Journal of the American Heart Association最新文献

{"title":"Predictive Effect of Atypical Right Bundle-Branch Block on In-Hospital Sudden Cardiac Death and Cardiac Rupture and Long-Term Prognosis in Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention.","authors":"Tiangui Yang, Jie Chen, Xi Fu, Changlu Xu, Xiaoxia Liu, Peng Fu, Tiesheng Niu","doi":"10.1161/JAHA.124.038344","DOIUrl":"https://doi.org/10.1161/JAHA.124.038344","url":null,"abstract":"<p><strong>Background: </strong>A study was conducted to explore the predictive effect of atypical right bundle-branch blocks (ARBBB) on in-hospital sudden cardiac death (SCD), cardiac rupture (CR), and long-term prognosis in patients with acute myocardial infarction undergoing percutaneous coronary intervention with a drug-eluting stent.</p><p><strong>Methods and results: </strong>A total of 13 886 patients with first-episode acute myocardial infarction who underwent percutaneous coronary intervention with a drug-eluting stent at 3 centers from January 2017 to January 2022 were included in this retrospective study. Patients were categorized into 4 groups: ARBBB (n=348), typical right BBB (n=374), left BBB (n=366), and non-BBB (n=12 798). The primary end points were in-hospital SCD and CR, the secondary end points were 2-year major adverse cardiovascular and cerebrovascular events. During the in-hospital observation period, 334 patients (2.4%) experienced SCD, with 98 (0.7%) attributed to CR. The incidences of in-hospital SCD and CR in the group with ARBBB were significantly higher than those in the other 3 groups (ARBBB versus left BBB versus typical right BBB versus non-BBB: SCD, 10.6% versus 5.7% versus 4.3% versus 2.0%, <i>P</i>=0.001; CR, 5.7% versus 2.7% versus 1.3% versus 0.5%, <i>P</i><0.001). ARBBB was a statistically significant predictor of in-hospital SCD (hazard ratio [HR], 2.45 [95% CI, 1.65-4.78], <i>P<</i>0.001) and CR (HR, 3.32 [95% CI, 1.77-7.74], <i>P<</i>0.001). ARBBB could also predicted the 2-year major adverse cardiovascular and cerebrovascular events (HR, 2.99 [95% CI, 1.65-5.53], <i>P<</i>0.001).</p><p><strong>Conclusions: </strong>ARBBB is a predictor of in-hospital SCD, CR, and 2-year major adverse cardiovascular and cerebrovascular events in patients with first-episode acute myocardial infarction undergoing percutaneous coronary intervention with a drug-eluting stent.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038344"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506008","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":"Genome-Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores.","authors":"Nahin Khan, Abdullah Shaar, Khalid Kunji, Atlas Khan, Mohamed Elshrif, Mohammed Bashir, Mohammed Thamer Ali, Ayman Al Haj Zen, Krzysztof Kiryluk, Georges Nemer, Akl C Fahed, Mohamad Saad","doi":"10.1161/JAHA.124.038341","DOIUrl":"https://doi.org/10.1161/JAHA.124.038341","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Electrocardiography is one of the most valuable noninvasive diagnostic tools in determining the presence of many cardiovascular diseases. Genetic factors are important in determining ECG abnormalities and their link to cardiovascular diseases. Genome-wide association studies and polygenic risk scores (PRSs) have been conducted for various ECG traits such as QT interval and QRS duration. However, these studies mainly focused on cohorts of European descent.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this cohort study, genome-wide association studies for 6 ECG traits (RR, PR, corrected QT interval [QTc], QRS, JT, and &lt;i&gt;P&lt;/i&gt; wave duration) were conducted in a Middle Eastern cohort from the Qatar Precision Health Institute, comprising 13 827 subjects with whole-genome sequence data. Middle Eastern PRSs were developed using clumping and thresholding, and their performance was compared with 26 published PRSs. Genetic predisposition to long QT syndrome was explored using rare variant analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Seventy-four independent loci were obtained with genome-wide significance across the 6 traits (&lt;i&gt;P&lt;/i&gt;&lt;5×10&lt;sup&gt;-8&lt;/sup&gt;). Of the 74 loci, 67 (90.5%) were previously reported, and 7 loci (9.5%) were novel and contained 6 genes: &lt;i&gt;STAC&lt;/i&gt; and &lt;i&gt;CSMD1&lt;/i&gt; for PR, &lt;i&gt;ANK1&lt;/i&gt; and &lt;i&gt;NCOA2&lt;/i&gt; for QRS, &lt;i&gt;LSP1&lt;/i&gt; for QTc, and &lt;i&gt;MKLN1&lt;/i&gt; for &lt;i&gt;P&lt;/i&gt; wave duration. All 26 published PRSs showed good performance in our cohort. PGS002276 showed the best performance for QTc (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;=0.059, &lt;i&gt;P&lt;/i&gt;=4.83×10&lt;sup&gt;-185&lt;/sup&gt;), PGS002166 showed the best performance for QRS (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;=0.024, &lt;i&gt;P&lt;/i&gt;=1.53×10&lt;sup&gt;-75&lt;/sup&gt;), and PGS000905 showed the best performance for PR (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;=0.053, &lt;i&gt;P&lt;/i&gt;=2.57×10&lt;sup&gt;-165&lt;/sup&gt;). Some of these PRSs were associated with cardiovascular diseases. For example, PGS003500, a QTc PRS, was significantly associated with cardiomyopathy (odds ratio per 1 SD=1.58 [95% CI, 1.23-2.01]; &lt;i&gt;P&lt;/i&gt;=2.42×10&lt;sup&gt;-4&lt;/sup&gt;). Middle Eastern PRSs substantially outperformed published PRSs and did not perform well in the UK Biobank data. Ten pathogenic variants, including 3 that are specific to Qatari individuals, were observed in 17 long QT syndrome genes and were carried by 19 individuals. The QTc average was larger for mutation carriers (415.6±23.5 versus 402.3±18.5 in noncarriers). Five-year follow-up data did not show a significant change in ECG patterns, regardless of mutation status and PRS values. Four of 2302 individuals had prolonged QTc intervals over the 2 time points.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this first genome-wide association study for ECG traits in the Middle East using whole-genome sequence data, 7 novel loci (6 genes) were identified. Published PRSs performed well, but newly developed Middle Eastern-specific PRSs performed the best. Novel variants in long QT syndrome genes were observed for the first time in Qatari individuals. Follo","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038341"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505938","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":"Body Composition Risk Assessment of All-Cause Mortality in Patients With Coronary Artery Disease Completing Cardiac Rehabilitation.","authors":"Kimberly L Yan, Icy Liang, Keeley Ravellette, Jeffrey Gornbein, Preethi Srikanthan, Tamara B Horwich","doi":"10.1161/JAHA.124.035006","DOIUrl":"https://doi.org/10.1161/JAHA.124.035006","url":null,"abstract":"<p><strong>Background: </strong>Obesity, measured by body mass index, is a risk factor for cardiovascular disease. However, the role of body composition, including body fat percentage and lean body mass (LBM), in cardiovascular outcomes has not been well studied in patients with coronary artery disease (CAD). This study aims to evaluate the association of body composition with cardiovascular outcomes and all-cause mortality in patients with CAD.</p><p><strong>Methods and results: </strong>Body composition was obtained via bioelectrical impedance analysis from 1291 patients with CAD before starting cardiac rehabilitation. Patients were divided into quintiles by body composition and analyzed in total and after sex stratification. All-cause mortality and a composite of major adverse cardiovascular events, including acute coronary syndrome, coronary revascularization, heart failure hospitalization, and stroke, were primary study outcomes. In the total cohort adjusted analyses, body mass index, body fat percentage, and LBM were not predictors of all-cause mortality or major adverse cardiovascular events. In sex-stratified analyses, among women, the third LBM quintile was associated with decreased risk of all-cause mortality compared with the lowest LBM quintile (adjusted hazard ratio, 0.07 [95% CI, 0.01-0.57]; <i>P</i>=0.01). No other body composition variables were associated with all-cause mortality or major adverse cardiovascular events in either sex.</p><p><strong>Conclusions: </strong>In women with CAD, moderate LBM was associated with lower mortality when compared with low LBM, whereas body fat percentage and body mass index were not associated with mortality or major adverse cardiovascular events in either sex. Future research studying the implications of changes in body composition on outcomes in men and women with CAD is warranted.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e035006"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505892","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":"Protocol-Driven Best Practices and Cardiogenic Shock Survival in Asian Patients.","authors":"Calvin Leung, Yan Hang Fong, Michael Chi Shing Chiang, Ivan Man Ho Wong, Cheuk Bong Ho, Yin Kei Yeung, Chung Yin Leung, Pok Him Lee, Tai Chung So, Yuet Wong Cheng, Shing Fung Chui, Alan Ka Chun Chan, Chi Yuen Wong, Kam Tim Chan, William W O'Neill, Michael Kang Yin Lee","doi":"10.1161/JAHA.124.037742","DOIUrl":"https://doi.org/10.1161/JAHA.124.037742","url":null,"abstract":"<p><strong>Background: </strong>Cardiogenic shock carries high mortality. This study investigated the relationship between protocol-advocated best practices and outcomes.</p><p><strong>Methods: </strong>Patients with cardiogenic shock supported by Impella CP in an Asian tertiary cardiac center were evaluated for 30-day post percutaneous ventricular assist device (PVAD) survival after adopting a standardized protocol emphasizing early mechanical circulatory support (shock-to-PVAD time ≤180 minutes), pulmonary artery catheterization for invasive hemodynamics, and safe vascular access.</p><p><strong>Results: </strong>Of 109 consecutive patients (mean age 58.5±11.2, 80.7% male, 67% acute myocardial infarction, 33% acute decompensated heart failure), 45 (41.3%), 33 (30.3%), and 31 (28.4%) were in SCAI Shock Stages C, D, and E, respectively. A suggestive trend of improving 30-day survival was observed (56.8%, 63.9%, and 72.2% in successive one thirds, P1, P2, and P3 of patients), paralleling a similar trend in achievement of best practices. Patients achieving all 3 best practices significantly increased from 35.1% (P1) to 52.8% (P3) (<i>P</i>=0.026). Median shock-to-PVAD time reduced from 5 [interquartile range: 2-23] hours (P1) to 1.5 [1-5] hours (P3) (<i>P</i> for trend=0.014), whereas pulmonary artery catheterization utilization (80.6-86.1%) and device-related major vascular complications (5.6-8.4%) remained relatively stable. Achieving more best practices was significantly associated with better 30-day survival, with patients achieving all 3, 2, and ≤1 best practices had 30-day survival rates of 75.0%, 63.6%, and 35.7%, respectively (<i>P</i>=0.043). In multivariate Cox regression analysis, shock-to-PVAD time >180 minutes remained an independent predictor of mortality (<i>P</i>=0.031).</p><p><strong>Conclusions: </strong>Achievement of protocol-advocated best practices, especially early shock recognition and prompt PVAD support in appropriate patients, was associated with improved outcomes with PVAD use in cardiogenic shock. Future studies are suggested to confirm the benefits of a protocolized approach and evaluate the value of individual best practices.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037742"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506032","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":"Right Ventricular Stiffening and Anisotropy Alterations in Pulmonary Hypertension: Mechanisms and Relations to Right Heart Failure.","authors":"Sunder Neelakantan, Alexander Vang, Rana Raza Mehdi, Haley Phelan, Preston Nicely, Tasnim Imran, Peng Zhang, Gaurav Choudhary, Reza Avazmohammadi","doi":"10.1161/JAHA.124.037126","DOIUrl":"https://doi.org/10.1161/JAHA.124.037126","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) results in increased right ventricular (RV) afterload, leading to RV dysfunction and failure. The mechanisms underlying maladaptive RV remodeling are poorly understood. In this study, we investigated the multiscale and mechanistic nature of RV free-wall (RVFW) biomechanical remodeling and its correlations with RV function adaptations.</p><p><strong>Methods: </strong>Mild and severe models of PH, consisting of a hypoxia model in Sprague-Dawley rats (n=6 each, control and PH) and a Sugen-hypoxia model in Fischer rats (n=6 each, control and PH), were used. Organ-level function, tissue-level stiffness, and microstructure were quantified through in vivo and ex vivo measures, respectively. Multiscale analysis was used to determine the association between fiber-level remodeling, tissue-level stiffness and anisotropy, and organ-level dysfunction.</p><p><strong>Results: </strong>Decreased RV-pulmonary artery coupling correlated strongly with RVFW stiffening but showed a weaker association with the loss of RVFW anisotropy. Machine-learning classification identified the range of adaptive and maladaptive RVFW stiffening. Multiscale modeling revealed that increased collagen fiber tautness was a key remodeling mechanism that differentiated severe from mild stiffening. Myofiber orientation analysis indicated a shift away from the predominantly circumferential fibers observed in healthy RVFW specimens, leading to a significant loss of tissue anisotropy.</p><p><strong>Conclusions: </strong>Multiscale biomechanical analysis indicated that, although hypertrophy and fibrosis occur in both mild and severe PH, certain fiber-level remodeling events, including increased tautness of collagen fibers and significant reorientations of myofibers, contributed to excessive biomechanical maladaptation of the RVFW leading to severe RV-pulmonary artery uncoupling. Collagen fiber remodeling and the loss of tissue anisotropy can provide an improved understanding of the transition from adaptive to maladaptive RV remodeling.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037126"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506037","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":"Extracellular Matrix Proteins Improve Risk Prediction in Patients Undergoing Transcatheter Aortic Valve Replacement.","authors":"Felicitas Boeckling, Tina Rasper, Lukas Zanders, Graziella Pergola, Sebastian Cremer, Silvia Mas-Peiro, Mariuca Vasa-Nicotera, David Leistner, Stefanie Dimmeler, Badder Kattih","doi":"10.1161/JAHA.124.037296","DOIUrl":"https://doi.org/10.1161/JAHA.124.037296","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibrosis is common in patients with severe aortic stenosis and an independent predictor of death. Therefore, we examined the additional value of circulating fibrosis markers as a putative biomarker platform to identify patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) who are at a higher risk of death.</p><p><strong>Methods: </strong>In this study, 2-year survival analyses were conducted in 378 consecutive patients undergoing TAVR to evaluate the association between fibrosis marker and risk of adverse long-term outcome. Implementation of fibrosis marker into TAVR risk stratification was tested by a machine-learning algorithm.</p><p><strong>Results: </strong>Among 20 circulating fibrosis markers involved in pathological extracellular matrix remodeling, high tissue inhibitor of metalloproteinase-1 (TIMP-1) levels independently predicted risk of death in univariable (hazard ratio, 5.0 [95% CI, 2.6-9.7]; <i>P</i><0.001) and multivariable (adjusted hazard ratio, 2.2 [95% CI, 1.0-4.7]; <i>P</i>=0.046) Cox regression analyses. Consequently, higher TIMP-1 levels offered a significantly higher overall prediction of reduced survival compared with the conventional Society of Thoracic Surgeons Predicted Risk of Mortality score (area under the curve, 0.753 [95% CI, 0.682-0.824] versus area under the curve, 0.656 [95% CI, 0.578-0.734]; <i>P</i><0.05). Applying an independent machine-learning algorithm allowed identification of a simple combination of 2 biomarkers (TIMP-1 and high-sensitivity cardiac troponin T) with superior prognostic value compared with Society of Thoracic Surgeons Predicted Risk of Mortality alone (area under the curve, 0.757 [95% CI, 0.686-0.828] versus 0.656 [95% CI, 0.578-0.34]; <i>P</i><0.05).</p><p><strong>Conclusions: </strong>Circulating TIMP-1 is an independent predictor of reduced 2-year overall survival in patients undergoing TAVR. Combined with high-sensitivity cardiac troponin T, circulating TIMP-1 should be incorporated into risk stratification to identify patients undergoing TAVR who are at a higher risk of death.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e037296"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505935","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":"Plasma Proteomic Assessment of Calcific Aortic Valve Disease in Older Adults.","authors":"Anna E Bortnick, Thomas R Austin, Emily Hamerton, Valborg Gudmundsdottir, Valur Emilsson, Lori L Jennings, Vilmundur Gudnason, David S Owens, Daniele Massera, Line Dufresne, Ta-Yu Yang, James C Engert, George Thanassoulis, Russell P Tracy, Robert E Gerszten, Bruce M Psaty, Jorge R Kizer","doi":"10.1161/JAHA.124.036336","DOIUrl":"https://doi.org/10.1161/JAHA.124.036336","url":null,"abstract":"<p><strong>Background: </strong>Calcific aortic valve disease (CAVD), and ensuing severe aortic stenosis (AS), is the foremost valvular disorder of aging, yet preventive therapies are lacking. A better understanding of the molecular underpinnings of aortic valve calcification (AVC) is necessary to develop pharmacologic interventions.</p><p><strong>Methods and results: </strong>We undertook large-scale plasma proteomics in a cohort study of adults ≥65 years old, the CHS (Cardiovascular Health Study), to identify individual proteins associated with echocardiographic AVC and incident moderate/severe AS. Proteomics measurements were performed with the aptamer-based SomaLogic platform of ~5000 proteins. Significant proteins were validated in a second cohort, the AGES-RS (Age, Gene/Environment Susceptibility-Reykjavik Study), which assessed AVC and AS by computed tomography. The potential causal associations of replicated proteins were tested in 2-sample Mendelian randomization using identified cis protein quantitative trait loci in consortia having computed tomography-quantified AVC or AS as outcomes. Six proteins showed Bonferroni-corrected significant relationships with AVC in CHS. Three of these, CXCL-12 (C-X-C chemokine ligand 12), KLKB1 (kallikrein), and leptin, replicated in AGES-RS, of which the former 2 are novel. Only 1 protein, CXCL6, which showed a near-significant association with AS in the replication cohort, was significantly (positively) associated with incident AS. Mendelian randomization analysis was conducted for KLKB1, CXCL12, and CXCL6, which supported a causal relationship for higher KLKB1 with lower AVC (beta=-0.25, <i>P</i>=0.009).</p><p><strong>Conclusions: </strong>This study of older adults newly identified and largely replicated associations of 3 circulating proteins with calcific aortic valve disease, of which the relationship of plasma KLKB1 may have a causal basis. Additional investigation is necessary to determine if KLKB1 could be harnessed for calcific aortic valve disease therapeutics.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e036336"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506005","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":"Role of Biological Age in the Determination of Long-Term Cause-Specific Death Following Percutaneous Coronary Interventions.","authors":"Mandeep Singh, Paul A Friedman, Rajiv Gulati, Abdallah El Sabbagh, Bradley R Lewis, Amrit Kanwar, Claire E Raphael, Mohammed A Al-Hijji, Zachi I Attia, Atta Behfar, James L Kirkland","doi":"10.1161/JAHA.124.036876","DOIUrl":"https://doi.org/10.1161/JAHA.124.036876","url":null,"abstract":"<p><strong>Background: </strong>We tested whether biologic age, as estimated by deficits, functional impairments, or Age-Gap or their combination, provide improved estimation of cause-specific death as compared with chronological age.</p><p><strong>Methods: </strong>Cardiovascular and noncardiovascular deficits, functional impairments, and Age-Gap were prospectively collected in 535 patients aged ≥55 years undergoing percutaneous coronary interventions between August 1, 2014, and March 31, 2018. Age-Gap was calculated as the difference between chronological age and age estimated by artificial intelligence ECG using a convolutional neural network. The full biological age model included deficits, functional impairments, and Age-Gap >2 SD. A multivariable reduced model with the least number of variables was also created to provide a comparable C index to the full model.</p><p><strong>Results: </strong>The average chronological age was 72.1±9.5 years, and there were 68% of men. During a median follow-up of 2.61 years, 124 (23%) patients died. There was a modest correlation between Age-Gap and biological age (<i>r</i>=0.28 [95% CI, 0.20-0.35]; <i>P</i><0.001). When modeled with chronologic age as a covariate, Age-Gap predicted all-cause (hazard ratio [HR], 1.07 [95% CI, 1.04-1.10]; <i>P</i><0.001) and cardiovascular (HR, 1.07 [95% CI, 1.04-1.11]; <i>P</i><0.001) mortality. As compared with chronological age, the full biological age model noted significant improvement in the prediction of long-term overall (95% CI, 0.65-0.78), cardiovascular (95% CI, 0.69-0.77), and noncardiovascular (95% CI, 0.55-0.86) mortality. In the reduced models, most prognostic information for noncardiovascular mortality (C index: 0.79) was obtained by subjective difficulty in performing tasks, whereas the deficit-based estimation predicted cardiovascular mortality (C index: 0.72).</p><p><strong>Conclusions: </strong>Estimated biological age from deficits and functional impairments was superior to chronological age in predicting long-term cause-specific mortality following percutaneous coronary interventions.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e036876"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506043","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":"Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes.","authors":"Ignatios Ikonomidis, George Pavlidis, Loukia Pliouta, Konstantinos Katogiannis, Eirini Maratou, John Thymis, Eleni Michalopoulou, Vasiliki Prentza, Eleni Katsanaki, Dimitrios Vlachomitros, Aikaterini Kountouri, Emmanouil Korakas, Ioanna Andreadou, Dimitrios Kouretas, John Parissis, Vaia Lambadiari","doi":"10.1161/JAHA.124.039129","DOIUrl":"https://doi.org/10.1161/JAHA.124.039129","url":null,"abstract":"<p><strong>Background: </strong>We investigated the effects of the combined treatment with glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on NT-proBNP (N-terminal pro-brain natriuretic peptide), GDF-15 (growth differentiation factor 15), and MOTS-c (mitochondrial-derived peptide-c) in patients with type 2 diabetes (T2D) and high or very high cardiovascular risk.</p><p><strong>Methods: </strong>We studied 163 consecutive patients with type 2 diabetes who were treated with insulin (n=40), liraglutide (n=41), empagliflozin (n=42), or their combination (GLP-1RA+SGLT-2i) (n=40) and were matched using propensity score analysis. We measured the following at baseline and 4 and 12 months of treatment: (1) NT-proBNP, GDF-15, and MOTS-c; (2) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and (3) left ventricular global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index using speckle-tracking imaging.</p><p><strong>Results: </strong>At 12 months, GLP-1RA, SGLT-2i, and their combination showed a greater reduction of NT-proBNP (-43.1% versus -54.2% versus -56.9% versus -14.7%) and GDF-15 than insulin. Only treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c. GLP-1RA, SGLT-2i, or GLP-1RA+SGLT-2i provided an increase of global longitudinal strain, left atrial strain, and global work index compared with insulin. In all patients, the reduction of NT-proBNP was associated with the improvement of global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index; the decrease of GDF-15 with the increase of ABTS and MOTS-c; and the increase of MOTs-c with improved global longitudinal strain and constructive myocardial work at 12 months (<i>P</i><0.05).</p><p><strong>Conclusions: </strong>Twelve-month treatment with combination of GLP-1RA+SGLT-2i was associated with a greater reduction of neurohumoral markers and increase of antioxidant ability than each treatment alone and insulin. SGLT-2i appear more effective in the improvement of neurohumoral and mitochondrial activation.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03878706.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e039129"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505894","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":"Nicotinamide Riboside: A Promising Treatment for Type 1 Cardiorenal Syndrome in Myocardial Infarction-Induced Acute Kidney Injury by Upregulating Nicotinamide Phosphoribosyltransferase-Mediated Nicotinamide Dinucleotide Levels.","authors":"Nada J Habeichi, Ghadir Amin, Solene Boitard, Cynthia Tannous, Rana Ghali, Iman Momken, Reine Diab, George W Booz, Mathias Mericskay, Fouad A Zouein","doi":"10.1161/JAHA.124.038603","DOIUrl":"https://doi.org/10.1161/JAHA.124.038603","url":null,"abstract":"<p><strong>Background: </strong>Cardiorenal syndrome type 1 is characterized by the development of acute kidney injury following acute cardiac illness and notably acute myocardial infarction (MI). Acute kidney injury is considered an independent risk factor that increases mortality rate substantially. Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in energy metabolism and oxidative phosphorylation, and in its oxidized form it is a substrate for multiple NAD⁺-dependent enzymes such as sirtuins and poly-ADP ribose polymerases. Decreased cardiac NAD levels, along with a downregulation of NAMPT (nicotinamide phosphoribosyl transferase), have been reported following MI. A compensatory upregulation in NMRK (nicotinamide riboside kinase) 2, an NAD⁺ biosynthetic enzyme that uses nicotinamide riboside (NR) to generate NAD⁺, takes place in the heart after MI, but the impact on kidney NAD metabolism and function has not been addressed before.</p><p><strong>Methods and results: </strong>MI was induced by ligating the left anterior descending coronary artery in 2-month-old C57BL6/J mice, followed by the administration of NR (IP injection, 400 mg/kg per day) for 4 and 7 days. We hypothesized that NR treatment could be a potentially promising therapy for MI-induced acute kidney injury. Our findings showed no significant improvement in cardiac ejection fraction following NR treatment at days 4 and 7 post-MI, whereas kidney functions were enhanced and morphological alterations and cell death decreased. The observed renal protection seems to be mediated by an upregulation of NAMPT-mediated increase in renal NAD levels, notably in the distal tubules.</p><p><strong>Conclusions: </strong>Our findings indicate that NR could potentially be a promising therapy for acute kidney injury following an early stage of MI.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038603"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506025","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}