Circulation最新文献

{"title":"Genotype-Specific Outcomes of Desmosomal Cardiomyopathies.","authors":"Valerio Pergola, Alessandro Trancuccio, Deni Kukavica, Andrea Mazzanti, Carlo Napolitano, Gabriele Gaetano Scilabra, Kenneth Steele, Mirella Memmi, Patrick Gambelli, Andrea Sugamiele, Alessia Chiara Latini, Nicola Pisani, Giulio Mazzotta, Raffaella Bloise, Massimo Morini, Maira Marino, Silvia G Priori","doi":"10.1161/CIRCULATIONAHA.124.073475","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.073475","url":null,"abstract":"<p><strong>Background: </strong>Desmosomal gene variants (DGVs) have been associated with a diverse spectrum of phenotypic manifestations within arrhythmogenic cardiomyopathy, but data on genotype-specific outcomes are lacking. We investigated genotype-specific arrhythmic and heart failure (HF) outcomes in DGV carriers.</p><p><strong>Methods: </strong>This cohort study included consecutive patients referred for screening for desmosomal genes. Carriers of pathogenic and rare (allele frequency <10^-⁴) variants of uncertain significance were included. The arrhythmic end point was the occurrence of a life-threatening arrhythmic event, defined as sudden cardiac death, aborted cardiac arrest, or hemodynamically unstable ventricular tachycardia. The end-stage HF outcome was the composite of a fatal HF episode or cardiac transplantation.</p><p><strong>Results: </strong>We included 533 DGV carriers (59% male; median [interquartile range] age, 39 [22-54] years) from 214 families: 503 of 533 had a single DGV (212 [40%] <i>PKP2</i>, 160 [30%] <i>DSP</i>, 97 [18%] <i>DSG2</i>, 34 [6%] <i>DSC2</i>) and 30 of 533 (6%) double DGVs. Overall, 83 of 533 (16%) experienced a life-threatening arrhythmic event (at age 40 [33-51] years), and 14 of 533 (3%) experienced end-stage HF (at age 57 [50-60] years). Multivariable analysis demonstrated that, compared with nonmissense <i>PKP2</i> variants, nonmissense <i>DSP</i> variants (hazard ratio [HR], 2.3 [95% CI, 1.3-4.1]; <i>P</i>=0.008), missense variants in hotspot domains in <i>DSP</i> (HR, 2.7 [95% CI, 1.2-6.2]; <i>P</i>=0.010) and <i>PKP2</i> (HR, 3.6 [95% CI, 2.0-6.5]; <i>P</i><0.001), male sex (HR, 1.7 [95% CI, 1.1-2.8]; <i>P</i>=0.021), and double DGVs (HR, 3.4 [95% CI, 1.7-6.9]; <i>P</i><0.001) were associated with a higher risk of a life-threatening arrhythmic event. Nonmissense <i>DSP</i> variants (HR, 5.0 [95% CI, 1.5-18.2]; <i>P</i>=0.009) and double DGVs (HR, 4.7 [95% CI, 1.0-19.3]; <i>P</i>=0.044) were also associated with increased risk of end-stage HF.</p><p><strong>Conclusions: </strong>Among carriers of DGVs, genotype was associated with arrhythmic and HF outcomes, with type and location of the variant further modulating the natural history.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126911","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":"Proteomic Signatures for Risk Prediction of Atrial Fibrillation.","authors":"Hanjin Park,Faye L Norby,Daehoon Kim,Eunsun Jang,Hee Tae Yu,Tae-Hoon Kim,Jae-Sun Uhm,Jung-Hoon Sung,Hui-Nam Pak,Moon-Hyoung Lee,Pil-Sung Yang,Boyoung Joung","doi":"10.1161/circulationaha.124.073457","DOIUrl":"https://doi.org/10.1161/circulationaha.124.073457","url":null,"abstract":"BACKGROUNDProteomic signatures might improve disease prediction and enable targeted disease prevention and management. We explored whether a protein risk score derived from large-scale proteomics data improves risk prediction of atrial fibrillation (AF).METHODSA total of 51 680 individuals with 1459 unique plasma protein measurements and without a history of AF were included from the UKB-PPP (UK Biobank Pharma Proteomics Project). A protein risk score was developed with lasso-penalized Cox regression from a random subset of 70% (36 176 individuals, 54.4% women, 2155 events) and was tested on the remaining 30% (15 504 individuals, 54.4% women, 910 events). The protein risk score was externally replicated with the ARIC study (Atherosclerosis Risk in Communities; 11 012 individuals, 54.8% women, 1260 events).RESULTSThe protein risk score formula developed from the UKB-PPP derivation set was composed of 165 unique plasma proteins, and 15 of them were associated with atrial remodeling. In the UKB-PPP test set, a 1-SD increase in protein risk score was associated with a hazard ratio of 2.20 (95% CI, 2.05-2.41) for incident AF. The C index for a model including CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation), NT-proBNP (N-terminal B-type natriuretic peptide), polygenic risk score, and protein risk score was 0.816 (95% CI, 0.802-0.829) compared with 0.771 (95% CI, 0.755-0.787) for a model including CHARGE-AF, NT-proBNP, and polygenic risk score (C-index change, 0.044 [95% CI, 0.039-0.055]). Protein risk score added to CHARGE-AF, NT-proBNP, and polygenic risk score resulted in a risk reclassification of 5.4% (95% CI, 2.9%-7.9%) with a 5-year risk threshold of 5%. In the decision curve, the predicted net benefit before and after the addition of protein risk score to a model including CHARGE-AF, NT-proBNP, and polygenic risk score was 3.8 and 5.4 per 1000 people, respectively, at a 5-year risk threshold of 5%. External replication of a protein risk score in the ARIC study showed consistent improvement in risk stratification of AF.CONCLUSIONSProtein risk score derived from a single plasma sample improved risk prediction of AF. Further research using proteomic signatures in AF screening and prevention is needed.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"4 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114198","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":"Intracellular L-PGDS-Derived 15d-PGJ2 Inhibits CaMKII Through Lipoxidation to Alleviate Cardiac Ischemia/Reperfusion Injury.","authors":"Qingmei Hu,Junxia Zhang,Xile Luo,Peiyu Hu,Jiayi Li,Fan Li,Zeyuan Wang,Shuyang Zhang,Zishan Jiao,Yitong Liu,Jiaxin Duanmu,Li Jin,Peng Xie,Wenneng Zhu,Wen Zheng,Haibao Shang,Xinli Hu,Zhixing Chen,Rui-Ping Xiao,Yan Zhang","doi":"10.1161/circulationaha.124.070936","DOIUrl":"https://doi.org/10.1161/circulationaha.124.070936","url":null,"abstract":"BACKGROUNDMyocardial ischemia/reperfusion (I/R) injury is a substantial challenge to the management of ischemic heart disease, the leading cause of mortality worldwide. Arachidonic acid (AA) is a prominent polyunsaturated fatty acid in the human body and plays an important role in various physiological and pathological conditions. AA metabolic enzymes determine AA levels; however, currently there is no comprehensive analysis of AA enzymes in cardiac I/R injury.METHODSThe profiling of AA metabolic enzymes was analyzed with the RNA sequencing transcriptome data from the mouse heart tissues with I/R injury. Cultured neonatal and adult rat ventricular myocytes, human embryonic stem cell-derived cardiomyocytes, and in vivo mouse I/R models were used to confirm the role of L-PGDS (lipocalin-type prostaglandin D2 synthase)/15d-PGJ2 in I/R injury. A biotin-tagged 15d-PGJ2 analog combined with liquid chromatography-tandem mass spectrometry was used to identify the downstream signaling of L-PGDS/15d-PGJ2.RESULTSBased on the transcriptome data and experimental validations, L-PGDS, together with its downstream metabolite 15d-PGJ2, was downregulated in cardiac tissue with I/R injury. Functionally, L-PGDS overexpression mitigates myocardial I/R injury, whereas knockdown exacerbates the damage. Supplementation of 15d-PGJ2 alleviated I/R injury. Mechanistically, 15d-PGJ2 covalently bound to the Ca2+/CaMKII (calmodulin protein kinase II) and induced lipoxidation of its cysteine 495 (CaMKII-δ9) to dampen the formation of CaMKII oligomers and alleviate its overactivation, consequently ameliorating cardiomyocyte death and cardiac injury.CONCLUSIONSOur study uncovered L-PGDS/15d-PGJ2/CaMKII signaling as a new mechanism underlying I/R-induced cardiomyocyte death. This provides new mechanistic insights and therapeutic targets for myocardial I/R injury and subsequent heart failure. We also showed that lipoxidation is a new post-translational modification type for CaMKII, deepening our understanding of the regulation of its activity.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"72 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103740","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":"Olmesartan Restores <i>LMNA</i> Function in Haploinsufficient Cardiomyocytes.","authors":"Eric J Kort, Nazish Sayed, Chun Liu, Gema Mondéjar-Parreño, Jens Forsberg, Emily Eugster, Sean M Wu, Joseph C Wu, Stefan Jovinge","doi":"10.1161/CIRCULATIONAHA.121.058621","DOIUrl":"10.1161/CIRCULATIONAHA.121.058621","url":null,"abstract":"<p><strong>Background: </strong>Gene mutations are responsible for a sizeable proportion of cases of heart failure. However, the number of patients with any specific mutation is small. Repositioning of existing US Food and Drug Administration-approved compounds to target specific mutations is a promising approach to efficient identification of new therapies for these patients.</p><p><strong>Methods: </strong>The National Institutes of Health Library of Integrated Network-Based Cellular Signatures database was interrogated to identify US Food and Drug Administration-approved compounds that demonstrated the ability to reverse the transcriptional effects of <i>LMNA</i> knockdown. Top hits from this screening were validated in vitro with patient-specific induced pluripotent stem cell-derived cardiomyocytes combined with force measurement, gene expression profiling, electrophysiology, and protein expression analysis.</p><p><strong>Results: </strong>Several angiotensin receptor blockers were identified from our in silico screen. Of these, olmesartan significantly elevated the expression of sarcomeric genes and rate and force of contraction and ameliorated arrhythmogenic potential. In addition, olmesartan exhibited the ability to reduce phosphorylation of extracellular signal-regulated kinase 1 in <i>LMNA</i>-mutant induced pluripotent stem cell-derived cardiomyocytes.</p><p><strong>Conclusions: </strong>In silico screening followed by in vitro validation with induced pluripotent stem cell-derived models can be an efficient approach to identifying repositionable therapies for monogenic cardiomyopathies.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1436-1448"},"PeriodicalIF":35.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Fatty Acid Metabolism Activates Neighboring Hematopoietic Stem Cells to Promote Heart Failure With Preserved Ejection Fraction.","authors":"Mallory Filipp, Zhi-Dong Ge, Matthew DeBerge, Connor Lantz, Kristofor Glinton, Peng Gao, Sasha Smolgovsky, Jingbo Dai, You-Yang Zhao, Laurent Yvan-Charvet, Pilar Alcaide, Samuel E Weinberg, Gabriele G Schiattarella, Joseph A Hill, Matthew J Feinstein, Sanjiv J Shah, Edward B Thorp","doi":"10.1161/CIRCULATIONAHA.124.070248","DOIUrl":"10.1161/CIRCULATIONAHA.124.070248","url":null,"abstract":"<p><strong>Background: </strong>Despite the high morbidity and mortality of heart failure with preserved ejection fraction (HFpEF), treatment options remain limited. The HFpEF syndrome is associated with a high comorbidity burden, including high prevalence of obesity and hypertension. Although inflammation is implicated to play a key role in HFpEF pathophysiology, underlying causal mechanisms remain unclear.</p><p><strong>Methods: </strong>Comparing patient samples and animal models, we defined the innate immune response during HFpEF in situ and through flow cytometry and single-cell RNA sequencing. After identifying transcriptional and cell signatures, we implemented a high-fat diet and hypertensive model of HFpEF and tested roles for myeloid and hematopoietic stem cells during HFpEF. Contributions of macrophage metabolism were also evaluated, including through mass spectrometry and carbon labeling. Primary macrophages were studied ex vivo to gain insight into complementary cell-intrinsic mechanisms.</p><p><strong>Results: </strong>Here we report evidence that patients with cardiometabolic HFpEF exhibit elevated peripheral blood hematopoietic stem cells. This phenotype was conserved across species in a murine mode of high-fat diet and hypertension. Hematopoietic stem cell proliferation was coupled to striking remodeling of the peripheral hematopoietic stem cell niche and expression of the macrophage adhesion molecule <i>Vcam1</i>. This could be partially inhibited by sodium-glucose cotransporter-2 inhibitors and explained by elevated fatty acid metabolism in macrophage mitochondria, which in turn remodeled the <i>Vcam1</i> promoter to enhance its expression.</p><p><strong>Conclusions: </strong>These findings identify a significant new stem cell signature of cardiometabolic HFpEF and support a role for myeloid maladaptive fatty acid metabolism in the promotion of systemic inflammation and cardiac diastolic dysfunction.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1451-1466"},"PeriodicalIF":35.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial.","authors":"Albert Wiegman,Amy L Peterson,Robert A Hegele,Eric Bruckert,Anja Schweizer,Anastasia Lesogor,Yibo Wang,Joep Defesche","doi":"10.1161/circulationaha.124.073233","DOIUrl":"https://doi.org/10.1161/circulationaha.124.073233","url":null,"abstract":"BACKGROUNDHomozygous familial hypercholesterolemia (HoFH) is a genetic disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C) present from birth, leading to early-onset and progressive atherosclerotic cardiovascular disease. Early treatment initiation is crucial for cardiovascular risk reduction; however, many patients do not reach LDL-C treatment goals. Inclisiran, a small interfering RNA targeting hepatic PCSK9 (proprotein convertase subtilisin/kexin type 9), is effective and well tolerated in adult patients with hyperlipidemia; however, it has not yet been studied in pediatric patients.METHODSHerein we report results of the 1-year, double-blind, placebo-controlled part of the phase 3 study ORION-13 (Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia) in adolescents with HoFH. This 2-part multicenter study included 13 patients ≥12 to <18 years of age with a genetic diagnosis of HoFH (excluding LDL [low-density lipoprotein] receptor [LDLR] null/null genotypes) and elevated LDL-C levels (>130 mg/dL) on maximally tolerated statin treatment, with or without other lipid-lowering therapies. Eligible patients were randomized 2:1 to receive either 300 mg of inclisiran sodium or placebo, administered on days 1, 90, and 270. The primary end point was the mean percentage change in LDL-C from baseline to day 330.RESULTSThe mean age of patients was 14.8 years, and mean baseline LDL-C was 272 mg/dL. The placebo-adjusted mean (95% CI) percentage change in LDL-C from baseline to day 330 was -33.3% (-59.2% to -7.3%). Six of 9 (66.7%) inclisiran-treated patients (versus 1 of 4 [25%] on placebo) achieved a >15% reduction in LDL-C, and 5 of 9 (55.6%) inclisiran-treated patients (versus none on placebo) achieved a >20% reduction. The placebo-adjusted mean (95% CI) percentage change in PCSK9 from baseline to day 330 was -60.2% (-79.8% to -40.7%); corresponding changes in apoB (apolipoprotein B), non-high-density lipoprotein cholesterol, and total cholesterol were -23.0%, -32.7%, and -27.8%, respectively. No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred. No new safety findings were reported.CONCLUSIONSIn a 1-year randomized controlled study (part 1 of ORION-13), inclisiran was effective in lowering LDL-C in adolescents with HoFH and was well tolerated. These results support inclisiran as a potentially useful addition for the treatment of adolescents with HoFH and a minimum of LDLR residual activity.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT04659863.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"35 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097799","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":"Leveraging Transcriptional Readouts as a Platform for Drug Repurposing in Cardiomyopathy.","authors":"Ahmed I Mahmoud,Hesham A Sadek","doi":"10.1161/circulationaha.125.074556","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074556","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"6 1","pages":"1449-1450"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097731","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":"Letter by Berry and McCartney Regarding Article, \"Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention (The PITRI Trial)\".","authors":"Colin Berry,Peter McCartney","doi":"10.1161/circulationaha.124.071295","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071295","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"135 1","pages":"e1002-e1003"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097727","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":"Response by Bulluck and Hausenloy to Letter Regarding Article, \"Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (the PITRI Trial)\".","authors":"Heerajnarain Bulluck,Derek J Hausenloy,","doi":"10.1161/circulationaha.124.072689","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072689","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"211 1","pages":"e1004-e1005"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097724","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":"Partial Heart Transplantation: Early Experience With Pediatric Heart Valve Replacements That Grow.","authors":"Neel K Prabhu,Berk Aykut,Michael Mensah-Mamfo,Douglas M Overbey,Joseph W Turek","doi":"10.1161/circulationaha.124.072626","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072626","url":null,"abstract":"Heart valve replacement in children is fraught with long-term morbidity and mortality rates, largely because conventional implants lack the capacity to grow with the child. Partial heart transplantation presents a potential solution by transplanting only specific segments of a donor heart, thereby providing a living and growing heart valve implant. This approach harnesses the full spectrum of cardiac tissues, which, when freshly procured and supported by immunosuppression, can integrate as functional and potentially growth-capable tissue. This state-of-the-art review discusses the history and development of partial heart transplantation, its indications, recent clinical experiences, regulation, and future directions.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"31 1","pages":"1477-1490"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097723","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}