Circulation最新文献

{"title":"Activation of Imprinted Gene <i>PW1</i> Promotes Cardiac Fibrosis After Ischemic Injury.","authors":"Shan Kou, Zhengkai Lu, Defang Deng, Min Ye, Yu Sui, Lieyang Qin, Teng Feng, Zhen Jiang, Jufeng Meng, Chao-Po Lin, Xiajun Li, Chen Liu, Juan Tang, Hui Zhang","doi":"10.1161/CIRCULATIONAHA.124.070738","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070738","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. <i>Pw1</i> (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.</p><p><strong>Methods: </strong>To induce myocardial damage, we performed left anterior descending coronary artery ligation. We generated <i>Pw1</i>^{<i>CreER-2A-eGFP</i>} and <i>Pw1</i>^{<i>2A-CreER</i>} knock-in mouse lines to evaluate the expression of the 2 <i>Pw1</i> alleles in normal and injured hearts. Bisulfite sequencing was used to analyze the DNA methylation of the <i>Pw1</i> imprinting control region. We identified the phosphoribosylformylglycinamidine synthase (<i>Pfas</i>) gene, encoding the DNPB enzyme PFAS, as a direct target of PW1 using chromatin immunoprecipitation sequencing and real-time quantitative polymerase chain reaction. The role of DNPB in ECM production and cardiac fibrosis after injury was examined in vitro using cultured cardiac fibroblasts and in vivo with <i>Pfas</i>-deficient mice.</p><p><strong>Results: </strong>Our study demonstrates that myocardial infarction reduces DNA methylation at the imprinting control region of the maternally imprinted gene <i>Pw1</i>, triggering a switch from monoallelic imprinting to biallelic expression of <i>Pw1</i> in cardiac fibroblasts. In activated cardiac fibroblasts, increased <i>Pw1</i> expression promotes purine biosynthesis and induces ECM production by transcriptionally activating the DNPB factor <i>Pfas</i>. We identified that DNPB is essential for ECM production in activated fibroblasts and that loss of <i>Pfas</i> in fibroblasts limits cardiac fibrosis and improves heart function after injury.</p><p><strong>Conclusions: </strong>This study demonstrates that <i>Pw1</i> imprinting is disrupted after injury and reveals a novel role for the downstream target PFAS in ECM production and cardiac fibrogenesis. Targeting the PW1/PFAS signaling pathway presents a promising therapeutic strategy for improving cardiac repair after injury.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863546","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":"Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.","authors":"Eric Rosenthal, Shakeel A Qureshi, Kothandam Sivakumar, Matthew Jones, San-Fui Yong, Saleha Kabir, Pramod Sagar, Puthiyedath Thejaswi, Sebastien Hascoet, Clement Batteux, Younes Boudjemline, Ziyad M Hijazi, Jamil A Aboulhosn, Daniel S Levi, Morris M Salem, Edwin Francis, Aleksander Kempny, Alain Fraisse, Carles Bautista-Rodriguez, Kevin Walsh, Damien Kenny, Brian Traynor, Salim N Al Maskari, James R Bentham, László Környei, Muthukumaran C Sivaprakasam, Ata Firouzi, Zahra Khajali, Lee Benson, Mark Osten, Alban-Elouen Baruteau, Matthew A Crystal, Thomas J Forbes, Stanimir Georgiev, Horst Sievert, Do Nguyen Tin, Daniel Springmuller, Anand Subramanian, Hussein A M Abdullah, Radwa Bedair, Francisco Chamié, Ahmet Celebi, Jesus Damsky Barbosa, Pieter De Meester, Luca Giugno, Zakaria Jalal, Clement Karsenty, Anastasia Schleiger, Gregory Fleming, Andre Jakob, Tevfik Karagoaz, Gur Mainzer, Gareth J Morgan, Nazmi Narin, Shabana Shahanavaz, Zachary L Steinberg, Osamah Aldoss, Elnur Alizade, Oliver Aregullin, Hélène Bouvaist, Thilo Fleck, Francois Godart, Sophie Malekzadeh-Milani, Paulo Motta, Angel Sanchez-Recalde, Juan Pablo Sandoval, Weiyi Tan, John Thomson, Pablo Tome, Evan M Zahn","doi":"10.1161/CIRCULATIONAHA.124.070271","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070271","url":null,"abstract":"<p><strong>Background: </strong>Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair. However, covered stent correction for SVASD is not recognized by regulatory authorities, and in the minds of many pediatric and adult congenital cardiologists and surgeons, the condition is viewed as treatable only by cardiac surgery with cardiopulmonary bypass.</p><p><strong>Methods: </strong>In April 2023, all centers identified from international conferences, publications, and colleague networks to be undertaking covered stent correction for SVASD were invited to participate in a retrospective audit of their procedures.</p><p><strong>Results: </strong>Data were received on 381 patients from 54 units over a 12-year period with 90% of procedures being performed over the past 5 years. Balloon-expandable stents (8 types) were used in the majority; self-expanding stents (4 types) were used in 4.5%. The commonest stent was the 10-zig covered Cheatham Platinum stent in 62% of cases. In 10 procedures, the stent embolized requiring surgical retrieval and repair of the defect, resulting in technically successful implantation in 371 of 381 (97.4%). Major complications (surgical drainage of tamponade, pacemaker implantation, surgery for pulmonary vein occlusion, and late stent removal) occurred in 5 patients (1.3%). Repeat catheterization to correct residual leaks was required in 7 patients (1.8%). Thus, 359 of 381 patients (94.2%) had successful correction without major complications or additional catheter interventions.</p><p><strong>Conclusions: </strong>This article details the exponential uptake of covered stent correction for SVASD during the past 5 years. Cardiopulmonary bypass was avoided in the majority of patients, and major complications were infrequent. Prospective registries with standardized definitions, inclusion criteria, and follow-up and comparative studies with surgery are now required to help support the extension of covered stent correction as an alternative standard-of-care option for patients with an SVASD.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853043","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":"Optimizing AHA/ACC Guidelines for the Digital Age: Guidelines in Evolution.","authors":"Catherine M Otto, Mariell Jessup, Richard J Kovacs, Joshua A Beckman","doi":"10.1161/CIR.0000000000001294","DOIUrl":"10.1161/CIR.0000000000001294","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e708-e711"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399593","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":"METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.","authors":"Longbin Zheng, Xiang Chen, Xian He, Huiyuan Wei, Xinyu Li, Yongkang Tan, Jiao Min, Minghong Chen, Yunjia Zhang, Mengdie Dong, Quanwen Yin, Mengdie Xue, Lulu Zhang, Da Huo, Hong Jiang, Tingyou Li, Fei Li, Xin Wang, Xuesong Li, Hongshan Chen","doi":"10.1161/CIRCULATIONAHA.124.069574","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.069574","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown. This study aims to investigate the potential involvement of METTL4 in atherosclerosis, explore the underlying mechanism, and develop targeted strategies for treating atherosclerosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Expression levels of mtDNA 6mA and METTL4 were determined in atherosclerotic lesions. We explored the mechanism of METTL4 involvement in atherosclerosis using &lt;i&gt;Mettl4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;Mac&lt;/i&gt;&lt;/sup&gt;&lt;sup&gt;&lt;i&gt;-KO&lt;/i&gt;&lt;/sup&gt;-&lt;i&gt;Apoe&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/&lt;/i&gt;-&lt;/sup&gt; and &lt;i&gt;Mettl4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt;-&lt;i&gt;Apoe&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/&lt;/i&gt;-&lt;/sup&gt; mice and cell models, as well as bone marrow transplantation. Natural compound libraries were screened to identify potent METTL4 antagonists. In addition, bioinspired proteolysis targeting chimera technology targeting macrophages within plaques was used to increase the efficacy of the METTL4 antagonist.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The expression levels of mtDNA 6mA and METTL4 were significantly increased in plaque macrophages. &lt;i&gt;Mettl4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;Mac-KO&lt;/i&gt;&lt;/sup&gt;-&lt;i&gt;Apoe&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/&lt;/i&gt;-&lt;/sup&gt; mice displayed suppressed mtDNA 6mA levels and atherosclerotic progression, which were reversed by METTL4 restoration through bone marrow transplantation (n=6). Mechanistically, elevated METTL4 expression reduces MT-ATP6 expression by suppressing its transcription, thereby impairing the activity of mitochondrial respiration chain complex V. This disruption leads to the accumulation of excess protons in the mitochondrial intermembrane space, causing mitochondrial dysfunction. Consequently, mtDNA is released into the cytoplasm, ultimately triggering inflammasome activation. All results were reversed by the mutation in the METTL4 methyltransferase active site. &lt;i&gt;Mettl4&lt;/i&gt;&lt;sup&gt;&lt;i&gt;MUT&lt;/i&gt;&lt;/sup&gt;-&lt;i&gt;Apoe&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/&lt;/i&gt;-&lt;/sup&gt; mice showed suppressed mtDNA 6mA levels and atherosclerotic progression and repaired mitochondrial function of macrophage, which were reversed by METTL4 restoration through bone marrow transplantation (n=6). Pemetrexed was identified as the first METTL4 antagonist to effectively alleviate atherosclerotic progression. Furthermore, we generated a proteolysis targeting chimera drug based on pemetrexed that specifically targeted METTL4 in macrophages within plaques, showing a promising therapeutic effect on atherosclerosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study revealed a novel mechanism by which mtDNA 6mA orchestrated mitochondrial function-related gene expression in macrophages, thereby promoting atherosclerosis. Through various experimental techniques, such as gene manipulation, pharmacological inhibition, and proteolysis targeting chimera, this study demonstrated that mt","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834247","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":"Long-Term Management of Right Ventricular Outflow Tract Dysfunction in Repaired Tetralogy of Fallot: A Scientific Statement From the American Heart Association.","authors":"Tal Geva, Rachel M Wald, Emily Bucholz, James F Cnota, Doff B McElhinney, Laura M Mercer-Rosa, Carlos M Mery, Andrea Leann Miles, Jeremy Moore","doi":"10.1161/CIR.0000000000001291","DOIUrl":"10.1161/CIR.0000000000001291","url":null,"abstract":"<p><p>Right ventricular outflow dysfunction, manifesting as stenosis, regurgitation, or both, is nearly universal in patients with repaired tetralogy of Fallot, precipitating a complex pathophysiological cascade that leads to increasing rates of morbidity and mortality with advancing age. As the number of adolescent and adult patients with repaired tetralogy of Fallot continues to grow as a result of excellent survival during infancy, the need to improve late outcomes has become an urgent priority. This American Heart Association scientific statement provides an update on the current state of knowledge of the pathophysiology, methods of surveillance, risk stratification, and latest available therapies, including transcatheter and surgical pulmonary valve replacement strategies, as well as management of life-threatening arrhythmias. It reviews emerging evidence on the roles of comorbidities and patient-reported outcomes and their impact on quality of life. In addition, this scientific statement explores contemporary evidence for clinical choices such as transcatheter or surgical pulmonary valve replacement, discusses criteria and options for intervention for failing implanted bioprosthetic pulmonary valves, and considers a new approach to determining optimal timing and indications for pulmonary valve replacement.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e689-e707"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680973","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":"Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.","authors":"Ibrahim Bedioune, Marine Gandon-Renard, Matthieu Dessillons, Aurélien Barthou, Audrey Varin, Delphine Mika, Saïd Bichali, Joffrey Cellier, Patrick Lechène, Sarah Karam, Maya Dia, Susana Gomez, Walma Pereira de Vasconcelos, Françoise Mercier-Nomé, Philippe Mateo, Audrey Dubourg, Constantine A Stratakis, Jean-Jacques Mercadier, Jean-Pierre Benitah, Vincent Algalarrondo, Jérôme Leroy, Rodolphe Fischmeister, Ana-Maria Gomez, Grégoire Vandecasteele","doi":"10.1161/CIRCULATIONAHA.124.068858","DOIUrl":"10.1161/CIRCULATIONAHA.124.068858","url":null,"abstract":"<p><strong>Background: </strong>The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.</p><p><strong>Methods: </strong>We measured PKA subunit expression in human heart and developed a conditional mouse model with cardiomyocyte-specific knockout of RIα (RIα-icKO). Myocardial structure and function were evaluated by echocardiography, histology, and ECG and in Langendorff-perfused hearts. PKA activity and cAMP levels were determined by immunoassay, and phosphorylation of PKA targets was assessed by Western blot. L-type Ca²⁺ current (<i>I</i>_Ca,L), sarcomere shortening, Ca²⁺ transients, Ca²⁺ sparks and waves, and subcellular cAMP were recorded in isolated ventricular myocytes (VMs).</p><p><strong>Results: </strong>RIα protein was decreased by 50% in failing human heart with ischemic cardiomyopathy and by 75% in the ventricles and in VMs from RIα-icKO mice but not in atria or sinoatrial node. Basal PKA activity was increased ≈3-fold in RIα-icKO VMs. In young RIα-icKO mice, left ventricular ejection fraction was increased and the negative inotropic effect of propranolol was prevented, whereas heart rate and the negative chronotropic effect of propranolol were not modified. Phosphorylation of phospholamban, ryanodine receptor, troponin I, and cardiac myosin-binding protein C at PKA sites was increased in propranolol-treated RIα-icKO mice. Hearts from RIα-icKO mice were hypercontractile, associated with increased <i>I</i>_Ca,L, and [Ca²⁺]_i transients and sarcomere shortening in VMs. These effects were suppressed by the PKA inhibitor, H89. Global cAMP content was decreased in RIα-icKO hearts, whereas local cAMP at the phospholamban/sarcoplasmic reticulum Ca²⁺ ATPase complex was unchanged in RIα-icKO VMs. RIα-icKO VMs had an increased frequency of Ca²⁺ sparks and proarrhythmic Ca²⁺ waves, and RIα-icKO mice had an increased susceptibility to ventricular tachycardia. On aging, RIα-icKO mice showed progressive contractile dysfunction, cardiac hypertrophy, and fibrosis, culminating in congestive heart failure with reduced ejection fraction that caused 50% mortality at 1 year.</p><p><strong>Conclusions: </strong>These results identify RIα as a key negative regulator of cardiac contractile function, arrhythmia, and pathological remodeling.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"2031-2045"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361228","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":"Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock: A Secondary Analysis of the DanGer Shock Trial.","authors":"Elric Zweck, Christian Hassager, Rasmus P Beske, Lisette O Jensen, Hans Eiskjær, Norman Mangner, Amin Polzin, P Christian Schulze, Carsten Skurk, Peter Nordbeck, Peter Clemmensen, Vasileios Panoulas, Sebastian Zimmer, Andreas Schäfer, Malte Kelm, Thomas Engstrøm, Lene Holmvang, Anders Junker, Henrik Schmidt, Christian J Terkelsen, Axel Linke, Ralf Westenfeld, Jacob E Møller","doi":"10.1161/CIRCULATIONAHA.124.072370","DOIUrl":"10.1161/CIRCULATIONAHA.124.072370","url":null,"abstract":"<p><strong>Background: </strong>In DanGer Shock (the Danish-German Cardiogenic Shock trial), use of a microaxial flow pump (mAFP) in patients with ST-segment-elevation myocardial infarction-related cardiogenic shock led to lower all-cause mortality but higher rates of renal replacement therapy (RRT). In this prespecified analysis, rates and predictors of acute kidney injury (AKI) and RRT were assessed.</p><p><strong>Methods: </strong>In this international, randomized, open-label, multicenter trial, 355 adult patients with ST-segment-elevation myocardial infarction-related cardiogenic shock were randomized to mAFP (n=179) or standard care alone (n=176). AKI was defined according to RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease) and assessed using logistic regression models. Use of RRT was assessed accounting for the competing risk of death using Fine-Gray subdistribution hazard models.</p><p><strong>Results: </strong>AKI (RIFLE ≥1) was recorded in 110 patients (61%) in the mAFP group and 79 patients (45%) in the control group (<i>P</i><0.01); RRT was used in 75 (42%) and 47 (27%) patients, respectively (<i>P</i><0.01). About two-thirds of the RRTs were initiated within the first 24 hours from admission (n=48 [64%] in the mAFP group and n=31 [66%] in the control group). Occurrence of AKI and RRT were associated with higher 180-day mortality in both study arms. At 180 days, all patients alive were free of RRT. mAFP use was associated with higher rates of RRT, even when accounting for competing risk of death (subdistribution hazard, 1.67 [1.18-2.35]). This association was largely consistent among prespecified subgroups. Allocation to mAFP was associated with lower 180-day mortality irrespective of AKI or RRT (<i>P</i>_interaction=0.84). Relevant predictors of AKI in both groups comprised reduced left ventricular ejection fraction, baseline kidney function, shock severity, bleeding events, and positive fluid balance. Predictors of AKI specific to mAFP were suction events, higher pump speed, and longer duration of support.</p><p><strong>Conclusions: </strong>Shock severity, allocation to mAFP, and device-related complications were associated with an increased risk of AKI. AKI was generally associated with higher mortality, but the allocation to mAFP consistently led to lower mortality rates at 180 days irrespective of the occurrence of AKI with or without RRT initiation.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT01633502.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1990-2003"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496242","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":"End-Organ Injury and Failure: The True DanGer in Cardiogenic Shock.","authors":"Saraschandra Vallabhajosyula","doi":"10.1161/CIRCULATIONAHA.124.072571","DOIUrl":"10.1161/CIRCULATIONAHA.124.072571","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"2004-2006"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496239","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":"Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults.","authors":"Roshan A Ananda, StellaMay Gwini, Lawrence J Beilin, Markus P Schlaich, Michael Stowasser, Morag J Young, Brendan Adler, Peter J Fuller, Trevor A Mori, Jun Yang","doi":"10.1161/CIRCULATIONAHA.124.070039","DOIUrl":"10.1161/CIRCULATIONAHA.124.070039","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease.</p><p><strong>Methods: </strong>The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006-2009) and 27 (2016-2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure.</p><p><strong>Results: </strong>This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; <i>P</i><0.001) and 27 (12.0 mU/L versus 15.4 mU/L; <i>P</i><0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; <i>P</i><0.001) and 27 (21.0 versus 15.6; <i>P</i><0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 [95% CI, 0.001-0.017]; <i>P</i>=0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 [95% CI, 0.001-0.196]; <i>P</i>=0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age.</p><p><strong>Conclusions: </strong>Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"2019-2030"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342769","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":"Future of Antihypertensive Therapies.","authors":"Luke J Laffin","doi":"10.1161/CIRCULATIONAHA.124.072417","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072417","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"150 25","pages":"1987-1989"},"PeriodicalIF":35.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834320","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}