Journal of the American Heart Association最新文献

{"title":"Informing Management of Patients Developing Cardiogenic Shock at a Spoke and Being Transferred to a Hub.","authors":"Christos P Kyriakopoulos, Iosif Taleb, Konstantinos Sideris, Eleni Maneta, Rana Hamouche, Eleni Tseliou, Ethan Krauspe, Sean Selko, Spencer Carter, Tara L Jones, Chong Zhang, Angela P Presson, Elizabeth Dranow, Laura Geer, Josef Stehlik, Craig H Selzman, Matthew L Goodwin, Joseph E Tonna, Thomas C Hanff, Stavros G Drakos","doi":"10.1161/JAHA.124.035464","DOIUrl":"10.1161/JAHA.124.035464","url":null,"abstract":"<p><strong>Background: </strong>Multidisciplinary teams and regionalized care systems have been suggested to improve cardiogenic shock (CS) outcomes. We sought to identify clinical factors associated with successful outcomes for patients developing CS at an outside healthcare facility (spoke) and being transferred to a quaternary medical center (hub).</p><p><strong>Methods and results: </strong>Consecutive patients with CS were evaluated (N=1162). Our study cohort comprised 412 patients developing CS at a spoke. Our primary end point was native heart survival (NHS) defined as survival to discharge without receiving advanced heart failure therapies. Secondary end points were survival to discharge, 30-day and 1-year survival after discharge, and adverse events. Association of clinical data with NHS was analyzed using logistic regression. Overall, 246 (59.7%) patients achieved NHS, 125 (30.3%) died, and 41 (10.0%) were discharged after advanced heart failure therapies. Of the 287 patients who were discharged (69.7%), 276 (67.0%) were alive at 30 days, and 250 (60.7%) at 1 year. Patients with NHS less commonly had bleeding or vascular complications or acute kidney injury requiring renal replacement therapy compared with patients who died or received advanced heart failure therapies. Significant multivariable factors associated with NHS likelihood included younger age; shorter length of stay and transfer from a secondary compared with a tertiary/quaternary level of care spoke; absence of cardiac arrest, intubation, or type 3 bleeding; lower vasoactive-inotropic score; higher left ventricular ejection fraction at admission to the hub; and shorter CS onset-to-temporary mechanical circulatory support deployment time.</p><p><strong>Conclusions: </strong>We identified clinical factors reflecting disease severity and management practices including length of stay and spoke level of care, inotrope/vasopressor utilization, and CS onset-to-temporary mechanical circulatory support deployment time, that might inform the management of patients developing CS at a spoke.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e035464"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416277","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":"Comparative Outcomes of Glucagon-Like Peptide-1 Receptor Agonists to Dipeptidyl Peptidase 4 Inhibitors in Patients With Heart Failure and Type 2 Diabetes.","authors":"Takefumi Kishimori, Takao Kato, Atsuyuki Wada, Akira Tani, Ryosuke Yamaji, Jumpei Koike, Yoshihiro Iwasaki, Takehiro Matsumoto, Takafumi Yagi, Masaharu Okada","doi":"10.1161/JAHA.124.037510","DOIUrl":"10.1161/JAHA.124.037510","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials showed that glucagon-like peptide-1 receptor agonist (GLP1-RA) significantly improved the control of diabetes and reduced body weight compared with dipeptidyl peptidase 4 inhibitor (DPP-4i). However, it is unclear whether GLP1-RA is effective compared with DPP-4i in patients with heart failure (HF) with type 2 diabetes (T2D). The purpose of this study was to evaluate the risk of GLP1-RA compared with DPP-4i in all-cause death and hospitalization in patients with HF and T2D.</p><p><strong>Methods: </strong>This multicenter retrospective observational study using TriNetX, a global health care data and analytics platform, included patients with HF and T2D who had received GLP1-RA or DPP-4i from January 1, 2018, to December 31, 2022. Primary outcome was 12-month incidence of all-cause death. Secondary outcome was hospitalization. We used odds ratios (ORs) and 95% CIs to evaluate outcome measures.</p><p><strong>Results: </strong>Among 1 005 097 patients with HF and T2D, 57 965 initiated GLP1-RA and 77 098 initiated DPP-4i. After propensity score matching, the number of participants in both the GLP1-RA group and the DPP-4i group was 36 557. The proportion of 12-month incidence of all-cause death was lower in the GLP1-RA group than in the DPP-4i group (5.9% [2140/36 557] versus 8.5% [3103/36 557]; OR, 0.67 [95% CI, 0.63-0.71]).The proportion of 12-month incidence of hospitalization was also lower in the GLP1-RA group than in the DPP-4i group (42.3% [15 455/36 557] versus 48.5% [17 733/36 557]; OR, 0.78 [95% CI, 0.76-0.80]).</p><p><strong>Conclusions: </strong>Use of GLP1-RA for patients with HF and T2D was associated with reduced 12-month incidence of all-cause death and hospitalization compared with DPP-4i.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037510"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374956","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":"Wildfire Air Pollution and Rates of Cardiovascular Events and Mortality in Northern California in 2018.","authors":"Stacey E Alexeeff, Stephen K Van Den Eeden, Kamala Deosaransingh, Stephen Sidney, Noelle S Liao, Jamal S Rana","doi":"10.1161/JAHA.124.036264","DOIUrl":"10.1161/JAHA.124.036264","url":null,"abstract":"<p><strong>Background: </strong>We examined the association between acute cardiovascular disease (CVD) events and wildfire air pollution in California in 2018.</p><p><strong>Methods: </strong>The study included adult (≥18 years) members of Kaiser Permanente Northern California, an integrated health care system. Outcomes included CVD events (hospitalizations for acute myocardial infarction, heart failure, or stroke, and CVD death) and death from any cause. Fine particulate air pollution (particulate matter <2.5 microns in diameter; PM_2.5) exposure was assessed in categories (Good <12 μg/m³, Moderate 12-34 μg/m³, High ≥35 μg/m³) and continuously. Poisson time series regression was used to model daily event rates during July 1 to December 31, 2018, using a spline to adjust for long-term time trends. We calculated rate ratios (RR) to estimate the association between wildfire air pollution and daily rate of CVD events and deaths.</p><p><strong>Results: </strong>Our study included 3.2 million adults with a total follow-up of 587.9 million person-days. High PM_2.5 concentrations during the Mendocino Complex wildfire in July to August was associated with an increased rate of CVD events (RR, 1.231 [95% CI, 1.039-1.458]) and death (RR, 1.358 [95% CI, 1.128-1.635]) compared with Good PM_2.5 concentrations. In contrast, there was no evidence of increased risk during the Camp wildfire in November (RR for CVD events, 0.966 [95% CI, 0.894-1.044]; RR for all-cause mortality, 0.985 [95% CI, 0.904-1.074] High versus Good PM_2.5 concentrations).</p><p><strong>Conclusions: </strong>There was some evidence of increased rates of CVD events and death during wildfires, but results were inconsistent. With ongoing climate change, large wildfires are a pressing public health concern and future work is needed to understand differences in health outcomes by wildfire.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e036264"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257390","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":"Cardiopulmonary Exercise Test Interpretation Across the Lifespan in Congenital Heart Disease: A Scientific Statement From the American Heart Association.","authors":"Barbara Cifra, Rachael L Cordina, Naomi Gauthier, Laura C Murphy, Tam Dan Pham, Gruschen R Veldtman, Kendra Ward, David A White, Stephen M Paridon, Adam W Powell","doi":"10.1161/JAHA.124.038200","DOIUrl":"10.1161/JAHA.124.038200","url":null,"abstract":"<p><p>Survivorship from congenital heart disease has improved rapidly secondary to advances in surgical and medical management. Because these patients are living longer, treatment and disease surveillance targets have shifted toward enhancing quality of life and functional status. Cardiopulmonary exercise testing is a valuable tool for assessing functional capacity, evaluating cardiac and pulmonary pathology, and providing guidance on prognosis and interventional recommendations. Despite the extensive evidence supporting the ability of cardiopulmonary exercise testing to quantitatively evaluate cardiovascular function, there remains confusion on how to properly interpret cardiopulmonary exercise testing in patients with congenital heart disease. The purpose of this statement is to provide a lifespan approach to the interpretation of cardiopulmonary exercise testing in patients with congenital heart disease. This is an updated report of the American Heart Association's previous publications on exercise in children. This evidence-based update on the significance of cardiopulmonary exercise testing findings in pediatric, adolescent, and adult patients with various congenital cardiac pathologies and surgically modified physiology is formatted in a way to guide cardiopulmonary exercise testing interpretation practically for the clinicians and exercise physiologists who care for patients with congenital heart disease. Focus is placed on the indications for exercise testing, expected findings, and how exercise testing should guide the management of patients with various congenital heart disease subtypes. Areas for future intervention that could lead to improved care and outcomes for those with congenital heart disease are noted.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038200"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958878","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":"One-Year Functional Outcome of Patients After Surgery for Acute Stanford Type A Aortic Dissection.","authors":"Murat Yildiz, Maria Nucera, Selim Mosbahi, Kai Münker, Cem Kapkin, Silvan Jungi, Matthias Siepe, Florian Schoenhoff","doi":"10.1161/JAHA.124.036495","DOIUrl":"10.1161/JAHA.124.036495","url":null,"abstract":"<p><strong>Background: </strong>Our aim was to report the functional outcome of Stanford type A aortic dissection (TAAD) after 1 year as well as morbidity and mortality.</p><p><strong>Methods and results: </strong>This is a retrospective analysis including 642 patients with TAAD from January 2005 to December 2021. Mean age at TAAD was 62 years (95% CI, 61-63), and 30% of the population were women. One year after surgery for TAAD, 75% of patients were living at home with New York Heart Association functional class I. No patients were observed with New York Heart Association functional class IV. Less than 2% resided in an assisted-living facility. Eighty-five percent of nonretired patients had returned to work. Two hundred twelve (33%) patients were retired after 1 year at a mean age of 73 years (95% CI, 72-74). Stroke (defined as any kind of neurological symptoms) occurred in 148 (23%) patients and was the cause of death in 33 patients. Of the remaining patients with stroke, 115 (30%) had no residual limitations 1 year after TAAD. The cross-clamp time was significantly higher in patients with stroke (98 minutes [95% CI, 94.0-101.1] in patients without stroke versus 106 minutes [95% CI, 98.5-114.1] in patients with stroke; <i>P</i>=0.026). Sixty-nine percent of patients with stroke lived at home, 28% lived at home with support, and 3% lived in an assisted-living facility. One year after stroke, 77% of the patients achieved a modified Rankin Scale score ≤2, whereas no patient had a modified Rankin Scale score of 5. There was no significant correlation between sex and recovery rate (<i>P</i>=0.48). However, experiencing a stroke significantly increased the likelihood of residing in an assisted-living facility or receiving support at home 1 year after TAAD (odds ratio, 9.46 [95% CI, 5.06-17.70]; <i>P</i><0.001). Thirty-day mortality was 11.8%, and 92 patients (14%) died within the first year after TAAD. There was no significant sex difference in mortality (<i>P</i>=0.101).</p><p><strong>Conclusions: </strong>One year after surgery for Stanford acute type A aortic dissection, almost 3 out of 4 patients lived unassisted at home. Stroke survivors have a favorable outcome, with the majority having mild or no residual neurological deficits at 1 year.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e036495"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375041","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":"Association Between Inflammatory Arthritis, Genetic Risk, and the Long-Term Risk of Degenerative Aortic Stenosis: A Prospective Cohort Study.","authors":"Baohua Peng, Lihuang Zha, Mukamengjiang Juaiti, Wenchao Lin, Xinyi Zhou, Ziwei Ou, Mengqiu Zhang, Zaixin Yu, Yiyang Tang","doi":"10.1161/JAHA.124.038815","DOIUrl":"10.1161/JAHA.124.038815","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis is not well understood.</p><p><strong>Methods: </strong>This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout. The primary outcome was the incidence of degenerative aortic stenosis. The primary analysis used Cox proportional hazards models to evaluate the association between inflammatory arthritis and the long-term risk of degenerative aortic stenosis, as well as to explore potential effect modifiers. Genetic risk was evaluated using polygenic risk scores and self-reported family history of cardiovascular diseases.</p><p><strong>Results: </strong>The study included 497 567 participants, with 271 129 women (54.5%) and 468 015 White individuals (94.1%). The median age was 58 years. Over a median follow-up of 12.58 years, 4571 cases (0.9%) of degenerative aortic stenosis were identified. Compared with the control group, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and gout were associated with increased risks of degenerative aortic stenosis by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28-1.85]), 72% (HR, 1.72 [95% CI, 1.19-2.50]), 176% (HR, 2.76 [95% CI, 1.43-5.32]), and 36% (HR, 1.36 [95% CI, 1.20-1.54]), respectively. These associations were independent of genetic risk (<i>P</i> for interaction>0.05). Additionally, we identified significant interactions between sex (<i>P</i> for interaction=0.036), age (<i>P</i> for interaction<0.001), and socioeconomic status (<i>P</i> for interaction=0.014) with rheumatoid arthritis, ankylosing spondylitis, and gout on the incidence of degenerative aortic stenosis, respectively.</p><p><strong>Conclusions: </strong>Inflammatory arthritis is significantly associated with an increased long-term risk of degenerative aortic stenosis, underscoring the need for enhanced risk assessment for degenerative aortic stenosis in these populations.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038815"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374952","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":"Racial and Ethnic and Sex Disparities in the Outcomes and Treatment of In-Hospital Cardiac Arrest: A Nationwide Analysis From the United States.","authors":"Abdilahi Mohamoud, Nadhem Abdallah, Mahmoud Ismayl, Mark Linzer, Rehan M Karim, Abdirahman Wardhere, Dawn Johnson, Andrew Goldsweig","doi":"10.1161/JAHA.124.038683","DOIUrl":"10.1161/JAHA.124.038683","url":null,"abstract":"<p><strong>Background: </strong>In-hospital cardiac arrest (IHCA) is associated with significant morbidity and mortality. The relationships between race and ethnicity and sex on outcomes and treatment patterns among patients with IHCA remain poorly understood.</p><p><strong>Methods and results: </strong>We conducted a retrospective study using the National (Nationwide) Inpatient Sample (NIS) database from 2016 to 2020 to identify adult patients with IHCA and examine the associations between in-hospital outcomes and race and ethnicity (White, Black, Hispanic) and sex. The primary outcome was in-hospital mortality. Secondary outcomes included rates of in-hospital procedures. Multivariable logistic regression analysis was used to adjust for potential confounders. Among 207 770 patients with IHCA, 26.6% had ventricular tachycardia/ventricular fibrillation and 73.4% had pulseless electrical activity/asystole. For ventricular tachycardia/ventricular fibrillation arrest, Black men (adjusted odds ratio [aOR], 1.42 [95% CI, 1.21-1.66]), Black women (aOR, 1.25 [95% CI, 1.05-1.50]), and Hispanic women (aOR, 1.30 [95% CI, 1.01-1.66]) had higher odds of mortality compared with White men (corresponding adjusted risk ratios [aRRs], 1.10 [CI, 1.06-1.14], 1.06 [95% CI, 1.02-1.11], and 1.08 [95% CI, 1.01-1.14], respectively). In the pulseless electrical activity/asystole arrest subgroup, Black men (aOR, 1.25 [95% CI, 1.11-1.39]) and Hispanic men (aOR, 1.22 [95% CI, 1.07-1.40]) had higher odds of mortality (corresponding aRRs, 1.04 [95% CI, 1.02-1.06] and 1.04 [95% CI, 1.01-1.06], respectively). Black patients with IHCA were less likely to receive percutaneous coronary intervention, coronary artery bypass grafting, and mechanical circulatory support compared with White men.</p><p><strong>Conclusions: </strong>Significant racial and ethnic and sex disparities exist in outcomes and treatment patterns among patients with IHCA. Targeted efforts and further studies are needed to better understand and address these disparities and improve outcomes.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038683"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632690","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":"Dietary Branched-Chain Amino Acids Modify Postinfarct Cardiac Remodeling and Function in the Murine Heart.","authors":"Daniel C Nguyen, Collin K Wells, Madison S Taylor, Yania Martinez-Ondaro, Richa Singhal, Kenneth R Brittian, Robert E Brainard, Joseph B Moore, Bradford G Hill","doi":"10.1161/JAHA.124.037637","DOIUrl":"10.1161/JAHA.124.037637","url":null,"abstract":"<p><strong>Background: </strong>Branched-chain amino acids (BCAAs), which are derived from the diet, are markedly elevated in cardiac tissue following myocardial infarction (MI). Nevertheless, it remains unclear whether dietary BCAA levels influence post-MI remodeling.</p><p><strong>Methods: </strong>To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, we fed mice a low or a high BCAA diet for 2 weeks before MI and for 4 weeks after MI. Cardiac structural and functional changes were evaluated by echocardiography, gravimetry, and histopathological analyses. Immunoblotting was used to evaluate the effects of BCAAs on isolated cardiac myofibroblast differentiation.</p><p><strong>Results: </strong>The low BCAA diet decreased circulating BCAA concentrations by >2-fold when compared with the high BCAA diet. Although neither body weights nor heart masses were different in female mice fed the custom diets, male mice fed the high BCAA diet had significantly higher body and heart masses than those on the low BCAA diet. The low BCAA diet preserved stroke volume and cardiac output after MI, whereas the high BCAA diet promoted progressive decreases in cardiac function. Although BCAAs were required for myofibroblast differentiation in vitro, cardiac fibrosis, scar collagen topography, and cardiomyocyte cross-sectional area were not different between the dietary groups; however, male mice fed the high BCAA diet had longer cardiomyocytes and higher capillary density compared with the low BCAA group.</p><p><strong>Conclusions: </strong>A low BCAA diet mitigates eccentric cardiomyocyte remodeling and loss of cardiac function after MI in mice, with dietary effects more prominent in males.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037637"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416265","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":"Examination of Inter-α Inhibitor Proteins in Permanent and Transient Focal Ischemia.","authors":"Takahiko Imai, Andreia Lopes de Morais, Tao Qin, Yuichi Sasaki, Yow-Pin Lim, Cenk Ayata","doi":"10.1161/JAHA.124.036034","DOIUrl":"10.1161/JAHA.124.036034","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is among the most prevalent diseases, with high death and morbidity. Numerous preclinical studies have reported efficacious interventions in rodent stroke models. However, reperfusion therapies remain the only clinically efficacious intervention to date. Rigor and reproducibility are now recognized as critical to bridge the preclinical-clinical disconnect. Inter-α inhibitor proteins (IαIPs) are a family of structurally related glycoproteins with 2 major forms (inter-α inhibitor and pre-α inhibitor) in blood. Purified human plasma-derived IαIP has beneficial effects in sepsis and hypoxic-ischemic brain injury. More recently, IαIP improved focal ischemic stroke outcomes in mouse models. Here, we tested IαIP efficacy in both transient and permanent stroke mouse models, mimicking previously published study designs and protocols to seek reproducibility.</p><p><strong>Methods and results: </strong>Using healthy young male and female C57BL/6 mice, we induced transient or permanent endovascular filament middle cerebral artery occlusion (MCAO). Mice were divided into transient MCAO+vehicle, transient MCAO+IαIP (30 mg/kg), permanent MCAO+vehicle, and permanent MCAO+IαIP groups. IαIP or vehicle was administered intravenously at 6 and 18 hours after MCAO. End points were assessed at 2 days. Efficacy readouts included death, infarct volume and swelling, and 3 neurological tests. Contrary to the previous work, we did not find IαIP efficacious on any outcome readout in either transient MCAO or permanent MCAO.</p><p><strong>Conclusions: </strong>Our data highlight the contribution of interlaboratory heterogeneity to study outcomes and suggest that interventions considered for clinical development should undergo rigorous testing in multiple single-laboratory studies before entering a multicenter preclinical trial.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e036034"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375023","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":"Direct Oral Anticoagulants Compared With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease Without Mechanical Valves.","authors":"Ghadeer K Dawwas, James D Lewis, Adam Cuker","doi":"10.1161/JAHA.124.035478","DOIUrl":"10.1161/JAHA.124.035478","url":null,"abstract":"<p><strong>Background: </strong>Despite proven efficacy and safety of direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), data on patients with AF and valvular heart disease remain scarce. We aimed to evaluate the DOACs compared with warfarin among patients with AF and valvular heart disease.</p><p><strong>Methods and results: </strong>We conducted a retrospective cohort study of patients ≥18 years of age, who had AF and valvular heart disease, and were new users of DOACs or warfarin. The primary effectiveness outcomes were ischemic stroke or systemic embolism, and bleeding for safety. We used Cox proportional-hazards regression after propensity score matching to estimate hazard ratios (HRs) and 95% CIs. In the matched cohort, DOAC use (versus warfarin) was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.70 [95% CI, 0.61-0.81]) and bleeding (HR, 0.72 [95% CI, 0.65-0.80]). We found a lower rate of ischemic stroke or systemic embolism with rivaroxaban (HR, 0.74 [95% CI, 0.62-0.89]) and apixaban (HR, 0.62 [95% CI, 0.52-0.74]) but not dabigatran (HR, 0.89 [95% CI, 0.63-1.26]). We found a lower rate of bleeding with rivaroxaban (HR, 0.84 [95% CI, 0.74-0.95]), apixaban (HR, 0.60 [95% CI, 0.53-0.68]), dabigatran (HR, 0.75 [95% CI, 0.58-0.97]), and edoxaban (HR, 0.21 [95% CI, 0.05-0.83]). We were unable to obtain estimates for the effectiveness outcome with edoxaban due to the small number of events.</p><p><strong>Conclusions: </strong>In this study of patients with AF and valvular heart disease, DOAC treatment was associated with a lower risk of ischemic stroke or systemic embolism and bleeding compared with warfarin.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e035478"},"PeriodicalIF":5.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416267","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}