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Wuqiang Zhu, Eric Zhang, Meng Zhao, Zechen Chong, Chengming Fan, Yawen Tang, Jervaughn D Hunter, Anton V Borovjagin, Gregory P Walcott, Jake Y Chen, Gangjian Qin, Jianyi Zhang
Background -Rodent hearts can regenerate myocardium lost to apical resection or myocardial infarction for up to 7 days after birth, but whether a similar window for myocardial regeneration also exists in large mammals is unknown. Methods -Acute myocardial infarction (AMI) was surgically induced in neonatal pigs on postnatal days 1, 2, 3, 7, and 14 (i.e., the P1, P2, P3, P7, and P14 groups, respectively). Cardiac systolic function was evaluated before AMI and at 30 days post AMI via transthoracic echocardiography...
July 20, 2018: Circulation
Lei Ye, Giuseppe D'Agostino, Sze Jie Loo, Chen Xu Wang, Li Ping Su, Shi Hua Tan, Gui Zhen Tee, Chee Jian Pua, Edgar Macabe Pena, Redmond Belen Cheng, Way Cherng Chen, Desiree Abdurrachim, Janise Lalic, Ru San Tan, Teck Hock Lee, JianYi Zhang, Stuart Alexander Cook
Background -The adult mammalian heart has limited ability to repair itself following injury. Zebrafish, newts and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown if hearts of young large mammals can regenerate. Methods -We examined the regenerative capacity of the pig heart in neonatal animals (ages: 2, 3 or 14 days postnatal) after myocardial infarction (MI) or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance (CMR) imaging and echocardiography...
July 20, 2018: Circulation
Tal Geva, Barbara Mulder, Kimberlee Gauvreau, Sonya V Babu-Narayan, Rachel Wald, Kelsey Hickey, Andrew J Powell, Michael A Gatzoulis, Anne Marie Valente
Background -Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot (rTOF) before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia (VT) and death have not been identified. Methods -Patients with rTOF enrolled in the INDICATOR cohort-a 4-center international cohort study- who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Pre-procedural clinical, electrocardiogram, cardiovascular magnetic resonance (CMR), and postoperative outcome data were analyzed...
July 20, 2018: Circulation
Toru Hashimoto, Grace E Kim, Richard S Tunin, Tolulope Adesiyun, Steven Hsu, Ryo Nakagawa, Guangshuo Zhu, Jennifer J O'Brien, Joseph P Hendrick, Robert E Davis, Wei Yao, David Beard, Helen R Hoxie, Lawrence P Wennogle, Dong I Lee, David A Kass
Background -Phosphodiesterase type-1 (PDE1) hydrolyzes cyclic AMP and cGMP and is constitutively expressed in the heart, though cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly express PDE1C with balanced selectivity for cAMP and cGMP. Here, we determined acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs and rabbits, in normal and failing hearts, and explored its regulatory pathways...
July 20, 2018: Circulation
Georg Fuernau, Johannes Beck, Steffen Desch, Ingo Eitel, Christian Jung, Sandra Erbs, Norman Mangner, Philipp Lurz, Karl Fengler, Alexander Jobs, Reinhard Vonthein, Suzanne de Waha-Thiele, Marcus Sandri, Gerhard Schuler, Holger Thiele
Background -Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock following acute myocardial infarction. The objective of this study was to inves-tigate hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction. Methods -Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary in-tervention without classical indication for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 h or control...
July 19, 2018: Circulation
Hilary S Gammill, Rakesh Chettier, Alina Brewer, James M Roberts, Raj Shree, Eleni Tsigas, Kenneth Ward
Background -Preeclampsia (PE), is associated with diastolic dysfunction, peripartum cardiomyopathy (CM), and both preexisting and subsequent maternal cardiovascular disease (CVD). Gene mutations causing idiopathic CM were recently implicated in peripartum CM. We sought to determine whether CM gene mutations are also a contributory factor in PE. Methods -Subjects were participants in The Preeclampsia Registry and Biobank. After providing informed consent, subjects with a history of PE completed a detailed questionnaire and provided medical records for diagnostic confirmation...
July 18, 2018: Circulation
Aaron W Aday, Patrick R Lawler, Nancy R Cook, Paul M Ridker, Samia Mora, Aruna D Pradhan
Background -Despite strong and consistent prospective associations of elevated low-density lipoprotein-cholesterol (LDL-C) concentration with incident coronary and cerebrovascular disease (CCVD), data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle concentration (LDL-P), rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein-cholesterol (HDL-C) may be the primary lipid driver of PAD risk...
July 18, 2018: Circulation
Angela L Jefferson, Francis E Cambronero, Dandan Liu, Elizabeth E Moore, Jacquelyn E Neal, James G Terry, Sangeeta Nair, Kimberly R Pechman, Swati Rane, L Taylor Davis, Katherine A Gifford, Timothy J Hohman, Susan P Bell, Thomas J Wang, Joshua A Beckman, John J Carr
Background -Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. Methods -Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (NC, n=155, 72±7, 59% male) or mild cognitive impairment (MCI, n=115, 73±7, 57% male)...
July 17, 2018: Circulation
Yu Liming, Yang Guang, Zhang Xinjian, Wang Peng, Weng Xinyu, Yang Yuyu, Li Zilong, Fang Mingming, Yong Xu, Sun Aijun, Ge Junbo
Background -Excessive accumulation of reactive oxygen species (ROS), catalyzed by the NADPH oxidases (NOX), is involved in the pathogenesis of ischemia-reperfusion (I/R) injury. The underlying epigenetic mechanism remains elusive. Methods -We evaluated the potential role of megakaryocytic leukemia 1, or MKL1, as a bridge linking epigenetic activation of NOX to ROS production and cardiac ischemia-reperfusion injury. Results -Following I/R injury, MKL1 deficient (KO) mice exhibited smaller myocardial infarction along with improved heart function compared to wild type (WT) littermates...
July 17, 2018: Circulation
Laurens E Swart, Anna Gomes, Asbjørn M Scholtens, Bhanu Sinha, Wilco Tanis, Marnix G E H Lam, Maureen J van der Vlugt, Sebastian A F Streukens, Erik H J G Aarntzen, Jan Bucerius, Sander van Assen, Chantal P Bleeker-Rovers, Peter Paul van Geel, Gabriel P Krestin, Joost P van Melle, Jolien W Roos-Hesselink, Riemer H J A Slart, Andor W J M Glaudemans, Ricardo P J Budde
Background -18 F-Fluorodeoxyglucose (FDG) Positron-Emission Tomography/Computed Tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve (PV) endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, as well as several confounders. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients suspected of PVE by identifying and excluding possible confounders, using both visual and standardized quantitative assessments...
July 17, 2018: Circulation
Tarique A Musa, Thomas A Treibel, Vassiliou S Vassiliou, Gabriella Captur, Anvesha Singh, Calvin Chin, Laura E Dobson, Silvia Pica, Margaret Loudon, Tamir Malley, Marzia Rigolli, James R J Foley, Petra Bijsterveld, Graham R Law, Marc R Dweck, Saul G Myerson, Gerry P McCann, Sanjay K Prasad, James C Moon, John P Greenwood
Background -Aortic valve replacement (AVR) for aortic stenosis (AS) is timed primarily on the development of symptoms; but late surgery can result in irreversible myocardial dysfunction and additional risk. This study aimed to determine whether presence of focal myocardial scar pre-operatively was associated with long-term mortality. Methods -In a longitudinal observational outcome study, survival analysis was performed in patients with severe AS listed for valve intervention at six UK cardiothoracic centers...
July 12, 2018: Circulation
Richard Haynes, Parminder K Judge, Natalie Staplin, William G Herrington, Benjamin C Storey, Angelyn Bethel, Louise Bowman, Nigel Brunskill, Paul Cockwell, Michael Hill, Philip A Kalra, John J V McMurray, Maarten Taal, David C Wheeler, Martin J Landray, Colin Baigent
Background -Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate-to-severe chronic kidney disease are unknown. Methods -UK HARP-III was a randomised double-blind trial which included 414 participants with an estimated glomerular filtration rate (GFR) 20-60 mL/min/1.73m2 who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily...
July 12, 2018: Circulation
Prabhu Mathiyalagan, Marta Adamiak, Joshua Mayourian, Yassine Sassi, Yaxuan Liang, Neha Agarwal, Divya Jha, Shihong Zhang, Erik Kohlbrenner, Elena Chepurko, Jiqiu Chen, Maria G Trivieri, Rajvir Singh, Rihab Bouchareb, Kenneth Fish, Kiyotake Ishikawa, Djamel Lebeche, Roger J Hajjar, Susmita Sahoo
Background -Despite its functional importance in various fundamental bioprocesses, the studies of N6-methyladenosine (m6A) in the heart are lacking. Here we show that, fat mass and obesity-associated (FTO), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling and regeneration. Methods -We used clinical human samples, preclinical pig and mouse models and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes...
July 11, 2018: Circulation
Anton Gisterå, Maria L Klement, Konstantinos A Polyzos, Reiner K Mailer, Amanda Duhlin, Mikael C I Karlsson, Daniel F J Ketelhuth, Göran K Hansson
Background -Atherosclerotic cardiovascular disease is a chronic inflammatory process initiated when cholesterol-carrying low-density lipoprotein (LDL) is retained in the arterial wall. CD4+ T cells, some of which recognize peptide components of LDL as antigen, are recruited to the forming lesion, resulting in T-cell activation. Although these T cells are thought to be proatherogenic, LDL immunization reduces disease in experimental animals. These seemingly contradictory findings have hampered the development of immune-based cardiovascular therapy...
July 11, 2018: Circulation
Somasundaram Raghavan, Nikhlesh K Singh, Sivaiah Gali, Arul M Mani, Gadiparthi N Rao
Background -Although the role of thrombin in atherothrombosis is well studied, its role in the pathogenesis of diet-induced atherosclerosis is not known. Methods -Using a mouse model of diet-induced atherosclerosis and molecular biological approaches, here we have explored the role of thrombin and its G protein-coupled receptor (GPCR) signaling in diet-induced atherosclerosis. Results -In exploring the role of GPCR signaling in atherogenesis, we found that thrombin triggers foam cell formation via inducing CD36 expression and these events require Par1-mediated Gα12-Pyk2-Gab1-PKCθ-dependent ATF2 activation...
July 10, 2018: Circulation
Ronald J Vagnozzi, Michelle A Sargent, Suh-Chin J Lin, Nathan J Palpant, Charles E Murry, Jeffery D Molkentin
Background -The adult mammalian heart displays a cardiomyocyte turnover rate of ~1% per year throughout postnatal life and after injuries such as myocardial infarction (MI), but the question of which cell types drive this low level of new cardiomyocyte formation remains contentious. Cardiac-resident stem cells marked by stem cell antigen-1 (Sca-1, gene name Ly6a ) have been proposed as an important source of cardiomyocyte renewal. However, the in vivo contribution of endogenous Sca-1+ cells to the heart at baseline or after MI has not been investigated...
July 10, 2018: Circulation
Lena M Chen, Brahmajee K Nallamothu, John A Spertus, Yuanyuan Tang, Paul S Chan
Background -Black patients have worse in-hospital survival than white patients after in-hospital cardiac arrest (IHCA), but less is known about longterm outcomes. We sought to assess among IHCA survivors whether there are additional racial differences in survival after hospital discharge and to explore potential reasons for differences. Methods -This was a longitudinal study of patients ≥65 years of age who had an IHCA and survived until hospital discharge between 2000 and 2011 from the national Get With The Guidelines-Resuscitation registry whose data could be linked to Medicare claims data...
July 9, 2018: Circulation
Roxana Ola, Sandrine H Künzel, Feng Zhang, Gael Genet, Raja Chakraborty, Laurence Pibouin-Fragner, Kathleen Martin, William Sessa, Alexandre Dubrac, Anne Eichmann
Background -Hereditary Hemorrhagic Telangiectasia (HHT) is an inherited vascular disorder that causes arterial-venous malformations (AVMs). Mutations in the genes encoding Endoglin ( ENG ) and Activin-receptor-like kinase 1 ( AVCRL1 encoding ALK1) cause HHT type 1 and 2, respectively. Mutations in the SMAD4 gene are present in families with Juvenile Polyposis/HHT syndrome that involves AVMs. SMAD4 is a downstream effector of Transforming growth factor-β (TGFβ)/Bone morphogenetic protein (BMP) family ligands that signal via Activin like kinase receptors (ALKs)...
July 5, 2018: Circulation
Michael Goldfarb, Sandra Lauck, John G Webb, Anita W Asgar, Louis P Perrault, Nicolo Piazza, Giuseppe Martucci, Kevin Lachapelle, Nicolas Noiseux, Dae H Kim, Jeffrey J Popma, Thierry Lefèvre, Marino Labinaz, Andre Lamy, Mark D Peterson, Rakesh C Arora, José A Morais, Jean-Francois Morin, Lawrence Rudski, Jonathan Afilalo
Background -Older adults undergoing aortic valve replacement are at risk for malnutrition. The association between pre-procedural nutritional status and midterm mortality has yet to be determined. Methods -The FRAILTY-AVR prospective multi-center international cohort study was conducted between 2012-2017 in 14 centers in 3 countries. Patients ≥70 years of age who underwent transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) were eligible. The Mini Nutritional Assessment-Short Form (MNA-SF) was assessed by trained observers pre-procedure, with scores ≤7 of 14 considered malnourished and 8-11 of 14 considered at-risk for malnutrition...
July 5, 2018: Circulation
Sofia-Iris Bibli, Jiong Hu, Frangiska Sigala, Ilka Wittig, Juliana Heidler, Sven Zukunft, Diamantis I Tsilimigras, Voahanginirina Randriamboavonjy, Janina Wittig, Baktybek Kojonazarov, Christoph Schürmann, Mauro Siragusa, Daniel Siuda, Bert Luck, Randa Abdel Malik, Konstantinos A Filis, George Zografos, Chen Chen, Dao Wen Wang, Josef Pfeilschifter, Ralf P Brandes, Csaba Szabo, Andreas Papapetropoulos, Ingrid Fleming
Background -Hydrogen sulfide (H2 S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and pro-atherogenic conditions. Methods -Endothelial cell CSE knock out mice were generated and lung endothelial cells were studied in vitro (gene expression, protein sulfhydration and monocyte adhesion). Mice were crossed onto the ApoE-/- background and atherogenesis (partial carotid artery ligation) was monitored over 21 days...
July 3, 2018: Circulation
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