Mckay Hanna, Marianne Khoury, Qasem N Al Shaer, Digvijaya Navalkele, Bryan Wells, Fadi Nahab, Ghada A Mohamed
Background: Fibromuscular dysplasia (FMD) is a non-inflammatory arteriopathy that may result in arterial stenosis, dissection, aneurysm, and tortuosity. Data remain limited on clinical features and outcomes of patients with FMD presenting with spontaneous cervical artery dissection (SCeAD). This study aimed to describe the characteristics and long-term outcomes of this population.
Methods: We conducted a retrospective multicenter cohort study of patients diagnosed with both SCeAD and FMD at three U.S. comprehensive stroke centers (2018-2023). Patients were identified through hospital records and vascular registries. Diagnosis of FMD and SCeAD was confirmed through imaging review by vascular neurologists or cardiologists. Outcomes included recurrent dissections, cardiovascular events (ischemic stroke, transient ischemic attack, myocardial infarction, subarachnoid hemorrhage) and mortality.
Results: Among 1,632 patients with SCeAD, 97 (6%) had FMD diagnosis. The cohort was predominantly female (91%) and median age at FMD diagnosis was 50 years(IQR 42-63). Carotid dissections were more frequent than vertebral dissections (86%vs.27%, p<0.001). Multiple dissections occurred in 32 patients (33%): 24 (75%) had bilateral dissections, 4(13%) had recurrent dissections in the same artery, and 7 (22%) had dissections in other vascular beds including the renal, iliac, mesenteric, and coronary arteries. Younger age [OR 0.945; 95%CI 0.908-0.983; p=0.005] and classical FMD "beading" on imaging [OR 3.06; 95%CI 1.28-7.36; p=0.012] were associated with multiple dissections. Aneurysms were detected in 27%, more frequently in patients with multiple dissections [OR 1.66; 95%CI 1.02-2.71;p=0.04]. Most patients were discharged on single (49%) or dual (29%) antiplatelet therapy and 22% received anticoagulation with no significant differences in event rates. Over a mean follow-up of 5±2.5 years, 13% developed recurrent dissections and 28% experienced cardiovascular events. Recurrent dissections were associated with future cardiovascular events [OR11.56; 95%CI 2.22-60.07; p=0.004].
Conclusions: FMD should be considered in patients presenting with SCeAD, particularly middle-aged women with multifocal dissections and no traditional vascular risk factors. There is an increased risk of dissection recurrence, future cardiovascular events and harboring aneurysms. These findings highlight the need for further prospective studies that can guide surveillance and management strategies for this high-risk population.
{"title":"Fibromuscular Dysplasia and Cerebrovascular Dissection: Insights from a Multicenter Cohort.","authors":"Mckay Hanna, Marianne Khoury, Qasem N Al Shaer, Digvijaya Navalkele, Bryan Wells, Fadi Nahab, Ghada A Mohamed","doi":"10.1161/JAHA.125.046580","DOIUrl":"https://doi.org/10.1161/JAHA.125.046580","url":null,"abstract":"<p><strong>Background: </strong>Fibromuscular dysplasia (FMD) is a non-inflammatory arteriopathy that may result in arterial stenosis, dissection, aneurysm, and tortuosity. Data remain limited on clinical features and outcomes of patients with FMD presenting with spontaneous cervical artery dissection (SCeAD). This study aimed to describe the characteristics and long-term outcomes of this population.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter cohort study of patients diagnosed with both SCeAD and FMD at three U.S. comprehensive stroke centers (2018-2023). Patients were identified through hospital records and vascular registries. Diagnosis of FMD and SCeAD was confirmed through imaging review by vascular neurologists or cardiologists. Outcomes included recurrent dissections, cardiovascular events (ischemic stroke, transient ischemic attack, myocardial infarction, subarachnoid hemorrhage) and mortality.</p><p><strong>Results: </strong>Among 1,632 patients with SCeAD, 97 (6%) had FMD diagnosis. The cohort was predominantly female (91%) and median age at FMD diagnosis was 50 years(IQR 42-63). Carotid dissections were more frequent than vertebral dissections (86%vs.27%, p<0.001). Multiple dissections occurred in 32 patients (33%): 24 (75%) had bilateral dissections, 4(13%) had recurrent dissections in the same artery, and 7 (22%) had dissections in other vascular beds including the renal, iliac, mesenteric, and coronary arteries. Younger age [OR 0.945; 95%CI 0.908-0.983; p=0.005] and classical FMD \"beading\" on imaging [OR 3.06; 95%CI 1.28-7.36; p=0.012] were associated with multiple dissections. Aneurysms were detected in 27%, more frequently in patients with multiple dissections [OR 1.66; 95%CI 1.02-2.71;p=0.04]. Most patients were discharged on single (49%) or dual (29%) antiplatelet therapy and 22% received anticoagulation with no significant differences in event rates. Over a mean follow-up of 5±2.5 years, 13% developed recurrent dissections and 28% experienced cardiovascular events. Recurrent dissections were associated with future cardiovascular events [OR11.56; 95%CI 2.22-60.07; p=0.004].</p><p><strong>Conclusions: </strong>FMD should be considered in patients presenting with SCeAD, particularly middle-aged women with multifocal dissections and no traditional vascular risk factors. There is an increased risk of dissection recurrence, future cardiovascular events and harboring aneurysms. These findings highlight the need for further prospective studies that can guide surveillance and management strategies for this high-risk population.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e046580"},"PeriodicalIF":5.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121035","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":"A Decade of Game of Strokes at the International Stroke Conference: Reflections and Future Directions.","authors":"Jorge Ortiz-Garcia, José Biller","doi":"10.1161/JAHA.125.044043","DOIUrl":"https://doi.org/10.1161/JAHA.125.044043","url":null,"abstract":"","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e044043"},"PeriodicalIF":5.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115140","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}
Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye
Background: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi-arm Optimization of Stroke Thrombolysis) trial.
Methods: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The primary outcome of interest was the utility weighted modified Rankin Scale (mRS) score at 90 days after stroke. The secondary outcomes were mRS score ≤1, ≤2 at 90 days, 90-day mRS score, thrombolysis in cerebral infarction 2B or better, 24-hour National Institutes of Health Stroke Scale score, 24-hour change in National Institutes of Health Stroke Scale score, and 90-day mortality.
Results: A total of 219 patients underwent mechanical thrombectomy with 101 patients receiving GA and 118 patients receiving CS. Our analysis showed that GA was associated with a lower average utility weighted mRS score at 90 days compared with CS (P≤0.02). Similarly, GA was associated with higher odds of worse outcomes on 90-day mRS 0 to 2 (P<0.001), 90-day mRS median score (P<0.001), a higher 24-hour National Institutes of Health Stroke Scale score (P<0.001), and a lower change in baseline 24-hour National Institutes of Health Stroke Scale score (P<0.001). A sensitivity analysis of patients with anterior stroke alone also favored better neurologic outcomes in the CS group compared with the GA group.
Conclusions: In patients undergoing endovascular thrombectomy in the MOST trial, GA was associated with poorer functional outcomes compared with CS.
{"title":"General Anesthesia Versus Conscious Sedation for Mechanical Thrombectomy in Patients With Acute Ischemic Stroke in the MOST Trial.","authors":"Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye","doi":"10.1161/JAHA.125.044874","DOIUrl":"https://doi.org/10.1161/JAHA.125.044874","url":null,"abstract":"<p><strong>Background: </strong>Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi-arm Optimization of Stroke Thrombolysis) trial.</p><p><strong>Methods: </strong>Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The primary outcome of interest was the utility weighted modified Rankin Scale (mRS) score at 90 days after stroke. The secondary outcomes were mRS score ≤1, ≤2 at 90 days, 90-day mRS score, thrombolysis in cerebral infarction 2B or better, 24-hour National Institutes of Health Stroke Scale score, 24-hour change in National Institutes of Health Stroke Scale score, and 90-day mortality.</p><p><strong>Results: </strong>A total of 219 patients underwent mechanical thrombectomy with 101 patients receiving GA and 118 patients receiving CS. Our analysis showed that GA was associated with a lower average utility weighted mRS score at 90 days compared with CS (<i>P</i>≤0.02). Similarly, GA was associated with higher odds of worse outcomes on 90-day mRS 0 to 2 (<i>P</i><0.001), 90-day mRS median score (<i>P</i><0.001), a higher 24-hour National Institutes of Health Stroke Scale score (<i>P</i><0.001), and a lower change in baseline 24-hour National Institutes of Health Stroke Scale score (<i>P</i><0.001). A sensitivity analysis of patients with anterior stroke alone also favored better neurologic outcomes in the CS group compared with the GA group.</p><p><strong>Conclusions: </strong>In patients undergoing endovascular thrombectomy in the MOST trial, GA was associated with poorer functional outcomes compared with CS.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e044874"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114687","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}
Yiting Liu, Xinyi Zeng, Min Zhang, Xiangdong Yang, Chunshu Li, Hai Tian, Mengying Zhu, Pengyun Li, Jun Cheng, Qingbo Xu, Yan Yang
Background: Vascular restenosis, a common complication following vascular reconstruction, results in stenosis or blockage that impairs vascular remodeling. This process is driven by the activation of vascular stem cells. Growing evidence suggests that intermediate conductance calcium-activated potassium (IKCa) channels play a crucial role in regulating the function of these cells. This study aims to explore how IKCa channels influence Sca-1+ (stem cell antigen-1 positive) stem cells in the context of vascular anastomotic restenosis.
Methods: To investigate the role and mechanism of the IKCa channel in Sca-1+ cell activation and its involvement in vascular anastomosis restenosis, we assessed the impact of IKCa channel deficiency on the vascular restenosis-promoting ability of Sca-1+ cells using a mouse femoral artery anastomosis model. Mechanistic insights were gained through patch-clamp electrophysiology, intracellular Ca2+ measurement, and molecular biology techniques.
Results: Genetic deletion of IKCa channels in IKCa-/- mice led to reduced neointimal formation and decreased proliferation of Sca-1+ cells at the anastomotic site. In vitro studies confirmed the presence of functional IKCa channels in Sca-1+ cells and demonstrated that IKCa and TRPC1 (transient receptor potential canonical 1) channels cooperate in regulating membrane potential and intracellular Ca2+ levels. Furthermore, our findings suggest that IKCa channel-mediated modulation of ERK (extracellular signal-regulated kinase) and p38 phosphorylation underpins a key signaling mechanism in this process.
Conclusions: This study clarifies the role of the IKCa-TRPC1-Ca2+ pathway in activating vascular Sca-1+ cells and establishes the contribution of the IKCa channel to vascular restenosis development. Understanding how IKCa channels affect the function of vascular Sca-1+ cells provides valuable insights into the complex mechanisms of vascular remodeling during vascular stenosis.
{"title":"Intermediate Conductance Calcium-Activated Potassium Channel Activation in Stem Cell Antigen-1 Positive Cells Contributed to Vascular Restenosis.","authors":"Yiting Liu, Xinyi Zeng, Min Zhang, Xiangdong Yang, Chunshu Li, Hai Tian, Mengying Zhu, Pengyun Li, Jun Cheng, Qingbo Xu, Yan Yang","doi":"10.1161/JAHA.125.045943","DOIUrl":"https://doi.org/10.1161/JAHA.125.045943","url":null,"abstract":"<p><strong>Background: </strong>Vascular restenosis, a common complication following vascular reconstruction, results in stenosis or blockage that impairs vascular remodeling. This process is driven by the activation of vascular stem cells. Growing evidence suggests that intermediate conductance calcium-activated potassium (IK<sub>Ca</sub>) channels play a crucial role in regulating the function of these cells. This study aims to explore how IK<sub>Ca</sub> channels influence Sca-1<sup>+</sup> (stem cell antigen-1 positive) stem cells in the context of vascular anastomotic restenosis.</p><p><strong>Methods: </strong>To investigate the role and mechanism of the IK<sub>Ca</sub> channel in Sca-1<sup>+</sup> cell activation and its involvement in vascular anastomosis restenosis, we assessed the impact of IK<sub>Ca</sub> channel deficiency on the vascular restenosis-promoting ability of Sca-1<sup>+</sup> cells using a mouse femoral artery anastomosis model. Mechanistic insights were gained through patch-clamp electrophysiology, intracellular Ca<sup>2+</sup> measurement, and molecular biology techniques.</p><p><strong>Results: </strong>Genetic deletion of IK<sub>Ca</sub> channels in IK<sub>Ca</sub><sup>-/-</sup> mice led to reduced neointimal formation and decreased proliferation of Sca-1<sup>+</sup> cells at the anastomotic site. In vitro studies confirmed the presence of functional IK<sub>Ca</sub> channels in Sca-1<sup>+</sup> cells and demonstrated that IK<sub>Ca</sub> and TRPC1 (transient receptor potential canonical 1) channels cooperate in regulating membrane potential and intracellular Ca<sup>2+</sup> levels. Furthermore, our findings suggest that IK<sub>Ca</sub> channel-mediated modulation of ERK (extracellular signal-regulated kinase) and p38 phosphorylation underpins a key signaling mechanism in this process.</p><p><strong>Conclusions: </strong>This study clarifies the role of the IK<sub>Ca</sub>-TRPC1-Ca<sup>2+</sup> pathway in activating vascular Sca-1<sup>+</sup> cells and establishes the contribution of the IK<sub>Ca</sub> channel to vascular restenosis development. Understanding how IK<sub>Ca</sub> channels affect the function of vascular Sca-1<sup>+</sup> cells provides valuable insights into the complex mechanisms of vascular remodeling during vascular stenosis.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e045943"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114712","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}
Jacobina Kristiansen, Steen Dalby Kristensen, Anne-Mette Hvas, Helga Ellingsgaard, Magni Mohr, Erik Lerkevang Grove, Tórur Sjúrðarson
Background: Persistent low-grade inflammation contributes to coronary artery disease (CAD), but how acute vigorous exercise and structured training affect systemic inflammatory biomarkers in stable CAD remains unclear. We evaluated the acute response to a single vigorous bout and the effects of a 12-week high-intensity interval training program on systemic inflammation in patients with stable CAD.
Methods: In 168 patients with stable CAD, blood samples were collected before, immediately after, and 2 hours after a maximal incremental cycling test. Participants were then randomized to 12 weeks of high-intensity interval training or standard care; 142 completed follow-ups. High-sensitivity CRP (C-reactive protein), leukocytes, interleukin-2, interleukin-6, interleukin-10, interferon-γ, and tumor necrosis factor-α were measured at baseline, week 6, and week 12.
Results: Acute exercise elevated CRP by 7.7% [95% CI, 5.5-10.0] and leukocytes by 50.5% [95% CI, 48.2-52.8]; CRP returned to baseline by 2 hours, whereas leukocytes remained elevated. Interferon-γ increased by 13.1% [95% CI, 9.2-17.3] following exercise but fell below baseline after 2 hours. Tumor necrosis factor-α (12.9% [95% CI, 8.4-17.4]), interleukin-2 (22.8% [95% CI, 17.5-28.5]), and interleukin-6 (42.4% [95% CI, 36.5-48.5]) also increased following acute exercise and stayed elevated after 2 hours, while interleukin-10 decreased by 9.2% [95% CI, -14.1 to -4.0] and returned to baseline after 2 hours. Over 12 weeks, high-intensity interval training did not significantly alter these inflammatory markers compared with standard care.
Conclusions: Acute strenuous exercise induces transient increases in inflammatory markers in stable CAD, which begin to resolve within 2 hours. In this optimally treated cohort, regular high-intensity interval training did not produce a sustained anti-inflammatory effect.
{"title":"Effects of Acute Exercise and 12-Week High-Intensity Interval Training on Inflammatory Biomarkers in Stable Coronary Artery Disease: A Randomized Controlled Trial.","authors":"Jacobina Kristiansen, Steen Dalby Kristensen, Anne-Mette Hvas, Helga Ellingsgaard, Magni Mohr, Erik Lerkevang Grove, Tórur Sjúrðarson","doi":"10.1161/JAHA.125.042256","DOIUrl":"https://doi.org/10.1161/JAHA.125.042256","url":null,"abstract":"<p><strong>Background: </strong>Persistent low-grade inflammation contributes to coronary artery disease (CAD), but how acute vigorous exercise and structured training affect systemic inflammatory biomarkers in stable CAD remains unclear. We evaluated the acute response to a single vigorous bout and the effects of a 12-week high-intensity interval training program on systemic inflammation in patients with stable CAD.</p><p><strong>Methods: </strong>In 168 patients with stable CAD, blood samples were collected before, immediately after, and 2 hours after a maximal incremental cycling test. Participants were then randomized to 12 weeks of high-intensity interval training or standard care; 142 completed follow-ups. High-sensitivity CRP (C-reactive protein), leukocytes, interleukin-2, interleukin-6, interleukin-10, interferon-γ, and tumor necrosis factor-α were measured at baseline, week 6, and week 12.</p><p><strong>Results: </strong>Acute exercise elevated CRP by 7.7% [95% CI, 5.5-10.0] and leukocytes by 50.5% [95% CI, 48.2-52.8]; CRP returned to baseline by 2 hours, whereas leukocytes remained elevated. Interferon-γ increased by 13.1% [95% CI, 9.2-17.3] following exercise but fell below baseline after 2 hours. Tumor necrosis factor-α (12.9% [95% CI, 8.4-17.4]), interleukin-2 (22.8% [95% CI, 17.5-28.5]), and interleukin-6 (42.4% [95% CI, 36.5-48.5]) also increased following acute exercise and stayed elevated after 2 hours, while interleukin-10 decreased by 9.2% [95% CI, -14.1 to -4.0] and returned to baseline after 2 hours. Over 12 weeks, high-intensity interval training did not significantly alter these inflammatory markers compared with standard care.</p><p><strong>Conclusions: </strong>Acute strenuous exercise induces transient increases in inflammatory markers in stable CAD, which begin to resolve within 2 hours. In this optimally treated cohort, regular high-intensity interval training did not produce a sustained anti-inflammatory effect.</p><p><strong>Registration: </strong>URL: https://clinicaltrials.gov; Unique identifier: NCT04268992.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042256"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115254","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}
Pub Date : 2026-02-03Epub Date: 2026-01-22DOI: 10.1161/JAHA.125.044310
Mingjing Chen, Yixi Sun, Guanhong Miao, Xiaoxiao Wen, Alexander C Razavi, Camilo Fernandez, Mary J Roman, Richard B Devereux, Richard R Fabsitz, Ying Zhang, Jason G Umans, Shelley A Cole, Lydia A Bazzano, Oliver Fiehn, Tanika N Kelly, Jinying Zhao
Background: Subclinical alterations in left ventricular (LV) structure, diastolic function, and metabolic disturbances are associated with coronary heart disease (CHD) risk, but their relationships remained unclear. Large-scale longitudinal metabolomic profiling of LV measures is lacking.
Methods: Using untargeted metabolomics, we quantified 563 fasting plasma metabolites from 1799 American Indian individuals attending 2 exams (~5.5 years apart). We examined associations between metabolites and measures of LV structure (LV mass index, relative wall thickness), and diastolic function (peak early filling velocity to peak late filling velocity, isovolumic relaxation time, and deceleration time) using generalized estimating equation model. Findings were then replicated in an independent biracial cohort. Frailty Cox proportional hazards models were used to examine whether LV-related metabolites are associated with the risk of CHD over a 20-year follow-up. Pathway enrichment analysis was performed to identify relevant metabolic pathways.
Results: We identified 173 metabolites (47 named; q<0.05) associated with LV structure or diastolic function in the SHFS (Strong Heart Family Study), and some metabolites were confirmed in the biracial cohort. Three metabolites were additionally associated with incident CHD. Aspartic acid and palmitoleic acid were associated with lower LV mass index and peak early filling velocity to peak late filling velocity ratio and lower CHD risk (hazard ratios [HRs], 0.75 [95% CI, 0.56-0.99] to 0.81 [95% CI, 0.67-0.99]), whereas isothreonic acid was associated with higher relative wall thickness and higher CHD risk (HR, 1.15 [95% CI, 1.01-1.32]). LV-related metabolites were enriched in arginine biosynthesis, alanine-aspartate-glutamate metabolism, and starch and sucrose metabolism.
Conclusions: We identified metabolomic markers of LV structure and diastolic function, several of which that were independently associated with CHD risk, providing insight into metabolic pathways underlying LV subclinical changes and CHD.
{"title":"Metabolomic Markers of Left Ventricular Structure, Diastolic Function, and Risk of Coronary Heart Disease: A Longitudinal Study in American Indian Individuals.","authors":"Mingjing Chen, Yixi Sun, Guanhong Miao, Xiaoxiao Wen, Alexander C Razavi, Camilo Fernandez, Mary J Roman, Richard B Devereux, Richard R Fabsitz, Ying Zhang, Jason G Umans, Shelley A Cole, Lydia A Bazzano, Oliver Fiehn, Tanika N Kelly, Jinying Zhao","doi":"10.1161/JAHA.125.044310","DOIUrl":"10.1161/JAHA.125.044310","url":null,"abstract":"<p><strong>Background: </strong>Subclinical alterations in left ventricular (LV) structure, diastolic function, and metabolic disturbances are associated with coronary heart disease (CHD) risk, but their relationships remained unclear. Large-scale longitudinal metabolomic profiling of LV measures is lacking.</p><p><strong>Methods: </strong>Using untargeted metabolomics, we quantified 563 fasting plasma metabolites from 1799 American Indian individuals attending 2 exams (~5.5 years apart). We examined associations between metabolites and measures of LV structure (LV mass index, relative wall thickness), and diastolic function (peak early filling velocity to peak late filling velocity, isovolumic relaxation time, and deceleration time) using generalized estimating equation model. Findings were then replicated in an independent biracial cohort. Frailty Cox proportional hazards models were used to examine whether LV-related metabolites are associated with the risk of CHD over a 20-year follow-up. Pathway enrichment analysis was performed to identify relevant metabolic pathways.</p><p><strong>Results: </strong>We identified 173 metabolites (47 named; <i>q</i><0.05) associated with LV structure or diastolic function in the SHFS (Strong Heart Family Study), and some metabolites were confirmed in the biracial cohort. Three metabolites were additionally associated with incident CHD. Aspartic acid and palmitoleic acid were associated with lower LV mass index and peak early filling velocity to peak late filling velocity ratio and lower CHD risk (hazard ratios [HRs], 0.75 [95% CI, 0.56-0.99] to 0.81 [95% CI, 0.67-0.99]), whereas isothreonic acid was associated with higher relative wall thickness and higher CHD risk (HR, 1.15 [95% CI, 1.01-1.32]). LV-related metabolites were enriched in arginine biosynthesis, alanine-aspartate-glutamate metabolism, and starch and sucrose metabolism.</p><p><strong>Conclusions: </strong>We identified metabolomic markers of LV structure and diastolic function, several of which that were independently associated with CHD risk, providing insight into metabolic pathways underlying LV subclinical changes and CHD.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e044310"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020612","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}
Pub Date : 2026-02-03Epub Date: 2026-01-22DOI: 10.1161/JAHA.125.045453
Catherine M Montgomery, Radhika Rastogi, Aaron Dewitt, Benjamin W Kozyak, Lynne Ha, Farrell Weiss, Jessica R Eichner, Humera Ahmed, Jessica Tang, Katsuhide Maeda, Anila A Chaudhary, Meghan Lane-Fall, Tami Rosenthal, Monique M Gardner, Zeyu Nancy Li, Joseph Rossano, Matthew J O'Connor, Carol Wittlieb-Weber, Jonathan B Edelson
Background: In October 2022, our center implemented a standardized program to promote ventricular recovery in pediatric patients supported with durable ventricular assist devices. We report our experience and outcomes.
Methods: The initiative consists of 4 core components for all patients with ventricular assist devices: (1) cultural shift: routine assessment for ventricular recovery for possible device explant or, in complex congenital heart disease (CHD), for further surgical palliation; (2) reverse remodeling-use of goal-directed medical therapy as tolerated; (3) assessment of recovery: stepwise evaluation by echocardiography, exercise testing, and cardiac catheterization; and (4) multidisciplinary review of patients. This retrospective cohort study includes all patients who underwent durable ventricular assist device implantation between October 2022 and October 2024. Patient characteristics and outcomes are described for those explanted for recovery.
Results: The cohort included 35 patients, 22 (63%) with Berlin Heart EXCOR and 13 (37%) with HeartMate 3. Indications included cardiomyopathy (60%, n=21), CHD (31%, n=11), coronary pathology (6%, n=2), and myocarditis (3%, n=1). Nine patients underwent explant (26% of all patients, 38% of patients without CHD). No patients with CHD met criteria for recovery. Median age of explanted patients was 1 year (interquartile range, 3 months-10 years), and all were discharged postexplant. Median follow-up was 10 months (interquartile range, 5.5-20 months). One patient was relisted for transplant; the others remained outpatient with, at worst, mild ventricular dysfunction.
Conclusions: A standardized approach to ventricular recovery was associated with explant in 26% of patients, exclusively among those without CHD. Short-term postexplant outcomes are encouraging, supporting further study in larger cohorts.
{"title":"Implementing a Programmatic Approach to Identify and Promote Ventricular Recovery in Pediatric Patients Supported With Ventricular Assist Devices.","authors":"Catherine M Montgomery, Radhika Rastogi, Aaron Dewitt, Benjamin W Kozyak, Lynne Ha, Farrell Weiss, Jessica R Eichner, Humera Ahmed, Jessica Tang, Katsuhide Maeda, Anila A Chaudhary, Meghan Lane-Fall, Tami Rosenthal, Monique M Gardner, Zeyu Nancy Li, Joseph Rossano, Matthew J O'Connor, Carol Wittlieb-Weber, Jonathan B Edelson","doi":"10.1161/JAHA.125.045453","DOIUrl":"10.1161/JAHA.125.045453","url":null,"abstract":"<p><strong>Background: </strong>In October 2022, our center implemented a standardized program to promote ventricular recovery in pediatric patients supported with durable ventricular assist devices. We report our experience and outcomes.</p><p><strong>Methods: </strong>The initiative consists of 4 core components for all patients with ventricular assist devices: (1) cultural shift: routine assessment for ventricular recovery for possible device explant or, in complex congenital heart disease (CHD), for further surgical palliation; (2) reverse remodeling-use of goal-directed medical therapy as tolerated; (3) assessment of recovery: stepwise evaluation by echocardiography, exercise testing, and cardiac catheterization; and (4) multidisciplinary review of patients. This retrospective cohort study includes all patients who underwent durable ventricular assist device implantation between October 2022 and October 2024. Patient characteristics and outcomes are described for those explanted for recovery.</p><p><strong>Results: </strong>The cohort included 35 patients, 22 (63%) with Berlin Heart EXCOR and 13 (37%) with HeartMate 3. Indications included cardiomyopathy (60%, n=21), CHD (31%, n=11), coronary pathology (6%, n=2), and myocarditis (3%, n=1). Nine patients underwent explant (26% of all patients, 38% of patients without CHD). No patients with CHD met criteria for recovery. Median age of explanted patients was 1 year (interquartile range, 3 months-10 years), and all were discharged postexplant. Median follow-up was 10 months (interquartile range, 5.5-20 months). One patient was relisted for transplant; the others remained outpatient with, at worst, mild ventricular dysfunction.</p><p><strong>Conclusions: </strong>A standardized approach to ventricular recovery was associated with explant in 26% of patients, exclusively among those without CHD. Short-term postexplant outcomes are encouraging, supporting further study in larger cohorts.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e045453"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020628","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}
Pub Date : 2026-02-03Epub Date: 2026-01-22DOI: 10.1161/JAHA.125.044241
Areesha Moiz, Tetiana Zolotarova, Mark J Eisenberg
Background: The role of colchicine, an anti-inflammatory agent, in improving cardiovascular outcomes in patients with recent myocardial infarction remains unclear. We sought to evaluate the efficacy and safety of colchicine compared with placebo in patients with recent myocardial infarction (within 1 month of symptom onset) at a follow-up of at least 1 year.
Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library until January 2025 for randomized controlled trials comparing colchicine to placebo in recent myocardial infarction. The primary outcome was major adverse cardiovascular events (MACE; as defined by the included studies) at maximum follow-up. Secondary outcomes included individual MACE components and safety (serious adverse events [AEs], any AEs, and gastrointestinal AEs). Count data were pooled using random-effects models with inverse variance weighting to estimate risk ratios (RRs) and 95% CIs.
Results: A total of 5 randomized controlled trials were included with 6620 patients randomized to colchicine and 6625 to placebo. Most participants (79%) were male, with mean ages ranging from 59 to 61 years. Follow-up durations ranged from 1 to 3 years. At maximum follow-up, there was no statistically significant difference in MACE between colchicine and placebo (8.2% versus 9.3%; RR, 0.83 [95% CI, 0.66-1.04]). Analyses of individual MACE components were also inconclusive. Randomization to colchicine did not increase the overall incidence of AEs or serious AEs compared with placebo.
Conclusions: In patients with recent myocardial infarction, the available evidence assessing the effect of colchicine, in addition to standard therapy, on MACE remains inconclusive over a median follow-up duration of 1 year.
背景:秋水仙碱,一种抗炎药,在改善近期心肌梗死患者心血管预后中的作用尚不清楚。我们试图在至少1年的随访中评估秋水仙碱与安慰剂在近期心肌梗死(症状出现1个月内)患者中的疗效和安全性。方法:我们系统地检索MEDLINE, Embase和Cochrane图书馆,直到2025年1月,以比较秋水仙碱和安慰剂在近期心肌梗死中的随机对照试验。主要结局是最大随访时的主要不良心血管事件(MACE;由纳入的研究定义)。次要结局包括单个MACE成分和安全性(严重不良事件[ae]、任何ae和胃肠道ae)。计数数据采用随机效应模型合并,采用方差反加权来估计风险比(rr)和95% ci。结果:共纳入5项随机对照试验,6620例患者随机接受秋水仙碱治疗,6625例患者随机接受安慰剂治疗。大多数参与者(79%)为男性,平均年龄在59岁至61岁之间。随访时间为1至3年。在最大随访时,秋水仙碱与安慰剂的MACE差异无统计学意义(8.2% vs 9.3%; RR, 0.83 [95% CI, 0.66-1.04])。对单个MACE成分的分析也没有定论。与安慰剂相比,随机分配秋水仙碱组并没有增加不良事件或严重不良事件的总发生率。结论:在新近发生心肌梗死的患者中,评估秋水仙碱在标准治疗之外对MACE的影响的现有证据在中位随访1年期间仍然没有定论。
{"title":"Colchicine in Patients With Recent Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Areesha Moiz, Tetiana Zolotarova, Mark J Eisenberg","doi":"10.1161/JAHA.125.044241","DOIUrl":"10.1161/JAHA.125.044241","url":null,"abstract":"<p><strong>Background: </strong>The role of colchicine, an anti-inflammatory agent, in improving cardiovascular outcomes in patients with recent myocardial infarction remains unclear. We sought to evaluate the efficacy and safety of colchicine compared with placebo in patients with recent myocardial infarction (within 1 month of symptom onset) at a follow-up of at least 1 year.</p><p><strong>Methods: </strong>We systematically searched MEDLINE, Embase, and the Cochrane Library until January 2025 for randomized controlled trials comparing colchicine to placebo in recent myocardial infarction. The primary outcome was major adverse cardiovascular events (MACE; as defined by the included studies) at maximum follow-up. Secondary outcomes included individual MACE components and safety (serious adverse events [AEs], any AEs, and gastrointestinal AEs). Count data were pooled using random-effects models with inverse variance weighting to estimate risk ratios (RRs) and 95% CIs.</p><p><strong>Results: </strong>A total of 5 randomized controlled trials were included with 6620 patients randomized to colchicine and 6625 to placebo. Most participants (79%) were male, with mean ages ranging from 59 to 61 years. Follow-up durations ranged from 1 to 3 years. At maximum follow-up, there was no statistically significant difference in MACE between colchicine and placebo (8.2% versus 9.3%; RR, 0.83 [95% CI, 0.66-1.04]). Analyses of individual MACE components were also inconclusive. Randomization to colchicine did not increase the overall incidence of AEs or serious AEs compared with placebo.</p><p><strong>Conclusions: </strong>In patients with recent myocardial infarction, the available evidence assessing the effect of colchicine, in addition to standard therapy, on MACE remains inconclusive over a median follow-up duration of 1 year.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e044241"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020656","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}
Pub Date : 2026-02-03Epub Date: 2026-01-22DOI: 10.1161/JAHA.125.042320
Shahnawaz Amdani, Madeleine Townsend, Drishti Tolani, Samantha Noreen, Alice Toll, Bradley S Marino
Background: Donor discard rates for pediatric heart transplant (HT) remain high (≈40%), often driven by concerns about elevated donor troponin levels. This study evaluated the association between peak donor troponin levels, donor troponin trends, and post transplant survival among pediatric HT recipients.
Methods: Children (aged <18 years at listing) who underwent HT between January 2007, and June 2020 were identified from the Organ Procurement and Transplantation Network registry. Recipient and donor characteristics, as well as 1-year post-HT survival, were compared across peak donor troponin I percentiles (0 to <25th, 25th to <75th, ≥75th) and troponin trend categories (increasing, persistently high, persistently low, decreasing).
Results: Among 4572 donors with reported troponin I values, 67% (n=3097) had abnormal levels. Recipients of donors with peak troponin ≥75th percentile were more frequently aged 11 to 17 years (47.1% versus 22.9% versus 33.1%), had implantable cardioverter-defibrillators (12.8% versus 5.5% versus 8.2%), and exhibited higher creatinine and bilirubin at transplant. Donors with troponin ≥75th percentile were more likely to have undergone cardiopulmonary resuscitation (63.3% versus 44.3% versus 53.7%) and had left ventricular ejection fraction ≤55% (8.7% versus 4.2% versus 6.4%) (P<0.05 for all). In adjusted analyses, peak donor troponin ≥75th percentile was associated with increased 1-year graft loss (hazard ratio, 1.22 [95% CI, 1.00-1.47]; P=0.045). Troponin trends were not associated with post-HT graft survival.
Conclusions: Most pediatric HT donors exhibit abnormal troponin levels. Elevated peak donor troponin (>0.66 ng/mL) correlates with donor hemodynamic instability and predicts worse 1-year post transplant graft survival, whereas troponin trajectories are not prognostic.
{"title":"Impact of Peak Donor Troponin and Donor Troponin Trends on Pediatric Heart Transplant Outcomes.","authors":"Shahnawaz Amdani, Madeleine Townsend, Drishti Tolani, Samantha Noreen, Alice Toll, Bradley S Marino","doi":"10.1161/JAHA.125.042320","DOIUrl":"10.1161/JAHA.125.042320","url":null,"abstract":"<p><strong>Background: </strong>Donor discard rates for pediatric heart transplant (HT) remain high (≈40%), often driven by concerns about elevated donor troponin levels. This study evaluated the association between peak donor troponin levels, donor troponin trends, and post transplant survival among pediatric HT recipients.</p><p><strong>Methods: </strong>Children (aged <18 years at listing) who underwent HT between January 2007, and June 2020 were identified from the Organ Procurement and Transplantation Network registry. Recipient and donor characteristics, as well as 1-year post-HT survival, were compared across peak donor troponin I percentiles (0 to <25th, 25th to <75th, ≥75th) and troponin trend categories (increasing, persistently high, persistently low, decreasing).</p><p><strong>Results: </strong>Among 4572 donors with reported troponin I values, 67% (n=3097) had abnormal levels. Recipients of donors with peak troponin ≥75th percentile were more frequently aged 11 to 17 years (47.1% versus 22.9% versus 33.1%), had implantable cardioverter-defibrillators (12.8% versus 5.5% versus 8.2%), and exhibited higher creatinine and bilirubin at transplant. Donors with troponin ≥75th percentile were more likely to have undergone cardiopulmonary resuscitation (63.3% versus 44.3% versus 53.7%) and had left ventricular ejection fraction ≤55% (8.7% versus 4.2% versus 6.4%) (<i>P</i><0.05 for all). In adjusted analyses, peak donor troponin ≥75th percentile was associated with increased 1-year graft loss (hazard ratio, 1.22 [95% CI, 1.00-1.47]; <i>P</i>=0.045). Troponin trends were not associated with post-HT graft survival.</p><p><strong>Conclusions: </strong>Most pediatric HT donors exhibit abnormal troponin levels. Elevated peak donor troponin (>0.66 ng/mL) correlates with donor hemodynamic instability and predicts worse 1-year post transplant graft survival, whereas troponin trajectories are not prognostic.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042320"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020658","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}
Background: The impact of endovascular thrombectomy-mediated reperfusion on malignant cerebral edema (MCE) in large-core infarction remains unclear. We assessed the reperfusion-MCE relationship and MCE's mediating role in poor outcomes.
Methods: This retrospective analysis used data from the national MAGIC (Prospective Multicenter Registry on Early Management of Acute Ischemic Stroke) registry (750 patients with large-core infarction, 38 Chinese centers, 2021-2023). MCE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 hours after stroke onset. Recanalization was confirmed by computed tomography angiogram or magnetic resonance angiogram during hospitalization in the overall cohorts. Successful reperfusion was defined using the modified Treatment in Cerebral Ischemia classification 2b-3 in the endovascular thrombectomy arm. Functional outcome was 90-day modified Rankin scale score. Mediation analysis used reperfusion status as the independent variable and MCE as the mediator.
Results: Among 698 patients, (306 women [43.8%]; median age, 70 [interquartile range, 61-78] years; median, Alberta Stroke Program Early Computed Tomography] Scores, 4 [interquartile range, 2-5]), successful recanalization (adjusted odds ratio [aOR], 0.68 [95% CI, 0.47-0.99]; P=0.042) and reperfusion (aOR, 0.34 [95% CI, 0.18-0.67]; P=0.002) reduced MCE likelihood. MCE was partially responsible for worse modified Rankin Scale scores in patients without recanalization or reperfusion (MCE changed the logistic regression coefficients by 15.0% and 32.5%, respectively). Recanalization improved functional outcomes partly by mitigating MCE formation (indirect effect β=-0.10, 11.5% mediation proportion, P=0.028) in those with Alberta Stroke Program Early Computed Tomography Scores 3 to 5 but not in those with 0 to 2 (β=-0.26, P=0.140).
Conclusions: Successful reperfusion attenuates MCE formation and improves clinical outcomes in patients with large-core infarction.
{"title":"Clinical Benefit of Thrombectomy in Large-Core Infarction Patients Is Mediated by Malignant Cerebral Edema Reduction.","authors":"Xiangjun Xu, Xu Xu, Jinfu Ma, Changwei Guo, Linyu Li, Jie Yang, Wenjie Zi, Wenzhe Sun, Xianjun Huang","doi":"10.1161/JAHA.125.044521","DOIUrl":"10.1161/JAHA.125.044521","url":null,"abstract":"<p><strong>Background: </strong>The impact of endovascular thrombectomy-mediated reperfusion on malignant cerebral edema (MCE) in large-core infarction remains unclear. We assessed the reperfusion-MCE relationship and MCE's mediating role in poor outcomes.</p><p><strong>Methods: </strong>This retrospective analysis used data from the national MAGIC (Prospective Multicenter Registry on Early Management of Acute Ischemic Stroke) registry (750 patients with large-core infarction, 38 Chinese centers, 2021-2023). MCE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 hours after stroke onset. Recanalization was confirmed by computed tomography angiogram or magnetic resonance angiogram during hospitalization in the overall cohorts. Successful reperfusion was defined using the modified Treatment in Cerebral Ischemia classification 2b-3 in the endovascular thrombectomy arm. Functional outcome was 90-day modified Rankin scale score. Mediation analysis used reperfusion status as the independent variable and MCE as the mediator.</p><p><strong>Results: </strong>Among 698 patients, (306 women [43.8%]; median age, 70 [interquartile range, 61-78] years; median, Alberta Stroke Program Early Computed Tomography] Scores, 4 [interquartile range, 2-5]), successful recanalization (adjusted odds ratio [aOR], 0.68 [95% CI, 0.47-0.99]; <i>P</i>=0.042) and reperfusion (aOR, 0.34 [95% CI, 0.18-0.67]; <i>P</i>=0.002) reduced MCE likelihood. MCE was partially responsible for worse modified Rankin Scale scores in patients without recanalization or reperfusion (MCE changed the logistic regression coefficients by 15.0% and 32.5%, respectively). Recanalization improved functional outcomes partly by mitigating MCE formation (indirect effect β=-0.10, 11.5% mediation proportion, <i>P</i>=0.028) in those with Alberta Stroke Program Early Computed Tomography Scores 3 to 5 but not in those with 0 to 2 (β=-0.26, <i>P</i>=0.140).</p><p><strong>Conclusions: </strong>Successful reperfusion attenuates MCE formation and improves clinical outcomes in patients with large-core infarction.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e044521"},"PeriodicalIF":5.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020671","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}