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    Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart.
    Circulation 2018 Jan 20. Epub 2018 Jan 20.
    Vascular Signaling and Cancer, DKFZ-ZMBH Alliance and German Cancer Research Center (DKFZ), Heidelberg, Germany; Vascular Biology (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
    Background -Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Read More

    Right Ventricular Myofilament Functional Differences in Humans with Systemic Sclerosis-associated versus Idiopathic Pulmonary Arterial Hypertension.
    Circulation 2018 Jan 19. Epub 2018 Jan 19.
    Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD & Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD.
    Background -Patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) have a far worse prognosis than those with idiopathic PAH (IPAH). In the intact heart, SSc-PAH exhibits depressed rest and reserve right ventricular (RV) contractility as compared to IPAH. We tested whether this disparity involves underlying differences in myofilament function. Read More

    Sex and Race Differences in Lifetime Risk of Heart Failure with Preserved Ejection Fraction and Heart Failure with Reduced Ejection Fraction.
    Circulation 2018 Jan 19. Epub 2018 Jan 19.
    Division of Cardiology, UTSW Medical Center, Dallas, TX & Department of Clinical Sciences, UTSW Medical Center, Dallas, TX
    Background -Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the two HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), is not known. Methods -Participant-level data from 2 large prospective cohort studies, the Cardiovascular Health Study (CHS) and the Multiethnic Study of Atherosclerosis (MESA), were pooled excluding individuals with prevalent HF at baseline. Read More

    Worsening Renal Function in Acute Heart Failure Patients Undergoing Aggressive Diuresis is Not Associated with Tubular Injury.
    Circulation 2018 Jan 19. Epub 2018 Jan 19.
    Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT
    Background -Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers-NAG, NGAL, and KIM-1- are now available that can quantify the degree of renal tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients. Read More

    Phosphoinositide 3-Kinase Gamma Inhibition Protects from Anthracycline Cardiotoxicity and Reduces Tumor Growth.
    Circulation 2018 Jan 18. Epub 2018 Jan 18.
    Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy
    Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Read More

    DAWN of a New Era for Stroke Treatment: Implications of the DAWN Study for Acute Stroke Care and Stroke Systems of Care.
    Circulation 2018 Jan 18. Epub 2018 Jan 18.
    Department of Neurology, Hartford Hospital, Hartford, CT.
    Until recently, the selection of patients with large artery occlusion and ischemic stroke for reperfusion therapy was based on time criteria (typically within 6 hours) and basic imaging protocols (head CT, CT angiogram, ASPECTS score). The recently published DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) study has changed this paradigm by using a tissue-based selection criteria and a greatly expanded treatment time window (up to 24 hours).1 This is a transformational change in acute stroke therapy and has implications for many healthcare providers and EMS systems. Read More

    Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration.
    Circulation 2018 Jan 18. Epub 2018 Jan 18.
    Department of Stem Cell and Regenerative Biology, the Harvard Stem Cell Institute, Harvard University, Cambridge, MA & Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
    Background -Defining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Insight into the transcriptomic landscape of early cardiac regeneration from model organisms will shed light on evolutionarily conserved pathways in successful cardiac regeneration. Methods -Here we describe a cross-species transcriptomic screen in three model organisms for cardiac regeneration -axolotl, neonatal mice and zebrafish. Read More

    Cardiorespiratory Fitness, Coronary Artery Calcium and Cardiovascular Disease Events in a Cohort of Generally Healthy, Middle Aged Men: Results from the Cooper Center Longitudinal Study.
    Circulation 2018 Jan 17. Epub 2018 Jan 17.
    Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX & Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, and University of Texas Southwestern Medical Center, Dallas, TX
    Background -A robust literature demonstrates that coronary artery calcification (CAC) and cardiorespiratory fitness (CRF) are independent predictors of cardiovascular disease (CVD) events. Much less is known about the joint associations of CRF and CAC with CVD risk. In the setting of high CAC, high versus low CRF has been associated with decreased CVD events. Read More

    High-Target vs Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients - A Randomized Controlled Trial.
    Circulation 2018 Jan 16. Epub 2018 Jan 16.
    Department of Cardiothoracic Anesthesia, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Background -Cerebral injury is an important complication following cardiac surgery with the use of cardiopulmonary bypass (CPB). The rate of overt stroke after cardiac surgery is 1-2%, whereas silent strokes, detected by diffusion-weighed magnetic resonance imaging (DWI), are found in up to 50% of patients. It is unclear if a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. Read More


    Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis.
    Circulation 2018 01;137(3):286-297
    Scuola Superiore Sant'Anna, Pisa, Italy (A.A., G.V., C.P., M.E.)
    Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach. Read More

    Establishing an Evidence-Based Method to Diagnose Cardiac Sarcoidosis: The Complementary Use of Cardiac Magnetic Resonance Imaging and FDG-PET.
    Circ Cardiovasc Imaging 2018 Jan;11(1):e007408
    From the Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT (E.J.M.); and Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, OH (D.A.C.).

    Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis.
    Circ Cardiovasc Imaging 2018 Jan;11(1):e007030
    From the Cardiovascular Division, Department of Medicine, Cardiovascular Imaging Program (T.V., M.V.-C., P.E.B., E.M., E.H., V.R.T., M.S., H.S., R.Y.K., S.D., M.F.D.C., R.B.), Department of Radiology (T.V., M.V.-C., P.E.B., E.M., E.H., V.R.T., M.S., H.S., R.Y.K., S.D., M.F.D.C., R.B.), Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (M.A., S.D., M.F.D.C., R.B.), Division of Thoracic Radiology, Department of Radiology (R.M.), and Cardiovascular Division (H.S., R.Y.K., G.S., M.F.D.C., R.B.), Brigham and Women's Hospital, Boston, MA; Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD (D.R.O.); Division of Medicine, Cardiology Service, Walter Reed National Military Medical Center, Bethesda, MD (E.H.); and Uniformed Services University of Health Sciences, Bethesda, MD (E.H.).
    Background: Although cardiac magnetic resonance (CMR) and positron emission tomography (PET) detect different pathological attributes of cardiac sarcoidosis (CS), the complementary value of these tests has not been evaluated. Our objective was to determine the value of combining CMR and PET in assessing the likelihood of CS and guiding patient management.

    Methods And Results: In this retrospective study, we included 107 consecutive patients referred for evaluation of CS by both CMR and PET. Read More

    Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation in the Treatment of Ventricular Tachycardia.
    Circ Arrhythm Electrophysiol 2018 Jan;11(1):e005973
    From the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (T.Z., E.G.I., R.H., H.A., R.D.B., J.E.M., D.D.S., H.T., H.H., H.C., C.H.); Department of Radiology and Radiological Sciences, Johns Hopkins Medicine, Baltimore, MD (S.L.Z., H.H.); Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD (H.H.); Department of Cardiology, Providence St. Vincent Medical Center, Portland, OR (S.B.); Division of Cardiology, Oregon Health Sciences University, Portland (C.H.); and Division of Cardiology, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.N.).

    Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation.
    Circ Arrhythm Electrophysiol 2018 Jan;11(1):e005258
    From the Department of Cardiovascular Medicine, Stanford University, Palo Alto, CA (J.A.B.Z., M.I.A., T.B., C.A.B.K., P.C.Z., S.P., M.N.V., P.J.W., S.M.N.); Imperial Centre for Cardiac Engineering, Imperial College London, United Kingdom (J.A.B.Z., N.S.P.); Cardiac Electrophysiology, Cedars Sinai Heart Institute, Los Angeles, CA (J.A.B.Z.); Department of Cardiology, University of Colorado, Aurora (W.H.S., R.T.B.); Departments of Medicine (T.B., D.E.K.) and Physics (W.J.R.), University of California San Diego; Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany (C.A.B.K.); Department of Cardiology, Klinikum Coburg, Germany (S.B., J.B.); and Department of Medicine, Indiana University, Bloomington (J.M.M.).
    Background: The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation.

    Methods And Results: We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. Read More

    miR-195 Regulates Metabolism in Failing Myocardium via Alterations in SIRT3 Expression and Mitochondrial Protein Acetylation.
    Circulation 2018 Jan 12. Epub 2018 Jan 12.
    Department of Medicine, Division of Cardiology, Columbia University Medical Center, New York, NY & Department of Medicine I, Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany
    Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Interestingly, unique cardiac and systemic miRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium. Read More

    Statins Have a Dose-Dependent Effect on Amputation and Survival in Peripheral Artery Disease Patients.
    Circulation 2018 Jan 12. Epub 2018 Jan 12.
    Division of Cardiology, Emory University School of Medicine, Atlanta, GA & Epidemiology and Genomic Medicine, Atlanta VA Medical Center, Decatur, GA.
    Background -Statin dose guidelines for Peripheral Artery Disease (PAD) patients are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. Methods -Using an observational cohort study design and a validated algorithm we identified incident PAD patients (2003-2014) in the national Veterans Affairs data. Read More

    Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients.
    Circ Heart Fail 2018 Jan;11(1):e004313
    From the School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta (O.T.I., M.B.P., A.Q.J., A.D., A.O.B.); Division of Cardiology (S.D., T.D.M., L.K.) and Department of Bioengineering and Therapeutic Sciences (S.R.), University of California, San Francisco; and Department of Anesthesiology and Department of Biomedical Engineering, Northwestern University, Chicago, IL (M.E., J.A.H.).
    Background: Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise.

    Methods And Results: Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Read More

    Heart Failure in Pregnant Women: A Concern Across the Pregnancy Continuum.
    Circ Heart Fail 2018 Jan;11(1):e004005
    From the College of Nursing, Department of Women, Children, and Family Health Science (M.F.M., B.L.M., K.L.L.) and Division of Cardiology, Department of Medicine (J.E.B.), University of Illinois at Chicago; School of Nursing, Vanderbilt University, Nashville, TN (M.R.P.); and Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX (J.L.S.).
    Background: Heart failure (HF) is a leading cause of maternal morbidity and mortality in the United States, but prevalence, correlates, and outcomes of HF-related hospitalization during antepartum, delivery, and postpartum periods remain unknown. The objective was to examine HF prevalence, correlates, and outcomes among pregnancy-related hospitalizations among women 13 to 49 years of age.

    Methods And Results: We used the 2001 to 2011 Nationwide Inpatient Sample. Read More

    Novel Care Pathway for Patients Presenting to the Emergency Department With Atrial Fibrillation.
    Circ Cardiovasc Qual Outcomes 2018 Jan;11(1):e004129
    From the Division of Cardiology, Department of Medicine (A.G., P.M., T.J.W., S.C., J.O., K.G.), University of North Carolina Medical Center (Z.D., L.H.), Division of Practice Advancement and Clinical Education, University of North Carolina Eshelman School of Pharmacy (Z.D., P.M., L.H.), Gillings School of Global Public Health (J.L., J.A., S.S.), and Department of Emergency Medicine (K.B.), University of North Carolina at Chapel Hill; and Department of Psychology (S.S.), Department of Cardiovascular Sciences (S.S.), and Department of Public Health (S.S.), East Carolina University, Greenville, NC.

    Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial.
    Circ Cardiovasc Interv 2018 Jan;11(1):e005891
    From the Hawaii Permanente Medical Group, Kaiser Foundation Hospital, Honolulu, HI (P.A.S.); Adventist Heart and Vascular Institute, St Helena Hospital, CA (J.R.L.); Department of Diagnostic and Interventional Radiology, RoMed Klinikum, Rosenheim, Germany (G.T.); Department of Internal Medicine, Division of Angiology, Medical University, Graz, Austria (M.B.); Angiology Division, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Germany (T.Z.); Department of Angiology, University Hospital Leipzig, Germany (D.S.); Wellmont Holston Valley Medical Center, Kingsport, TN (C.M.); GVM Care and Research, Maria Cecilia Hospital, Cotignola, Italy (A.M.); North Carolina Heart and Vascular, UNC-REX Health Care, Raleigh, NC (R.S.); Newton-Wellesley Hospital, MA (M.R.J.); Medtronic, Santa Rosa, CA (H.W., M.S.H.); and Icahn School of Medicine, Mount Sinai Medical Center, New York, NY (P.K.).
    Background: Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term.

    Methods And Results: IN. Read More

    Decision Analytic Markov Model Weighting Expected Benefits and Current Limitations of First-Generation Bioresorbable Vascular Scaffolds: Implications for Manufacturers and Next Device Iterations.
    Circ Cardiovasc Interv 2018 Jan;11(1):e005768
    From the Cardiac-Thoracic-Vascular Department, Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele Presidio Ferrarotto, Catania, Italy (D.C., S.B., S.R., P.C., B.F., C.T.); and Department of General Surgery and Medical-Surgical Specialties, University of Catania, Italy (D.C., P.C., C.T.).
    Background: Relative benefits of bioresorbable vascular scaffolds (BVS) compared with everolimus-eluting stents (EES) are expected to accrue after complete bioresorption.

    Methods And Results: We built a decision analytic Markov model comparing BVS and EES for a contemporary percutaneous coronary intervention population. Procedure-related morbidity and outcome data from the available literature were used to derive model probabilities. Read More

    Sex-Based Assessment of Patient Presentation, Lesion Characteristics, and Treatment Modalities in Patients Undergoing Peripheral Vascular Intervention.
    Circ Cardiovasc Interv 2018 Jan;11(1):e005749
    From the Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH (N.R., J.R.B., P.P.G.); Section of Vascular Surgery, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH (B.D.S., J.L.C., P.P.G.); and Weill Cornell Medical College, Cornell University, New York, NY (A.S.).
    Background: Limited evidence suggests that women and men might be treated differently for peripheral arterial disease. This analysis evaluated sex-based differences in disease presentation and its effect on treatment modality among patients who underwent endovascular treatment for peripheral arterial disease.

    Methods And Results: Using national registry data from the Vascular Quality Initiative between 2010 and 2013, we examined patient, limb, and artery characteristics by sex through descriptive statistics. Read More

    Diagnostic Performance of the Instantaneous Wave-Free Ratio: Comparison With Fractional Flow Reserve.
    Circ Cardiovasc Interv 2018 Jan;11(1):e004613
    From the Division of Cardiology, Department of Medical and Surgical Sciences (S.D.R., A.P., C.I.) and URT-CNR of IFC (C.I.), Magna Graecia University, Catanzaro, Italy; and National Heart and Lung Institute, Imperial College London, United Kingdom (R.P., J.E.D.).
    Background: Aim of the present study was to perform a meta-analysis of all available studies comparing the instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR).

    Methods And Results: Published trials comparing the iFR with FFR were searched for in PubMed, Google Scholar, and Scopus electronic databases. A total of 23 studies were available for the analysis, including 6381 stenoses. Read More

    Elephant in the Room: Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors.
    Circ Cardiovasc Qual Outcomes 2018 Jan;11(1):e004425
    From the Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA; Institute for Clinical Evaluative Sciences, Toronto, Canada; Veterans Affairs Greater Los Angeles Healthcare System, CA; Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto, Canada); and University Health Network, Toronto, Canada.

    Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers.
    Circ Cardiovasc Qual Outcomes 2018 Jan;11(1):e003939
    From the Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Dr Doshi, J.T. Puckett, Dr Parmacek, and Dr Rader) and the Leonard Davis Institute of Health Economics, Philadelphia (Dr Doshi).
    Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol. However, the high costs of these agents have spurred payers to implement utilization management policies to ensure appropriate use. We examined prior authorization (PA) requirements for PCSK9is across private and public US payers. Read More

    Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest.
    Circ Cardiovasc Qual Outcomes 2018 Jan;11(1):e003566
    From the Department of Clinical Sciences (G.L., T.C.) and Department of Clinical Sciences, Anesthesiology and Intensive Care Medicine (N.N., H.F.), Skane University Hospital, Lund University, Sweden; Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet, Denmark (J.B.-J., J.K.); Adult Critical Care, University Hospital of Wales, Cardiff, United Kingdom (H.D., M.P.W.); Institute of Neuroscience and Physiology, Section of Health and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Sweden (C.H.); Intensive Care, Academic Medical Center, Amsterdam, The Netherlands (J.H., T.W.); Anesthesia and Intensive Care, IRCCS AOU San Martino IST, Genova, Italy (A.I.); Research and Development Centre Skane, Medical Statistics and Epidemiology, Lund, Sweden (F.N.); and Department of Surgical Sciences and Integrated Diagnostics, Ospedale Policlinico San Martino - IRCCS per l'Oncologia, University of Genova, Italy (P.P.).
    Background: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment.

    Methods And Results: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment. Read More

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