Circulation: Heart Failure最新文献

{"title":"Empagliflozin Improves Diastolic Function in HFpEF by Restabilizing the Mitochondrial Respiratory Chain.","authors":"Antje Schauer, Volker Adams, Susanne Kämmerer, Erik Langner, Antje Augstein, Peggy Barthel, Anita Männel, Gunar Fabig, Paula Ketilly Nascimento Alves, Mario Günscht, Ali El-Armouche, Thomas Müller-Reichert, Axel Linke, Ephraim B Winzer","doi":"10.1161/CIRCHEARTFAILURE.123.011107","DOIUrl":"10.1161/CIRCHEARTFAILURE.123.011107","url":null,"abstract":"<p><strong>Background: </strong>Clinical studies demonstrated beneficial effects of sodium-glucose-transporter 2 inhibitors on the risk of cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF). However, underlying processes for cardioprotection remain unclear. The present study focused on the impact of empagliflozin (Empa) on myocardial function in a rat model with established HFpEF and analyzed underlying molecular mechanisms.</p><p><strong>Methods: </strong>Obese ZSF1 (Zucker fatty and spontaneously hypertensive) rats were randomized to standard care (HFpEF, n=18) or Empa (HFpEF/Empa, n=18). ZSF1 lean rats (con, n=18) served as healthy controls. Echocardiography was performed at baseline and after 4 and 8 weeks, respectively. After 8 weeks of treatment, hemodynamics were measured invasively, mitochondrial function was assessed and myocardial tissue was collected for either molecular and histological analyses or transmission electron microscopy.</p><p><strong>Results: </strong>In HFpEF Empa significantly improved diastolic function (E/é: con: 17.5±2.8; HFpEF: 24.4±4.6; <i>P</i><0.001 versus con; HFpEF/Empa: 19.4±3.2; <i>P</i><0.001 versus HFpEF). This was accompanied by improved hemodynamics and calcium handling and by reduced inflammation, hypertrophy, and fibrosis. Proteomic analysis demonstrated major changes in proteins involved in mitochondrial oxidative phosphorylation. Cardiac mitochondrial respiration was significantly impaired in HFpEF but restored by Empa (V_max complex IV: con: 0.18±0.07 mmol O₂/s/mg; HFpEF: 0.13±0.05 mmol O₂/s/mg; <i>P</i><0.041 versus con; HFpEF/Empa: 0.21±0.05 mmol O₂/s/mg; <i>P</i>=0.012 versus HFpEF) without alterations of mitochondrial content. The expression of cardiolipin, an essential stability/functionality-mediating phospholipid of the respiratory chain, was significantly decreased in HFpEF but reverted by Empa (con: 15.9±1.7 nmol/mg protein; HFpEF: 12.5±1.8 nmol/mg protein; <i>P</i>=0.002 versus con; HFpEF/Empa: 14.5±1.8 nmol/mg protein; <i>P</i>=0.03 versus HFpEF). Transmission electron microscopy revealed a reduced size of mitochondria in HFpEF, which was restored by Empa.</p><p><strong>Conclusions: </strong>The study demonstrates beneficial effects of Empa on diastolic function, hemodynamics, inflammation, and cardiac remodeling in a rat model of HFpEF. These effects were mediated by improved mitochondrial respiratory capacity due to modulated cardiolipin and improved calcium handling.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011107"},"PeriodicalIF":9.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283165","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":"Comparison of Blood Volume Profiles in Heart Failure With Preserved and Reduced Ejection Fractions: Sex Makes a Difference.","authors":"Wayne L Miller, Diane E Grill, Brian P Mullan","doi":"10.1161/CIRCHEARTFAILURE.123.010906","DOIUrl":"10.1161/CIRCHEARTFAILURE.123.010906","url":null,"abstract":"<p><strong>Background: </strong>Blood volume (BV) profiles vary markedly in patients with heart failure (HF), but how HF phenotypes and patient sex impact volume profiles remain to be explored. The aim of the study was to differentiate BV, plasma volume, and red blood cell mass profiles by phenotypes of preserved and reduced left ventricular ejection fractions and assess the impact of patient sex on profile heterogeneity.</p><p><strong>Methods: </strong>Retrospective analysis of clinical and BV data was undertaken in patients with chronic New York Heart Association II-III heart failure. BV was quantitated using the nuclear medicine indicator-dilution methodology.</p><p><strong>Results: </strong>A total of 530 BV analyses (360 HF with reduced ejection fraction and 170 HF with preserved ejection fraction) were identified in 395 unique patients. Absolute BV was greater in HF with reduced ejection fraction (6.7±1.8 versus 5.9±1.6 liters: <i>P</i><0.001); however, large variability in frequency distribution of volume profiles was observed in both phenotypes (-22% deficit to +109% excess relative to normal volumes). HF with reduced ejection fraction was characterized by a higher prevalence of BV expansion ≥+25% of normal (39% versus 26%; <i>P</i>=0.003), and HF with preserved ejection fraction was characterized a by more frequent normal BV (42% versus 24%; <i>P</i><0.001). Male sex in both phenotypes was associated with a larger absolute BV (7.0±1.6 versus 5.1±1.3 liters; <i>P</i><0.001) and higher frequency of large BV and plasma volume expansions above normal (both <i>P</i><0.001), while females in both phenotypes demonstrated a higher prevalence of normal BV and plasma volume (both <i>P</i><0.001).</p><p><strong>Conclusions: </strong>Findings support significant differences in BV, plasma volume, and red blood cell mass profile distributions between heart failure phenotypes, driven in large part by sex-specific factors. This underscores the importance of identifying and distinguishing individual patient volume profiles to help guide volume management strategies.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e010906"},"PeriodicalIF":9.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260668","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":"Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.","authors":"Shohei Ichimura, Tomofumi Misaka, Ryo Ogawara, Yusuke Tomita, Fumiya Anzai, Yu Sato, Shunsuke Miura, Tetsuro Yokokawa, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Akiomi Yoshihisa, Yasuchika Takeishi","doi":"10.1161/CIRCHEARTFAILURE.123.011057","DOIUrl":"10.1161/CIRCHEARTFAILURE.123.011057","url":null,"abstract":"<p><strong>Background: </strong>The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated.</p><p><strong>Methods: </strong>We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted.</p><p><strong>Results: </strong>The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation.</p><p><strong>Conclusions: </strong>NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011057"},"PeriodicalIF":9.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283168","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":"Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.","authors":"Yan Gao, Bowang Chen, Yi Han, Jiapeng Lu, Xi Li, Aoxi Tian, Lihua Zhang, Bin Wang, Yun Hong, Jiamin Liu, Yan Li, Wuhan Bilige, Haibo Zhang, Xin Zheng, Jing Li","doi":"10.1161/CIRCHEARTFAILURE.123.011118","DOIUrl":"10.1161/CIRCHEARTFAILURE.123.011118","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death.</p><p><strong>Methods: </strong>We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set. One hundred seventy-one and 120 patients with heart failure with preserved ejection fraction were randomly selected as a test set and a validation set, respectively. We performed mRNA microarrays in all patients.</p><p><strong>Results: </strong>We constructed a 5-mRNA signature for predicting 1-year all-cause death. The scores of the 5-mRNA signature were significantly associated with the 1-year risk of all-cause death in both the test set (hazard ratio, 2.72 [95% CI, 1.98-3.74]; <i>P</i><0.001) and the validation set (hazard ratio, 3.95 [95% CI, 2.40-6.48]; <i>P</i><0.001). Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set. A composite model integrating the 5-mRNA risk score and variables in the reference model demonstrated an excellent discrimination capability, with an area under the curve of 0.861 (95% CI, 0.784-0.939) in the test set and an area under the curve of 0.859 (95% CI, 0.755-0.963) in the validation set. The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (<i>P</i><0.001).</p><p><strong>Conclusions: </strong>The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011118"},"PeriodicalIF":9.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283169","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":"Intermittent Fasting After ST-Segment–Elevation Myocardial Infarction Improves Left Ventricular Function: The Randomized Controlled INTERFAST-MI Trial","authors":"Jochen Dutzmann, Zoe Kefalianakis, Florian Kahles, Jan-Marcus Daniel, Hubert Gufler, Walter Alexander Wohlgemuth, Kai Knöpp, Daniel G. Sedding","doi":"10.1161/circheartfailure.123.010936","DOIUrl":"https://doi.org/10.1161/circheartfailure.123.010936","url":null,"abstract":"BACKGROUND:Intermittent fasting has shown positive effects on numerous cardiovascular risk factors. The INTERFAST-MI trial (Intermittent Fasting in Myocardial Infarction) has been designed to study the effects of intermittent fasting on cardiac function after STEM (ST-segment–elevation myocardial infarction) and the feasibility of future multicenter trials.METHODS:The INTERFAST-MI study was a prospective, randomized, controlled, nonblinded, single-center investigator-initiated trial. From October 1, 2020, to July 15, 2022, 48 patients were randomized to the study groups intermittent fasting or regular diet and followed for 6 months with follow-up visits at 4 weeks and 3 months.RESULTS:In all, 22 of 24 patients in the intermittent fasting group with a mean age of 58.54±12.29 years and 20 of 24 patients in the regular diet group with a mean age of 59.60±13.11 years were included in the intention-to-treat population. The primary efficacy end point (improvement in left ventricular ejection fraction after 4 weeks) was significantly greater in the intermittent fasting group compared with the control group (mean±SD, 6.636±7.122%. versus 1.450±4.828%; <i>P</i>=0.038). This effect was still significant and even more pronounced after 3 and 6 months. The patients in the intermittent fasting group showed a greater reduction in diastolic blood pressure and body weight compared with the control group. The mean adherence of patients in the intermittent fasting group was a median of 83.7% (interquartile range, 69.0%–98.4%) of all days. None of the patients from either group reported dizziness, syncope, or collapse.CONCLUSIONS:Our results suggest that intermittent fasting after myocardial infarction may be safe and could improve left ventricular function after STEMI.REGISTRATION:URL: https://www.drks.de; Unique identifier: DRKS00021784.","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":"8 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840516","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":"Is My Patient Fit for Surgery? Navigating Between the Rock of Heart Failure and the Hard Place of Semiurgent Surgery.","authors":"Aws Almufleh, Michael M Givertz","doi":"10.1161/CIRCHEARTFAILURE.124.011609","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.011609","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011609"},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847661","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 Shahriar et al Regarding Article, \"Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response in Acute Heart Failure: The Multicenter ENACT-HF Study\".","authors":"Arman A Shahriar, Tess E Allan, Mark N Belkin","doi":"10.1161/CIRCHEARTFAILURE.124.011703","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.011703","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011703"},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916217","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 Albulushi Regarding Article, \"Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response in Acute Heart Failure: The Multicenter ENACT-HF Study\".","authors":"Arif Albulushi","doi":"10.1161/CIRCHEARTFAILURE.124.011579","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.011579","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011579"},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916215","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":"Response by Dauw and Mullens to Letters Regarding Article, \"Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study\".","authors":"Jeroen Dauw, Wilfried Mullens","doi":"10.1161/CIRCHEARTFAILURE.124.011695","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.011695","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011695"},"PeriodicalIF":9.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916221","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":"Improving Upon the Ice Ages: Is SherpaPak the Solution?","authors":"Amy G Fiedler","doi":"10.1161/CIRCHEARTFAILURE.124.011623","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.011623","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011623"},"PeriodicalIF":7.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848277","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}