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    69 results match your criteria Circulation: Heart Failure [Journal]

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    Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure.
    Circ Heart Fail 2017 Sep;10(9)
    From the Department of Cardiology, Cliniques Universitaires de Bruxelles, Hôpital Académique Erasme, Brussels, Belgium (R.N., J.-L.V., S.C.); Department of Internal Medicine II, Division of Cardiology, General Hospital of Vienna (AKH-Wien), Medical University of Vienna, Austria (M.G., C.G., I.M.L.); and Department of Cardiovascular, Neural and Metabolic Sciences, Ospedale S. Luca IRCCS Istituto Auxologico Italiano, Milan, Italy (S.C.).
    Increased pulmonary venous pressure secondary to left heart disease is the most common cause of pulmonary hypertension (PH). The diagnosis of PH due to left heart disease relies on a clinical probability assessment followed by the invasive measurements of a mean pulmonary artery pressure (PAP) ≥25 mm Hg and mean wedged PAP (PAWP) >15 mm Hg. A combination of mean PAP and mean PAWP defines postcapillary PH. Read More

    Extracorporeal Membrane Oxygenation in New York State: Trends, Outcomes, and Implications for Patient Selection.
    Circ Heart Fail 2016 Dec;9(12)
    From the Department of Cardiovascular Surgery (J.B., N.T., S.I., J.C.) and Department of Population Health Science and Policy (N.N.E.), Icahn School of Medicine at Mount Sinai, New York, NY; and Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (A.B.G.).
    Background: Utilization of extracorporeal membrane oxygenation (ECMO) is expanding despite limited outcome data defining appropriate use.

    Methods And Results: To quantify determinants of early and 1-year survival after ECMO in adult patients, we conducted a retrospective cohort analysis of 1286 patients aged ≥18 years who underwent ECMO in New York State from 2003 to 2014. Median follow-up time was 4. Read More

    Characteristics and Outcomes of Patients With Myocarditis Listed for Heart Transplantation.
    Circ Heart Fail 2016 Dec;9(12)
    From the Advanced Heart Failure and Transplant Center, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, OH.
    Background: Myocarditis can cause dilated cardiomyopathy resulting in end-stage heart failure requiring advanced therapies. There is little contemporary information on the clinical progression, need for mechanical circulatory support, and outcomes of orthotopic heart transplantation of these patients.

    Methods And Results: We queried the UNOS database (United Network for Organ Sharing) for all adults listed for orthotopic heart transplantation (2000-2015) with a listed diagnosis of myocarditis. Read More

    Skeletal Muscle Alterations Are Exacerbated in Heart Failure With Reduced Compared With Preserved Ejection Fraction: Mediated by Circulating Cytokines?
    Circ Heart Fail 2016 Sep;9(9)
    From the Department of Cardiology (M.S., T.S.B., S.W., T.F., N.M., A.L., G.S., V.A.) and Department of Cardiac Surgery (M.-T.D.), University of Leipzig, Heart Center, Germany; Department of Circulation and Medical Imaging, Faculty of Medicine, K.G. Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, Norway (N.R., U.W.); Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Japan (T.H.); Department of Prevention, Rehabilitation and Sports Medicine, Else Kröner-Fresenius-Zentrum, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany (M.H.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (M.H.).
    Background: A greater understanding of the different underlying mechanisms between patients with heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction is urgently needed to better direct future treatment. However, although skeletal muscle impairments, potentially mediated by inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying cellular and molecular alterations that exist between groups are yet to be systematically evaluated. The present study, therefore, used established animal models to compare whether alterations in skeletal muscle (limb and respiratory) were different between HFrEF and HFpEF, while further characterizing inflammatory cytokines. Read More

    Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed.
    Circ Heart Fail 2016 Aug;9(8):e002922
    From the Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
    Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Read More

    Reduced Myocardial Flow in Heart Failure Patients With Preserved Ejection Fraction.
    Circ Heart Fail 2016 Jul;9(7)
    From the Division of Cardiology, University of Ottawa Heart Institute, Ontario, Canada.
    Background: There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. Read More

    Right Ventricular Contractile Reserve and Pulmonary Circulation Uncoupling During Exercise Challenge in Heart Failure: Pathophysiology and Clinical Phenotypes.
    JACC Heart Fail 2016 Aug 11;4(8):625-35. Epub 2016 May 11.
    Heart Failure Unit, IRCCS Policlinico San Donato, University of Milan, Milan, Italy.
    Objectives: Right ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study.

    Background: Although the role of the right ventricle in HF syndrome might be fundamental, the pathophysiology of the failing right ventricle has not been extensively investigated.

    Methods: Ninety-seven patients with HF (mean age 64 years, 70% men, mean left ventricular ejection fraction 33 ± 10%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing. Read More

    Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.
    Circ Heart Fail 2016 Apr;9(4):e002729
    From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
    Background: Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. Read More

    Development of a Transplantation Risk Index in Patients With Mechanical Circulatory Support: A Decision Support Tool.
    JACC Heart Fail 2016 Apr 10;4(4):277-86. Epub 2016 Feb 10.
    Department of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:
    Objectives: The aim of this study was to develop a risk index specific to patients on mechanical circulatory support that accurately predicts 1-year mortality after orthotopic heart transplantation using the United Network for Organ Sharing database.

    Background: Few clinical tools are available to aid in the decision between continuing long-term device support and performing transplantation in patients bridging with mechanical circulatory support.

    Methods: Using a prospectively collected, open cohort, 6,036 patients receiving mechanical circulatory support who underwent orthotopic heart transplantation between 2000 and 2013 were evaluated and randomly separated into derivation (80%) and validation (20%) groups. Read More

    Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice.
    Circ Heart Fail 2016 Jan;9(1):e002424
    From the Department of Anesthesiology (S.L.B., M.P., Z.J.B., D.C.W., J.R.K., Z.-D.G.), Department of Pediatrics (J.F.), Department of Medicine (D.X.Z.), Department of Physiology (Z.J.B.), and Department of Pharmacology and Toxicology (D.C.W., J.R.K.), Medical College of Wisconsin, Milwaukee; and Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (T.M.L.).
    Background: Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known. Read More

    Choline Diet and Its Gut Microbe-Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload-Induced Heart Failure.
    Circ Heart Fail 2016 Jan 23;9(1):e002314. Epub 2015 Dec 23.
    From the Department of Pharmacology, Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans (C.L.O., H.O., S.B., J.B., R.T., D.J.P., D.J.L.); Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, OH (Z.W., W.H.W.T., S.L.H.); and Department of Mathematics, Cleveland State University, OH (Y.W.).
    Background: Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, is both elevated in the circulation of patients having heart failure and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerates atherosclerotic lesion development in ApoE-deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the low-density lipoprotein receptor knockout mouse.

    Methods And Results: C57BL6/J mice were fed either a control diet, a diet containing choline (1. Read More

    Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction.
    JACC Heart Fail 2016 Apr 9;4(4):312-24. Epub 2015 Dec 9.
    Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands; Department of Cardiovascular Physiology, Ruhr University Bochum, Bochum, Germany.
    Objectives: The present study investigated whether systemic, low-grade inflammation of metabolic risk contributed to diastolic left ventricular (LV) dysfunction and heart failure with preseved ejection fraction (HFpEF) through coronary microvascular endothelial activation, which alters paracrine signalling to cardiomyocytes and predisposes them to hypertrophy and high diastolic stiffness.

    Background: Metabolic risk is associated with diastolic LV dysfunction and HFpEF.

    Methods: We explored inflammatory endothelial activation and its effects on oxidative stress, nitric oxide (NO) bioavailability, and cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signalling in myocardial biopsies of HFpEF patients and validated our findings by comparing obese Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1)-HFpEF rats to ZSF1-Control (Ctrl) rats. Read More

    Pro-Atrial Natriuretic Peptide: A Novel Guanylyl Cyclase-A Receptor Activator That Goes Beyond Atrial and B-Type Natriuretic Peptides.
    JACC Heart Fail 2015 Sep;3(9):715-23
    Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
    Objectives: The aim of this study was to determine if the atrial natriuretic peptide (ANP) precursor proANP is biologically active compared with ANP and B-type natriuretic peptide (BNP).

    Background: ProANP is produced in the atria and processed to ANP and activates the guanylyl cyclase receptor-A (GC-A) and its second messenger, cyclic guanosine monophosphate (cGMP). ProANP is found in the human circulation, but its bioavailability is undefined. Read More

    No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure.
    Circ Heart Fail 2015 Nov 2;8(6):1088-93. Epub 2015 Sep 2.
    From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine (S.D., O.J.R., M.M., M.R., E.S., H.W., H.A., T.D.K., S.N.) and Department of Physiology, Anatomy, and Genetics (C.J.H., L.E.C., K.C.), Oxford University, Oxford, United Kingdom.
    Background: Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Read More

    Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages.
    Circ Heart Fail 2015 Sep 31;8(5):980-7. Epub 2015 Jul 31.
    From the Center for Systems Biology, Massachusetts General Hospital, Boston (S.H., B.G.C., A.F., A.A., M.N., I.H., Y.S., Y.-X.Y., Y.I., B.T., R.W., M.N., F.K.S.); Biological Sciences, GlaxoSmithKline, Collegeville, PA (M.B.); Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.); GlaxoSmithKline, King of Prussia, PA (C.M.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (P.L.).
    Background: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Read More

    Extracorporeal Membrane Oxygenation as a Bridge to Pediatric Heart Transplantation: Effect on Post-Listing and Post-Transplantation Outcomes.
    Circ Heart Fail 2015 Sep 23;8(5):960-9. Epub 2015 Jul 23.
    From the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (A.I.D.); Children's Healthcare of Atlanta, GA (W.T.M.); University of Alabama at Birmingham (M.T., D.C.N., J.K.K., E.P.); Stanford University, Palo Alto, CA (C.A.); and Vanderbilt University School of Medicine, Nashville, TN (S.A.W.).
    Background: Current organ allocation algorithms direct hearts to the sickest recipients to mitigate death while waiting. This may result in lower post-transplant (Tx) survival for high-risk candidates mandating close examination to determine the appropriateness of different technologies as a bridge to Tx.

    Methods And Results: We analyzed all patients (<18 years old) from the Pediatric Heart Transplant Study (PHTS) database listed for heart Tx (1993-2013) to determine the effect of extracorporeal membrane oxygenation (ECMO) support at the time of listing and the time of Tx on waitlist mortality and post-Tx outcomes. Read More

    Cardiomyocyte A Disintegrin And Metalloproteinase 17 (ADAM17) Is Essential in Post-Myocardial Infarction Repair by Regulating Angiogenesis.
    Circ Heart Fail 2015 Sep 1;8(5):970-9. Epub 2015 Jul 1.
    From the Department of Physiology (D.F., A.T., M.S., X.W., Z.K.), Division of Cardiology, Department of Medicine (W.W., R.B., G.Y.O.), Cardiovascular Research Center (D.F., A.T., M.S., X.W., Z.K., W.W., R.B.), Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
    Background: A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme that mediates shedding of many membrane-bound molecules, thereby regulating multiple cellular responses. We investigated the role of cardiomyocyte ADAM17 in myocardial infarction (MI).

    Methods And Results: Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/α-MHC-Cre; f/f/Cre) and parallel controls (ADAM17(flox/flox); f/f) were subjected to MI by ligation of the left anterior descending artery. Read More

    Prognostic Significance and Determinants of the 6-Min Walk Test in Patients With Heart Failure and Preserved Ejection Fraction.
    JACC Heart Fail 2015 Jun;3(6):459-466
    Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria. Electronic address:
    Objectives: This study sought to define the prognostic significance and clinical determinants of the 6-min walk distance (6-MWD) in affected patients.

    Background: Symptoms of exertional fatigue and dyspnea, as well as a reduced exercise tolerance, are cardinal features of pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF). Mechanisms limiting exercise capacity in this specific entity remain incompletely understood. Read More

    Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.
    Circ Heart Fail 2015 May 9;8(3):542-50. Epub 2015 Apr 9.
    From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
    Background: Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF.

    Methods And Results: In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. Read More

    Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients.
    Circ Heart Fail 2015 May 2;8(3):565-71. Epub 2015 Apr 2.
    From the Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (J.O.M.O., S.A., J.D.W.E., R.B., M.M.); Department of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham NHS Trust, Birmingham, United Kingdom (M.M., R.S.B.); Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (B.O.F., M.F.); and Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom (M.P.F.).
    Background: Nitrite exhibits hypoxia-dependent vasodilator properties, selectively dilating capacitance vessels in healthy subjects. Unlike organic nitrates, it seems not to be subject to the development of tolerance. Currently, therapeutic options for decompensated heart failure (HF) are limited. Read More

    Survival and neurocognitive outcomes after cardiac extracorporeal life support in children less than 5 years of age: a ten-year cohort.
    Circ Heart Fail 2015 Mar 9;8(2):312-21. Epub 2015 Jan 9.
    From the Department of Pediatrics (L.M.R., G.G.G., A.R.J., C.M.T.R., L.L.), Department of Public Health Sciences (I.A.D.), and Department of Surgery (I.M.R., D.B.R.), University of Alberta, Edmonton, Alberta, Canada; Pediatric Rehabilitation Outcomes Evaluation and Research Unit, Glenrose Rehabilitation Hospital, Edmonton, Alberta, Canada (C.M.T.R., G.Y.A.); and Pediatric Critical Care Unit, Stollery Children's Hospital, Edmonton, Alberta, Canada (D.G.).
    Background: Survival after pediatric cardiac extracorporeal life support (ECLS) is guarded, and neurological morbidity varies widely. Our objective is to report our 10-year experience with cardiac ECLS, including survival and kindergarten entry neurocognitive outcomes; to identify predictors of mortality or adverse neurocognitive outcomes; and to compare 2 eras, before and after 2005.

    Methods And Results: From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Read More

    Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction.
    Circ Heart Fail 2015 Mar 30;8(2):278-85. Epub 2014 Dec 30.
    From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
    Background: The mechanism of functional limitation in heart failure with preserved ejection fraction remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH).

    Methods And Results: We compared 31 ePVH patients (peak VO2<80% of predicted and peak pulmonary arterial wedge pressure≥20 mm Hg) with 31 age- and sex-matched controls (peak VO2>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. Read More

    Cerebral hypoperfusion is exaggerated with an upright posture in heart failure: impact of depressed cardiac output.
    JACC Heart Fail 2015 Feb 31;3(2):168-75. Epub 2014 Oct 31.
    Schlegel-University of Waterloo Research Institute for Aging, Faculty of Applied Health Sciences, Waterloo, Ontario, Canada. Electronic address:
    Objectives: The purpose of this study was to examine cerebral blood flow (CBF) supine and during upright sitting in HF patients and control subjects to test the hypothesis that patients with HF will have a greater reduction in CBF from supine to seated compared with the control group.

    Background: Reduced CBF has been reported in patients with heart failure (HF). However, previous work has only examined CBF while supine, although an upright posture common to daily living may lead to further reductions. Read More

    Patients with heart failure with reduced ejection fraction have exaggerated reductions in cerebral blood flow during upright posture.
    JACC Heart Fail 2015 Feb 31;3(2):176-9. Epub 2014 Oct 31.
    Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, Texas; Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

    Effect of macitentan on hospitalizations: results from the SERAPHIN trial.
    JACC Heart Fail 2015 Jan 11;3(1):1-8. Epub 2014 Nov 11.
    Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna University Hospital, Bologna, Italy.
    Objectives: This study sought to evaluate the effect of macitentan on hospitalization of patients with symptomatic pulmonary arterial hypertension (PAH).

    Background: PAH is a progressive, life-threatening disease often requiring hospitalization.

    Methods: In the multicenter, double-blind, randomized, event-driven, phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. Read More

    Characterization of pulmonary hypertension in heart failure using the diastolic pressure gradient: limitations of a solitary measurement.
    JACC Heart Fail 2015 Jan 11;3(1):17-21. Epub 2014 Nov 11.
    Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

    Pro-B-type natriuretic peptide-1-108 processing and degradation in human heart failure.
    Circ Heart Fail 2015 Jan 22;8(1):89-97. Epub 2014 Oct 22.
    From the Cardiorenal Research Laboratory, Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN.
    Background: We have reported that pro-B-type natriuretic peptide (BNP)-1-108 circulates and is processed to mature BNP1-32 in human blood. Building on these findings, we sought to determine whether proBNP1-108 processed forms in normal circulation are biologically active and stimulate cGMP, and whether proBNP1-108 processing and activity are altered in human heart failure (HF) compared with normal. Because BNP1-32 is deficient whereas proBNP1-108 is abundant in HF, we hypothesize that proBNP1-108 processing and degradation are impaired in HF patients ex vivo. Read More

    Clinical outcomes after continuous-flow left ventricular assist device: a systematic review.
    Circ Heart Fail 2014 Nov 7;7(6):1003-13. Epub 2014 Oct 7.
    From the Division of Cardiology (C.K.M., A.V.A., L.A.A.), Adult and Child Center for Health Outcomes Research and Delivery Science (K.H.M., J.S.T.), and Division of General Internal Medicine (D.D.M.), University of Colorado School of Medicine, Aurora; Brown University, School of Public Health, Providence, RI (K.H.M.); and Colorado Cardiovascular Outcomes Research Consortium, Denver (C.K.M., D.D.M., L.A.A.).
    Background: Conveying the complex trade-offs of continuous-flow left ventricular assist devices is challenging and made more difficult by absence of an evidence summary for the full range of possible outcomes. We aimed to summarize the current evidence on outcomes of continuous-flow left ventricular assist devices.

    Methods And Results: PubMed and Cochrane Library were searched from January 2007 to December 2013, supplemented with manual review. Read More

    Renal hemodynamic effects of serelaxin in patients with chronic heart failure: a randomized, placebo-controlled study.
    Circ Heart Fail 2014 Nov 6;7(6):994-1002. Epub 2014 Oct 6.
    From the University of Groningen, University Medical Center Groningen, The Netherlands (A.A.V., S.M., R.H.J.A.S., G.J.N.); Novartis Pharma AG, Basel, Switzerland (M.D., A.J., D.L.); Institute of Cardiology, Warsaw, Poland (J.S.); University of Maryland, Baltimore (S.S.G.); and Novartis Pharmaceuticals, East Hanover, NJ (Y.Z.).
    Background: Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown.

    Methods And Results: In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association Class II to III chronic heart failure, left ventricular ejection fraction ≤45%, and estimated glomerular filtration rate (GFR) 30 to 89 mL/min per 1. Read More

    Pulmonary hypertension is related to peripheral endothelial dysfunction in heart failure with preserved ejection fraction.
    Circ Heart Fail 2014 Sep 21;7(5):791-8. Epub 2014 Jul 21.
    From the Heart Failure and Heart Transplantation Program, Cardiology Department, Hospital Clinic (M.F., E.S., M.C., M.A.C., F.P.-V.), and Pulmonary Medicine Department, Hospital Clinic (I.B., J.A.B.), Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS) (I.B., M.B., J.A.B., F.P.-V.); Cardiac Imaging Section, Cardiology Department, Hospital Clinic (B.V.), Barcelona, Spain; and Biomedical Research Networking Centers on Respiratory Diseases (CIBERES) (I.B., J.A.B.), Madrid, Spain.
    Background: Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF. Read More

    Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis.
    JACC Heart Fail 2014 Aug 9;2(4):358-67. Epub 2014 Jul 9.
    Cardiovascular Division and Cardiac Amyloidosis Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
    Objectives: The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis.

    Background: Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD).

    Methods: Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). Read More

    Serum biomarkers in severe refractory cardiogenic shock.
    JACC Heart Fail 2013 Jun 3;1(3):200-6. Epub 2013 Jun 3.
    Texas Heart Institute, University of Texas Health Sciences Center, Houston, Texas. Electronic address:
    Objectives: The aim of this study was to characterize levels of serum biomarkers in patients with severe refractory cardiogenic shock (SRCS) and to document temporal changes in these levels during restoration of circulation.

    Background: Patients with SRCS have been challenging to study because of their rapidly changing clinical condition while undergoing multiple simultaneous interventions.

    Methods: Twenty-one patients with SRCS received circulatory support via a percutaneously implanted ventricular assist device (PVAD). Read More

    Emergency parallel mechanical circulatory support for ventricular fibrillation.
    Circ Heart Fail 2014 Jan;7(1):229-30
    Department of Medicine, Unit of Cardiology and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; and Department of Cardiology and Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, Stockholm, Sweden.

    Vascular endothelial growth factor blockade prevents the beneficial effects of β-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure.
    Circ Heart Fail 2013 Nov 12;6(6):1259-67. Epub 2013 Sep 12.
    Division of Cardiology, "Salvatore Maugeri" Foundation-IRCCS-Institute of Telese Terme.
    Background: Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, β-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart. Read More

    Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension.
    Circ Heart Fail 2013 Sep;6(5):953-63
    Background: Systemic sclerosis–associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis–related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function.

    Methods And Results: We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis–related pulmonary hypertension with interstitial lung disease, and 67 IPAH). Read More

    Coronary collaterals predict improved survival and allograft function in patients with coronary allograft vasculopathy.
    Circ Heart Fail 2013 Jul 24;6(4):773-84. Epub 2013 May 24.
    Division of Cardiology, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA.
    Background: Despite improvements in the care of patients who have received cardiac transplants, coronary allograft vasculopathy (CAV) remains the most prevalent cause of late allograft failure and cardiac mortality. Few proven therapies are available for this important disease. The presence of coronary collaterals imparts a favorable prognosis in patients with native ischemic heart disease; however, the impact of collaterals in CAV is unknown. Read More

    Invasive measures of afterload in low gradient severe aortic stenosis with preserved ejection fraction.
    Circ Heart Fail 2013 Jul 24;6(4):703-10. Epub 2013 May 24.
    Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
    Background: The pathophysiology of low flow, low gradient severe aortic stenosis (LGSAS) with preserved ejection fraction is poorly understood. It has been proposed that abnormalities of arterial circulation are a major contributor to this syndrome.

    Methods And Results: We invasively examined systemic arterial afterload (effective arterial elastance, Ea; total arterial compliance, Ca; and systemic vascular resistance index) in patients with LGSAS (mean gradient, <40 mm Hg; aortic valve area, <1. Read More

    Preoperative INTERMACS profiles determine postoperative outcomes in critically ill patients undergoing emergency heart transplantation: analysis of the Spanish National Heart Transplant Registry.
    Circ Heart Fail 2013 Jul 14;6(4):763-72. Epub 2013 May 14.
    Heart Transplant Unit, Hospital Universitario A Coruña, A Coruña, Spain.
    Background: Postoperative outcomes of patients with advanced heart failure undergoing ventricular assist device implantation are strongly influenced by their preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles. We sought to investigate whether a similar association exists in patients undergoing emergency heart transplantation.

    Methods And Results: By means of the Spanish National Heart Transplant Registry database, we identified 704 adult patients treated with emergency heart transplantation in 15 Spanish centers between 2000 and 2009. Read More

    Prognostic value of exercise testing during heart transplant evaluation in children.
    Circ Heart Fail 2013 Jul 11;6(4):792-9. Epub 2013 Apr 11.
    Department of Pediatrics, Mount Sinai Medical Center, New York, NY, USA.
    Background: Maximum oxygen consumption (peak VO2) <50% predicted on exercise testing is a class I indication for heart transplant (HT) listing in children. This recommendation is based on exercise data in adults. We assessed the association of peak VO2<50% predicted during HT evaluation with freedom from death or deterioration in children. Read More

    Prolonged mean VO2 response time in systolic heart failure: an indicator of impaired right ventricular-pulmonary vascular function.
    Circ Heart Fail 2013 May 9;6(3):499-507. Epub 2013 Apr 9.
    Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
    Background: In patients with left ventricular systolic dysfunction (LVSD), the rate at which oxygen uptake (VO2) increases on initiation of exercise is inadequate to match metabolic demands. To gain mechanistic insights into delayed VO2 kinetics in LVSD, we simultaneously assessed hemodynamic measurements, ventilatory parameters, and peripheral oxygen usage during exercise.

    Methods And Results: Forty-two patients with symptomatic LVSD (age, 59±2 years [mean±SEM]; LV ejection fraction, 30±1%) and 17 controls (LV ejection fraction, 68±1%) underwent maximum upright cycle ergometry cardiopulmonary exercise testing. Read More

    Chronic heart failure does not attenuate the total activity of sympathetic outflow to skin during whole-body heating.
    Circ Heart Fail 2013 Mar 8;6(2):271-8. Epub 2013 Feb 8.
    Penn State Hershey Heart and Vascular Institute, Hershey, PA 17033, USA.
    Background: Previous studies show that the rise in skin blood flow and cutaneous vascular conductance during heat stress is substantially attenuated in chronic heart failure (CHF) patients. The mechanisms responsible for this finding are not clear. In particular, little is known regarding the responses of skin sympathetic nerve activity (SSNA) that control the skin blood flow during heat stress in CHF patients. Read More

    Clinical and functional correlates of early microvascular dysfunction after heart transplantation.
    Circ Heart Fail 2012 Nov 29;5(6):759-68. Epub 2012 Aug 29.
    Department of Medicine, Stanford University, Stanford, CA, USA.
    Background: Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients. Read More

    TRV120027, a novel β-arrestin biased ligand at the angiotensin II type I receptor, unloads the heart and maintains renal function when added to furosemide in experimental heart failure.
    Circ Heart Fail 2012 Sep 13;5(5):627-34. Epub 2012 Aug 13.
    Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
    Background: TRV120027 is a novel β-arrestin biased ligand of the angiotensin II type 1 receptor; it antagonizes canonical G-protein-mediated coupling while, in contrast to classical angiotensin II type 1 receptor antagonists, it engages β-arrestin-mediated signaling. Consequently, TRV120027 inhibits angiotensin II-mediated vasoconstriction while, via β-arrestin coupling, it increases cardiomyocyte contractility. We hypothesized that TRV120027 would elicit beneficial cardiorenal actions when added to furosemide in experimental heart failure. Read More

    Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution.
    Circ Heart Fail 2012 Jul 1;5(4):452-61. Epub 2012 Jun 1.
    Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics/Physiology and Cell Biology, The Ohio State University, 700 Children’s Drive, Columbus, OH 43205, USA.
    Background: Air pollution is a pervasive environmental health hazard that occurs over a lifetime of exposure in individuals from many industrialized societies. However, studies have focused primarily on exposure durations that correspond to only a portion of the lifespan. We therefore tested the hypothesis that exposure over a considerable portion of the lifespan would induce maladaptive cardiovascular responses. Read More

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