Shayan Ebrahimian, Troy Coaston, Amulya Vadlakonda, Joseph Hadaya, Sara Sakowitz, Ali Nsair, Radoslav Zinoviev, Boback Ziaeian, Eric H Yang, Gregg C Fonarow, Olcay Aksoy, Peyman Benharash
{"title":"Outcomes of Out-of-Hospital Cardiac Arrest at Centers With and Without On-Site Coronary Angiography: A Nationwide Analysis.","authors":"Shayan Ebrahimian, Troy Coaston, Amulya Vadlakonda, Joseph Hadaya, Sara Sakowitz, Ali Nsair, Radoslav Zinoviev, Boback Ziaeian, Eric H Yang, Gregg C Fonarow, Olcay Aksoy, Peyman Benharash","doi":"10.1161/JAHA.125.042369","DOIUrl":"https://doi.org/10.1161/JAHA.125.042369","url":null,"abstract":"<p><strong>Background: </strong>The American Heart Association has advocated for regionalized systems of care for out-of-hospital cardiac arrest (OHCA), emphasizing admission to specialized centers with onsite coronary angiography. However, national data evaluating outcomes of OHCA admission to such centers remain limited.</p><p><strong>Methods: </strong>Using the 2021 National Inpatient Sample, we identified all direct OHCA hospitalizations across US facilities. Hospitals were categorized as angio-capable if they performed ≥1 coronary angiography in 2021 (others: angio-incapable). The primary outcome was in-hospital mortality. Mixed-effects modeling quantified interhospital variation in mortality. Multivariable logistic regression modeling compared mortality between groups.</p><p><strong>Results: </strong>Of 251 260 OHCA hospitalizations across 2867 centers, 92.6% occurred at angio-capable hospitals and 7.4% at angio-incapable facilities. Patients at angio-capable centers were younger, more frequently male, and had higher rates of ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, cardiogenic shock, and shockable rhythms. Crude mortality was higher at angio-incapable centers than at angio-capable facilities (83.0 versus 67.7%, <i>P</i><0.001). After adjustment for patient characteristics, hospital-level factors accounted for 13.5% of mortality variation. Admission to angio-incapable centers was associated with 60% greater odds of death (adjusted odds ratio, 1.60 [95% CI, 1.42-1.80]). Marginal effects analysis demonstrated stepwise reduction in predicted mortality rate, from 87.0% (95% CI, 85.5-88.5) at rural angio-incapable centers to 67.3% (95% CI, 66.7-67.9) at urban angio-capable centers.</p><p><strong>Conclusions: </strong>Admission to hospitals without coronary angiography is associated with higher mortality following OHCA, with the greatest risk observed in rural settings. These findings support regionalized systems of postarrest care and the role of coronary angiography-capable centers as resuscitation hubs.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042369"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318746","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}
Yuki Ikeda, Keita Saku, Jun Nakata, Takashi Unoki, Takeshi Yamamoto, Tomohiro Sakamoto, Junya Ako
{"title":"Phase-Specific Hemodynamic Criteria and Outcomes in Patients With Cardiogenic Shock Receiving Percutaneous Ventricular Assist Devices.","authors":"Yuki Ikeda, Keita Saku, Jun Nakata, Takashi Unoki, Takeshi Yamamoto, Tomohiro Sakamoto, Junya Ako","doi":"10.1161/JAHA.125.042249","DOIUrl":"https://doi.org/10.1161/JAHA.125.042249","url":null,"abstract":"<p><strong>Background: </strong>Standardized protocols with optimal hemodynamic targets for percutaneous ventricular assist device (PVAD) management remain undefined. We aimed to evaluate the proportion of phase-specific hemodynamic criteria achieved during PVAD support and their association with outcomes in patients with cardiogenic shock.</p><p><strong>Methods: </strong>This multicenter retrospective study enrolled patients with cardiogenic shock requiring PVAD (Impella). Patients were evaluated at 24 hours post-PVAD, venoarterial extracorporeal membrane oxygenation weaning, and PVAD weaning. Hemodynamic criteria consisted of key targets, including mean arterial pressure ≥60 mm Hg, lactate <2.0 mmol/L, right atrial pressure <15 mm Hg, pulmonary artery wedge pressure <20 mm Hg, pulmonary artery pulsatility index ≥1.0, and cardiac power output ≥0.6 W. The primary outcome was a composite of 30-day all-cause mortality and unplanned mechanical circulatory support reintroduction.</p><p><strong>Results: </strong>A total of 501 patients were enrolled: 206 (41%) with PVAD alone and 295 (59%) with PVAD and venoarterial extracorporeal membrane oxygenation. The majority of patients were supported with Impella CP (406, 81%). Fulfillment of criteria was observed in 37%, 52%, and 45% at 24 hours post-PVAD, venoarterial extracorporeal membrane oxygenation weaning, and PVAD weaning, respectively. Patients with unfulfilled criteria at each evaluation point were at high risk for the primary outcome (hazard ratio, 3.2 [95% CI, 2.1-4.8]; hazard ratio, 2.1 [1.2-3.7]; and hazard ratio, 2.0 [95% CI, 1.1-3.6]). Hemodynamic criteria achievement consistently stratified the risk of the primary outcome across different subgroups, including shock cause, shock stage, and concomitant use of venoarterial extracorporeal membrane oxygenation.</p><p><strong>Conclusions: </strong>Phase-specific hemodynamic criteria are often unmet and are associated with significantly higher risks of short-term fatal events.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e042249"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318747","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}
Weicheng Ni, Xingxing Chen, Kun Guo, Qingwei Ni, Ken Lin, Ruihao Jiang, Zhan Gao, Changxi Chen, Hao Zhou
{"title":"Prevalence and Prognostic Value of the Novel Consensus Definition of Metabolic Hyperferritinemia in Patients With Heart Failure With Preserved Ejection Fraction Across Different Glucose Metabolism States.","authors":"Weicheng Ni, Xingxing Chen, Kun Guo, Qingwei Ni, Ken Lin, Ruihao Jiang, Zhan Gao, Changxi Chen, Hao Zhou","doi":"10.1161/JAHA.124.040100","DOIUrl":"https://doi.org/10.1161/JAHA.124.040100","url":null,"abstract":"<p><strong>Background: </strong>Metabolic hyperferritinemia (MHF) is associated with the occurrence and progression of cardiovascular disease. Our aim is to investigate the prevalence of MHF, as defined by the latest consensus, and validate its association with major adverse cardiovascular events (MACEs) in heart failure with preserved ejection fraction with different glucose metabolism conditions.</p><p><strong>Methods and results: </strong>This retrospective study included 7498 patients with heart failure with preserved ejection fraction, with a median follow-up duration of 2.5 years. MHF is defined as an elevation in serum ferritin accompanied by metabolic dysfunction, and is categorized into different grades based on ferritin levels. The outcome of the study is MACEs. Among the 7498 patients with heart failure with preserved ejection fraction (with an average age of 70.23±10.85 years; 52.68% male), nearly one third (29.7%) had MHF. The majority of these patients were classified as Grade 1 (21.7%), with Grade 2 accounting for 5.2% and Grade 3 for 2.9%. As the severity of MHF increased, the proportion of patients with abnormal glucose metabolism (prediabetes and diabetes) also increased. Cox regression analysis revealed that, even after full adjustment, MHF Grade 2/3 remained significantly associated with a higher risk of MACEs compared with non-MHF (hazard ratio [HR], 1.43 [95% CI, 1.26-1.62]). The correlation between MHF and MACEs remained consistent across different glucose metabolism statuses.</p><p><strong>Conclusions: </strong>In the population with heart failure with preserved ejection fraction, the baseline prevalence of MHF is notably high. Furthermore, patients who exhibit higher grades of MHF are at an increased risk of MACEs. Additionally, patients with elevated MHF grades also suffer from higher proportions of diabetes and prediabetes.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e040100"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318749","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}
Bhargav Makwana, Sumanth Khadke, Ashish Kumar, Khurram Nasir, Rishi Wadhera, Rikin Shah, Sudip Sheth, Yixin Kong, Ana Navas-Acien, Gary Adamkiewicz, Sanjay Rajagopalan, Sadeer Al-Kindi, Sourbha S Dani, Susan Moffatt-Bruce, Sarju Ganatra
{"title":"Marine Microplastic Levels and the Prevalence of Cardiometabolic Diseases in US Coastline Counties.","authors":"Bhargav Makwana, Sumanth Khadke, Ashish Kumar, Khurram Nasir, Rishi Wadhera, Rikin Shah, Sudip Sheth, Yixin Kong, Ana Navas-Acien, Gary Adamkiewicz, Sanjay Rajagopalan, Sadeer Al-Kindi, Sourbha S Dani, Susan Moffatt-Bruce, Sarju Ganatra","doi":"10.1161/JAHA.124.039891","DOIUrl":"https://doi.org/10.1161/JAHA.124.039891","url":null,"abstract":"<p><strong>Background: </strong>Although micro- and nanoplastics are an emerging risk factor for the development of cardiovascular diseases, the association of marine microplastic levels (MMLs) with the burden of cardiometabolic diseases at a population level remains unexplored. We investigated the relationship between the mean microplastic concentration in ocean water within 200 nautical miles of the US coastline and the prevalence of type 2 diabetes, coronary artery disease, and stroke in nearby counties.</p><p><strong>Methods: </strong>Microplastic concentration data within 200 nautical miles of the US coastline were geospatially analyzed to calculate mean MMLs. The coastal counties were stratified into 4 categories based on MMLs in the adjacent ocean water body: low, medium, high, or very high. The Behavioral Risk Factor Surveillance System 2019 to 2020 survey data were used to identify the prevalence of type 2 diabetes, coronary artery disease, and stroke in these counties. Univariate and population-weighted multivariate quasi-Poisson regression, adjusted for county-level confounding variables, was used to evaluate the unadjusted and adjusted associations between disease prevalence and MMLs.</p><p><strong>Results: </strong>The mean age of the population was 43±6 years. After adjusting for age, sex, physician access, and socioenvironmental vulnerabilities at the county level, counties with very high MMLs exhibited an 18%, 7%, and 9% higher adjusted prevalence of type 2 diabetes, coronary artery disease, and stroke, respectively, compared with those with low levels.</p><p><strong>Conclusion: </strong>Marine microplastic levels were significantly associated with the prevalence of cardiometabolic diseases in coastal counties. Comprehensive studies at an individual level are needed to further investigate the health impacts of microplastic pollution.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e039891"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318744","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}
Johannes Brachmann, Thomas Vogtmann, John Hummel, Vijay Swarup, David Wilber, Joshua Rapkin, Shlomo Shpun, Anne Sarver, Tamás Szili-Törok
{"title":"Prospective Randomized Trial of Rotor Ablation vs Conventional Ablation for Persistent Atrial Fibrillation: REAFFIRM Trial.","authors":"Johannes Brachmann, Thomas Vogtmann, John Hummel, Vijay Swarup, David Wilber, Joshua Rapkin, Shlomo Shpun, Anne Sarver, Tamás Szili-Törok","doi":"10.1161/JAHA.121.022346","DOIUrl":"https://doi.org/10.1161/JAHA.121.022346","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary vein isolation (PVI) is the cornerstone therapy for symptomatic drug-refractory atrial fibrillation yet is not curative in a large segment of patients. Focal and rotational drivers are proposed to be involved in atrial fibrillation mechanisms but their ablation has produced variable outcomes. REAFFIRM (The Randomized Evaluation of Atrial Fibrillation Treatment with Focal Impulse and Rotor Modulation Guided Procedures) trial (NCT-02274857) objective was to compare the safety and effectiveness of conventional ablation with and without Focal Impulse and Rotor Modulated (FIRM) ablation, guided by global basket mapping, for the treatment of persistent atrial fibrillation.</p><p><strong>Methods: </strong>Three hundred seventy-five patients were enrolled and randomized at 18 centers. The Intent-to-Treat population consisted of 350 patients (171 FIRM, 179 Conventional). Primary effectiveness was defined as single procedure freedom from atrial fibrillation/atrial tachycardia recurrence at 3 to 12 months post index procedure.</p><p><strong>Results: </strong>Three hundred twenty-four patients completed the 12-month follow-up. Patients in the FIRM arm had a larger left atrium (<i>P</i> <0.01). Primary effectiveness at 3 to 12 months was 69.3% in FIRM and 67.5% in Conventional (NS), with no difference in ablation procedure time or safety. A subset of patients (41% FIRM, 49% Conventional) received extra ablation. Primary effectiveness in the on-treatment subgroups was 65% PVI-only, 69.6% PVI +extra, 77.7% FIRM+ PVI-only, and 57.7% FIRM+ PVI +extra (<i>P</i>=0.09).</p><p><strong>Conclusions: </strong>Intention-to-treat analysis failed to provide evidence for the superiority of adding ablation of focal or rotational sites to conventional ablation.</p><p><strong>Registration: </strong>URL: https://clinicaltrials.gov; Unique Identifier: NCT-02274857.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e022346"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318720","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}
Zhiyong Shi, Mingkai Yun, Binbin Nie, Yujie Bai, Yaqi Zheng, Enjun Zhu, Yuetao Wang, Marcus Hacker, Yongqiang Lai, Baoci Shan, Sijin Li, Xiaoli Zhang, Xiang Li
{"title":"Incremental Prognostic Value of Hippocampal Metabolic Activity for Sudden Cardiac Death in Patients With Heart Failure With Reduced Ejection Fraction.","authors":"Zhiyong Shi, Mingkai Yun, Binbin Nie, Yujie Bai, Yaqi Zheng, Enjun Zhu, Yuetao Wang, Marcus Hacker, Yongqiang Lai, Baoci Shan, Sijin Li, Xiaoli Zhang, Xiang Li","doi":"10.1161/JAHA.124.039147","DOIUrl":"https://doi.org/10.1161/JAHA.124.039147","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal injury is linked to cognitive impairment and cardiac events in patients with heart failure with reduced ejection fraction. However, the predictive value of hippocampal metabolic activity (HMA) for sudden cardiac death (SCD) and the underlying mechanisms remain unclear. This study aimed to evaluate the independent and incremental predictive value of HMA over myocardial scar for SCD-related events in patients with heart failure with reduced ejection fraction and to explore the potential mechanism.</p><p><strong>Methods: </strong>This prospective study included 270 patients with heart failure with reduced ejection fraction undergoing gated single-photon emission computed tomography and brain/cardiac <sup>18</sup>F-fluorodeoxyglucose positron emission tomography. HMA and myocardial scarring were evaluated. The independent and incremental predictive values of HMA for SCD-related events were explored via the log-rank test, Cox model, C statistic, global χ<sup>2</sup> test, and net reclassification improvement. Mediation analysis was used to examine the direct and indirect effects of HMA on SCD-related events by setting left ventricular electrical instability as a mediator.</p><p><strong>Results: </strong>Overall, 34 (12.6%; median follow-up, 4.3 years) patients experienced SCD-related events. Functional myocardial scarring and HMA were strongly associated with SCD-related events (all <i>P</i><0.01). HMA resulted in significant incremental improvements in prognostic value (χ<sup>2</sup> increased by 6.598), discrimination (C statistics of 0.760 versus 0.715), and reclassification (net reclassification improvement, 25.6%) for SCD-related events. HMA was associated with SCD-related events via corrected QT interval.</p><p><strong>Conclusions: </strong>Functional myocardial scarring and HMA had strong independent prognostic value in the risk stratification of SCD-related events in patients with heart failure with reduced ejection fraction. Additionally, HMA had incremental prognostic value based on myocardial scarring. HMA impairment may induce SCD-related events, partly mediated by corrected QT interval.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e039147"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327751","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}
Ian J Neeland, Fang Zhu, Goncalo Graca, Anastasios Lymperopoulos, Gianluca Iacobellis, Ali Farzaneh, Daniel Bos, Mohsen Ghanbari, Jeffrey J Goldberger, Maryam Kavousi, Philip Greenland
{"title":"Metabolomics Profiling of Epicardial Adipose Tissue: MESA and the Rotterdam Study.","authors":"Ian J Neeland, Fang Zhu, Goncalo Graca, Anastasios Lymperopoulos, Gianluca Iacobellis, Ali Farzaneh, Daniel Bos, Mohsen Ghanbari, Jeffrey J Goldberger, Maryam Kavousi, Philip Greenland","doi":"10.1161/JAHA.124.039750","DOIUrl":"https://doi.org/10.1161/JAHA.124.039750","url":null,"abstract":"<p><strong>Background: </strong>Excess epicardial adipose tissue (EAT) has been associated with cardiovascular diseases such as atrial fibrillation, coronary artery disease, and heart failure. The metabolomic signature of EAT is not well studied.</p><p><strong>Methods: </strong>Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed (1-dimensional nuclear magnetic resonance, Carr-Purcell-Meiboom-Gill Echo Train Acquisition, lipidomics) and EAT was measured with computed tomography in MESA (Multi-Ethnic Study of Atherosclerosis; N=3936) and the Rotterdam study (N=465). Associations between fasting serum metabolites and EAT volume were assessed using cross-sectional linear regression of individual-level data in MESA and validated in Rotterdam.</p><p><strong>Results: </strong>A total of 23 571 metabolomic spectral variables were evaluated. In MESA, after adjustment for age, sex, and race and ethnicity, 38 metabolites were positively and 19 metabolites negatively associated with EAT at a false discovery rate <i>P</i><0.01. Several metabolites were replicated in Rotterdam, including 1,5-anhydrosorbitol and N-acetyl (glycoproteins) that were positively associated with EAT and trimethylamine (phospholipids) that were inversely associated with EAT. Branched-chain amino acids (leucine, isoleucine, and valine) and 3-hydroxybutyrate were also associated with EAT in the Rotterdam study. In MESA, apolipoprotein B and very-low-density and intermediate-density lipoprotein fractions were positively associated with EAT and the majority of high-density lipoprotein subclasses were inversely associated with EAT. Associations were partially attenuated in MESA and fully attenuated in Rotterdam after further adjustment for health and socioeconomic factors.</p><p><strong>Conclusions: </strong>From >20 000 metabolomic features, 1,5-anhydrosorbitol, glycoproteins, phospholipids, and atherogenic dyslipidemia markers emerged as significant markers of EAT. Further investigation is warranted to determine whether nuclear magnetic resonance-based metabolic profiling can improve EAT detection with implications for cardiometabolic health.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e039750"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327752","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}
Antonin Trimaille, Adrien Carmona, Sandy Hmadeh, Dinh Phi Truong, Benjamin Marchandot, Shinnosuke Kikuchi, Kensuke Matsushita, Patrick Ohlmann, Valérie Schini-Kerth, Josep Rodés-Cabau, Philippe Pibarot, Olivier Morel
{"title":"Transcatheter Aortic Valve Durability: Focus on Structural Valve Deterioration.","authors":"Antonin Trimaille, Adrien Carmona, Sandy Hmadeh, Dinh Phi Truong, Benjamin Marchandot, Shinnosuke Kikuchi, Kensuke Matsushita, Patrick Ohlmann, Valérie Schini-Kerth, Josep Rodés-Cabau, Philippe Pibarot, Olivier Morel","doi":"10.1161/JAHA.125.041505","DOIUrl":"https://doi.org/10.1161/JAHA.125.041505","url":null,"abstract":"<p><p>Transcatheter aortic valve replacement has emerged as a valuable alternative to surgical aortic valve replacement in patients with severe aortic stenosis. Given the expansion of transcatheter aortic valve replacement to lower-risk and younger populations with longer life expectancy, the durability of transcatheter heart valves (THVs) has become an important issue that may impact cardiovascular outcomes. THVs share similarities with surgical valves but have unique features, including a trend to larger effective orifice area and less prosthesis-patient mismatch, interactions with the native valve, and crimping process, that may all potentially influence a THV's life span. Multiple mechanisms may lead to bioprosthetic valve dysfunction, including structural valve deterioration, thrombosis, endocarditis, and nonstructural valve deterioration. With an incidence of up to 12.3% 5 years after transcatheter aortic valve replacement, structural valve deterioration represents the ultimate consequence of fibrotic remodeling and calcification within the bioprosthesis, driven by thrombotic and inflammatory processes involving the native aortic valve and influenced by patient and procedural factors. Understanding these mechanisms is crucial for improving THV durability.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e041505"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318722","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}
James A Brown, Jack Donohue, Sarah Yousef, Nidhi Iyanna, Danial Ahmad, Dustin Kliner, Catalin Toma, Derek Serna-Gallegos, Amber Makani, David West, Irsa Hasan, Takuya Ogami, Ibrahim Sultan
{"title":"Natural History of Tricuspid Regurgitation After Transcatheter Aortic Valve Implantation.","authors":"James A Brown, Jack Donohue, Sarah Yousef, Nidhi Iyanna, Danial Ahmad, Dustin Kliner, Catalin Toma, Derek Serna-Gallegos, Amber Makani, David West, Irsa Hasan, Takuya Ogami, Ibrahim Sultan","doi":"10.1161/JAHA.125.040955","DOIUrl":"https://doi.org/10.1161/JAHA.125.040955","url":null,"abstract":"<p><strong>Background: </strong>To determine the impact of tricuspid regurgitation (TR) on outcomes after transcatheter aortic valve implantation (TAVI), and to determine the evolution of TR severity after TAVI.</p><p><strong>Methods: </strong>This was an observational study of TAVIs for aortic stenosis from November 2012 to December 2021. Patients were dichotomized according to the severity of pre-TAVI TR: less than moderate versus moderate or greater. Logistic regression was used to determine the risk factors for progression or persistence of moderate or greater TR at 1 year after TAVI.</p><p><strong>Results: </strong>A total of 2250 patients were included for analysis, of which 301 (13.4%) had moderate or greater TR before TAVI. Baseline moderate or greater TR was associated with reduced survival and a higher incidence of heart failure readmission at 5 years after TAVI. Twelve percent of patients had progression or persistence of moderate or greater TR at 1 year after TAVI. On multivariable logistic regression, increasing age, female sex, lower mean pre-TAVI aortic transvalvular pressure gradient, pulmonary artery systolic pressure ≥40 mm Hg, pulmonary vascular disease, and transfemoral vascular access were associated with progression or persistence of moderate or greater TR at 1 year after TAVI, while periprocedural variables related to valve implantation were not.</p><p><strong>Conclusions: </strong>Significant TR before TAVI was associated with poor outcomes after TAVI. The incidence of moderate or greater TR at 1 year after TAVI was reasonable at 12%. Periprocedural factors, such as valve size, type of implanted valve, and paravalvular leak, were not associated with the development of TR. Evolution of TR and heart failure symptoms must be carefully surveilled after TAVI.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e040955"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318745","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":"Circ-myh8/KAT7 Affects PANoptosis in Pulmonary Arterial Smooth Muscle Cells: Involvement of Super-Enhancers in FOSL2 Expression.","authors":"Jingya Zhang, Xinru Wang, Xu Wang, Songyue Li, Jianli Hou, Yibin Zhang, Xinyue Song, Shukun Cao, Ya Xu, Jing Qi, Baoshan Zhao, Xiaodong Zheng, Yan Xing","doi":"10.1161/JAHA.124.040334","DOIUrl":"https://doi.org/10.1161/JAHA.124.040334","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension is a pathophysiological condition characterized by multiple forms of regulated cell death. PANoptosis, which is an inflammation-driven mode of regulated cell death, is regulated by the PANoptosome. Super-enhancers (SEs) have been implicated in the pathology of pulmonary hypertension by modulating the transcriptional regulation of target genes. However, it remains unclear whether SEs influence the onset of PANoptosis in pulmonary arterial smooth muscle cells (PASMCs) via the regulation of specific target genes.</p><p><strong>Methods: </strong>Chromatin immunoprecipitation (ChIP)-sequencing was integrated with RNA sequencing to identify SE-regulated target genes in hypoxic PASMCs. Bioinformatics analysis was used to predict transcription factors with potential binding sites in the promoter or SE regions of these target genes. Coimmunoprecipitation and ChIP-polymerase chain reaction were conducted to validate the epigenetic regulatory mechanisms governing SE-regulated target genes. Immunoblotting was performed to assess the expression of PANoptosis proteins, whereas YP1 (YO-PRO-1; Oxazole yellow) and PI (propidium iodide) fluorescence staining and immunofluorescence were used to evaluate the effects of transcription factors and SE on PANoptosis in PASMCs. Additionally, reverse transcriptase-quantitative polymerase chain reaction, immunoblotting, and ChIP-polymerase chain reaction assays were used to investigate the impact of the SE region of the target gene on PANoptosis in PASMCs following CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9)-mediated knockdown of the SE regions of the target genes.</p><p><strong>Results: </strong>A combination of ChIP sequencing and RNA sequencing analyses confirmed that <i>FOSL2</i> (Fos-like antigen 2) is a target gene regulated by SEs. Bioinformatics predictions revealed that the transcription factor MAZ (myc-associated zinc finger protein) has binding sites within both the SE and promoter regions of <i>FOSL2</i>. Coimmunoprecipitation and ChIP-polymerase chain reaction experiments demonstrated that KAT7 (lysine acetyltransferase 7) interacts with H3K27ac (acetylation of lysine 27 of histone H3) and that circ_chr11_67292179-67294612 (circ-myh8) and KAT7 enhances H3K27ac enrichment in the SE region of <i>FOSL2</i>. CRISPR-Cas9-mediated knockdown of the <i>FOSL2</i> SE resulted in a reduction in PANoptosis in PASMCs. Additionally, ChIP-polymerase chain reaction assays revealed that FOSL2 functions as a transcription factor that binds to the promoters of PANoptosis-related genes.</p><p><strong>Conclusions: </strong>Circ-myh8 RNA, which functions jointly with KAT7, enhances H3K27ac enrichment, thereby promoting SE activity for FOSL2 transcription. This process ultimately contributes to the induction of PANoptosis in PASMCs. These findings elucidate the role of the circ-myh8/KAT7/SE/FOSL2 axis in the regulation of PANoptosi","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e040334"},"PeriodicalIF":5.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318716","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}