Pub Date : 2026-03-26DOI: 10.1161/CIR.0000000000001419
Kate Hanneman, Barrak Alahmad, Arnab Ghosh, Sameed Ahmed M Khatana, Mu Huang, Jingwen Liu, Azar Abadi, Haitham Khraishah, Theresa Beckie, Sanjay Rajagopalan, Sonia Angell
Ambient temperature is a key environmental driver of cardiovascular health. With rising global temperatures and increasing frequency, intensity, and duration of extreme temperature events, understanding the cardiovascular impacts of nonoptimal temperature is more urgent than ever. Short-term exposures to both heat and cold increase the risk of cardiovascular events, including myocardial infarction, stroke, heart failure decompensation, arrhythmias, and sudden cardiac death. Climate, built environment, socioeconomic variables, physiological vulnerability, and systemic inequities exacerbate these risks. There is also a growing appreciation of the importance of contextual factors such as geographic location, housing, occupation, and individual-level exposure. A range of biological mechanisms, including autonomic and neurohormonal activation, endothelial dysfunction, inflammation, hemoconcentration, and impaired thermoregulation, mediate temperature-related cardiovascular risk. Nonoptimal temperatures affect not only the incidence of cardiovascular disease but also health care access and delivery. They can increase demand for emergency care, disrupt operations, and pose challenges to the resilience and sustainability of health systems. Meanwhile, cardiovascular care contributes significantly to health care-related greenhouse gas emissions, highlighting a paradox in which efforts to protect cardiovascular health can indirectly contribute to climate-driven risks. This scientific statement synthesizes current knowledge of the relationship between nonoptimal temperature and cardiovascular health, highlights inequalities in exposure and outcomes, and identifies actionable strategies at the individual, community, health system, and public policy levels. Last, this scientific statement outlines significant research gaps and future priorities, including the need for improved exposure assessment, better understanding and measurement of the impact of long-term exposures, interactions with medications and coexposures, and identification of risk modifiers. Coordinated action is needed in research, clinical practice, and policy to mitigate the rising risks of nonoptimal temperatures on cardiovascular health in a changing climate.
{"title":"Nonoptimal Temperature and Cardiovascular Health: A Scientific Statement From the American Heart Association.","authors":"Kate Hanneman, Barrak Alahmad, Arnab Ghosh, Sameed Ahmed M Khatana, Mu Huang, Jingwen Liu, Azar Abadi, Haitham Khraishah, Theresa Beckie, Sanjay Rajagopalan, Sonia Angell","doi":"10.1161/CIR.0000000000001419","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001419","url":null,"abstract":"<p><p>Ambient temperature is a key environmental driver of cardiovascular health. With rising global temperatures and increasing frequency, intensity, and duration of extreme temperature events, understanding the cardiovascular impacts of nonoptimal temperature is more urgent than ever. Short-term exposures to both heat and cold increase the risk of cardiovascular events, including myocardial infarction, stroke, heart failure decompensation, arrhythmias, and sudden cardiac death. Climate, built environment, socioeconomic variables, physiological vulnerability, and systemic inequities exacerbate these risks. There is also a growing appreciation of the importance of contextual factors such as geographic location, housing, occupation, and individual-level exposure. A range of biological mechanisms, including autonomic and neurohormonal activation, endothelial dysfunction, inflammation, hemoconcentration, and impaired thermoregulation, mediate temperature-related cardiovascular risk. Nonoptimal temperatures affect not only the incidence of cardiovascular disease but also health care access and delivery. They can increase demand for emergency care, disrupt operations, and pose challenges to the resilience and sustainability of health systems. Meanwhile, cardiovascular care contributes significantly to health care-related greenhouse gas emissions, highlighting a paradox in which efforts to protect cardiovascular health can indirectly contribute to climate-driven risks. This scientific statement synthesizes current knowledge of the relationship between nonoptimal temperature and cardiovascular health, highlights inequalities in exposure and outcomes, and identifies actionable strategies at the individual, community, health system, and public policy levels. Last, this scientific statement outlines significant research gaps and future priorities, including the need for improved exposure assessment, better understanding and measurement of the impact of long-term exposures, interactions with medications and coexposures, and identification of risk modifiers. Coordinated action is needed in research, clinical practice, and policy to mitigate the rising risks of nonoptimal temperatures on cardiovascular health in a changing climate.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":38.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509993","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 : 2026-03-25DOI: 10.1161/CIRCULATIONAHA.125.078996
Shuang Li, Krishan Gupta, Rajul K Ranka, Alexander J Lu, Felix Naegele, Michael Graber, Kaylee N Carter, Lili Zhang, Arvind Bhimaraj, Li Lai, Anahita Mojiri, Keith A Youker, Kaifu Chen, John P Cooke
Background: Heart failure (HF) is a significant global health problem. Left ventricular assist device (LVAD) implantation serves as a bridge for patients awaiting heart transplantation. Intriguingly, LVAD support often improves cardiac histology and function, sometimes enough to avoid transplantation after LVAD removal. However, the cellular programs underlying this recovery remain unclear.
Methods: Myocardial tissues were obtained from patients with HF at the time of LVAD implantation (pre LVAD) and explantation (post LVAD) for histological analysis and single-nucleus RNA sequencing. A murine model of HF recovery, combined with lineage tracing studies, was employed to define cellular sources of vascular repair. Cardiac function, fibrosis, and vascular density were assessed using echocardiography, histology, and fluorescent microsphere perfusion. A patient-derived cardiac nonmyocyte culture system was established to interrogate mechanisms of cell fate regulation.
Results: Post-LVAD myocardial tissues exhibited reduced fibrosis and increased capillary density compared with pre-LVAD samples. Across samples, fibroblast abundance was inversely correlated with endothelial cell abundance, consistent with enhanced angiogenesis during recovery. Single-nucleus RNA sequencing identified a fibroblast subset predisposed to undergo mesenchymal-to-endothelial transition, acquiring an endothelial cell identity. Additionally, nonmyocytes from pre-LVAD hearts proliferated poorly and failed to form vascular structures, whereas nonmyocytes from post-LVAD hearts displayed greater proliferation and angiogenesis capacity, forming vessel-like structures, reinforcing the association of HF recovery with angiogenic reprogramming. Mechanistically, knockdown of c-Myc by siRNA shifted post-LVAD nonmyocytes to a pre-LVAD-like state, while c-Myc overexpression by mRNA in pre-LVAD cells induced a post-LVAD-like phenotype, implicating c-Myc as 1 contributor to this fate switch. A model of HF recovery in mice mimicked the histological and functional changes in patients, with physiological evidence of increased microvascular perfusion, associated with a fibroblast-to-endothelial transition, documented by lineage tracing.
Conclusions: HF recovery involves reduced fibrosis and enhanced microvascularization, partly driven by fibroblast-to-endothelial cell fate transition. c-Myc functions as 1 regulator of this transition, offering a mechanistic entry point to develop regenerative therapies in HF.
{"title":"Recovery From Heart Failure: Microvascular Mechanisms.","authors":"Shuang Li, Krishan Gupta, Rajul K Ranka, Alexander J Lu, Felix Naegele, Michael Graber, Kaylee N Carter, Lili Zhang, Arvind Bhimaraj, Li Lai, Anahita Mojiri, Keith A Youker, Kaifu Chen, John P Cooke","doi":"10.1161/CIRCULATIONAHA.125.078996","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.078996","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is a significant global health problem. Left ventricular assist device (LVAD) implantation serves as a bridge for patients awaiting heart transplantation. Intriguingly, LVAD support often improves cardiac histology and function, sometimes enough to avoid transplantation after LVAD removal. However, the cellular programs underlying this recovery remain unclear.</p><p><strong>Methods: </strong>Myocardial tissues were obtained from patients with HF at the time of LVAD implantation (pre LVAD) and explantation (post LVAD) for histological analysis and single-nucleus RNA sequencing. A murine model of HF recovery, combined with lineage tracing studies, was employed to define cellular sources of vascular repair. Cardiac function, fibrosis, and vascular density were assessed using echocardiography, histology, and fluorescent microsphere perfusion. A patient-derived cardiac nonmyocyte culture system was established to interrogate mechanisms of cell fate regulation.</p><p><strong>Results: </strong>Post-LVAD myocardial tissues exhibited reduced fibrosis and increased capillary density compared with pre-LVAD samples. Across samples, fibroblast abundance was inversely correlated with endothelial cell abundance, consistent with enhanced angiogenesis during recovery. Single-nucleus RNA sequencing identified a fibroblast subset predisposed to undergo mesenchymal-to-endothelial transition, acquiring an endothelial cell identity. Additionally, nonmyocytes from pre-LVAD hearts proliferated poorly and failed to form vascular structures, whereas nonmyocytes from post-LVAD hearts displayed greater proliferation and angiogenesis capacity, forming vessel-like structures, reinforcing the association of HF recovery with angiogenic reprogramming. Mechanistically, knockdown of c-Myc by siRNA shifted post-LVAD nonmyocytes to a pre-LVAD-like state, while c-Myc overexpression by mRNA in pre-LVAD cells induced a post-LVAD-like phenotype, implicating c-Myc as 1 contributor to this fate switch. A model of HF recovery in mice mimicked the histological and functional changes in patients, with physiological evidence of increased microvascular perfusion, associated with a fibroblast-to-endothelial transition, documented by lineage tracing.</p><p><strong>Conclusions: </strong>HF recovery involves reduced fibrosis and enhanced microvascularization, partly driven by fibroblast-to-endothelial cell fate transition. c-Myc functions as 1 regulator of this transition, offering a mechanistic entry point to develop regenerative therapies in HF.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":38.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509193","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 : 2026-03-25DOI: 10.1161/CIRCULATIONAHA.125.078152
Thomas M Glenn, Nadine A Kasparian, Shahnawaz Amdani, David Renaud, Michael V DiMaria, Jennifer Teh, David M Leone, Arjun K Mahendran, Nancy A Pike, Stephen J Dolgner, Andrew L Cheng, Rahul H Rathod, Sumeet S Vaikunth, Surendranath R Veeram Reddy, Rohith Vanam, Jeff Theobald, Kurt R Schumacher, Sarah A Hummel, Jennifer Conway, David J Goldberg, Dala Zakaria, Sarah B Clauss, Divya Suthar, Roni M Jacobsen, Evonne M Morell, John C Dykes, Angela J Weingarten, Deepti P Bhat, Benjamin E Reinking, Tarek Alsaied, Carole Lannon, Kiona Y Allen, Jeff B Anderson, Lacie B Patterson, David W Brown, Richard James, Jack Rychik, Alexander R Opotowsky
Background: Survival after Fontan palliation for single ventricle heart disease has improved substantially, yet the long-term trajectory remains poorly defined. The Fontan Outcomes Network, a learning health network of 38 congenital heart centers in the United States and Canada, was established to address this gap. We report baseline characteristics and early findings from the first 1121 participants enrolled in this prospective clinical registry.
Methods: We performed a cross-sectional analysis of individuals who had undergone Fontan palliation enrolled in the Fontan Outcomes Network from August 2022 through August 2024. Demographic, clinical, imaging, procedural, and medication data were analyzed descriptively, overall and by age group (<12, 12 to <18, and ≥18 years).
Results: A total of 1121 participants were enrolled (mean age, 16.3±10.2 years; 471 [42%] female). Hypoplastic left heart syndrome (n=431 [38.5%]) and right ventricular-dominant anatomy (n=615 [54.9%]) were the most common primary cardiac diagnoses, especially in younger age groups. Extracardiac conduit was the most frequent Fontan type (n=749 [66.8%]). Typical Fontan-related adverse events were noted in 59% of cases (n=662), including chylous pleural effusions (n=108 [9.6%]), Fontan thrombosis (n=79 [7.1%]), and nonperioperative stroke (n=73 [6.5%]). A history of arrhythmia was present in 41.3% of patients (n=463) overall, increasing with age. Acquired comorbidities were present in 57.5% of patients (n=645), including asthma (n=132 [12%]) and sleep apnea (n=103 [9%]), with burden increasing by age. Antithrombotic medication use was nearly universal. Use of other medications varied widely by age, and included β-blockers, angiotensin-converting enzyme inhibitors, and pulmonary vasodilators. A clinical diagnosis of an anxiety disorder was present in 34.1% of patients (n=382), including 48.1% of adults (n=194 of 403), and antidepressants were prescribed in 11.8% of patients (n=132), including 23.6% of adults (n=95 of 403), highlighting the mental health needs of this population.
Conclusions: The Fontan Outcomes Network includes one of the largest prospective, multi-institutional data sets of patients with Fontan circulation. These initial findings demonstrate the potential for a collaborative learning health network to advance research and quality improvement for this rare disease population.
{"title":"The Fontan Outcomes Network: Findings After 2 Years and 1121 Participants.","authors":"Thomas M Glenn, Nadine A Kasparian, Shahnawaz Amdani, David Renaud, Michael V DiMaria, Jennifer Teh, David M Leone, Arjun K Mahendran, Nancy A Pike, Stephen J Dolgner, Andrew L Cheng, Rahul H Rathod, Sumeet S Vaikunth, Surendranath R Veeram Reddy, Rohith Vanam, Jeff Theobald, Kurt R Schumacher, Sarah A Hummel, Jennifer Conway, David J Goldberg, Dala Zakaria, Sarah B Clauss, Divya Suthar, Roni M Jacobsen, Evonne M Morell, John C Dykes, Angela J Weingarten, Deepti P Bhat, Benjamin E Reinking, Tarek Alsaied, Carole Lannon, Kiona Y Allen, Jeff B Anderson, Lacie B Patterson, David W Brown, Richard James, Jack Rychik, Alexander R Opotowsky","doi":"10.1161/CIRCULATIONAHA.125.078152","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.078152","url":null,"abstract":"<p><strong>Background: </strong>Survival after Fontan palliation for single ventricle heart disease has improved substantially, yet the long-term trajectory remains poorly defined. The Fontan Outcomes Network, a learning health network of 38 congenital heart centers in the United States and Canada, was established to address this gap. We report baseline characteristics and early findings from the first 1121 participants enrolled in this prospective clinical registry.</p><p><strong>Methods: </strong>We performed a cross-sectional analysis of individuals who had undergone Fontan palliation enrolled in the Fontan Outcomes Network from August 2022 through August 2024. Demographic, clinical, imaging, procedural, and medication data were analyzed descriptively, overall and by age group (<12, 12 to <18, and ≥18 years).</p><p><strong>Results: </strong>A total of 1121 participants were enrolled (mean age, 16.3±10.2 years; 471 [42%] female). Hypoplastic left heart syndrome (n=431 [38.5%]) and right ventricular-dominant anatomy (n=615 [54.9%]) were the most common primary cardiac diagnoses, especially in younger age groups. Extracardiac conduit was the most frequent Fontan type (n=749 [66.8%]). Typical Fontan-related adverse events were noted in 59% of cases (n=662), including chylous pleural effusions (n=108 [9.6%]), Fontan thrombosis (n=79 [7.1%]), and nonperioperative stroke (n=73 [6.5%]). A history of arrhythmia was present in 41.3% of patients (n=463) overall, increasing with age. Acquired comorbidities were present in 57.5% of patients (n=645), including asthma (n=132 [12%]) and sleep apnea (n=103 [9%]), with burden increasing by age. Antithrombotic medication use was nearly universal. Use of other medications varied widely by age, and included β-blockers, angiotensin-converting enzyme inhibitors, and pulmonary vasodilators. A clinical diagnosis of an anxiety disorder was present in 34.1% of patients (n=382), including 48.1% of adults (n=194 of 403), and antidepressants were prescribed in 11.8% of patients (n=132), including 23.6% of adults (n=95 of 403), highlighting the mental health needs of this population.</p><p><strong>Conclusions: </strong>The Fontan Outcomes Network includes one of the largest prospective, multi-institutional data sets of patients with Fontan circulation. These initial findings demonstrate the potential for a collaborative learning health network to advance research and quality improvement for this rare disease population.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":38.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509692","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 : 2026-03-24Epub Date: 2026-03-02DOI: 10.1161/CIRCULATIONAHA.125.074748
Ivo Roca-Luque, Paz Garre, Sara Vázquez-Calvo, José Tomás Ortiz-Pérez, Susana Prat-González, Rosario Jesús Perea, Pasquale Valerio Falzone, Jean-Baptiste Guichard, Mariona Regany-Closa, Till F Althoff, Eduard Guasch, Jose María Tolosana, Elena Arbelo, Paula Sánchez-Somonte, Levio Quinto, Roger Borràs, Rebeca Domingo, Mireia Niebla, Ana García-Alvarez, Marta Sitges, Josep Brugada, Lluís Mont, Andreu Porta-Sánchez
<p><strong>Background: </strong>Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is useful for identifying ventricular tachycardia (VT) substrate in patients with structural heart disease. While preprocedural LGE-CMR is widely used for planning, the role of postprocedural LGE-CMR in evaluating VT ablation success and long-term scar evolution has been less explored. This study aimed to prospectively and systematically assess the long-term evolution of scar and ablation lesions using serial postablation LGE-CMR with long-term follow-up.</p><p><strong>Methods: </strong>This prospective study included 51 patients (mean age, 65.2±9.8 years; men, 95.8%; ischemic heart disease, 83%; left ventricular ejection fraction, 34.5±10.4%) undergoing their first substrate-based VT ablation between March 2019 and July 2020. Preprocedural LGE-CMR and 2 postprocedural scans at 3 to 6 months (CMR-1) and 18 to 24 months (CMR-2) were performed. Scar characteristics, including core scar, border zone, and conducting channels, were analyzed. VT recurrence was monitored, and factors associated with recurrence were evaluated using a Cox proportional hazards model. A Kaplan-Meier curve was used to represent the VT-free survival function.</p><p><strong>Results: </strong>Core scar mass increased significantly from baseline to CMR-1 (12.2±1.5 to 19.8±1.6 g, <i>P</i><0.01) and remained stable at CMR-2. In contrast, the border zone decreased significantly over time (pre, 25.3±1.8 g; CMR-1, 20.8±2.0 g; CMR-2, 16.7±2.1 g; <i>P</i><0.01). A significant decrease in conducting channels was noted after ablation and persisted at CMR-2 (pre, mean 2.4±0.2/median 2 [interquartile range, 1-3]; CMR-1, mean 1.4±0.2/median 1 [interquartile range, 0-1]; CMR-2, mean 1.6±1.0/median 1 [interquartile range, 0-1]; <i>P</i><0.001). VT recurrence occurred in 29.4% of patients during a median follow-up of 3.1 years. The number of conducting channels at CMR-1 and their relative reduction from baseline were related to VT recurrence. The persistence of 2 or more conducting channels at CMR-1 was associated with a higher recurrence rate: 75.6 versus 19.5% (hazard ratio [HR]; 4.1; 95% CI, 2.4-12.1; <i>P</i>=0.012). Evidence of favorable left ventricular remodeling was observed, with a significant reduction in left ventricular volume at CMR-2 (131.8±8.6 mL; CMR-1, 156.7±8.1 mL and 160.8±7.6 mL at baseline <0.01).</p><p><strong>Conclusions: </strong>Postablation LGE-CMR reveals durable changes in scar characteristics, with early scar evaluation at 3 to 6 months strongly associated with long-term VT recurrence. The reduction in scar heterogeneity and conducting channels is sustained over time, underscoring the usefulness of LGE-CMR for assessing ablation success. Additionally, VT ablation appeared to be associated with favorable reverse remodeling, highlighting potential benefits beyond arrhythmia control. These findings support the use of LGE-CMR for personalized management following VT ablatio
{"title":"PAM-VT 2 Study: Long-Term Scar Evolution and Ablation Lesion Assessment by Late Gadolinium Enhancement Cardiac Magnetic Resonance After Ventricular Tachycardia Ablation.","authors":"Ivo Roca-Luque, Paz Garre, Sara Vázquez-Calvo, José Tomás Ortiz-Pérez, Susana Prat-González, Rosario Jesús Perea, Pasquale Valerio Falzone, Jean-Baptiste Guichard, Mariona Regany-Closa, Till F Althoff, Eduard Guasch, Jose María Tolosana, Elena Arbelo, Paula Sánchez-Somonte, Levio Quinto, Roger Borràs, Rebeca Domingo, Mireia Niebla, Ana García-Alvarez, Marta Sitges, Josep Brugada, Lluís Mont, Andreu Porta-Sánchez","doi":"10.1161/CIRCULATIONAHA.125.074748","DOIUrl":"10.1161/CIRCULATIONAHA.125.074748","url":null,"abstract":"<p><strong>Background: </strong>Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is useful for identifying ventricular tachycardia (VT) substrate in patients with structural heart disease. While preprocedural LGE-CMR is widely used for planning, the role of postprocedural LGE-CMR in evaluating VT ablation success and long-term scar evolution has been less explored. This study aimed to prospectively and systematically assess the long-term evolution of scar and ablation lesions using serial postablation LGE-CMR with long-term follow-up.</p><p><strong>Methods: </strong>This prospective study included 51 patients (mean age, 65.2±9.8 years; men, 95.8%; ischemic heart disease, 83%; left ventricular ejection fraction, 34.5±10.4%) undergoing their first substrate-based VT ablation between March 2019 and July 2020. Preprocedural LGE-CMR and 2 postprocedural scans at 3 to 6 months (CMR-1) and 18 to 24 months (CMR-2) were performed. Scar characteristics, including core scar, border zone, and conducting channels, were analyzed. VT recurrence was monitored, and factors associated with recurrence were evaluated using a Cox proportional hazards model. A Kaplan-Meier curve was used to represent the VT-free survival function.</p><p><strong>Results: </strong>Core scar mass increased significantly from baseline to CMR-1 (12.2±1.5 to 19.8±1.6 g, <i>P</i><0.01) and remained stable at CMR-2. In contrast, the border zone decreased significantly over time (pre, 25.3±1.8 g; CMR-1, 20.8±2.0 g; CMR-2, 16.7±2.1 g; <i>P</i><0.01). A significant decrease in conducting channels was noted after ablation and persisted at CMR-2 (pre, mean 2.4±0.2/median 2 [interquartile range, 1-3]; CMR-1, mean 1.4±0.2/median 1 [interquartile range, 0-1]; CMR-2, mean 1.6±1.0/median 1 [interquartile range, 0-1]; <i>P</i><0.001). VT recurrence occurred in 29.4% of patients during a median follow-up of 3.1 years. The number of conducting channels at CMR-1 and their relative reduction from baseline were related to VT recurrence. The persistence of 2 or more conducting channels at CMR-1 was associated with a higher recurrence rate: 75.6 versus 19.5% (hazard ratio [HR]; 4.1; 95% CI, 2.4-12.1; <i>P</i>=0.012). Evidence of favorable left ventricular remodeling was observed, with a significant reduction in left ventricular volume at CMR-2 (131.8±8.6 mL; CMR-1, 156.7±8.1 mL and 160.8±7.6 mL at baseline <0.01).</p><p><strong>Conclusions: </strong>Postablation LGE-CMR reveals durable changes in scar characteristics, with early scar evaluation at 3 to 6 months strongly associated with long-term VT recurrence. The reduction in scar heterogeneity and conducting channels is sustained over time, underscoring the usefulness of LGE-CMR for assessing ablation success. Additionally, VT ablation appeared to be associated with favorable reverse remodeling, highlighting potential benefits beyond arrhythmia control. These findings support the use of LGE-CMR for personalized management following VT ablatio","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"874-886"},"PeriodicalIF":38.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324820","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: Tissue-specific regulatory T cells (Tregs) accumulate in the heart after myocardial infarction (MI) and play a vital role in limiting inflammation and promoting tissue repair. However, the developmental trajectory of heart Tregs and the molecular cues that guide their recruitment to the heart remain poorly understood, impeding therapeutic strategies that leverage Treg-mediated cardiac protection.
Methods: We used single-cell and bulk RNA sequencing in a murine MI model to delineate the differentiation trajectory of Tregs from mediastinal lymph nodes to the heart. Functional validation was performed using Treg-specific Ccr8 (CC motif chemokine receptor 8) knockout mice (Ccr8flox/floxFoxp3Cre), Ccl1 (CC motif chemokine ligand 1) knockout mice (Ccl1-/-), macrophage-targeted Ccl1 knockdown mice, Ccl1-overexpressing mice, and DEREG mice. The CCL1-CCR8 axis was evaluated in cardiac tissues and circulating blood from patients with MI.
Results: Single-cell RNA sequencing revealed a stepwise differentiation of mediastinal lymph node-derived naive Tregs into heart Tregs, marked by the progressive acquisition of CCR8 expression and reparative capacity. CCR8+ Tregs in the heart exhibited enhanced immunosuppressive and tissue-repair signatures. Treg-specific Ccr8 deletion led to reduced Treg accumulation and worsened cardiac function after MI, along with increased proinflammatory macrophage features and number of CD8+ T cells and natural killer cells. In addition, Tregs promoted a shift of macrophages toward an anti-inflammatory phenotype by secreting IL-1R2 (interleukin 1 receptor, type 2). We identified cardiac macrophages as the main source of CCL1, which was essential for CCR8+ Treg recruitment. Ccl1 deficiency or macrophage-specific Ccl1 knockdown impaired Treg infiltration and aggravated ventricular remodeling; Ccl1 overexpression promoted Treg recruitment and improved cardiac outcomes. Moreover, the cardioprotective effects of CCL1 were abolished in DEREG mice upon Treg depletion and Ccr8flox/floxFoxp3Cre mice, establishing a CCR8+ Treg-dependent mechanism. Furthermore, circulating CCR8+ Tregs and cardiac CCL1 were elevated in humans with MI, and the presence of CCR8+ Tregs and CCL1-expressing macrophages was confirmed in the hearts of patients with MI, suggesting important clinical relevance.
Conclusions: Our findings reveal a 2-phase Treg specialization process and establish the CCL1-CCR8 axis as a crucial pathway for Treg recruitment and function in the infarcted heart. Therapeutic targeting of this axis may improve immune-regulated cardiac repair after MI.
{"title":"CCR8 Expression on Regulatory T Cells Reveals Trajectories of Tissue Adaptation and Protects Against Myocardial Infarction-Induced Tissue Damage.","authors":"Nana Li, Zhiheng Hao, Haoyi Yang, Jie Cai, Meilin Liu, Junyi He, Rui Gao, Yuhan Shen, Zhehao Chen, Yuzhi Lu, Tingting Tang, Min Zhang, Jiao Jiao, Fen Yang, Jingyong Li, Muyang Gu, Desheng Hu, Weimin Wang, Qing Wang, Chen Chen, Zhilei Shan, Ni Xia, Xiang Cheng","doi":"10.1161/CIRCULATIONAHA.125.076426","DOIUrl":"10.1161/CIRCULATIONAHA.125.076426","url":null,"abstract":"<p><strong>Background: </strong>Tissue-specific regulatory T cells (Tregs) accumulate in the heart after myocardial infarction (MI) and play a vital role in limiting inflammation and promoting tissue repair. However, the developmental trajectory of heart Tregs and the molecular cues that guide their recruitment to the heart remain poorly understood, impeding therapeutic strategies that leverage Treg-mediated cardiac protection.</p><p><strong>Methods: </strong>We used single-cell and bulk RNA sequencing in a murine MI model to delineate the differentiation trajectory of Tregs from mediastinal lymph nodes to the heart. Functional validation was performed using Treg-specific <i>Ccr8</i> (CC motif chemokine receptor 8) knockout mice (<i>Ccr8</i><sup>flox/flox</sup><i>Foxp3</i><sup>Cre</sup>), <i>Ccl1</i> (CC motif chemokine ligand 1) knockout mice (<i>Ccl1</i><sup>-/-</sup>), macrophage-targeted <i>Ccl1</i> knockdown mice, <i>Ccl1</i>-overexpressing mice, and DEREG mice. The CCL1-CCR8 axis was evaluated in cardiac tissues and circulating blood from patients with MI.</p><p><strong>Results: </strong>Single-cell RNA sequencing revealed a stepwise differentiation of mediastinal lymph node-derived naive Tregs into heart Tregs, marked by the progressive acquisition of CCR8 expression and reparative capacity. CCR8<sup>+</sup> Tregs in the heart exhibited enhanced immunosuppressive and tissue-repair signatures. Treg-specific <i>Ccr8</i> deletion led to reduced Treg accumulation and worsened cardiac function after MI, along with increased proinflammatory macrophage features and number of CD8<sup>+</sup> T cells and natural killer cells. In addition, Tregs promoted a shift of macrophages toward an anti-inflammatory phenotype by secreting IL-1R2 (interleukin 1 receptor, type 2). We identified cardiac macrophages as the main source of CCL1, which was essential for CCR8<sup>+</sup> Treg recruitment. <i>Ccl1</i> deficiency or macrophage-specific <i>Ccl1</i> knockdown impaired Treg infiltration and aggravated ventricular remodeling; <i>Ccl1</i> overexpression promoted Treg recruitment and improved cardiac outcomes. Moreover, the cardioprotective effects of CCL1 were abolished in DEREG mice upon Treg depletion and <i>Ccr8</i><sup>flox/flox</sup><i>Foxp3</i><sup>Cre</sup> mice, establishing a CCR8<sup>+</sup> Treg-dependent mechanism. Furthermore, circulating CCR8<sup>+</sup> Tregs and cardiac CCL1 were elevated in humans with MI, and the presence of CCR8<sup>+</sup> Tregs and CCL1-expressing macrophages was confirmed in the hearts of patients with MI, suggesting important clinical relevance.</p><p><strong>Conclusions: </strong>Our findings reveal a 2-phase Treg specialization process and establish the CCL1-CCR8 axis as a crucial pathway for Treg recruitment and function in the infarcted heart. Therapeutic targeting of this axis may improve immune-regulated cardiac repair after MI.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"922-940"},"PeriodicalIF":38.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178163","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 : 2026-03-24Epub Date: 2026-02-19DOI: 10.1161/CIR.0000000000001415
Mark A Creager, Geoffrey D Barnes, Jay Giri, Debabrata Mukherjee, William Schuyler Jones, Allison E Burnett, Teresa Carman, Ana I Casanegra, Lana A Castellucci, Sherrell M Clark, Mary Cushman, Kerstin de Wit, Jennifer M Eaves, Margaret C Fang, Joshua B Goldberg, Stanislav Henkin, Hillary Johnston-Cox, Sabeeda Kadavath, Daniella Kadian-Dodov, William Brent Keeling, Andrew J P Klein, Jun Li, Michael C McDaniel, Lisa K Moores, Gregory Piazza, Karen S Prenger, Steven C Pugliese, Mona Ranade, Rachel P Rosovsky, Farla Russo, Eric A Secemsky, Akhilesh K Sista, Leben Tefera, Ido Weinberg, Lauren M Westafer, Michael N Young
Aim: The "2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults" is a de novo guideline that provides comprehensive recommendations for the evaluation, management, and follow-up of adult patients (≥18 years of age) with acute pulmonary embolism (PE). A key feature of this guideline is the introduction of the AHA/ACC Acute Pulmonary Embolism Clinical Categories, which enhance the precision of severity classification, prognosis assessment, and evidence-based therapeutic decision-making.
Methods: A comprehensive literature search was conducted from February 2024 to October 2024 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Select key studies published until April 2025 were added by the guideline writing committee as appropriate.
Structure: The focus of this clinical practice guideline is an evidence-based and patient-centered approach for acute PE evaluation and management of the adult patient. This guideline encompasses the period from the onset of symptoms through clinical follow-up, focusing on risk outcomes assessment, clinical diagnosis of acute PE, appropriate use of adjunctive cardiovascular testing, and management in both the acute and early post-acute phases of PE. It addresses evidence-based diagnostic and management strategies (including pharmacological therapies, advanced interventional therapies, and in-hospital support) for acute PE and associated outcomes.
{"title":"2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.","authors":"Mark A Creager, Geoffrey D Barnes, Jay Giri, Debabrata Mukherjee, William Schuyler Jones, Allison E Burnett, Teresa Carman, Ana I Casanegra, Lana A Castellucci, Sherrell M Clark, Mary Cushman, Kerstin de Wit, Jennifer M Eaves, Margaret C Fang, Joshua B Goldberg, Stanislav Henkin, Hillary Johnston-Cox, Sabeeda Kadavath, Daniella Kadian-Dodov, William Brent Keeling, Andrew J P Klein, Jun Li, Michael C McDaniel, Lisa K Moores, Gregory Piazza, Karen S Prenger, Steven C Pugliese, Mona Ranade, Rachel P Rosovsky, Farla Russo, Eric A Secemsky, Akhilesh K Sista, Leben Tefera, Ido Weinberg, Lauren M Westafer, Michael N Young","doi":"10.1161/CIR.0000000000001415","DOIUrl":"10.1161/CIR.0000000000001415","url":null,"abstract":"<p><strong>Aim: </strong>The \"2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults\" is a de novo guideline that provides comprehensive recommendations for the evaluation, management, and follow-up of adult patients (≥18 years of age) with acute pulmonary embolism (PE). A key feature of this guideline is the introduction of the AHA/ACC Acute Pulmonary Embolism Clinical Categories, which enhance the precision of severity classification, prognosis assessment, and evidence-based therapeutic decision-making.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted from February 2024 to October 2024 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Select key studies published until April 2025 were added by the guideline writing committee as appropriate.</p><p><strong>Structure: </strong>The focus of this clinical practice guideline is an evidence-based and patient-centered approach for acute PE evaluation and management of the adult patient. This guideline encompasses the period from the onset of symptoms through clinical follow-up, focusing on risk outcomes assessment, clinical diagnosis of acute PE, appropriate use of adjunctive cardiovascular testing, and management in both the acute and early post-acute phases of PE. It addresses evidence-based diagnostic and management strategies (including pharmacological therapies, advanced interventional therapies, and in-hospital support) for acute PE and associated outcomes.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e977-e1051"},"PeriodicalIF":38.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225720","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 : 2026-03-24Epub Date: 2026-02-06DOI: 10.1161/CIRCULATIONAHA.125.074318
Song Sun, Xuan Zhang, Hongwei Yue, Cuiqin Fan, Yi Zhang, Yunyun Guo, Xingming Li, Sumei Cui, Kehui Yang, Xiangkai Zhao, Cheng Zhang, Chang Pan, Feng Xu, Yuguo Chen
<p><strong>Background: </strong>Acute myocardial infarction (AMI) caused by thrombosis is a major cause of mortality. A polymorphism in <i>Aldh2</i> gene (rs671) is found in approximately 30% to 50% of East Asians, and it is a risk factor for AMI. This mutation impairs aldehyde dehydrogenase 2 (ALDH2) function, but the effect of ALDH2 on platelet activation and thrombosis is unknown.</p><p><strong>Methods: </strong>Platelets were isolated from platelet-specific <i>Aldh2</i> knockout (<i>Aldh2</i><sup>-/-</sup>) and ALDH2<sup>E506K</sup> knock-in mice (which corresponds to human <i>Aldh2</i> rs671 gene mutation), as well as from healthy human donors with the <i>Aldh2</i> rs671. Arterial thrombosis was measured in a FeCl<sub>3</sub>-induced thrombosis mouse model. The efficacy of Alda-1, an ALDH2 activator, in mitigating thrombogenesis was measured in ALDH2<sup>E506K</sup> mice. Using a murine model of myocardial infarction (MI) model, we analyzed the effects of platelet <i>Aldh2</i> on micro-thrombosis and infarct expansion post-MI. In addition, we enrolled 118 patients of different <i>Aldh2</i> rs671 genotypes (GG, GA, and AA) diagnosed with ST elevation myocardial infarction (STEMI) to analyze the association between rs671 genotype and platelet activation and thrombosis.</p><p><strong>Results: </strong>Platelets from <i>Aldh</i>2<sup>-/-</sup> and ALDH2<sup>E506K</sup> mice showed enhanced agonist induced aggregation, ATP release, integrin αIIbβ3 activation, P-selectin release, spreading, and clot retraction. Human platelets with the <i>Aldh2</i> rs671 variant also exhibited increased activation. Mutation of <i>Aldh2</i> or platelet-specific knockout of <i>Aldh2</i> exacerbated thrombus formation in a mouse model of thrombosis. The ALDH2 activator, Alda-1, reduced thrombosis in ALDH2<sup>E506K</sup> mice. We explored pathways mediating the effect of <i>Aldh2</i> on platelet activation. We found that platelets lacking <i>Aldh2</i> produced more reactive oxygen species (ROS) and less nitric oxide (NO) than wild-type platelets. Furthermore, platelets lacking <i>Aldh2</i> are also more susceptible to activation by aldehydes. Additionally, platelets from mice lacking <i>Aldh2</i> had increased elevated mitophagy and hyperactivity. ACAD10 mediated some of the effects of ALDH2 on mitophagy. Mice lacking <i>Aldh2</i> had increased micro-thrombosis and myocardial infarct expansion. Finally, elevated platelet activation and thrombus markers were also observed in plasma from patients with STEMI patients who had the rs671 variant.</p><p><strong>Conclusions: </strong>The <i>Aldh2</i> rs671 variant, which impairs ALDH2 function, increases platelet activation and thrombus formation in vivo through aldehyde accumulation and ROS buildup. Abnormal ACAD10 homeostasis might also contribute to this hyperactivity via enhancing platelet mitophagy. Our findings suggest the potential of ALDH2 as a novel antiplatelet target. Future studies are needed to explore the effec
{"title":"The Aldehyde Dehydrogenase 2 rs671 Variant Enhances Platelet Activation and Arterial Thrombosis.","authors":"Song Sun, Xuan Zhang, Hongwei Yue, Cuiqin Fan, Yi Zhang, Yunyun Guo, Xingming Li, Sumei Cui, Kehui Yang, Xiangkai Zhao, Cheng Zhang, Chang Pan, Feng Xu, Yuguo Chen","doi":"10.1161/CIRCULATIONAHA.125.074318","DOIUrl":"10.1161/CIRCULATIONAHA.125.074318","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) caused by thrombosis is a major cause of mortality. A polymorphism in <i>Aldh2</i> gene (rs671) is found in approximately 30% to 50% of East Asians, and it is a risk factor for AMI. This mutation impairs aldehyde dehydrogenase 2 (ALDH2) function, but the effect of ALDH2 on platelet activation and thrombosis is unknown.</p><p><strong>Methods: </strong>Platelets were isolated from platelet-specific <i>Aldh2</i> knockout (<i>Aldh2</i><sup>-/-</sup>) and ALDH2<sup>E506K</sup> knock-in mice (which corresponds to human <i>Aldh2</i> rs671 gene mutation), as well as from healthy human donors with the <i>Aldh2</i> rs671. Arterial thrombosis was measured in a FeCl<sub>3</sub>-induced thrombosis mouse model. The efficacy of Alda-1, an ALDH2 activator, in mitigating thrombogenesis was measured in ALDH2<sup>E506K</sup> mice. Using a murine model of myocardial infarction (MI) model, we analyzed the effects of platelet <i>Aldh2</i> on micro-thrombosis and infarct expansion post-MI. In addition, we enrolled 118 patients of different <i>Aldh2</i> rs671 genotypes (GG, GA, and AA) diagnosed with ST elevation myocardial infarction (STEMI) to analyze the association between rs671 genotype and platelet activation and thrombosis.</p><p><strong>Results: </strong>Platelets from <i>Aldh</i>2<sup>-/-</sup> and ALDH2<sup>E506K</sup> mice showed enhanced agonist induced aggregation, ATP release, integrin αIIbβ3 activation, P-selectin release, spreading, and clot retraction. Human platelets with the <i>Aldh2</i> rs671 variant also exhibited increased activation. Mutation of <i>Aldh2</i> or platelet-specific knockout of <i>Aldh2</i> exacerbated thrombus formation in a mouse model of thrombosis. The ALDH2 activator, Alda-1, reduced thrombosis in ALDH2<sup>E506K</sup> mice. We explored pathways mediating the effect of <i>Aldh2</i> on platelet activation. We found that platelets lacking <i>Aldh2</i> produced more reactive oxygen species (ROS) and less nitric oxide (NO) than wild-type platelets. Furthermore, platelets lacking <i>Aldh2</i> are also more susceptible to activation by aldehydes. Additionally, platelets from mice lacking <i>Aldh2</i> had increased elevated mitophagy and hyperactivity. ACAD10 mediated some of the effects of ALDH2 on mitophagy. Mice lacking <i>Aldh2</i> had increased micro-thrombosis and myocardial infarct expansion. Finally, elevated platelet activation and thrombus markers were also observed in plasma from patients with STEMI patients who had the rs671 variant.</p><p><strong>Conclusions: </strong>The <i>Aldh2</i> rs671 variant, which impairs ALDH2 function, increases platelet activation and thrombus formation in vivo through aldehyde accumulation and ROS buildup. Abnormal ACAD10 homeostasis might also contribute to this hyperactivity via enhancing platelet mitophagy. Our findings suggest the potential of ALDH2 as a novel antiplatelet target. Future studies are needed to explore the effec","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"902-921"},"PeriodicalIF":38.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124162","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 : 2026-03-24Epub Date: 2026-02-10DOI: 10.1161/CIRCULATIONAHA.125.075875
Mahesh V Madhavan, John Gregson, Bjorn Redfors, Shmuel Chen, Joseph F Sabik, Akiko Fujino, Lak N Kotinkaduwa, Dimitri Karmpaliotis, Jeffrey W Moses, Ori Ben-Yehuda, Patrick W Serruys, Stuart Pocock, A Pieter Kappetein, Akiko Maehara, Gregg W Stone
Background: Limited data are available regarding the relative rates, etiology, and long-term prognostic implications of spontaneous myocardial infarction (MI) after percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery for left main coronary artery disease (LMCAD).
Methods: MIs after PCI and CABG for LMCAD were adjudicated from the EXCEL trial (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Cox proportional hazards regression was performed to assess the association between spontaneous (and procedural) MI and cardiovascular and all-cause mortality at 5 years.
Results: Among 1882 patients who underwent LMCAD revascularization, spontaneous MI during 5-year follow-up occurred in 60 (6.8%) patients after PCI and in 29 (3.4%) patients after CABG (adjusted hazard ratio [adjHR], 2.01; 95 CI, 1.29-3.15; P=0.002). By multivariable analysis, spontaneous MI (as a time-adjusted covariate) was a strong independent predictor of subsequent cardiovascular mortality (adjHR, 9.39; 95% CI, 5.22-16.87) and all-cause mortality (adjHR, 4.77; 95% CI, 2.92-7.80) within 5 years, with consistent effects after PCI and CABG (Pinteraction=0.60 and 0.78, respectively). In the same models, procedural MI as defined by extensive myonecrosis was associated with 5-year cardiovascular (adjHR, 3.02; 95% CI, 1.64-5.56) and all-cause mortality (adjHR, 2.38; 95% CI, 1.48-3.80), with consistent effects after PCI and CABG (Pinteraction=0.23 and 0.34, respectively).
Conclusions: In the EXCEL trial, spontaneous MI occurred relatively infrequently within 5 years after LMCAD revascularization but at a higher rate after PCI compared with CABG. Spontaneous MI after revascularization was strongly related to subsequent cardiovascular and all-cause mortality, consistently after PCI and CABG, and was more strongly associated with mortality than was large procedural MI.
{"title":"Spontaneous Myocardial Infarction After Left Main Revascularization: The EXCEL Trial.","authors":"Mahesh V Madhavan, John Gregson, Bjorn Redfors, Shmuel Chen, Joseph F Sabik, Akiko Fujino, Lak N Kotinkaduwa, Dimitri Karmpaliotis, Jeffrey W Moses, Ori Ben-Yehuda, Patrick W Serruys, Stuart Pocock, A Pieter Kappetein, Akiko Maehara, Gregg W Stone","doi":"10.1161/CIRCULATIONAHA.125.075875","DOIUrl":"10.1161/CIRCULATIONAHA.125.075875","url":null,"abstract":"<p><strong>Background: </strong>Limited data are available regarding the relative rates, etiology, and long-term prognostic implications of spontaneous myocardial infarction (MI) after percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery for left main coronary artery disease (LMCAD).</p><p><strong>Methods: </strong>MIs after PCI and CABG for LMCAD were adjudicated from the EXCEL trial (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Cox proportional hazards regression was performed to assess the association between spontaneous (and procedural) MI and cardiovascular and all-cause mortality at 5 years.</p><p><strong>Results: </strong>Among 1882 patients who underwent LMCAD revascularization, spontaneous MI during 5-year follow-up occurred in 60 (6.8%) patients after PCI and in 29 (3.4%) patients after CABG (adjusted hazard ratio [adjHR], 2.01; 95 CI, 1.29-3.15; <i>P</i>=0.002). By multivariable analysis, spontaneous MI (as a time-adjusted covariate) was a strong independent predictor of subsequent cardiovascular mortality (adjHR, 9.39; 95% CI, 5.22-16.87) and all-cause mortality (adjHR, 4.77; 95% CI, 2.92-7.80) within 5 years, with consistent effects after PCI and CABG (<i>P</i><sub>interaction</sub>=0.60 and 0.78, respectively). In the same models, procedural MI as defined by extensive myonecrosis was associated with 5-year cardiovascular (adjHR, 3.02; 95% CI, 1.64-5.56) and all-cause mortality (adjHR, 2.38; 95% CI, 1.48-3.80), with consistent effects after PCI and CABG (<i>P</i><sub>interaction</sub>=0.23 and 0.34, respectively).</p><p><strong>Conclusions: </strong>In the EXCEL trial, spontaneous MI occurred relatively infrequently within 5 years after LMCAD revascularization but at a higher rate after PCI compared with CABG. Spontaneous MI after revascularization was strongly related to subsequent cardiovascular and all-cause mortality, consistently after PCI and CABG, and was more strongly associated with mortality than was large procedural MI.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01205776.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"890-901"},"PeriodicalIF":38.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149300","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 : 2026-03-23DOI: 10.1161/circulationaha.126.078841
Andrew E Arai,Ravi Ranjan
{"title":"Cardiac Magnetic Resonance Before Ventricular Tachycardia Ablation and During Follow-Up.","authors":"Andrew E Arai,Ravi Ranjan","doi":"10.1161/circulationaha.126.078841","DOIUrl":"https://doi.org/10.1161/circulationaha.126.078841","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"6 1","pages":"887-889"},"PeriodicalIF":37.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502462","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 : 2026-03-23DOI: 10.1161/circulationaha.125.075712
Anthony Y Zhu,Maggie S Chen,Annika M T Braun,Laura Ben Driss,Elizabeth K Griffin,Undine-Sophie Deumer,Angie Delgado,Niranjana Natarajan,Khanh Ha,Yuriy Milobog,Maddelyn Hoehn,Jason R McCarthy,Richard T Lee
{"title":"Epicardial Complement C3 Activation in Neonatal Cardiac Regeneration.","authors":"Anthony Y Zhu,Maggie S Chen,Annika M T Braun,Laura Ben Driss,Elizabeth K Griffin,Undine-Sophie Deumer,Angie Delgado,Niranjana Natarajan,Khanh Ha,Yuriy Milobog,Maddelyn Hoehn,Jason R McCarthy,Richard T Lee","doi":"10.1161/circulationaha.125.075712","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075712","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"31 1","pages":"941-944"},"PeriodicalIF":37.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502460","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}