Pub Date : 2026-01-12DOI: 10.1161/circulationaha.125.078644
Maryjane Farr,Joseph A Hill
{"title":"François Abboud: Pioneer, Mentor, and Friend to Many.","authors":"Maryjane Farr,Joseph A Hill","doi":"10.1161/circulationaha.125.078644","DOIUrl":"https://doi.org/10.1161/circulationaha.125.078644","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"1 1","pages":"69-70"},"PeriodicalIF":37.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956205","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 : 2026-01-12DOI: 10.1161/circulationaha.125.075210
Shiyu Yang,Ying Lu
{"title":"Letter by Yang and Lu Regarding Article, \"Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes\".","authors":"Shiyu Yang,Ying Lu","doi":"10.1161/circulationaha.125.075210","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075210","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"4 1","pages":"e4-e5"},"PeriodicalIF":37.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956035","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 : 2026-01-12DOI: 10.1161/circulationaha.125.077517
Weiyi Tan,Jamil Aboulhosn
{"title":"When Less Is More: Is It Time for a New Gold Standard?","authors":"Weiyi Tan,Jamil Aboulhosn","doi":"10.1161/circulationaha.125.077517","DOIUrl":"https://doi.org/10.1161/circulationaha.125.077517","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"51 1","pages":"82-85"},"PeriodicalIF":37.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956204","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 : 2026-01-12DOI: 10.1161/circulationaha.125.076926
Dilip Thomas,Amit Manhas,Yu Liu,Ravichandra Venkateshappa,Nadjet Belbachir,Shane R Zhao,Cody Juguilon,Ian Y Chen,Javid Moslehi,Nazish Sayed,Joseph C Wu
{"title":"Profiling Immune-Independent Response to Immune Checkpoint Inhibitors on Stem Cell-Derived Cardiomyocytes, Organoids, and Mouse Models.","authors":"Dilip Thomas,Amit Manhas,Yu Liu,Ravichandra Venkateshappa,Nadjet Belbachir,Shane R Zhao,Cody Juguilon,Ian Y Chen,Javid Moslehi,Nazish Sayed,Joseph C Wu","doi":"10.1161/circulationaha.125.076926","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076926","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"1 1","pages":"132-135"},"PeriodicalIF":37.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956034","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}
Many patients with severe aortic stenosis present with concomitant multivalvular heart disease. The management of this condition remains challenging and requires a multidisciplinary approach that integrates clinical, hemodynamic, and multimodality imaging data to define the most effective and durable treatment strategy. Although randomized evidence to guide treatment decisions in this setting is limited, percutaneous interventions to address additional valvular lesions are being increasingly adopted. This review provides an overview of the pathophysiology of valvular diseases commonly associated with severe aortic stenosis, highlighting their prognostic implications after surgical or transcatheter treatment and their impact on risk stratification and therapeutic management.
{"title":"Multivalve Involvement in Aortic Stenosis: Insights From a Narrative Review.","authors":"Quentin Battistolo,Marisa Avvedimento,Patrice Guerin,Pierre Yves Turgeon,Mathieu Bernier,Michael J Mack,Patrick O'Gara,Josep Rodés-Cabau","doi":"10.1161/circulationaha.125.075978","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075978","url":null,"abstract":"Many patients with severe aortic stenosis present with concomitant multivalvular heart disease. The management of this condition remains challenging and requires a multidisciplinary approach that integrates clinical, hemodynamic, and multimodality imaging data to define the most effective and durable treatment strategy. Although randomized evidence to guide treatment decisions in this setting is limited, percutaneous interventions to address additional valvular lesions are being increasingly adopted. This review provides an overview of the pathophysiology of valvular diseases commonly associated with severe aortic stenosis, highlighting their prognostic implications after surgical or transcatheter treatment and their impact on risk stratification and therapeutic management.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"250 1","pages":"115-131"},"PeriodicalIF":37.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956051","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 : 2026-01-07DOI: 10.1161/circulationaha.125.076976
Amir Z Munir,Alan Gutierrez,Cade J Krawiec,Priyanka Manandhar,Anya C Shyani,Pan Ma,Paul Gougis,Richard A Baylis,Lifei Hou,Eileen Remold-O'Donnell,Justin M Balko,Joe-Elie Salem,Kory J Lavine,Andrew H Lichtman,Juan Qin,Javid J Moslehi
BACKGROUNDMyocarditis is a severe complication of immune checkpoint inhibitors (ICIs). The major risk factor for ICI myocarditis is the use of combination ICI treatment, especially when relatlimab, a novel anti-LAG-3 (lymphocyte-activation gene 3) antibody, is combined with anti-PD-1 (programmed cell death protein 1) therapy. Although pathogenic T cells are necessary for ICI myocarditis, the specific signaling and T-cell populations that drive cardiac infiltration have not been fully elucidated, especially in setting of anti-LAG-3/PD-1 treatment.METHODSWe used VigiBase, an international pharmacovigilance database, to assess the risk of myocarditis with anti-LAG-3 compared with other ICI treatment regimens. We identified a mouse model of LAG-3/PD-1-associated ICI myocarditis through genetic deletion of immune checkpoints LAG-3 and PD-1 (Lag3-/-, Pdcd1-/- mice) and performed rigorous cardiac phenotyping using histology, flow cytometry, electrocardiography, single-cell RNA sequencing, and antibody-induced cellular depletion.RESULTSWe found an increased risk of myocarditis with anti-LAG-3 combination treatment clinically, confirming early clinical trial data. Lag3-/-, Pdcd1-/- mice were found to develop severe cardiac inflammation by histology with increased cardiac macrophages and clonal T cells, which was associated with the development of spontaneous arrhythmias leading to premature death by 6 to 8 weeks. We identified CXCR6 (C-X-C motif chemokine receptor 6) as a key marker of activated cardiac T cells in this model, along with analogous signals in other preclinical models and patient data. CXCR6 marked a heterogenous group of cardiac T cells, including distinct clusters of Gzmk, Gzmb, Cd4, and actively dividing T cells. CXCL16 (C-X-C motif chemokine ligand 16), the sole known ligand for CXCR6, was similarly upregulated in the cardiac macrophage population. Treatment with anti-CXCR6 antibody prevented premature lethality, attenuated arrhythmias, and reduced the histological severity of myocarditis, demonstrating that CXCR6+ T cells are necessary for disease pathogenesis.CONCLUSIONSOur findings suggest that ICI myocarditis is driven by an expansion of CXCR6+ T cells and identifies CXCR6 as a putative therapeutic target for this highly morbid condition.
{"title":"CXCR6+ T Cells Drive Immune Checkpoint Inhibitor Myocarditis.","authors":"Amir Z Munir,Alan Gutierrez,Cade J Krawiec,Priyanka Manandhar,Anya C Shyani,Pan Ma,Paul Gougis,Richard A Baylis,Lifei Hou,Eileen Remold-O'Donnell,Justin M Balko,Joe-Elie Salem,Kory J Lavine,Andrew H Lichtman,Juan Qin,Javid J Moslehi","doi":"10.1161/circulationaha.125.076976","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076976","url":null,"abstract":"BACKGROUNDMyocarditis is a severe complication of immune checkpoint inhibitors (ICIs). The major risk factor for ICI myocarditis is the use of combination ICI treatment, especially when relatlimab, a novel anti-LAG-3 (lymphocyte-activation gene 3) antibody, is combined with anti-PD-1 (programmed cell death protein 1) therapy. Although pathogenic T cells are necessary for ICI myocarditis, the specific signaling and T-cell populations that drive cardiac infiltration have not been fully elucidated, especially in setting of anti-LAG-3/PD-1 treatment.METHODSWe used VigiBase, an international pharmacovigilance database, to assess the risk of myocarditis with anti-LAG-3 compared with other ICI treatment regimens. We identified a mouse model of LAG-3/PD-1-associated ICI myocarditis through genetic deletion of immune checkpoints LAG-3 and PD-1 (Lag3-/-, Pdcd1-/- mice) and performed rigorous cardiac phenotyping using histology, flow cytometry, electrocardiography, single-cell RNA sequencing, and antibody-induced cellular depletion.RESULTSWe found an increased risk of myocarditis with anti-LAG-3 combination treatment clinically, confirming early clinical trial data. Lag3-/-, Pdcd1-/- mice were found to develop severe cardiac inflammation by histology with increased cardiac macrophages and clonal T cells, which was associated with the development of spontaneous arrhythmias leading to premature death by 6 to 8 weeks. We identified CXCR6 (C-X-C motif chemokine receptor 6) as a key marker of activated cardiac T cells in this model, along with analogous signals in other preclinical models and patient data. CXCR6 marked a heterogenous group of cardiac T cells, including distinct clusters of Gzmk, Gzmb, Cd4, and actively dividing T cells. CXCL16 (C-X-C motif chemokine ligand 16), the sole known ligand for CXCR6, was similarly upregulated in the cardiac macrophage population. Treatment with anti-CXCR6 antibody prevented premature lethality, attenuated arrhythmias, and reduced the histological severity of myocarditis, demonstrating that CXCR6+ T cells are necessary for disease pathogenesis.CONCLUSIONSOur findings suggest that ICI myocarditis is driven by an expansion of CXCR6+ T cells and identifies CXCR6 as a putative therapeutic target for this highly morbid condition.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"88 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907660","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}
BACKGROUNDThe universal definition of percutaneous coronary intervention (PCI)-related myocardial infarction (MI) has been substantially updated over the years, including an increase in the biomarker threshold (from 3 to 5 times the upper reference limit) and the introduction of ancillary criteria such as ischemic symptoms and electrocardiographic or angiographic complication. The impact of these changes in patients with acute coronary syndrome (ACS) remains incompletely understood. The objective of this study was to compare prognostic implications of evolving universal definitions of PCI-MI in a large cohort of patients with ACS from the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX).METHODSAmong 6724 patients undergoing PCI in the MATRIX trial, PCI-MI was prospectively adjudicated by the second, third and fourth universal definition of MI (UDMI). The 2 co-primary end points were all-cause and cardiovascular death (from 24 hours to 1 year after PCI) in patients with non-ST-segment-elevation ACS. Hazard ratios and 95% CIs were generated for primary and secondary end points with the use of Cox proportional hazards time-to-event analyses for each MI definition.RESULTSPCI-MI occurred in 590 patients (9%) with the second UDMI, 193 (3%) with the third UDMI, and 182 (3%) with the fourth UDMI applied in the overall ACS population. Among patients with non-ST-segment-elevation ACS, the corresponding figures were 15%, 5%, and 5%. Only PCI-MI defined by the fourth UDMI in patients with non-ST-segment-elevation ACS was associated with increased risks of all-cause (hazard ratio, 2.08 [95% CI, 1.00-4.30]; P=0.048) and cardiovascular (hazard ratio, 2.62 [95% CI, 1.03-6.65]; P=0.043) death. In patients with ST-segment-elevation myocardial infarction, PCI-MI was uncommon (1% to 4% depending on the working definition) and was not associated with increased mortality. In the absence of objective ancillary criteria (electrocardiographic and angiographic complications), isolated troponin elevations up to 20 times the upper reference limit were not associated with increased mortality risk.CONCLUSIONSPCI-MI defined according to the fourth UDMI was associated with increased risks of 1-year mortality only in patients with non-ST-segment-elevation ACS. These data support the evolution of the universal definition of PCI-MI.REGISTRATIONURL: http://www.clinicaltrials.gov; Unique identifier: NCT01433627.
{"title":"Prognostic Implications of Evolving Universal Definitions of Periprocedural Myocardial Infarction in Patients With Acute Coronary Syndrome.","authors":"Sergio Leonardi,Antonio Landi,Andrea Zito,Mattia Branca,Enrico Frigoli,Giuseppe Ando',Carlo Briguori,Paolo Calabro',Andrea Gagnor,Roberto Garbo,Dik Heg,Ugo Limbruno,Andrea Milzi,Elmir Omerovic,Filippo Russo,Manel Sabaté,Andrea Santarelli,Gennaro Sardella,Paolo Tosi,Arnoud W J Van't Hof,Pascal Vranckx,Marco Valgimigli","doi":"10.1161/circulationaha.125.077174","DOIUrl":"https://doi.org/10.1161/circulationaha.125.077174","url":null,"abstract":"BACKGROUNDThe universal definition of percutaneous coronary intervention (PCI)-related myocardial infarction (MI) has been substantially updated over the years, including an increase in the biomarker threshold (from 3 to 5 times the upper reference limit) and the introduction of ancillary criteria such as ischemic symptoms and electrocardiographic or angiographic complication. The impact of these changes in patients with acute coronary syndrome (ACS) remains incompletely understood. The objective of this study was to compare prognostic implications of evolving universal definitions of PCI-MI in a large cohort of patients with ACS from the MATRIX trial (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX).METHODSAmong 6724 patients undergoing PCI in the MATRIX trial, PCI-MI was prospectively adjudicated by the second, third and fourth universal definition of MI (UDMI). The 2 co-primary end points were all-cause and cardiovascular death (from 24 hours to 1 year after PCI) in patients with non-ST-segment-elevation ACS. Hazard ratios and 95% CIs were generated for primary and secondary end points with the use of Cox proportional hazards time-to-event analyses for each MI definition.RESULTSPCI-MI occurred in 590 patients (9%) with the second UDMI, 193 (3%) with the third UDMI, and 182 (3%) with the fourth UDMI applied in the overall ACS population. Among patients with non-ST-segment-elevation ACS, the corresponding figures were 15%, 5%, and 5%. Only PCI-MI defined by the fourth UDMI in patients with non-ST-segment-elevation ACS was associated with increased risks of all-cause (hazard ratio, 2.08 [95% CI, 1.00-4.30]; P=0.048) and cardiovascular (hazard ratio, 2.62 [95% CI, 1.03-6.65]; P=0.043) death. In patients with ST-segment-elevation myocardial infarction, PCI-MI was uncommon (1% to 4% depending on the working definition) and was not associated with increased mortality. In the absence of objective ancillary criteria (electrocardiographic and angiographic complications), isolated troponin elevations up to 20 times the upper reference limit were not associated with increased mortality risk.CONCLUSIONSPCI-MI defined according to the fourth UDMI was associated with increased risks of 1-year mortality only in patients with non-ST-segment-elevation ACS. These data support the evolution of the universal definition of PCI-MI.REGISTRATIONURL: http://www.clinicaltrials.gov; Unique identifier: NCT01433627.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"29 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907548","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}
BACKGROUNDMitophagy is critically involved in cardiac injury and repair after myocardial infarction (MI), whereas the annexin A family plays an important role in mitophagy. However, the intrinsic molecular underpinnings that orchestrate the homeostasis of mitophagy in the infarcted heart remain to be fully characterized. Here, we aimed to evaluate the role of ANXA2 (annexin A2) in cardiac mitophagy in response to MI.METHODSTranscriptome analyses were conducted to identify differentially expressed genes and enriched pathways. Mitophagy, mitochondrial function, and cardiac injury and remodeling were analyzed in MI mice and neonatal rat ventricular myocytes with cardiomyocyte-specific ANXA2 knockdown or overexpression, as well as in models with ANXA2 knockdown combined with PHB2 (prohibitin 2) silencing. Immunoprecipitation, mass spectrometry, and glutathione S-transferase pull-down assays were used to identify the interacting proteins of ANXA2.RESULTSWe showed that ANXA2 was highly expressed in murine and human ischemic failing hearts, whereas increased circulating ANXA2 positively correlated with cardiac injury in patients with acute MI. Moreover, cardiomyocyte-specific ANXA2 depletion averted cardiac mitophagy inactivation, oxidative stress, cell death, and inflammatory cell infiltration, leading to significant improvements in infarct size, heart function, and cardiac remodeling after MI. Conversely, ANXA2 overexpression in cardiomyocytes suppressed mitophagy to exacerbate cardiac injury and deteriorate heart failure after MI. Moreover, ANXA2 silencing and overexpression, respectively, in neonatal rat ventricular myocytes under hypoxia in vitro recapitulated the in vivo findings on mitochondrial function and cell death. Mechanistically, we found that ANXA2 directly interacted with the mitophagy receptor PHB2 to competitively block the binding of LC3B with PHB2 and promote PHB2 proteasomal degradation through K48-linked polyubiquitination mediated by the E3 ligase TRIM29, resulting in mitophagy inhibition under hypoxia. Consequently, PHB2 knockdown abrogated the protective effects of ANXA2 deficiency on mitochondrial function, oxidative stress, and cell viability in stressed myocytes in vitro, as well as on heart function and remodeling under MI in vivo.CONCLUSIONSThese findings highlight the significance of ANXA2 inhibition as a molecular brake on mitophagy inactivation in cardiomyocytes under MI and uncover an ANXA2-mediated posttranslational mechanism essential for maintaining mitochondrial homeostasis and alleviating heart failure after MI.
{"title":"Inhibition of Annexin A2 Facilitates PHB2-Mediated Mitophagy in Cardiomyocytes to Alleviate Cardiac Injury and Remodeling After Infarction.","authors":"Ke-Qiong Deng,Zhendong Xu,Qiong-Xin Wang,Huan-Huan Cai,Di Fan,Qingqing Wu,Xiao-Jing Zhang,Peng Zhang,Zhi-Gang She,Xingguo Liu,Xianqing Li,Zhibing Lu","doi":"10.1161/circulationaha.125.077780","DOIUrl":"https://doi.org/10.1161/circulationaha.125.077780","url":null,"abstract":"BACKGROUNDMitophagy is critically involved in cardiac injury and repair after myocardial infarction (MI), whereas the annexin A family plays an important role in mitophagy. However, the intrinsic molecular underpinnings that orchestrate the homeostasis of mitophagy in the infarcted heart remain to be fully characterized. Here, we aimed to evaluate the role of ANXA2 (annexin A2) in cardiac mitophagy in response to MI.METHODSTranscriptome analyses were conducted to identify differentially expressed genes and enriched pathways. Mitophagy, mitochondrial function, and cardiac injury and remodeling were analyzed in MI mice and neonatal rat ventricular myocytes with cardiomyocyte-specific ANXA2 knockdown or overexpression, as well as in models with ANXA2 knockdown combined with PHB2 (prohibitin 2) silencing. Immunoprecipitation, mass spectrometry, and glutathione S-transferase pull-down assays were used to identify the interacting proteins of ANXA2.RESULTSWe showed that ANXA2 was highly expressed in murine and human ischemic failing hearts, whereas increased circulating ANXA2 positively correlated with cardiac injury in patients with acute MI. Moreover, cardiomyocyte-specific ANXA2 depletion averted cardiac mitophagy inactivation, oxidative stress, cell death, and inflammatory cell infiltration, leading to significant improvements in infarct size, heart function, and cardiac remodeling after MI. Conversely, ANXA2 overexpression in cardiomyocytes suppressed mitophagy to exacerbate cardiac injury and deteriorate heart failure after MI. Moreover, ANXA2 silencing and overexpression, respectively, in neonatal rat ventricular myocytes under hypoxia in vitro recapitulated the in vivo findings on mitochondrial function and cell death. Mechanistically, we found that ANXA2 directly interacted with the mitophagy receptor PHB2 to competitively block the binding of LC3B with PHB2 and promote PHB2 proteasomal degradation through K48-linked polyubiquitination mediated by the E3 ligase TRIM29, resulting in mitophagy inhibition under hypoxia. Consequently, PHB2 knockdown abrogated the protective effects of ANXA2 deficiency on mitochondrial function, oxidative stress, and cell viability in stressed myocytes in vitro, as well as on heart function and remodeling under MI in vivo.CONCLUSIONSThese findings highlight the significance of ANXA2 inhibition as a molecular brake on mitophagy inactivation in cardiomyocytes under MI and uncover an ANXA2-mediated posttranslational mechanism essential for maintaining mitochondrial homeostasis and alleviating heart failure after MI.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"84 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907549","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 : 2026-01-06Epub Date: 2025-11-08DOI: 10.1161/CIRCULATIONAHA.125.077494
Rayan A Ansari, Sabyasachi Bandyopadhyay, Rishi K Trivedi, Kelly A Brennan, Xichong Liu, Prasanth Ganesan, J Weston Hughes, Alexander C Perino, Euan A Ashley, Paul J Wang, Todd Coleman, Marco V Perez, David Ouyang, Sanjiv M Narayan, Albert J Rogers
Background: Drug-induced QT prolongation after successful inpatient loading of class III antiarrhythmics may occur during routine outpatient care. Insertable cardiac monitors offer continuous signals but are limited by single-lead configuration. We hypothesized that a spatially aware deep learning system (3DRECON-QT) can reconstruct spatial information from a single lead vector to quantify QT/QTc and identify high-risk prolongation.
Methods: We developed 3DRECON-QT using a multitask encoder-decoder that ingests a 10-s single-lead signal, reconstructs 12 leads, and predicts QT/QTc. The model was developed using 12-lead ECGs with clinician-adjudicated QT/RR from a large health system and tested in an external center with different ECG hardware. Continuous monitoring performance was assessed in a public dofetilide-loading data set with serial ECGs. In a real-world cohort of outpatients on dofetilide or sotalol presenting to the hospital or emergency room for any reason, rates of ventricular arrhythmias and QT prolongation were assessed. Device validation was tested in patients with insertable cardiac monitor recordings paired with clinical 12-lead ECGs.
Results: 3DRECON-QT classified prolonged QTc from single-lead signals with area under the receiver operating characteristics curve, 0.942 (mean absolute error, 17.5 ms) in the internal test set and 0.943 (mean absolute error, 21.1 ms) externally. During continuous dofetilide monitoring, predictions correlated with ground truth (r, 0.851; mean absolute error, 17.8 ms; area under the receiver operating characteristics curve, 0.936 for prolonged QTc, 0.816 for ≥15% QTc rise). QTc prediction from true insertable cardiac monitor recordings showed r=0.824 and mean absolute error, 17.5 ms. In outpatients on class III antiarrhythmics (n=1676), 16.5% had high-risk QTc prolongation. Ventricular arrhythmia events were 3.97% versus 0.86% without prolongation (adjusted odds ratio, 4.24 [95% CI, 1.81-9.90]). 3DRECON-QT detected these events with area under the receiver operating characteristics curve 0.94 (F1 score, 0.60).
Conclusions: A single-lead, deep-learning approach can achieve guideline-level measurement accuracy, enable continuous QTc surveillance from nonstandard ECG vectors, and identify clinically meaningful outpatient QTc prolongation associated with a >4-fold increase in serious ventricular arrhythmias. This strategy may enhance safety monitoring after class III antiarrhythmic initiation and support targeted intervention.
{"title":"Deep Learning-Based Continuous QT Monitoring to Identify High-Risk Prolongation Events After Class III Antiarrhythmic Initiation.","authors":"Rayan A Ansari, Sabyasachi Bandyopadhyay, Rishi K Trivedi, Kelly A Brennan, Xichong Liu, Prasanth Ganesan, J Weston Hughes, Alexander C Perino, Euan A Ashley, Paul J Wang, Todd Coleman, Marco V Perez, David Ouyang, Sanjiv M Narayan, Albert J Rogers","doi":"10.1161/CIRCULATIONAHA.125.077494","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.077494","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced QT prolongation after successful inpatient loading of class III antiarrhythmics may occur during routine outpatient care. Insertable cardiac monitors offer continuous signals but are limited by single-lead configuration. We hypothesized that a spatially aware deep learning system (3DRECON-QT) can reconstruct spatial information from a single lead vector to quantify QT/QTc and identify high-risk prolongation.</p><p><strong>Methods: </strong>We developed 3DRECON-QT using a multitask encoder-decoder that ingests a 10-s single-lead signal, reconstructs 12 leads, and predicts QT/QTc. The model was developed using 12-lead ECGs with clinician-adjudicated QT/RR from a large health system and tested in an external center with different ECG hardware. Continuous monitoring performance was assessed in a public dofetilide-loading data set with serial ECGs. In a real-world cohort of outpatients on dofetilide or sotalol presenting to the hospital or emergency room for any reason, rates of ventricular arrhythmias and QT prolongation were assessed. Device validation was tested in patients with insertable cardiac monitor recordings paired with clinical 12-lead ECGs.</p><p><strong>Results: </strong>3DRECON-QT classified prolonged QTc from single-lead signals with area under the receiver operating characteristics curve, 0.942 (mean absolute error, 17.5 ms) in the internal test set and 0.943 (mean absolute error, 21.1 ms) externally. During continuous dofetilide monitoring, predictions correlated with ground truth (<i>r</i>, 0.851; mean absolute error, 17.8 ms; area under the receiver operating characteristics curve, 0.936 for prolonged QTc, 0.816 for ≥15% QTc rise). QTc prediction from true insertable cardiac monitor recordings showed <i>r</i>=0.824 and mean absolute error, 17.5 ms. In outpatients on class III antiarrhythmics (n=1676), 16.5% had high-risk QTc prolongation. Ventricular arrhythmia events were 3.97% versus 0.86% without prolongation (adjusted odds ratio, 4.24 [95% CI, 1.81-9.90]). 3DRECON-QT detected these events with area under the receiver operating characteristics curve 0.94 (F1 score, 0.60).</p><p><strong>Conclusions: </strong>A single-lead, deep-learning approach can achieve guideline-level measurement accuracy, enable continuous QTc surveillance from nonstandard ECG vectors, and identify clinically meaningful outpatient QTc prolongation associated with a >4-fold increase in serious ventricular arrhythmias. This strategy may enhance safety monitoring after class III antiarrhythmic initiation and support targeted intervention.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"153 1","pages":"35-46"},"PeriodicalIF":38.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854728","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}
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