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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 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
Ophelia Q P Yin, Elliott M Antman, Eugene Braunwald, Michele F Mercuri, Raymond Miller, David Morrow, Christian T Ruff, Kenneth Truitt, Jeffrey I Weitz, Robert P Giugliano
Background -We previously reported exogenous anti-factor Xa activity as a pharmacokinetic surrogate marker for edoxaban plasma concentrations. Inhibition of endogenous FXa activity is a more biologically relevant pharmacodynamic measure of edoxaban activity. Here we describe the value of endogenous FXa activity as a pharmacodynamic marker linking edoxaban concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 trial. Methods -In ENGAGE AF-TIMI 48, edoxaban was administered in higher-dose (HDER, 60/30 mg QD) and lower-dose (LDER, 30/15 mg QD) regimens...
July 2, 2018: Circulation
Anoop S V Shah, Dominik Stelzle, Kuan Ken Lee, Eduard J Beck, Shirjel Alam, Sarah Clifford, Chris T Longenecker, Fiona E Strachan, Shashwatee Bagchi, William Whiteley, Sanjay Rajagopalan, Shyamasundaran Kottilil, Harish Nair, David E Newby, David A McAllister, Nicholas L Mills
Background -With advances in anti-retroviral therapy, most deaths in people with human immune-deficiency virus (HIV) are now due to non-communicable illnesses especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional and global burden of cardiovascular disease attributable to HIV. Methods -We conducted a systematic review across five databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection...
July 2, 2018: Circulation
Kohsuke Shirakawa, Jin Endo, Masaharu Kataoka, Yoshinori Katsumata, Naohiro Yoshida, Tsunehisa Yamamoto, Sarasa Isobe, Hidenori Moriyama, Shinichi Goto, Hiroki Kitakata, Takahiro Hiraide, Keiichi Fukuda, Motoaki Sano
Background -Both osteopontin (OPN) and galectin-3 have been implicated in phagocytic clearance of dead cells and reparative fibrosis during wound healing. CD206+ macrophages are involved in tissue repair through phagocytosis and fibrosis after myocardial infarction (MI). However, the relationship among OPN, galectin-3 and macrophage polarization in the context of MI remains unclear. Methods -The time course of Spp1 (encoding OPN) expression in the heart after MI showed a strong activation of Spp1 on day 3 after MI...
July 2, 2018: Circulation
S Mohsen Hosseini, Raymond Kim, Sharmila Udupa, Gregory Costain, Rebekah Jobling, Eriskay Liston, Seema M Jamal, Marta Szybowska, Chantal F Morel, Sarah Bowdin, John Garcia, Melanie Care, Amy C Sturm, Valeria Novelli, Michael J Ackerman, James S Ware, Ray E Hershberger, Arthur A M Wilde, Michael H Gollob
Background -Implicit in the genetic evaluation of patients with suspected genetic diseases is the assumption that the genes evaluated are causative for the disease based on robust scientific and statistical evidence. However, in the past 20 years considerable variability has existed in the study design and quality of evidence supporting reported gene-disease associations raising concerns of the validity of many published disease-causing genes. Brugada syndrome (BrS) is an arrhythmia syndrome with a risk of sudden death...
June 29, 2018: Circulation
Konstantinos C Siontis, Xiaosong Zhang, Ashley Eckard, Nicole Bhave, Doug E Schaubel, Kevin He, Anca Tilea, Austin G Stack, Rajesh Balkrishnan, Xiaoxi Yao, Peter A Noseworthy, Nilay D Shah, Rajiv Saran, Brahmajee K Nallamothu
Background -Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concern regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent ESKD patients with AF. Methods -We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015)...
June 28, 2018: Circulation
David A McAllister, Stephanie Read, Jan Kerssens, Shona Livingstone, Stuart McGurnaghan, Pardeep Jhund, John Petrie, Naveed Sattar, Colin Fischbacher, Soren L Kristensen, John McMurray, Helen M Colhoun, Sarah Wild
Background -Recent clinical trials of new glucose-lowering treatments have drawn attention to the importance of hospitalisation for heart failure as a complication of diabetes. However, the epidemiology is not well described, particularly for type 1 diabetes. We examined the incidence and case-fatality of heart failure hospitalisations in the entire population aged 30 and older resident in Scotland during 2004 to 2013. Methods -Date and type of diabetes diagnosis were linked to heart failure hospitalisations and deaths using the national Scottish registers...
June 27, 2018: Circulation
Shuin Park, Sara Ranjbarvazirj, Fides D Lay, Peng Zhao, Mark J Miller, Jasmeet S Dhaliwal, Adriana Huertas-Vazquez, Xiuju Wu, Rong Qiao, Justin M Soffer, Hanna K A Mikkola, Aldons J Lusis, Reza Ardehali
Background -Genetic diversity and the heterogeneous nature of cardiac fibroblasts (CFbs) have hindered characterization of the molecular mechanisms that regulate cardiac fibrosis. The Hybrid Mouse Diversity Panel (HMDP) offers a valuable tool to examine genetically diverse cardiac fibroblasts and their role in fibrosis. Methods -Three strains of mice (C57BL/6J, C3H/HeJ, and KK/HlJ) were selected from the HMDP and treated with either isoproterenol (ISO) or saline by an intraperitoneally implanted osmotic pump...
June 27, 2018: Circulation
Darwin R Labarthe, Donald M Lloyd-Jones
I. The Problem and a Proposal Throughout the 20th century, deaths, disability, disparities, and costs due to cardiovascular and cerebrovascular diseases (CVD) grew in importance in the U.S. and globally. Although many countries have shown marked reductions in resulting death rates at specific ages, these gains have largely been offset by growing numbers of people at the oldest ages, where rates are highest.
June 27, 2018: Circulation
Sripal Bangalore, Bora Toklu, Neil Patel, Frederick Feit, Gregg W Stone
Background -Contemporary second-generation drug-eluting stents (DES) have superior efficacy and safety compared with early generation stents in patients undergoing percutaneous coronary intervention (PCI), in part related to their thinner struts. Whether newer generation ultra-thin DES further improve clinical outcomes compared with older second-generation thicker strut DES is unknown. Methods -We searched PUBMED, EMBASE, and CENTRAL for randomized clinical trials that compared newer generation ultra-thin strut DES (defined as strut thickness <70 microns) versus thicker strut second-generation DES and reported clinical outcomes...
June 26, 2018: Circulation
Brendon L Neuen, Toshiaki Ohkuma, Bruce Neal, David R Matthews, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, Mehul Desai, Qiang Li, Hsiaowei Deng, Norm Rosenthal, Meg J Jardine, George Bakris, Vlado Perkovic
Background : Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. Methods : The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1...
June 25, 2018: Circulation
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