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Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial Circulation (IF 37.8) Pub Date : 2024-03-27 Kristoffer Berg-Hansen, Nigopan Gopalasingam, Kristian Hylleberg Christensen, Bertil Ladefoged, Mads Jønsson Andersen, Steen Hvitfeldt Poulsen, Barry A. Borlaug, Roni Nielsen, Niels Møller, Henrik Wiggers
BACKGROUND:Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction.METHODS:In a randomized, double-blind cross-over study, nondiabetic
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The American Heart Association’s Centennial and Percutaneous Coronary Intervention’s Semi-Centennial Circulation (IF 37.8) Pub Date : 2024-03-25 Patrick W. Serruys, Pruthvi C. Revaiah
In 1975 at a meeting in Frankfurt, Professor Paul Lichtlen, a key European opinion leader, quipped that a significant coronary lesion with a thin fibrous cap and a large atheromatous core (vulnerable plaque) could not be stretched with a balloon without the risk of major distal embolization as proposed by Dr Andreas Grüntzig, a young radiologist. During the meeting, Andreas Grüntzig’s poster described
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Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence? Circulation (IF 37.8) Pub Date : 2024-03-25 Enzo Lüsebrink, Leonhard Binzenhöfer, Daniel Hering, Laura Villegas Sierra, Benedikt Schrage, Clemens Scherer, Walter S. Speidl, Aitor Uribarri, Manel Sabate, Marko Noc, Elena Sandoval, Andrejs Erglis, Federico Pappalardo, Frederic De Roeck, Guido Tavazzi, Jordi Riera, Roberto Roncon-Albuquerque Jr, Benjamin Meder, Peter Luedike, Tienush Rassaf, Jörg Hausleiter, Christian Hagl, Sebastian Zimmer, Dirk
The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac
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Don’t Judge A Book By Its Cover Circulation (IF 37.8) Pub Date : 2024-03-25 Saurabh Deshpande, Rajesh Rajani, Ameya Udyavar
A 55-year-old woman with long-standing diabetes and hypertension with hypertrophic cardiomyopathy (diagnosed on cardiac magnetic resonance imaging) was implanted with a single-chamber, single-coil implantable cardioverter defibrillator (ICD; Abbott Laboratories) for primary prevention a few weeks previously. She presented to the emergency department with history of dyspnea and recent episodes of tachycardia
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Correction to: Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-03-25
In the article by Ndumele et al, “Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association,” which published ahead of print on Monday, October 9, 2023, and appeared in the November 14, 2023, issue of the journal (Circulation. 2023;148:1606–1635. DOI: 10.1161/CIR.0000000000001184), a correction was needed. On page 1619, in the Figure 4 legend, “Finorenone”
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Correction to: 2023 Scientific Sessions Abstract 15684 Circulation (IF 37.8) Pub Date : 2024-03-25
In the 2023 Scientific Sessions abstract by Kono et al, “Abstract 15684: Adherence and Persistence to SGLT2 Inhibitors in Patients With Heart Failure,” which published on November 6, 2023 (Circulation. 2023;148:A15684. DOI: 10.1161/circ.148.suppl_1.15684), a correction is needed. In the Methods section, the first sentence read, “This retrospective cohort study included patients ≤65 years discharged
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Correction to: 2023 Scientific Sessions Abstract 18539 Circulation (IF 37.8) Pub Date : 2024-03-25
In the 2023 Scientific Sessions abstract by Patel et al, “Abstract 18539: The Impact of Prophylactic Heparin on Pocket Hematoma Formation After Cardiac Implantable Electronic Device Implantation a Real-World Experience,” which published on November 6, 2023 (Circulation. 2023;148:A18539. DOI: 10.1161/circ.148.suppl_1.18539), a correction is needed. “Garrett Peters” has been added to the author byline
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Correction to: International Collaboration Identifies Gene Linked to Congenital Heart Defect Circulation (IF 37.8) Pub Date : 2024-03-25
In the article by Kuehn, “International Collaboration Identifies Gene Linked to Congenital Heart Defect,” which was published in the January 16, 2024, issue of the journal (Circulation. 2024;149:267–269. doi: 10.1161/CIRCULATIONAHA.123.067153), a correction is needed. It has come to the author’s attention that collaborator Simon Body’s information was not correct as displayed below. Collaborator Collaborator
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Retraction of: Abstract 13079: Prevalence and Incidence of Transthyretin Amyloid Cardiomyopathy in the USA From 2004 to 2022: An Observational Database Study Circulation (IF 37.8) Pub Date : 2024-03-25
For the American Heart Association’s 2023 Scientific Sessions Abstract 13079 by Kevin M Alexander, Anne S Ersboell, Christiane L Haase, Julie T Mortensen, and Mathew S Maurer (“Prevalence and Incidence of Transthyretin Amyloid Cardiomyopathy in the USA From 2004 to 2022: An Observational Database Study”; Circulation.2023;148;A13079. https://www.ahajournals.org/doi/10.1161/circ.148.suppl_1.13079), one
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Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart Circulation (IF 37.8) Pub Date : 2024-03-20 Jana Grune, Geetika Bajpai, Pervin Tülin Ocak, Eva Kaufmann, Kyle Mentkowksi, Steffen Pabel, Nina Kumowski, Fadi E. Pulous, Kim A. Tran, David Rohde, Shuang Zhang, Yoshiko Iwamoto, Gregory R. Wojtkiewicz, Claudio Vinegoni, Ursula Green, Filip K. Swirski, James R. Stone, Jochen K. Lennerz, Maziar Divangahi, Maarten Hulsmans, Matthias Nahrendorf
BACKGROUND:Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and
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Correction to: Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-03-18
In the article by Batra et al, “Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association,” which published ahead of print on February 5, 2024, and appeared in the March 5, 2024, issue of the journal (Circulation. 2024;149:e937–e952. DOI: 10.1161/CIR.0000000000001206), a correction was needed. On page e945, in Figure
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A Century of Heart Failure With Reduced Ejection Fraction: Mostly Drought, Followed by Rapid Progress Circulation (IF 37.8) Pub Date : 2024-03-18 Mariell Jessup
The clinical syndrome of heart failure (HF), encompassing a constellation of signs and symptoms, has been recognized for more than a century. The incremental steps over the past 100 years—discoveries from basic research, the use of investigational drugs, pivotal clinical trials—often have been indiscernible. Nevertheless, the century has witnessed a reduction in morbidity and mortality rates for this
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Wide Complex Tachycardia: Mind Your Medicine! Circulation (IF 37.8) Pub Date : 2024-03-18 Chan-Hee Lee, Melvin M. Scheinman
A 59-year-old male was referred to the emergency room with palpitations. He underwent radiofrequency ablation of persistent atrial fibrillation 2 years before and was taking flecainide 75 mg twice per day, bisoprolol 2.5 mg per day, and warfarin sodium 3.75 mg per day. His blood pressure was 120/80 mm Hg, heart rate 202 bpm, and oxygen saturation 99% on room air. His serum sodium level was 129 mEq/L
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Small Extracellular Vesicles From Infarcted and Failing Heart Accelerate Tumor Growth Circulation (IF 37.8) Pub Date : 2024-03-15 Tal Caller, Itai Rotem, Olga Shaihov-Teper, Daria Lendengolts, Yeshai Schary, Ruty Shai, Efrat Glick-Saar, Dan Dominissini, Menachem Motiei, Idan Katzir, Rachela Popovtzer, Merav Nahmoud, Alex Boomgarden, Crislyn D’Souza-Schorey, Nili Naftali-Shani, Jonathan Leor
BACKGROUND:Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex and unclear. Here, we aimed to test our hypothesis that cardiac small extracellular vesicles (sEVs), particularly cardiac mesenchymal stromal cell–derived sEVs (cMSC-sEVs), contribute to the link between post-MI left ventricular dysfunction (LVD) and cancer
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Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-03-11 Salim S. Hayek, Vlad G. Zaha, Carmel Bogle, Anita Deswal, Amelia Langston, Seth Rotz, Alexi Vasbinder, Eric Yang, Tochukwu Okwuosa, on behalf of the American Heart Association Cardio-Oncology Committee of the Council on Clinical Cardiology and Council on Genomic and Precision Medicine, and the Council on Cardiovascular and Stroke Nursing
Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance
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Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With or Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials Circulation (IF 37.8) Pub Date : 2024-03-11 Prakriti Gaba, Joseph F. Sabik, Sabina A. Murphy, Andrea Bellavia, Patrick T. O’Gara, Peter K. Smith, Patrick W. Serruys, A. Pieter Kappetein, Seung-Jung Park, Duk-Woo Park, Evald H. Christiansen, Niels R. Holm, Per H. Nielsen, Marc S. Sabatine, Gregg W. Stone, Brian A. Bergmark
BACKGROUND:Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes undergoing PCI versus CABG.METHODS:Individual patient data were pooled from
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Correction to: 2023 Scientific Sessions Abstract 18987 Circulation (IF 37.8) Pub Date : 2024-03-11
In the 2023 Scientific Sessions abstract by Umrani et al, “Abstract 18987: A 10-Year Contemporary Analysis of Outcomes of Patients With Amyloidosis and VT Underdoing Ventricular Tachycardia (VT) Ablation,” which published on November 6, 2023 (Circulation. 2023;148:A18987. DOI: 10.1161/circ.148.suppl_1.18987), a correction is needed. In the author byline, author “Yaser Khallid” has been updated to read
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Antiarrhythmic Drug Therapy: Where Do We Go From Here? Circulation (IF 37.8) Pub Date : 2024-03-11 Peter R. Kowey, Gerald V. Naccarelli
Most sufferers with heart disease cannot be cured. The purpose of intelligent care is the prolongation of life, the diminution of suffering, and the increase in the mental and physical efficiency of the patient. — Samuel Levine, Clinical Heart Disease Fourth Edition, Saunders, 1951 Antiarrhythmic drugs have been and will remain the mainstay of the chronic therapy of patients who have cardiac arrhythmias
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Correction to: Development and Validation of the American Heart Association’s PREVENT Equations Circulation (IF 37.8) Pub Date : 2024-03-11
In the article by Khan et al, “Development and Validation of the American Heart Association’s PREVENT Equations,” which appeared in the February 6, 2024, issue of the journal (Circulation. 2024;149:430–449. DOI: 10.1161/CIRCULATIONAHA.123.067626), a correction is needed. On page 433, the year range in the following sentence was updated from 2015–2020 to 2015–2019, to read, “The SDI was calculated at
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Correction to: 2023 Scientific Sessions Abstract 18918 Circulation (IF 37.8) Pub Date : 2024-03-11
In the 2023 Scientific Sessions abstract by Umrani et al, “Abstract 18918: Outcomes of Patients With Transcatheter Aortic Valve Replacement (TAVR) and Cardiac Resynchronization Therapy (CRT): A Retrospective Analysis,” which published on November 6, 2023 (Circulation. 2023;148:A18918. DOI: 10.1161/circ.148.suppl_1.18918), a correction is needed. In the author byline, Yaser Khalid has been added as
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Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-03-07 Vikas Aggarwal, Jay Giri, Scott H. Visovatti, Ehtisham Mahmud, Hiromi Matsubara, Michael Madani, Frances Rogers, Deepa Gopalan, Kenneth Rosenfield, Vallerie V. McLaughlin, on behalf of the American Heart Association Council on Clinical Cardiology, Council on Peripheral Vascular Disease, Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, and Council on Cardiovascular and Stroke
Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly
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Toward Heart-Healthy and Sustainable Cities: A Policy Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-03-04 Sanjay Rajagopalan, Anu Ramaswami, Aruni Bhatnagar, Robert D. Brook, Mark Fenton, Christopher Gardner, Roni Neff, Armistead G. Russell, Karen C. Seto, Laurie P. Whitsel, on behalf of the American Heart Association Council on Hypertension, Council on Lifestyle and Cardiometabolic Health, Council on Peripheral Vascular Disease, Council on Lifelong Congenital Heart Disease and Heart Health in the Young
Nearly 56% of the global population lives in cities, with this number expected to increase to 6.6 billion or >70% of the world’s population by 2050. Given that cardiometabolic diseases are the leading causes of morbidity and mortality in people living in urban areas, transforming cities and urban provisioning systems (or urban systems) toward health, equity, and economic productivity can enable the
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MBNL1 Regulates Programmed Postnatal Switching Between Regenerative and Differentiated Cardiac States Circulation (IF 37.8) Pub Date : 2024-03-01 Logan R.J. Bailey, Darrian Bugg, Isabella M. Reichardt, C. Dessirée Ortaç, Abigail Nagle, Jagadambika Gunaje, Amy Martinson, Richard Johnson, Michael J. MacCoss, Tomoya Sakamoto, Daniel P. Kelly, Michael Regnier, Jennifer M. Davis
BACKGROUND:Discovering determinants of cardiomyocyte maturity is critical for deeply understanding the maintenance of differentiated states and potentially reawakening endogenous regenerative programs in adult mammalian hearts as a therapeutic strategy. Forced dedifferentiation paired with oncogene expression is sufficient to drive cardiac regeneration, but elucidation of endogenous developmental regulators
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Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-02-28 Antonis A. Armoundas, Sanjiv M. Narayan, Donna K. Arnett, Kayte Spector-Bagdady, Derrick A. Bennett, Leo Anthony Celi, Paul A. Friedman, Michael H. Gollob, Jennifer L. Hall, Anne E. Kwitek, Elle Lett, Bijoy K. Menon, Katherine A. Sheehan, Salah S. Al-Zaiti, on behalf of the American Heart Association Institute for Precision Cardiovascular Medicine, Council on Cardiovascular and Stroke Nursing, Council
A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research
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mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis Circulation (IF 37.8) Pub Date : 2024-02-27 Sarah Hoedemakers, Nicola Riccardo Pugliese, Jan Stassen, Arnaud Vanoppen, Jade Claessens, Tin Gojevic, Youri Bekhuis, Maarten Falter, Sara Moura Ferreira, Sebastiaan Dhont, Nicolò De Biase, Lavinia Del Punta, Valerio Di Fiore, Marco De Carlo, Cristina Giannini, Andrea Colli, Raluca Elena Dulgheru, Jolien Geers, Alaaddin Yilmaz, Guido Claessen, Philippe Bertrand, Steven Droogmans, Patrizio Lancellotti
BACKGROUND:Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L−1·min−1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value
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Cardiogenic Shock in Older Adults: A Focus on Age-Associated Risks and Approach to Management: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-02-26 Vanessa Blumer, Manreet K. Kanwar, Christopher F. Barnett, Jennifer A. Cowger, Abdulla A. Damluji, Maryjane Farr, Sarah J. Goodlin, Jason N. Katz, Colleen K. McIlvennan, Shashank S. Sinha, Tracy Y. Wang, on behalf of the American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing, Council on
Cardiogenic shock continues to portend poor outcomes, conferring short-term mortality rates of 30% to 50% despite recent scientific advances. Age is a nonmodifiable risk factor for mortality in patients with cardiogenic shock and is often considered in the decision-making process for eligibility for various therapies. Older adults have been largely excluded from analyses of therapeutic options in patients
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Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial Circulation (IF 37.8) Pub Date : 2024-02-26 Yan Yan, Jincheng Guo, Xiao Wang, Guozhong Wang, Zeyuan Fan, Delu Yin, Zhifang Wang, Fuchun Zhang, Changming Tian, Wei Gong, Jiamin Liu, Jiapeng Lu, Yongjun Li, Changsheng Ma, Eric Vicaut, Gilles Montalescot, Shaoping Nie, on behalf of the RIGHT Investigators
BACKGROUND:Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment–elevation myocardial infarction, although no conclusive data support this practice.METHODS:The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized
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Targeting NPM1 Epigenetically Promotes Postinfarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism Circulation (IF 37.8) Pub Date : 2024-02-23 Sheng Zhang, Yunkai Zhang, Xuewen Duan, Bo Wang, Zhenzhen Zhan
BACKGROUND:Reparative macrophages play a crucial role in limiting excessive fibrosis and promoting cardiac repair after myocardial infarction (MI), highlighting the significance of enhancing their reparative phenotype for wound healing. Metabolic adaptation orchestrates the phenotypic transition of macrophages; however, the precise mechanisms governing metabolic reprogramming of cardiac reparative
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Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-02-22 Erica Sood, Jane W. Newburger, Julia S. Anixt, Adam R. Cassidy, Jamie L. Jackson, Richard A. Jonas, Amy J. Lisanti, Keila N. Lopez, Shabnam Peyvandi, Bradley S. Marino, on behalf of the American Heart Association Council on Lifelong Congenital Heart Disease and Heart Health in the Young and the Council on Cardiovascular and Stroke Nursing
Over the past decade, new research has advanced scientific knowledge of neurodevelopmental trajectories, factors that increase neurodevelopmental risk, and neuroprotective strategies for individuals with congenital heart disease. In addition, best practices for evaluation and management of developmental delays and disorders in this high-risk patient population have been formulated based on literature
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Addressing Barriers to Entry and Retention of Women in Interventional Vascular Specialties With Proposed Solutions: A Scientific Statement From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-02-20 S. Elissa Altin, Mimmie Kwong, Naomi M. Hamburg, Mark A. Creager, Subhash Banerjee, Lola Oladini, Marabel D. Schneider, Jean Marie Ruddy, on behalf of the American Heart Association Council on Peripheral Vascular Disease, Council on Cardiovascular Surgery and Anesthesia, Council on Clinical Cardiology, and Stroke Council
Representation of women in interventional vascular fields (interventional cardiology, interventional radiology, and vascular surgery) lags behind that in other specialties. With women representing half of all medical school graduates, encouraging parity of women in these fields needs to start in medical school. Barriers to pursuing careers in vascular intervention include insufficient exposure during
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FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System Circulation (IF 37.8) Pub Date : 2024-02-16 Bowen Li, Fangfang Liu, Xihui Chen, Tangdong Chen, Juan Zhang, Yifeng Liu, Yan Yao, Weihong Hu, Mengjie Zhang, Bo Wang, Liwen Liu, Kun Chen, Yuanming Wu
BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a common heritable myocardiopathy. Although HCM has been reported to be associated with many variants of genes involved in sarcomeric protein biomechanics, pathogenic genes have not been identified in patients with partial HCM. FARS2 (the mitochondrial phenylalanyl-tRNA synthetase), a type of mitochondrial aminoacyl-tRNA synthetase, plays a role in the
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Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation Circulation (IF 37.8) Pub Date : 2024-02-15 Amy Erica Lin, Aneesh C. Bapat, Ling Xiao, Abhishek Niroula, Jianchuan Ye, Waihay J. Wong, Mridul Agrawal, Christopher J. Farady, Andreas Boettcher, Christopher B. Hergott, Marie McConkey, Patricio Flores-Bringas, Veronica Shkolnik, Alexander G. Bick, David Milan, Pradeep Natarajan, Peter Libby, Patrick T. Ellinor, Benjamin L. Ebert
BACKGROUND:Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored.METHODS:CHIP prevalence
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Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells Circulation (IF 37.8) Pub Date : 2024-02-15 Ziwen Cai, Miaomiao Zhu, Li Xu, Yue Wang, Yin Xu, Wai Yen Yim, Hong Cao, Ruikang Guo, Xiang Qiu, Ximiao He, Jiawei Shi, Weihua Qiao, Nianguo Dong
BACKGROUND:A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation
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S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages Circulation (IF 37.8) Pub Date : 2024-02-15 Yan Zhang, Hao Zhang, Shuang Zhao, Zhenhua Qi, Yiwei He, Xuhong Zhang, Wencheng Wu, Ke Yan, Lulu Hu, Shixiu Sun, Xinlong Tang, Qing Zhou, Feng Chen, Aihua Gu, Liansheng Wang, Zhiren Zhang, Bo Yu, Dongjin Wang, Yi Han, Liping Xie, Yong Ji
BACKGROUND:S-Nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in cardiovascular disease. Aortic aneurysm and dissection are high-risk cardiovascular diseases without an effective cure. The aim of this study was to determine the role of SNO of Septin2 in macrophages in aortic aneurysm and dissection.METHODS:Biotin-switch assay combined with liquid chromatography–tandem
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Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification Circulation (IF 37.8) Pub Date : 2024-02-13 Xiaoxuan Zhai, Shengchuan Cao, Jiali Wang, Bao Qiao, Xuehao Liu, Rui Hua, Menglin Zhao, Shukun Sun, Yu Han, Shuo Wu, Jiaojiao Pang, Qiuhuan Yuan, Bailu Wang, Feng Xu, Shujian Wei, Yuguo Chen
BACKGROUND:Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product
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The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft Circulation (IF 37.8) Pub Date : 2024-02-12 Xiao Li, Diwakar Turaga, Rich G. Li, Chang-Ru Tsai, Julianna N. Quinn, Yi Zhao, Ruby Wilson, Katherine Carlson, Jun Wang, Joseph A. Spinner, Edward J. Hickey, Iki Adachi, James F. Martin
BACKGROUND:Much of our knowledge of organ rejection after transplantation is derived from rodent models.METHODS:We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus
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Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study) Circulation (IF 37.8) Pub Date : 2024-02-12 Jennifer B. Green, Brendan M. Everett, Alokananda Ghosh, Naji Younes, Heidi Krause-Steinrauf, Joshua Barzilay, Cyrus Desouza, Silvio E. Inzucchi, Yashashwi Pokharel, David Schade, Alexandra Scrymgeour, Meng H. Tan, Kristina M. Utzschneider, Sunder Mudaliar
BACKGROUND:Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. The effects of glucose-lowering medications on cardiovascular outcomes in individuals with type 2 diabetes and low cardiovascular risk are unclear. We investigated cardiovascular outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or
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Machine Learning for Myocardial Infarction Compared With Guideline-Recommended Diagnostic Pathways Circulation (IF 37.8) Pub Date : 2024-02-12 Jasper Boeddinghaus, Dimitrios Doudesis, Pedro Lopez-Ayala, Kuan Ken Lee, Luca Koechlin, Karin Wildi, Thomas Nestelberger, Raphael Borer, Òscar Miró, F. Javier Martin-Sanchez, Ivo Strebel, Maria Rubini Giménez, Dagmar I. Keller, Michael Christ, Anda Bularga, Ziwen Li, Amy V. Ferry, Chris Tuck, Atul Anand, Alasdair Gray, Nicholas L. Mills, Christian Mueller
BACKGROUND:Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended
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Coronary Angiography, Intravascular Ultrasound, and Optical Coherence Tomography in the Guidance of Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis. Circulation (IF 37.8) Pub Date : 2024-02-12 Daniele Giacoppo, Claudio Laudani, Giovanni Occhipinti, Marco Spagnolo, Antonio Greco, Carla Rochira, Federica Agnello, Davide Landolina, Maria Sara Mauro, Simone Finocchiaro, Placido Mazzone, Nicola Ammirabile, Antonino Imbesi, Carmelo Raffo, Sergio Buccheri, Davide Capodanno
BACKGROUND:Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)– and optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)–guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results.METHODS:Major electronic databases
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CEO Foreword: The Centennial Presidential Advisory Circulation (IF 37.8) Pub Date : 2024-02-12 Nancy Brown
I often describe the 3 greatest assets of the American Heart Association (AHA) as our brand, our grassroots volunteers, and our science. Each is critical to our mission, but without science, we would not be the same organization. We were founded by scientists who sought new insights into heart disease. Now, 100 years later, we remain squarely focused on the power of science and research to improve
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The American Heart Association at 100: A Century of Scientific Progress and the Future of Cardiovascular Science: A Presidential Advisory From the American Heart Association Circulation (IF 37.8) Pub Date : 2024-02-12 Mitchell S.V. Elkind, Donna K. Arnett, Ivor J. Benjamin, Robert H. Eckel, Augustus O. Grant, Steven R. Houser, Alice K. Jacobs, Daniel W. Jones, Rose Marie Robertson, Ralph L. Sacco, Sidney C. Smith Jr, Myron L. Weisfeldt, Joseph C. Wu, Mariell Jessup
In 1924, the founders of the American Heart Association (AHA) envisioned an international society focused on the heart and aimed at facilitating research, disseminating information, increasing public awareness, and developing public health policy related to heart disease. This presidential advisory provides a comprehensive review of the past century of cardiovascular and stroke science, with a focus
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Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy Circulation (IF 37.8) Pub Date : 2024-02-08 Aldostefano Porcari, Marianna Fontana, Marco Canepa, Elena Biagini, Francesco Cappelli, Christian Gagliardi, Simone Longhi, Linda Pagura, Giacomo Tini, Franca Dore, Rachele Bonfiglioli, Matteo Bauckneht, Alberto Miceli, Francesca Girardi, Anna Lisa Martini, Giulia Barbati, Egidio Natalino Costanzo, Angelo Giuseppe Caponetti, Andrea Paccagnella, Maurizio Sguazzotti, Giovanni La Malfa, Mattia Zampieri
BACKGROUND:The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome.METHODS:Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body
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Phosphorylation-Regulated Dynamic Phase Separation of HIP-55 Protects Against Heart Failure Circulation (IF 37.8) Pub Date : 2024-02-08 Yunqi Jiang, Jinge Gu, Xiaodou Niu, Jiaojiao Hu, Yongzhen Zhang, Dan Li, Yida Tang, Cong Liu, Zijian Li
BACKGROUND:Heart failure (HF), which is the terminal stage of many cardiovascular diseases, is associated with low survival rates and a severe financial burden. The mechanisms, especially the molecular mechanism combined with new theories, underlying the pathogenesis of HF remain elusive. We demonstrate that phosphorylation-regulated dynamic liquid–liquid phase separation of HIP-55 (hematopoietic progenitor
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A Galectin-9–Driven CD11chigh Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia Circulation (IF 37.8) Pub Date : 2024-02-05 Yanhong Li, Yifei Sang, Yunjian Chang, Chunfang Xu, Yikong Lin, Yao Zhang, Philip C.N. Chiu, William S.B. Yeung, Haisheng Zhou, Ningzheng Dong, Ling Xu, Jiajia Chen, Weijie Zhao, Lu Liu, Di Yu, Xingxing Zang, Jiangfeng Ye, Jinying Yang, Qingyu Wu, Dajin Li, Ligang Wu, Meirong Du
BACKGROUND:Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear.METHODS:Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based
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Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension Circulation (IF 37.8) Pub Date : 2024-02-05 Ya Luo, Xianmei Qi, Zhenxi Zhang, Jiawei Zhang, Bolun Li, Ting Shu, Xiaona Li, Huiyuan Hu, Jinqiu Li, Qihao Tang, Yitian Zhou, Mingyao Wang, Tianfei Fan, Wenjun Guo, Ying Liu, Jin Zhang, Junling Pang, Peiran Yang, Ran Gao, Wenhui Chen, Chen Yan, Yanjiang Xing, Wenjing Du, Jing Wang, Chen Wang
BACKGROUND:Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic
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Pediatric ECG-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling Circulation (IF 37.8) Pub Date : 2024-02-05 Joshua Mayourian, William G. La Cava, Akhil Vaid, Girish N. Nadkarni, Sunil J. Ghelani, Rebekah Mannix, Tal Geva, Audrey Dionne, Mark E. Alexander, Son Q. Duong, John K. Triedman
BACKGROUND:Artificial intelligence–enhanced ECG analysis shows promise to detect ventricular dysfunction and remodeling in adult populations. However, its application to pediatric populations remains underexplored.METHODS:A convolutional neural network was trained on paired ECG–echocardiograms (≤2 days apart) from patients ≤18 years of age without major congenital heart disease to detect human expert–classified
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Efficacy and Safety of Non–Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation Circulation (IF 37.8) Pub Date : 2024-01-24 Siddharth M. Patel, Eugene Braunwald, Jan Steffel, Giuseppe Boriani, Michael G. Palazzolo, Elliott M. Antman, Erin A. Bohula, Anthony P. Carnicelli, Stuart J. Connolly, John W. Eikelboom, Baris Gencer, Christopher B. Granger, David A. Morrow, Manesh R. Patel, Lars Wallentin, Christian T. Ruff, Robert P. Giugliano, on behalf of the COMBINE AF (A Collaboration Between Multiple Institutions to Better
BACKGROUND:The efficacy and safety of non–vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain.METHODS:We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal
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AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease Circulation (IF 37.8) Pub Date : 2024-01-23 Dong Han, Tingwen Zhou, Lifu Li, Yan Ma, Shiqi Chen, Chunguang Yang, Ning Ma, Moshi Song, Shaoshao Zhang, Jie Wu, Feng Cao, Yongjun Wang
BACKGROUND:Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and
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CRISPR Activation Reverses Haploinsufficiency and Functional Deficits Caused by TTN Truncation Variants Circulation (IF 37.8) Pub Date : 2024-01-18 Shahnaz Ghahremani, Aditya Kanwal, Anthony Pettinato, Feria Ladha, Nicholas Legere, Ketan Thakar, Yanfen Zhu, Harianto Tjong, Andrea Wilderman, W. Tom Stump, Lina Greenberg, Michael J. Greenberg, Justin Cotney, Chia-Lin Wei, J. Travis Hinson
BACKGROUND:TTN truncation variants (TTNtvs) are the most common genetic lesion identified in individuals with dilated cardiomyopathy, a disease with high morbidity and mortality rates. TTNtvs reduce normal TTN (titin) protein levels, produce truncated proteins, and impair sarcomere content and function. Therapeutics targeting TTNtvs have been elusive because of the immense size of TTN, the rarity of
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Piezo1-Mediated Neurogenic Inflammatory Cascade Exacerbates Ventricular Remodeling After Myocardial Infarction Circulation (IF 37.8) Pub Date : 2024-01-18 Meiyan Sun, Sui Mao, Chao Wu, Xiaoyong Zhao, Chengxiao Guo, Jun Hu, Shijin Xu, Fen Zheng, Guoqing Zhu, Hui Tao, Shufang He, Ji Hu, Ye Zhang
BACKGROUND:Heart failure is associated with a high rate of mortality and morbidity, and ventricular remodeling invariably precedes heart failure. Ventricular remodeling is fundamentally driven by mechanotransduction that is regulated by both the nervous system and the immune system. However, it remains unknown which key molecular factors govern the neuro/immune/cardio axis that underlies mechanotransduction
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Novel Role for Cardiolipin as a Target of Therapy to Mitigate Myocardial Injury Caused by Venoarterial Extracorporeal Membrane Oxygenation Circulation (IF 37.8) Pub Date : 2024-01-18 Lija Swain, Shreyas Bhave, Xiaoying Qiao, Lara Reyelt, Kay Everett, Junya Awata, Rahul Raghav, Sarah N. Powers, Genya Sunagawa, Peter S. Natov, Elena Mahmoudi, Mary Warner, Greg Couper, Masa Kawabori, Satoshi Miyashita, Tejasvi Aryaputra, Gordon S. Huggins, Michael T. Chin, Navin K. Kapur
BACKGROUND:Cardiolipin is a mitochondrial-specific phospholipid that maintains integrity of the electron transport chain (ETC) and plays a central role in myocardial ischemia/reperfusion injury. Tafazzin is an enzyme that is required for cardiolipin maturation. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use to provide hemodynamic support for acute myocardial infarction has grown exponentially
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Epigenetic Regulation of Cardiomyocyte Maturation by Arginine Methyltransferase CARM1 Circulation (IF 37.8) Pub Date : 2024-01-15 Tiffany A. Garbutt, Zhenhua Wang, Haofei Wang, Hong Ma, Hongmei Ruan, Yanhan Dong, Yifang Xie, Lianmei Tan, Ranan Phookan, Joy Stouffer, Vasanth Vedantham, Yuchen Yang, Li Qian, Jiandong Liu
BACKGROUND:During the neonatal stage, the cardiomyocyte undergoes a constellation of molecular, cytoarchitectural, and functional changes known collectively as cardiomyocyte maturation to increase myocardial contractility and cardiac output. Despite the importance of cardiomyocyte maturation, the molecular mechanisms governing this critical process remain largely unexplored.METHODS:We leveraged an
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Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex Circulation (IF 37.8) Pub Date : 2024-01-12 Chen Xu, Ge Zhang, Xinjian Wang, Xiaozhi Huang, Jiayin Zhang, Shuxian Han, Jinxi Wang, Duane D. Hall, Ruoqing Xu, Feng He, Xing Chang, Fudi Wang, Wenjun Xie, Zhichao Wu, Long-Sheng Song, Peidong Han
BACKGROUND:Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear.METHODS:Given
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ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension Circulation (IF 37.8) Pub Date : 2024-01-12 Jin-Song Bian, Jingyu Chen, Junting Zhang, Jianxin Tan, Yuan Chen, Xusheng Yang, Yiying Li, Lin Deng, Rongchang Chen, Xiaowei Nie
BACKGROUND:Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases.METHODS:Microarray
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A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network Circulation (IF 37.8) Pub Date : 2024-01-08 Michael T. Broman, Rangarajan D. Nadadur, Carlos Perez-Cervantes, Ozanna Burnicka-Turek, Sonja Lazarevic, Anna Gams, Brigitte Laforest, Jeffrey D. Steimle, Sabrina Iddir, Zhezhen Wang, Linsin Smith, Stefan R. Mazurek, Harold E. Olivey, Pingzhu Zhou, Margaret Gadek, Kaitlyn M. Shen, Zoheb Khan, Joshua W.M. Theisen, Xinan H. Yang, Kohta Ikegami, Igor R. Efimov, William T. Pu, Christopher R. Weber, Elizabeth
BACKGROUND:The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2) is observed in human ventricles during HF and causes HF in mice.METHODS:FOG2
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Metabolic Communication by SGLT2 Inhibition Circulation (IF 37.8) Pub Date : 2023-12-28 Anja M. Billing, Young Chul Kim, Søren Gullaksen, Benedikt Schrage, Janice Raabe, Arvid Hutzfeldt, Fatih Demir, Elina Kovalenko, Moritz Lassé, Aurelien Dugourd, Robin Fallegger, Birgit Klampe, Johannes Jaegers, Qing Li, Olha Kravtsova, Maria Crespo-Masip, Amelia Palermo, Robert A. Fenton, Elion Hoxha, Stefan Blankenberg, Paulus Kirchhof, Tobias B. Huber, Esben Laugesen, Tanja Zeller, Maria Chrysopoulou
BACKGROUND:SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood.METHODS:To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating
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INO80-Dependent Remodeling of Transcriptional Regulatory Network Underlies the Progression of Heart Failure Circulation (IF 37.8) Pub Date : 2023-12-28 Zongna Ren, Wanqing Zhao, Dandan Li, Peng Yu, Lin Mao, Quanyi Zhao, Luyan Yao, Xuelin Zhang, Yandan Liu, Bingying Zhou, Li Wang
BACKGROUND:Progressive remodeling of cardiac gene expression underlies decline in cardiac function, eventually leading to heart failure. However, the major determinants of transcriptional network switching from normal to failed hearts remain to be determined.METHODS:In this study, we integrated human samples, genetic mouse models, and genomic approaches, including bulk RNA sequencing, single-cell RNA
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Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension Circulation (IF 37.8) Pub Date : 2023-12-22 William R. Reay, Erin Clarke, Shaun Eslick, Carlos Riveros, Elizabeth G. Holliday, Mark A. McEvoy, Roseanne Peel, Stephen Hancock, Rodney J. Scott, John R. Attia, Clare E. Collins, Murray J. Cairns
BACKGROUND:Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics
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Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction Circulation (IF 37.8) Pub Date : 2023-12-21 Cristina Panico, Arianna Felicetta, Paolo Kunderfranco, Marco Cremonesi, Nicolò Salvarani, Pierluigi Carullo, Federico Colombo, Alessandra Idini, Mauro Passaretti, Riccardo Doro, Marcello Rubino, Alessandro Villaschi, Giorgio Da Rin, Clelia Peano, Marinos Kallikourdis, Carolina M. Greco, Gianluigi Condorelli
BACKGROUND:Metabolic distress is often associated with heart failure with preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities with HFpEF. How metabolic changes affect myocardial inflammation in the context of HFpEF is not known.METHODS:We found that ApoE knockout mice fed a Western diet recapitulate many features of
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Ago2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation Circulation (IF 37.8) Pub Date : 2023-12-21 Jiabing Zhan, Kunying Jin, Rong Xie, Jiahui Fan, Yuyan Tang, Chen Chen, Huaping Li, Dao Wen Wang
BACKGROUND:Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular Ago2 (Argonaute2), a core member of miRNA machinery, remain elusive.METHODS:We elucidated the function and mechanism of subcellular localized Ago2 on mouse models for diabetes and diabetic