Circulation: Heart Failure最新文献

{"title":"Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy.","authors":"Ahmad Masri, Francesco Cappelli, Margot K Davis, Marianna Fontana, Pablo Garcia-Pavia, Julian D Gillmore, Mazen Hanna, Laura Obici, Scott D Solomon, Brett W Sperry, Nobuhiro Tahara, Marcia Waddington-Cruz, Arnt V Kristen, Rodney H Falk, Sanjiv J Shah, Jose Nativi-Nicolau, Nicholas J Viney, Qingqing Yang, Jersey Chen, Sotirios Tsimikas, Mathew S Maurer","doi":"10.1161/CIRCHEARTFAILURE.126.014205","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.126.014205","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin amyloidosis with cardiomyopathy is a progressive, fatal disease characterized by deposition of extracellular misfolded transthyretin (TTR) in the myocardium. Eplontersen is an N-acetylgalactosamine ligand-conjugated antisense oligonucleotide targeting hepatocyte <i>TTR</i> messenger RNA to reduce the production of circulating TTR.</p><p><strong>Methods: </strong>CARDIO-TTRansform is a Phase 3, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of eplontersen in transthyretin amyloidosis with cardiomyopathy. Key inclusion criteria include histological evidence of amyloid deposits or grade 2 to 3 cardiac uptake on cardiac scintigraphy in the absence of plasma cell dyscrasia, New York Heart Association class I-III, and end-diastolic interventricular septum thickness >12 millimeters. Participants were randomized 1:1 to receive eplontersen 45 mg or placebo, administered subcutaneously every 4 weeks for up to 140 weeks, followed by a 20-week post-treatment evaluation period or open-label extension. Participants received locally available standard of care, including unrestricted use of TTR stabilizers. The primary end point is a composite of cardiovascular mortality and recurrent clinical cardiovascular events through 140 weeks. Secondary end points, in order of testing hierarchy, include changes from baseline in 6-minute walk distance and Kansas City Cardiomyopathy Questionnaire overall summary score, recurrent cardiovascular events, all-cause mortality, the primary end point in the patient subgroup receiving stabilizers at baseline, and cardiovascular mortality. Echocardiography was performed in all participants, with cardiovascular magnetic resonance imaging and technetium scintigraphy in a subset.</p><p><strong>Conclusions: </strong>CARDIO-TTRansform is fully enrolled, with 1432 randomized participants who were dosed with study drug or placebo. As the largest transthyretin amyloidosis with cardiomyopathy study to date, it will evaluate whether eplontersen improves cardiovascular outcomes in patients receiving locally available standard of care, including TTR stabilizers.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136171. URL: http://ClinicalTrialsRegister.eu; Unique identifier: EudraCT number 2019-002835-27.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014205"},"PeriodicalIF":8.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855921","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":"Variation in Vasoactive Treatment Selection for Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network (CCCTN).","authors":"David E Hamilton, Jackson L Shriver, Siddharth M Patel, Jeong-Gun Park, Zoe E Michos, Michael R Mathis, Sarah K Adie, Carlos L Alviar, Christopher F Barnett, David D Berg, Courtney E Bennett, Erin A Bohula, Anthony P Carnicelli, Lori B Daniels, Mark W Dodson, Ann Gage, Umesh Gidwani, Michael Goldfarb, Jason N Katz, Scott W Ketcham, Younghoon Kwon, Evan S Leibner, Daniel B Loriaux, Adriana Luk, Paul Marano, P Elliott Miller, Srini V Mukundan, Alexander I Papolos, Barbara A Pisani, Alastair G Proudfoot, Robert O Roswell, Kevin S Shah, Michael A Solomon, Matthew I Tomey, Sean van Diepen, Sammy Zakaria, David A Morrow, Andrea D Thompson","doi":"10.1161/CIRCHEARTFAILURE.125.013778","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013778","url":null,"abstract":"<p><strong>Background: </strong>The paucity of data to guide selection of specific vasoactive agents in patients with cardiogenic shock (CS) may lead to variability in practice patterns. The level of variability and specific factors that are associated with the use of vasoactive medications and inodilators have not been previously described.</p><p><strong>Methods: </strong>The CCCTN (Critical Care Cardiology Trials Network) is an international, multicenter network of cardiac intensive care units (CICUs) coordinated by the TIMI Study Group. This analysis included CICU admissions for CS from 2019 to 2023. Variation in the use of inodilator treatment (dobutamine/milrinone) was assessed with multivariable mixed-effects logistic modeling.</p><p><strong>Results: </strong>A total of 3282 admissions from 37 CICUs comprised the analysis cohort. The use of vasoactive medications, including inodilator treatment, varied substantially across institutions. Patient-level variables associated with greater use of inodilators included history of heart failure (odds ratio, 1.98 [95% CI, 1.61-2.44]), biventricular failure (1.59 [95% CI, 1.27-2.00]), Society of Cardiovascular Angiography and Interventions stage D (1.34 [95% CI, 1.07-1.68]), valvular disease (1.34 [95% CI, 1.03-1.74]), and male sex (1.23 [95% CI, 1.02-1.49]). Variables associated with less inodilator use included cardiac arrest (0.33 [95% CI, 0.27-0.42]), right ventricular failure (0.50 [95% CI, 0.33-0.73]), Society of Cardiovascular Angiography and Interventions stage E (0.57 [95% CI, 0.41-0.81]), acute myocardial infarction-CS (0.71 [95% CI, 0.56-0.90]), peripheral arterial disease (0.73 [95% CI, 0.54-0.99]), older age (0.77 [95% CI, 0.72-0.83], per 10-year increase), and estimated glomerular filtration rate (0.96 [95% CI, 0.93-0.99], per 10 mL/min per 1.73 m² increase). No individual measurable institution-level factors (eg, transplant center) were associated with variability in inodilator use. In mixed-effects logistic modeling, 45.7% of variation in inodilator use was attributed to patient-level factors and 22.7% to the random effect of individual CICU centers. Similarly, 35.3% of variation in the use of dobutamine versus milrinone was attributed to patient-level factors and 32.6% to the random effect of individual CICU centers.</p><p><strong>Conclusions: </strong>There is significant variation in vasoactive treatment and inodilator use in CS. Variation in inodilator use was associated with patient-level factors and with substantial individual CICU practice variation. Such variability underscores the need for additional high-quality evidence to guide vasoactive treatment strategies in CS.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013778"},"PeriodicalIF":8.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834345","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":"Bile Acids, Mitochondria, and Myocardial Stiffness: A Shared Mechanism in Fontan Circulation and Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Ashish H Shah, Alexander R Opotowsky, Jack Rychik, Richard A Krasuski","doi":"10.1161/CIRCHEARTFAILURE.126.014293","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.126.014293","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014293"},"PeriodicalIF":8.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834289","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":"Myosin ATPase Inhibition Relieves the Energetic Burden in Skeletal Myofibres of Patients With Heart Failure With Reduced Ejection Fraction.","authors":"Massimiliano Ansaldo, Chahida Chaami, Simone Porcelli, Roberto Bottinelli, Chengxin Zhang, Christopher T A Lewis, T Scott Bowen, Robert A E Seaborne, Hans Erik Bøtker, Kristian Vissing, Julien Ochala","doi":"10.1161/CIRCHEARTFAILURE.125.013827","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013827","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with reduced ejection fraction (HFrEF) affects millions worldwide and is characterized by chronic cardiac dysfunction, impaired perfusion, altered skeletal muscle energetics, and, thus, exercise intolerance. Efficient therapeutic strategies reducing the burden of the impaired muscle metabolism in HFrEF are currently lacking. Hence, in the present study, we sought to determine whether myosin dynamics and its important role in ATP consumption can constitute a potent biochemical target to optimize skeletal muscle energy usage in HFrEF.</p><p><strong>Methods: </strong>We used skeletal muscle tissue from 11 human patients with HFrEF and 10 controls with comparable age, sex, and body mass index. We isolated individual myofibres and incubated them ex vivo with varying concentrations of a myosin inhibitor, mavacamten. We then performed 2'-(or-3')-O-(N-Methylanthraniloyl) adenosine 5'-triphosphate chase experiments, together with LC/MS-based proteomics profiling.</p><p><strong>Results: </strong>We observed a distinct regulation of acetyl-lysine sites and higher myosin energy consumption in resting muscle fibers from patients with HFrEF than in controls. When exposed to mavacamten, we found a dose-dependent reduction in myosin ATP consumption in myofibres of patients with HFrEF, reversing the pathological over-consumption.</p><p><strong>Conclusions: </strong>Skeletal muscle myosin becomes inefficient in HFrEF. Pharmacological inhibition of myosin ATPase activity offers an inventive strategy to lower muscle energy demand and potentially address metabolic disturbances in HFrEF.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013827"},"PeriodicalIF":8.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834318","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":"Tolerogenic Dendritic Cells Are Pivotal for Pediatric Transplant Operational Tolerance by Restraining Alloreactive T Cells via TGFβRII.","authors":"Wai Yen Yim, Yating Li, Jincheng Hou, Yuqi Chen, Bingchuan Geng, Matiullah Masroor, Zongtao Liu, Yixuan Wang, Nianguo Dong","doi":"10.1161/CIRCHEARTFAILURE.125.014053","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.014053","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014053"},"PeriodicalIF":8.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834347","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 Avila to Letter Regarding Article, \"Impact of Pregnancy on Mortality in Dilated Cardiomyopathy: Immediate and 12-Month Postpartum Outcomes\".","authors":"Mônica Samuel Avila, Walkiria Samuel Avila","doi":"10.1161/CIRCHEARTFAILURE.126.014363","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.126.014363","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014363"},"PeriodicalIF":8.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764163","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 Wang and Sheu Regarding Article, \"Impact of Pregnancy on Mortality in Dilated Cardiomyopathy: Immediate and 12-Month Postpartum Outcomes\".","authors":"Po-Hui Wang, Kai-Lun Sheu","doi":"10.1161/CIRCHEARTFAILURE.126.014203","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.126.014203","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014203"},"PeriodicalIF":8.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764167","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":"Circulatory Support Escalation in Cardiogenic Shock Outcomes and Predictors of Successful Escalation from an International, Multi-Center Cardiac Intensive Care Registry.","authors":"Luca Baldetti, Guglielmo Gallone, Jorge A Ortega-Hernandez, Giulio Cacioli, Mariagiulia Festi, Francesca Pirone, Federica Curro Dossi, Pier Paolo Bocchino, Filippo Angelini, Lorenzo Brignone, Veronica Vitiello, Francesco Maria Perulli, Emilio D'Avino, Héctor González-Pacheco, Francesco Calvo, Stefania Sacchi, Marina Pieri, Antonio Loforte, Silvia Ajello, Simone Frea, Giampaolo Luzi, Alexandra Arias-Mendoza, Jaime A Hernandez-Montfort, Marco Metra, Gaetano Maria De Ferrari, Anna Mara Scandroglio","doi":"10.1161/CIRCHEARTFAILURE.125.014049","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.014049","url":null,"abstract":"<p><p><b>Background:</b> Circulatory support escalation is often required during cardiogenic shock (CS) treatment. Currently, no large-scale data is available to inform how escalation strategies integrate in contemporary CS management and affect outcomes. <b>Methods:</b> We assessed the frequency, outcomes, and prognostic implications of escalation from a retrospective international registry of CS patients from 4 cardiac intensive care units. Escalation was defined as any incremental change in the circulatory support strategy after an initial bundle of care was established for at least 4 hours. <b>Results:</b> Among 602 consecutive CS patients, escalation was required in 30%. Patients were escalated to inotropes/vasopressors (36%), IABP (39%), Impella (14%) or V-A ECMO (11%). Escalation was associated with a higher hospital mortality rate (43% vs 21%; <i>p</i><0.001; OR_adj 3.42; 95% CI 2.21-3.35) and a greater transition to heart replacement therapies (23% vs 5%; <i>p</i><0.001; OR_adj 6.01; 95% CI 3.31-11.27), when adjusted for age, sex, chronic kidney disease, markers of CS severity on admission, CS etiology, and admission source. Escalation was associated with a higher risk of complications including acute kidney injury, major bleeding, and stroke. These outcomes occurred more frequently with high-profile mechanical circulatory support (Impella, V-A ECMO). Complications mediated 24% (95%CI 9-40%) of the association between escalation and hospital death. Escalated patients were successfully discharged alive in 42%. Age, SCAI B to C stage at escalation, TAPSE at escalation, and mean urinary output ≥1 mL/kg/hour in the 6 hours preceding escalation were independently associated with successful escalation when adjusted for sex, chronic kidney disease, and markers of CS severity on admission and at time of escalation. <b>Conclusions:</b> Circulatory support escalation is prevalent in patients treated for CS. Escalation is associated with a higher risk of hospital death, complications and transition to HRT, consistently with the intrinsically higher risk profile and expected trajectory of escalated patients. However, outcomes may differ according to the specific escalation strategy. Resorting to escalation in younger patients, in less severe CS stages, when the right ventricular function and urinary output are still preserved is associated with a higher chance of subsequent survival.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764190","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":"Modest Contribution of Bradykinin to Blood Pressure Reduction by Sacubitril/Valsartan in Chronic Heart Failure.","authors":"Deepak K Gupta, Lynne W Stevenson, Erica M Garner, Christopher Maulion, Hui Nian, Patricia R Wright, Adina F Turcu, Shouzou Wei, Nancy J Brown","doi":"10.1161/CIRCHEARTFAILURE.125.014117","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.014117","url":null,"abstract":"<p><strong>Background: </strong>Symptomatic hypotension can limit sacubitril/valsartan therapy. Neprilysin inhibition may augment vasodilators, such as bradykinin. We hypothesized that bradykinin contributes to blood pressure (BP) lowering with sacubitril/valsartan in stable ambulatory patients with heart failure and reduced ejection fraction <50%.</p><p><strong>Methods: </strong>In a randomized, double-blind crossover trial, participants received intravenous infusion of the bradykinin B2 receptor inhibitor icatibant and a matching placebo for 6 hours following sacubitril/valsartan dosing at acute initiation (n=36) and after 8 weeks of chronic therapy (n=30). The primary end point was maximal change in mean arterial pressure (MAP). Plasma natriuretic peptides, urine cyclic GMP, urine volume, sodium excretion, renal plasma flow, and renovascular resistance were measured.</p><p><strong>Results: </strong>The first dose of sacubitril/valsartan (50 mg) significantly lowered MAP by a mean maximum of ≈10 mm Hg, which was similar during icatibant and placebo. Within 6 hours after the first sacubitril/valsartan dose, plasma ANP (atrial natriuretic peptide [1-28]) and urine cGMP/creatinine increased significantly, whereas B-type NP (1-32) and NT-proBNP (N-terminal pro B-type natriuretic peptide) did not. Icatibant partially blunted the rise in urine cGMP/creatinine, but did not affect other parameters. After 8 weeks of sacubitril/valsartan titrated to maximally tolerated doses, baseline ANP (1-28) remained increased, and baseline MAP and NT-proBNP were decreased compared with before sacubitril/valsartan initiation. MAP decreased further after dose administration of sacubitril/valsartan, and the mean maximal reduction in MAP was significantly attenuated during icatibant compared with placebo (9 versus 12 mm Hg; <i>P</i>=0.013). Icatibant also decreased renal plasma flow and increased renal vascular resistance after chronic dosing, without affecting heart rate, urine volume, urine sodium, cGMP/creatinine, or natriuretic peptides.</p><p><strong>Conclusions: </strong>BP lowering with sacubitril/valsartan occurs with both acute and chronic dosing. ANP (1-28) appears to mediate the initial BP reduction, whereas bradykinin contributes to BP lowering after dosing during chronic therapy. Clarifying these mechanisms may inform clinical management to optimize the benefit of this important heart failure and reduced ejection fraction therapy.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04113109.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e014117"},"PeriodicalIF":8.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764185","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":"Hemodynamic Impact of Ventricular Tachycardia: Insights From Pressure-Volume Loop Monitoring.","authors":"Giulio M Mondellini, Antoon J M van den Enden, Christiaan L Meuwese, Nicolas M Van Mieghem","doi":"10.1161/CIRCHEARTFAILURE.125.013910","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.013910","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e013910"},"PeriodicalIF":8.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721682","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}