <i>P</i><0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; <i>P</i><0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; <i>P</i>=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (<i>P</i> for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; <i>P</i>=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; <i>P</i>=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; <i>P</i>=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; <i>P</i>=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (<i>P</i> for interaction, 0.84). There was significant heterogeneity between trials.</p><p><strong>Conclusions: </strong>RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medications.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1599-1611"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361227","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}

{"title":"Myocardial Ischemic Syndromes: A New Nomenclature to Harmonize Evolving International Clinical Practice Guidelines.","authors":"William E Boden, Raffaele De Caterina, Juan Carlos Kaski, Noel Bairey Merz, Colin Berry, Mario Marzilli, Carl J Pepine, Emanuele Barbato, Giulio Stefanini, Eva Prescott, Philippe Gabriel Steg, Deepak L Bhatt, Joseph A Hill, Filippo Crea","doi":"10.1161/CIRCULATIONAHA.123.065656","DOIUrl":"10.1161/CIRCULATIONAHA.123.065656","url":null,"abstract":"<p><p>Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, \"stable coronary artery disease\" (CAD), \"stable ischemic heart disease,\" and \"chronic coronary syndromes\" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with \"acute coronary syndromes\" (ACS), the 2023 American guidelines endorsed the alternative term \"chronic coronary disease.\" An unintended consequence of these competing classifications is perpetuation of the restrictive terms \"coronary\" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of \"acute myocardial ischemic syndromes\" and \"non-acute myocardial ischemic syndromes,\" which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1631-1637"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104927","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}

{"title":"Increased Nitric Oxide Availability: The Explanation for Recent Improvements in Saphenous Vein Graft Patency?","authors":"Mario Gaudino, Sigrid Sandner, Antonio Maria Calafiore","doi":"10.1161/CIRCULATIONAHA.124.071157","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071157","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 20","pages":"1567-1569"},"PeriodicalIF":35.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615983","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}