Circulation: Heart Failure最新文献

{"title":"Lowering Cardiac Branched-Chain Keto Acid Levels Enhances Cardiac Glucose Oxidation and Cardiac Efficiency via Enhancing Mitochondrial Insulin Signaling in Heart Failure.","authors":"Qutuba G Karwi, Liyan Zhang, Keshav Gopal, Cory S Wagg, Kim L Ho, Qiuyu Sun, Sai Panidarapu, Kaya Persad, Betüol Altuany, Shaden Damen, Ezra Ketema, Jody Levasseur, Thomas Pulinilkunnil, John R Ussher, Jason R B Dyck, Gary D Lopaschuk","doi":"10.1161/CIRCHEARTFAILURE.124.012012","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012012","url":null,"abstract":"<p><strong>Background: </strong>Elevated levels of cardiac branched-chain amino acids (BCAAs) and their metabolites, namely branched-chain keto acids (BCKAs), contribute to the development of insulin resistance, contractile dysfunction, and adverse remodeling in the failing heart. However, there is still confusion about whether BCAA or BCKA mediate these detrimental effects in the failing heart.</p><p><strong>Methods: </strong>Cardiac-specific mitochondrial branched-chain aminotransferase, the enzyme that converts BCAA into BCKA, knockout (BCAT2^-^/-) mice underwent a sham or transverse aortic constriction surgery to induce heart failure. Changes in cardiac function and structure were monitored pre- and posttransverse aortic constriction using echocardiography, and metabolic flux through the tricarboxylic acid cycle was measured by perfusing isolated working hearts with radiolabeled energy substrates. Direct effects of BCAA and BCKA on cell hypertrophy were characterized using phenylephrine-induced cell hypertrophy in differentiated cells.</p><p><strong>Results: </strong>Lowering cardiac BCKA levels in BCAT2^-/- failing hearts increases insulin-stimulated glucose oxidation rates via enhancing mitochondrial protein kinase B and pyruvate dehydrogenase complex activities. Increased glucose oxidation rates in BCAT2^-/- failing hearts enhanced cardiac efficiency by decreasing myocardial oxygen consumption rates. However, cardiac BCAA accumulation was associated with excessive stimulation of the mammalian target of rapamycin signaling and aggravation of adverse cardiac remodeling in BCAT2^-/- failing hearts. As a result, the impact of BCAA accumulation offsets the beneficial effects of lowering cardiac BCKA levels on cardiac insulin sensitivity and cardiac efficiency.</p><p><strong>Conclusions: </strong>Lowering BCKA levels enhances cardiac glucose oxidation and cardiac efficiency by enhancing mitochondrial insulin signaling. BCAA accumulation worsens adverse cardiac remodeling by exacerbating cardiac mammalian target of rapamycin signaling.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012012"},"PeriodicalIF":7.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706552","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":"High Sensitivity Troponin for Contemporary Risk Stratification in Wild-Type ATTR Amyloidosis.","authors":"Kevin M Alexander","doi":"10.1161/CIRCHEARTFAILURE.125.013129","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013129","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013129"},"PeriodicalIF":7.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641926","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 Papathanasiou to Letter Regarding Article, \"Disseminated Intracardiac Thrombosis Due to Long-Standing, Asymptomatic Ventricular Fibrillation Under LVAD Support\".","authors":"Lara S Schlender, Reza Wakili, David M Leistner, Maria Papathanasiou","doi":"10.1161/CIRCHEARTFAILURE.125.013260","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013260","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013260"},"PeriodicalIF":7.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590581","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 Araj and Mammen Regarding Article, \"Disseminated Intracardiac Thrombosis Due to Long-Standing, Asymptomatic Ventricular Fibrillation Under LVAD Support\".","authors":"Faris G Araj, Pradeep P A Mammen","doi":"10.1161/CIRCHEARTFAILURE.125.013221","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013221","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013221"},"PeriodicalIF":7.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590580","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":"Guideline-Directed Medical Therapy Use in the STRONG-HF Trial.","authors":"Xiang Zhang, Beth Davison, Marianna Adamo, Mattia Arrigo, Jan Biegus, Ovidiu Chioncel, Alain Cohen-Solal, Gad Cotter, Christopher Edwards, Antoine Kimmoun, Carolyn S P Lam, Alexandre Mebazaa, Marco Metra, Maria Novosadova, Peter S Pang, Karen Sliwa, Koji Takagi, Adriaan A Voors, Justin A Ezekowitz","doi":"10.1161/CIRCHEARTFAILURE.124.012716","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012716","url":null,"abstract":"<p><strong>Background: </strong>Assessment of medication changes in heart failure trials and registries is complex and may not capture the entirety of care. A comprehensive and standardized method is needed. We used different methods to assess the use of guideline-directed medical therapies (GDMT) and verified the association between GDMT intensity score with the STRONG-HF trial (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing of Heart Failure Therapies) clinical outcomes.</p><p><strong>Methods: </strong>We used data from the STRONG-HF trial to examine the baseline GDMT use for all randomized patients by applying the GDMT intensity score and evaluated its change over time. We also examined their basic adherence, indication-corrected adherence, and dose-corrected adherence, and the association with clinical outcomes up to 180 days.</p><p><strong>Results: </strong>At 90 days, triple therapy indication-corrected use increased from 4.5% to 36% in the usual care group, and from 5.2% to 93.5% in the high-intensity care group (<i>P</i><0.001 between the 2 groups). Triple therapy dose-corrected use increased from 4.5% to 20.5% in the usual care group, and from 3.3% to 77.4% in the high-intensity care group (<i>P</i><0.001). The GDMT intensity score at baseline was <6 in 358 (33%) patients, 6 to 7 in 329 (31%) patients, and >7 in 386 (36%) patients. At 90 days, 88.4% of patients in the high-intensity arm achieved a score >7 versus 14.3% in the usual care arm (<i>P</i><0.0001). The GDMT intensity score was correlated with clinical outcomes at 180 days.</p><p><strong>Conclusions: </strong>The GDMT intensity score provides a comprehensive description of medication use by means of standardized measurements and is linked to clinical outcomes. Future studies should consider utilizing this as a trial end point.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03412201.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012716"},"PeriodicalIF":7.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552482","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":"Mid-Term Reassessment of Waitlist and Posttransplant Outcomes Under the 2018 Heart Allocation System: Improved All-Cause Survival.","authors":"Yeahwa Hong, Nidhi Iyanna, Ander Dorken-Gallastegi, Umar Nasim, Edward T Horn, Michael A Mathier, Dennis M McNamara, Gavin W Hickey, Mary E Keebler, David J Kaczorowski","doi":"10.1161/CIRCHEARTFAILURE.124.012663","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012663","url":null,"abstract":"<p><strong>Background: </strong>This study evaluates clinical trends and mid-term waitlist and posttransplant outcomes following the 2018 heart allocation policy change.</p><p><strong>Methods: </strong>The United Network for Organ Sharing registry was queried to analyze adult waitlisted and transplanted patients undergoing isolated heart transplantation. Two analyses were conducted: (1) waitlist and (2) posttransplant outcomes. For the waitlist analysis, candidates were stratified into seasonally matched prepolicy (October 18, 2012-June 30, 2017) and postpolicy (October 18, 2018-June 30, 2023) groups, with a 1-year follow-up period. Waitlist outcomes included 1-year cumulative incidences of transplantation, delisting due to death/clinical deterioration, and all-cause survival from the initial waitlisting. For the posttransplant analysis, recipients were stratified into seasonally matched prepolicy (October 18, 2014-June 30, 2018) and postpolicy (October 18, 2018-June 30, 2020) groups, with a 4-year follow-up period. Posttransplant outcomes included 4-year survival. Propensity score-matching and multivariable Cox regression were used for risk adjustment.</p><p><strong>Results: </strong>Under the 2018 allocation system, there was a continued shift toward the use of older donors, longer graft ischemic times, and shorter waitlist durations. In the waitlist analysis, 30 620 waitlisted candidates were analyzed, with 14 908 (48.7%) listed after the policy change. The postpolicy candidates had a higher 1-year cumulative incidence of transplantation (subhazard ratio, 2.06 [95% CI, 2.00-2.12]; <i>P</i><0.001) and a lower 1-year cumulative incidence of delisting (subhazard ratio, 0.58 [95% CI, 0.53-0.63]; <i>P</i><0.001) compared with the prepolicy candidates. In addition, the postpolicy candidates had significantly improved 1-year survival from initial waitlisting compared with the prepolicy candidates (90.0% versus 86.8%; <i>P</i><0.001). In the posttransplant analysis, 13 712 recipients were analyzed, with 4597 (33.5%) transplanted following the policy change. The 4-year post-transplant survival was similar between the groups (83.3% versus 82.8%; <i>P</i>=0.593). Furthermore, the comparable 4-year post-transplant survival persisted in the propensity score-matched comparison and multivariable Cox regression.</p><p><strong>Conclusions: </strong>Despite the changes in donor and recipient profiles following the 2018 allocation system change, this mid-term reassessment demonstrates its success in significantly improving waitlist survival, while maintaining comparable posttransplant survival.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012663"},"PeriodicalIF":7.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552483","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":"Determinants of Right Heart Hemodynamic Derangement in Patients With and Without Tricuspid Regurgitation.","authors":"Sergio Caravita, Michele Liberatore, Luigi P Badano, Maria Felicia Gagliardi, Leila De Lorenzo, Antonio Sorropago, Cosmo Godino, Michele Tomaselli, Ettore Lanzarone, Giovanni Battista Perego, Jean-Luc Vachiéry, Marat Fudim, Gianfranco Parati, Denisa Muraru, Claudia Baratto","doi":"10.1161/CIRCHEARTFAILURE.125.012813","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.012813","url":null,"abstract":"<p><strong>Background: </strong>The determinants of tricuspid regurgitation (TR) hemodynamic severity remain to be established. We explored the hemodynamic correlates of right atrial (RA) pressure and stroke volume (SV) in patients with and without TR, and assessed the reliability of the indirect Fick method in relation to TR severity.</p><p><strong>Methods: </strong>In this observational study, right ventricular (RV) 3-dimensional echocardiography (3DE) was obtained simultaneously with direct Fick right heart catheterization. RVSV_3DE and SV_RHC were combined to determine the TR regurgitant fraction (RegFr=RVSV_3DE-RVSV_RHC/RVSV_3DE). RA pressures and strain (or 3DE volumes) were combined to derive RA compliance.</p><p><strong>Results: </strong>Out of 74 patients, 61% had moderate or severe TR. TR severity was associated with larger right heart chambers, lower RA compliance, higher values and lower inspiratory decrease of RA pressure, and lower cardiac index (<i>P</i><0.01). In univariate analysis, RA V wave was associated with RegFr (<i>r</i>=-0.57) and with ln-transformed RA compliance_strain (<i>r</i>=-0.74); SV index was associated with RegFr (<i>r</i>=-0.65). The effect of RegFr on V wave was mediated by ln-transformed RA compliance_strain (β, 13.9 [95% CI, 7.6-20.2]). In multivariable analysis, RA V wave remained associated with 1/RA compliance_strain (β, 2.1 [95% CI, 1.4-2.7]), while SV index was associated with RegFr (β, -97.6 [95% CI, -120.1 to -75.0]). The indirect Fick method overestimated cardiac index proportionally to RegFr (<i>P</i><0.01).</p><p><strong>Conclusions: </strong>SV index is related to TR severity, while the effect of TR on RA V wave is mediated by RA compliance. Respiratory-related changes in RA hemodynamics are associated with TR severity. The indirect Fick method overestimates cardiac index proportionally to TR severity.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012813"},"PeriodicalIF":7.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539192","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":"Endothelin-1 and Accelerated Cardiac Allograft Vasculopathy After Heart Transplantation.","authors":"Rushi V Parikh, Alexandra Klomhaus, Juka S Kim, Abdul Assi, David Tehrani, Danielle Campbell, Lisa Bang, Rubine Fleming, Kan Saito, Takeshi Nishi, Yasuhiro Honda, Kiran K Khush, William F Fearon, Ali Nsair, Gregg C Fonarow","doi":"10.1161/CIRCHEARTFAILURE.125.013288","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013288","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013288"},"PeriodicalIF":7.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552481","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 Malnutrition, Frailty, and Physical Performance in Transthyretin Cardiac Amyloidosis: Insights From a Prospective Multicenter Cohort Study.","authors":"Carlo Fumagalli, Mattia Zampieri, Roberto Presta, Greta Pini, Giulia Vetere, Alessia Argirò, Simone Longhi, Giacomo Tini, Beatrice Musumeci, Giuseppe Limongelli, Giuseppe Palmiero, Federica Verrillo, Matteo Beltrami, Mario Bo, Gaetano De Ferrari, Lorenzo Tofani, Celestino Sardu, Raffaele Marfella, Niccolò Marchionni, Federico Perfetto, Iacopo Olivotto, Stefano Fumagalli, Mathew S Maurer, Marianna Fontana, Andrea Ungar, Francesco Cappelli","doi":"10.1161/CIRCHEARTFAILURE.125.012777","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.012777","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of transthyretin cardiac amyloidosis among older adults (often octogenarians) is increasing. We aimed to determine whether age and geriatric syndromes bear any impact on the management and outcomes in transthyretin cardiac amyloidosis and assess the risk of ageism.</p><p><strong>Methods: </strong>In a prospective, multicenter cohort study, 256 patients diagnosed with transthyretin cardiac amyloidosis from March 2021 to March 2024 underwent comprehensive geriatric assessment (CGA). The study evaluated the prevalence and clinical associations of CGAs across different disease stages (National Amyloidosis Centre stage). Key CGA domains included disability, malnutrition, depression, frailty, Short Physical Performance Battery, and cumulative deficits (sum of the single CGA items). Associations of these measures with disease-modifying therapy and overall mortality were analyzed.</p><p><strong>Results: </strong>Median age was 82 years (men: n=223 [87%]; variant: n=19 [7.4%]); 129 (50.3%) patients received disease modifiers. Those ≥85 years had significantly lower odds of receiving disease-modifying therapy even after adjusting for disability, frailty, and cumulative deficits. Over 1.9 (interquartile range, 1.0-2.3) years, 45 (17.6%) patients died. After adjustment for National Amyloidosis Centre stage, diuretics and disease modifiers, CGA domains of disability, malnutrition, Short Physical Performance Battery, frailty, and number of deficits, but not age, were significantly associated with mortality. Assessment of CGA domains improved National Amyloidosis Centre prognostic accuracy.</p><p><strong>Conclusions: </strong>In a national prospective cohort of patients with transthyretin cardiac amyloidosis, older age was associated with lower prescription of disease modifiers, even among individuals with a low burden of geriatric syndromes. However, when adjusted for geriatric domains, age was not associated with survival, indicating potential ageism. Because some geriatric syndromes may be modifiable, a CGA could enhance risk stratification, reduce age-related bias, and improve outcomes.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012777"},"PeriodicalIF":7.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539193","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":"Mucopolysaccharidosis Type IIIA Presenting as Hypertrophic Cardiomyopathy.","authors":"Filippo Pinto E Vairo, Jeffrey B Geske, Ravinder J Singh, Roy B Dyer, Konstantinos C Siontis, Maria O'Connell, Christopher Schmitz, Laura Lambert, Karl J Clark, Kimiyo M Raymond, Joseph J Maleszewski, Tim Wood, Pavel N Pichurin, Eric W Klee, Naveen L Pereira","doi":"10.1161/CIRCHEARTFAILURE.124.012632","DOIUrl":"10.1161/CIRCHEARTFAILURE.124.012632","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012632"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751247","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}