Journal of the American Heart Association最新文献

{"title":"Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post-Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest.","authors":"Sina Danesh, Fazal Khan, Trevor Chopko, Aurora Lee, Ran Huo, Shuyang Lu, Vincy Tam, Wenbin Gao, Austin Todd, Joseph J Maleszewski, Francis D Pagani, Hartzell Schaff, Y Eugene Chen, Paul A Friedman, Hakan Oral, Marco Metra, Bertram Pitt, Ienglam Lei, Paul C Tang","doi":"10.1161/JAHA.125.043661","DOIUrl":"https://doi.org/10.1161/JAHA.125.043661","url":null,"abstract":"<p><strong>Background: </strong>Postoperative atrial fibrillation occurs in ~40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We evaluated the association of preoperative MRA use with postoperative atrial fibrillation and investigated atrial cell types modulated by MRAs during cold preservation.</p><p><strong>Methods: </strong>We studied 19 042 cardiac surgery patients at Mayo Clinic. Propensity 1:3 matching identified 298 MRA users and 894 non-users. A subgroup analysis of patients on any preoperative diuretic was performed to isolate cardiac-specific effects of MRAs, matching 298 MRA users to 894 non-MRA diuretic users. AF recurrence was assessed for up to 6-years. Single-nucleus RNA sequencing (snRNA-seq) was performed on human donor atria exposed to canrenone (a water-soluble MRA) during cold preservation with ex-vivo reperfusion, and expression profiles were compared with atria from patients with AF.</p><p><strong>Results: </strong>After matching, preoperative MRA use was associated with a lower incidence of postoperative atrial fibrillation (19.8% versus 31.8%, <i>P</i><0.001). In the diuretic-only subgroup, MRA users also had lower postoperative atrial fibrillation (19.8% versus 33.2%, <i>P</i><0.001). MRA use was associated with a reduced incidence of paroxysmal and chronic AF at 6-years. snRNA-seq identified a cardiomyocyte subpopulation, CM2, with high mineralocorticoid receptor expression where canrenone suppressed cold preservation-induced mineralocorticoid receptor target gene expression, which was conversely elevated in chronic AF. Canrenone also attenuated stress-response in atrial macrophages and pericytes.</p><p><strong>Conclusions: </strong>Preoperative MRAs were associated with reduced postoperative and long-term AF after cardiac surgery. Mechanistically, our ex-vivo human atrial model revealed that MRAs suppress mineralocorticoid receptor -driven atrial stress responses, particularly in conduction-relevant cardiomyocytes.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e043661"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253736","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":"Prolonged Postnatal Hypoxia Impairs Lung Development and Causes Severe Pulmonary Hypertension in Mice.","authors":"Luca Zazzeron, Kakeru Shimoda, Paul Lichtenegger, Elizabeth Moore, Helena Tattersfield, Alexandra K Marenco, Jiayi Kang, Haobo Li, Eizo Marutani, Donald B Bloch, Fumito Ichinose","doi":"10.1161/JAHA.125.042608","DOIUrl":"https://doi.org/10.1161/JAHA.125.042608","url":null,"abstract":"<p><strong>Background: </strong>In children born at high altitude, lung development is affected by hypoxia, which can lead to pulmonary hypertension and right ventricular failure. Animal models of postnatal, transient, hypoxia failed to reproduce these conditions seen in children living at high altitude. The aim of this study was to establish a mouse model of pediatric pulmonary hypertension associated with abnormal lung development.</p><p><strong>Methods: </strong>C57bl/6J mice were exposed to normobaric hypoxia at 11% inspired fraction of oxygen starting on postnatal-days 1 to 4 (\"11%-birth\"). At age 8 weeks, pulmonary arterial pressure and right ventricular function were assessed using echocardiography and invasive hemodynamics. The physiology and the structure of lung parenchyma and vasculature were assessed through evaluations of gas exchange, respiratory mechanics, and histopathology. Results were compared with control mice breathing 21% inspired fraction of oxygen for 8 weeks (21%-birth), and to adult mice breathing 11% inspired fraction of oxygen for 8 weeks (11%-adult).</p><p><strong>Results: </strong>Seventy percent of 11%-birth mice survived until age 8 weeks; the mice subsequently experienced a steady decline in survival, with a median lifespan of 150 days. Mice that survived for 8 weeks had evidence of impaired lung development, such as alveolar and vascular simplification with muscularization of small pulmonary vessels, impaired gas exchange, and altered respiratory mechanics. These changes were associated with reduced exercise capacity, severe pulmonary hypertension, and right ventricular failure. Adult mice subjected to chronic hypoxia had mild changes in the pulmonary vasculature resulting in mild pulmonary hypertension without right ventricular dysfunction.</p><p><strong>Conclusions: </strong>This mouse model of prolonged hypoxia beginning early after birth offers a novel approach to explore treatments for pediatric pulmonary hypertension linked to abnormalities in lung development.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042608"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253763","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":"Longitudinal Intracardiac Right Ventricular Flow Analysis in Infants With Hypoplastic Left Heart Syndrome in Interstage I Using Novel Doppler Velocity Reconstruction.","authors":"Maren Brinken, Brett A Meyers, R Mark Payne, Roland Axt-Fliedner, Can Yerebakan, Pavlos Vlachos, Yue-Hin Loke","doi":"10.1161/JAHA.125.041734","DOIUrl":"https://doi.org/10.1161/JAHA.125.041734","url":null,"abstract":"<p><strong>Background: </strong>Echocardiography provides noninvasive frontline assessment of right ventricular (RV) function in hypoplastic left heart syndrome (HLHS). However, conventional metrics do not quantify RV intracardiac hemodynamics. A novel Doppler velocity reconstruction measures kinetic energy, vortex strength, and flow energy loss through conventional color Doppler acquisitions. We investigated longitudinal changes in RV intracardiac flow in infants with HLHS during the critical interstage period, hypothesizing that these trends may inform disease progression.</p><p><strong>Methods: </strong>This was a single-center, retrospective analysis of patients with HLHS who underwent stage 1 palliation (bilateral pulmonary artery bands/hybrid palliation or Norwood operation). Echocardiographic studies at 5 time points from before to 6 months after surgery were selected for postprocessing. Apical views of the RV with adequate color Doppler imaging were analyzed. Significant tricuspid regurgitation was defined as vena contracta jet width ≥2.5 mm. Adverse events included death, heart transplant, use of ventricular assist device, or extracorporeal membrane oxygenation.</p><p><strong>Results: </strong>Thirty-six patients with HLHS (21 hybrid, 15 Norwood) were included. Flow energy loss, vortex strength, and kinetic energy increased over time for all interstage patients with HLHS (<i>P</i><0.0001) and correlated with RV size, body surface area, and E wave. Significant tricuspid regurgitation was associated with elevated flow energy loss and vortex strength (<i>P</i>=0.0007 and <i>P</i><0.0001). Adverse events showed early changes in flow parameters and altered trends over the interstage period (vortex strength, <i>P</i><0.0001; kinetic energy, <i>P</i>=0.0009).</p><p><strong>Conclusions: </strong>Doppler velocity reconstruction can assess RV intracardiac flow in infants in HLHS interstage I. While the results should not be used to interpret the surgical strategies, the longitudinal analysis of intracardiac flow may elucidate diastolic filling dynamics, with deviations associated with adverse events throughout the interstage period.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e041734"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253646","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":"Thrombectomy for Distal Medium Vessel Occlusion: A Meta-Analysis of Randomized Controlled Trials.","authors":"Hong-Jie Jhou, Wei-Sheng Wang, Cho-Hao Lee, Li-Yu Yang, Po-Huang Chen","doi":"10.1161/JAHA.125.042299","DOIUrl":"https://doi.org/10.1161/JAHA.125.042299","url":null,"abstract":"<p><strong>Background: </strong>Approximately 25% to 40% of all acute ischemic strokes result from distal medium vessel occlusions. However, the effectiveness and safety of thrombectomy for distal medium vessel occlusions remain uncertain.</p><p><strong>Methods: </strong>A systematic search of PubMed, Cochrane, and Embase was conducted for randomized controlled trials published until February 2025. The primary outcomes were functional outcomes at 90 days (excellent, good, and favorable). The secondary outcomes included symptomatic intracranial hemorrhage (ICH), any ICH, and mortality at 90 days.</p><p><strong>Results: </strong>Three studies involving 1246 patients with stroke with distal medium vessel occlusion were included (614 patients receiving thrombectomy; others with medical management). At 3 months, the odds ratio for an excellent functional outcome was 0.92 (95%, 0.72-1.17), for a good functional outcome was 0.87 (95% CI, 0.70-1.09), and for a favorable functional outcome was 0.84 (95% CI, 0.64-1.10), indicating no significant difference between the 2 groups. However, thrombectomy was associated with a higher risk of hemorrhage, with an odds ratio of 2.18 (95% CI, 1.24-3.83) for symptomatic ICH and 1.96 (95% CI, 1.54-2.50) for any ICH. Mortality at 3 months was similar between the groups, with an odds ratio of 1.20 (95% CI, 0.85-1.70).</p><p><strong>Conclusions: </strong>Thrombectomy did not significantly improve functional outcomes or reduce mortality but increased symptomatic ICH and any ICH. Further recent randomized controlled trials are needed to define subgroups that may benefit.</p><p><strong>Registration: </strong>PROSPERO CRD420251073344.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042299"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253733","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":"Normobaric Hyperoxia in Patients With Acute Stroke: Enhancing Neuroprotection Through Inhibition of Inflammation.","authors":"Hongmei Niu, Jiayue Ding, Zhiying Chen, Shuhua Yuan, Zhifeng Qi, Xunming Ji, Weili Li","doi":"10.1161/JAHA.125.041825","DOIUrl":"https://doi.org/10.1161/JAHA.125.041825","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory response is an important pathological and physiological mechanism in the occurrence and development of acute ischemic stroke. This study investigated the effects of normobaric hyperoxia on the inflammatory response in acute ischemic stroke and explored the role of inflammation in stroke-induced brain injury.</p><p><strong>Methods: </strong>This secondary analysis of the OPENS (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) trial, included 86 acute ischemic stroke patients with anterior circulation large vessel occlusion: 43 received normobaric hyperoxia (10 L/min, 100% oxygen for 4 hours) with endovascular thrombectomy, and 43 received endovascular thrombectomy alone. Inflammatory markers were measured at different time points (admission, 24 hours, 7 days), and National Institutes of Health Stroke Scale score and cerebral infarction volume were also recorded. The main outcome measures were serum CRP (C-reactive protein) levels, peripheral blood leukocyte count, neutrophil count, and neutrophil-to-lymphocyte ratio. Correlation analysis was used to analyze the relationship between inflammatory markers and stroke.</p><p><strong>Results: </strong>The results showed that the normobaric hyperoxia group had significantly lower levels of inflammatory markers compared with the control group at 24 hours (<i>P</i><0.05). Early correlation analysis (within 24 hours) showed a significant positive association between 24-hour inflammatory marker levels and early neurological function scores (National Institutes of Health Stroke Scale) as well as early infarct volume (assessed at 24-48 hours).</p><p><strong>Conclusions: </strong>Normobaric hyperoxia attenuates early postthrombectomy inflammation, as evidenced by reduced CRP, neutrophil counts, and neutrophil-to-lymphocyte ratio. These inflammation markers were significantly associated with acute stroke severity and infarct volume.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03620370.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e041825"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253757","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":"Clinical Characteristics, Hemodynamic Profile, and Outcomes in Patients With Low-Gradient and High-Gradient Severe Mitral Stenosis: Influence of Flow Status.","authors":"Ryan Leow, Meei-Wah Chan, Tony Yi-Wei Li, William Kf Kong, Kian-Keong Poh, Ivandito Kuntjoro, Ching-Hui Sia, Tiong-Cheng Yeo","doi":"10.1161/JAHA.125.041884","DOIUrl":"https://doi.org/10.1161/JAHA.125.041884","url":null,"abstract":"<p><strong>Background: </strong>In severe mitral stenosis (MS), flow-status was recently recognized as potentially impactful in some patients with low transmitral gradients.</p><p><strong>Methods: </strong>We studied 172 patients with isolated rheumatic MS with mitral valve area ≤1.5 cm². Mean gradients <10 mm Hg and ≥10 mm Hg were considered low gradient and high gradient, respectively. Similarly, stroke volume index <35 mL/m² was considered low flow (LF) and ≥35 mL/m² was considered normal flow (NF). We compared clinical and echocardiographic characteristics including noninvasively determined net atrioventricular compliance, effective arterial elastance, end-systolic elastance, right ventricular function, and a composite outcome of all-cause mortality, heart failure hospitalization, mitral valve intervention, and stroke or transient ischemic attack.</p><p><strong>Results: </strong>Forty-three (25.0%) patients had NF low-gradient MS, 60 (34.9%) had LF low-gradient MS, 26 (15.1%) had NF high-gradient MS, and 43 (25.0%) had LF high-gradient MS. Patients with LF status were more symptomatic (<i>P</i>=0.008) and had lower atrioventricular compliance (LF 4.37±1.52 mL/mm Hg; NF 5.44±1.50 mL/mm Hg; <i>P</i><0.001). Despite lower left ventricular ejection fraction (LF 51.9±12.1%; NF 61.0±5.3%; <i>P</i><0.001), they had similar end-systolic elastance (<i>P</i>=0.106) with increased arterial elastance (LF 2.64±0.80 mm Hg/mL; NF 1.70±0.44 mm Hg/mL; <i>P</i><0.001), and more right ventricular dysfunction (LF 79.6%; NF 36.2%; <i>P</i><0.001). Subdividing patients with low flow into LF low-gradient and LF high-gradient subgroups showed similar findings, suggesting that LF status, rather than transmitral gradient, was linked to these findings. LF status was associated with poorer event-free survival (LF, 5.46 years [95% CI, 4.05-6.87]; NF, 7.44 years [95% CI, 6.17-8.72]; <i>P</i>=0.001) whereas there was no association between mean gradient and outcomes (<i>P</i>=0.284).</p><p><strong>Conclusions: </strong>Patients with LF severe MS demonstrated a characteristic pattern of echocardiographic abnormalities and poorer outcomes regardless of transmitral gradients.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e041884"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253712","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":"Competing Risks of Cardiac and Noncardiac Mortality in Patients With Secondary Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.","authors":"Luca Esposito, Marco Di Maio, Cesare Baldi, Emilio Di Lorenzo, Michele Bellino, Angelo Silverio, Marianna Adamo, Arturo Giordano, Francesco De Felice, Carmelo Grasso, Antonio Popolo Rubbio, Paolo Denti, Cosmo Godino, Federico De Marco, Fausto Castriota, Ida Monteforte, Annalisa Mongiardo, Anna Sonia Petronio, Gabriele Crimi, Diego Maffeo, Antonio L Bartorelli, Rodolfo Citro, Gennaro Galasso, Giuseppe Tarantini, Giovanni Esposito, Corrado Tamburino, Francesco Bedogni","doi":"10.1161/JAHA.124.040496","DOIUrl":"https://doi.org/10.1161/JAHA.124.040496","url":null,"abstract":"<p><strong>Background: </strong>The relative impact of cardiac and noncardiac mortality in patients with secondary mitral regurgitation undergoing mitral transcatheter edge-to-edge repair (M-TEER) has been poorly investigated. We aimed to assess the competing risks and independent predictors of cardiac and noncardiac mortality in a real-world secondary mitral regurgitation population treated with M-TEER and included in the GIOTTO (Italian Society of Interventional Cardiology [GIse] Registry Of Transcatheter Treatment of Mitral Valve Regurgitation) registry.</p><p><strong>Methods: </strong>Competing risks analysis was used to assess the cumulative incidence of cardiac and noncardiac mortality. Cox regression identified independent predictors of each outcome. Co-primary outcomes were cardiac and noncardiac death at 2 years.</p><p><strong>Results: </strong>The analysis included 1185 consecutive patients with secondary mitral regurgitation treated with M-TEER between January 2016 and March 2020 (median age 74 years). Two-year cumulative incidences of cardiac and noncardiac mortality were 19% and 12%, respectively. At multivariable analysis, predictors of cardiac mortality were age (hazard ratio [HR], 1.03; <i>P</i>=0.002), New York Heart Association class (HR, 1.44; <i>P</i>=0.018), previous hospitalization for heart failure (HR, 1.67; <i>P</i>=0.016), hemoglobin (HR, 0.89; <i>P</i>=0.016), left ventricular end-diastolic diameter (HR, 1.02; <i>P</i>=0.025), left ventricular ejection fraction (HR, 0.98; <i>P</i>=0.022), and daily furosemide dose (HR, 1.19; <i>P</i>=0.003). Predictors of noncardiac mortality were New York Heart Association class (HR, 1.70; <i>P</i>=0.03), estimated glomerular filtration rate (HR, 0.98; <i>P</i>=0.002), and smoking habit (HR, 1.82; <i>P</i>=0.009).</p><p><strong>Conclusions: </strong>Patients with secondary mitral regurgitation treated with M-TEER show a high 2-year incidence of both cardiac and noncardiac mortality. Understanding competing risks of mortality may improve patient selection for M-TEER.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e040496"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253211","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":"Impact of Heart Failure Guideline Publication on Medicare Drug Coverage Policies: A Quasi-Experimental Analysis.","authors":"Amrita Mukhopadhyay, Nathalia Ladino, Tyrel Stokes, Aparna Narendrula, Stuart D Katz, Harmony R Reynolds, Allison P Squires, Rishi K Wadhera, Donglan Stacy Zhang, Samrachana Adhikari, Saul Blecker","doi":"10.1161/JAHA.125.043610","DOIUrl":"https://doi.org/10.1161/JAHA.125.043610","url":null,"abstract":"<p><strong>Background: </strong>Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations and high out-of-pocket costs. To promote better coverage for high value therapies and inform policymakers about cost effectiveness, the American Heart Association/American College of Cardiology/Heart Failure Society of America added Value Statements to HF guidelines. We assessed whether these guidelines influenced Medicare drug coverage policies for 2 life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI-guideline \"high value\") and sodium glucose cotransporter-2 inhibitors (SGLT2i-guideline \"intermediate value\").</p><p><strong>Methods: </strong>We performed an observational study using Medicare prescription drug plan formulary files from April 2020 to April 2023 to separately assess for changes in coverage barriers to ARNI and SGLT2i after Value Statement publication (April 2022), and subsequent Medicare plan online update (October 2022). The primary outcome was the percentage of plans each month with any barrier to drug coverage (prior authorizations, tier ≥3 out-of-pocket cost-sharing, step therapy, or no coverage). Analyses used interrupted time series and difference-in-differences approaches. Difference-in-differences analyses used direct oral anticoagulants as a control due to their comparable cost and use as ARNI and SGLT2i, but without a Value Statement.</p><p><strong>Results: </strong>Among 7396 Medicare drug plans, monthly rates of any coverage barrier ranged from 94.3% to 97.4% for ARNI and 93.2% to 96.6% for SGLT2i. Most barriers were due to tier ≥3 out-of-pocket cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in April 2022 and declined slightly in October 2022. In difference-in-differences analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for both ARNI (difference-in-differences estimate, -1.07% [95% CI, -1.44% to -0.70%]) and SGLT2i (-1.32% [95% CI, -1.63% to -1.00%]).</p><p><strong>Conclusions: </strong>Coverage barriers to ARNI and SGLT2i were common and changed only slightly after publication of Value Statements in HF guidelines. There is a critical need for robust strategies to improve access to life-saving HF medications.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e043610"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253598","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 Cell-Related Proteins in Plasma Predict Major Adverse Cardiovascular Events and Worsening Heart Failure in Patients With Hypertrophic Cardiomyopathy.","authors":"Shogo Tamura, Keitaro Akita, Michael A Fifer, Albree Tower-Rader, Mathew S Maurer, Yuichi J Shimada","doi":"10.1161/JAHA.125.042887","DOIUrl":"https://doi.org/10.1161/JAHA.125.042887","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) often causes major adverse cardiovascular events (MACE) and worsening heart failure (HF). Endothelial cell (EC) dysfunction is known to be involved in the pathogenesis of HCM. However, the prognostic value of proteins related to EC function (EC-related proteins) in HCM is unknown.</p><p><strong>Methods: </strong>In this prospective cohort study of patients with HCM, we measured plasma levels of 90 EC-related proteins upon enrollment. The primary outcome measure was MACE. The secondary outcome measure was worsening HF. We developed machine learning models based on EC-related proteins to predict MACE or worsening HF using data from one institution (training set). We tested the predictive ability in independent samples from the other institution (test set) and performed time-to-event analyses.</p><p><strong>Results: </strong>The study included 722 patients (n=458 in the training set and n=264 in the test set). Using our EC-related protein-based model, the area under the receiver-operating-characteristic curve to predict MACE was 0.71 (95% CI, 0.64-0.77) and that for worsening HF was 0.71 (95% CI, 0.63-0.79). When we divided the test set into low- and high-risk groups according to the predicted probabilities derived from the training set, the high-risk groups had significantly higher risks of developing MACE and worsening HF compared with the low-risk groups (both <i>P</i>_logrank<0.001).</p><p><strong>Conclusions: </strong>The present prospective study demonstrated that EC-related proteins in plasma predict MACE and worsening HF in patients with HCM. These EC-related proteins have a potential to become novel biomarkers for risk stratification in HCM to improve current prediction models.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042887"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253607","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":"Individual and County-Level Social Determinants of Health and Acute Reperfusion Therapies: Get With The Guidelines-Stroke Registry Results.","authors":"Manav V Vyas, Moira K Kapral, Amy Y X Yu, Raed A Joundi, Peter C Austin, Jiming Fang, Mathew J Reeves","doi":"10.1161/JAHA.124.038402","DOIUrl":"https://doi.org/10.1161/JAHA.124.038402","url":null,"abstract":"<p><strong>Background: </strong>The associations between individual- and county-level social determinants of health and reperfusion therapies (thrombolysis or thrombectomy) for acute ischemic stroke have been described separately, but they are rarely studied together.</p><p><strong>Methods and results: </strong>We identified 1.5 million patients aged ≥40 years with acute ischemic stroke between January 1, 2015 and December 31, 2019 from the Get With The Guidelines-Stroke registry in the United States. We ascertained age, sex, rural residence, and ethnicity or race at the individual level, and poverty, unemployment, and lower education (defined as less than high school) at the county level. We used multivariable log-binomial regression models estimated using generalized estimating equations methods to account for county-level clustering and adjusted for comorbidities. About 13.4% (n=203 800) patients received reperfusion therapy. Black (adjusted risk ratio [aRR, 1.06 [95% CI, 1.04-1.07]) and Hispanic (aRR, 1.36 [95% CI, 1.33-1.40]) patients were more likely to receive it compared with White patients, as were those in counties with lower education (aRR, 1.08 [95% CI, 1.07-1.09]). Older adults (5-year increase in age aRR, 97 [95% CI, 0.97-0.97]), rural residents (aRR, 0.58 [95% CI, 0.56-0.59]), and those with missing last known well time (aRR, 0.30 [95% CI, 0.29-0.30]) were less likely to receive it. Missing last known well was less likely in Hispanic (aRR, 0.94 [95% CI, 0.92-0.95]) and Asian (aRR, 0.93 [95% CI, 0.90-0.96]) patients compared with White patients and more likely in those residing in counties with high unemployment (aRR, 1.07 [95% CI, 1.06-1.08]).</p><p><strong>Conclusions: </strong>Individual- and county-level social determinants of health were associated with reperfusion therapies and missing last known well times. Understanding the mechanisms by which these factors could affect treatment eligibility through time-based criteria can help increase reperfusion therapies for all.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038402"},"PeriodicalIF":5.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253655","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}