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Turning the Retrospectroscope on Heart Failure With Preserved Ejection Fraction

  • Walter J. Paulus
    Correspondence
    Reprint requests: Walter J. Paulus, MD, PhD, ICaR-VU, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands. Tel: 31 20 4448110; Fax: 31 20 4448255.
    Affiliations
    Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
    Search for articles by this author
Published:September 30, 2016DOI:https://doi.org/10.1016/j.cardfail.2016.09.022
      In 1977, Julius H. Comroe, director of the cardiovascular research institute at UCSF, introduced the “retrospectroscope”,
      • Comroe Jr, J.H.
      Retrospectroscope. Insights into medical discovery.
      a device that enabled him to retrace the path of medical progress looking backwards from today's clarity to yesterday's haziness. When turning the “retrospectroscope” on heart failure (HF) with preserved ejection fraction (HFpEF), one sees no smooth track but a bumpy road covered with outdated acronyms and a challenged existence that finally led to a HFpEF specific paradigm,
      • Paulus W.J.
      • Tschoepe C.
      A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.
      • Shah S.J.
      • Kitzman D.W.
      • Borlaug B.A.
      • van Heerebeek L.
      • Zile M.R.
      • Kass D.A.
      • et al.
      Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap.
      which is currently gaining widespread acceptance. According to this paradigm, left ventricular (LV) remodeling and dysfunction in HFpEF result from multiple, especially metabolic comorbidities, which induce myocardial microvascular endothelial inflammation
      • Franssen C.
      • Chen S.
      • Unger A.
      • Korkmaz H.I.
      • De Keulenaer G.W.
      • Tschöpe C.
      • et al.
      Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction.
      with altered signalling to underlying cardiomyocytes.
      • Van Heerebeek L.
      • Hamdani N.
      • Falcão-Pires I.
      • Leite-Moreira A.F.
      • Begieneman M.P.V.
      • Bronzwaer J.G.F.
      • et al.
      Low myocardial protein kinase G activity in heart failure with preserved ejection fraction.
      As a consequence, the cardiomyocytes become stiff and hypertrophied and vascular permeability changes allowing for infiltration by leucocytes, which turn fibroblasts into myofibroblasts with enhanced collagen deposition.
      • Westermann D.
      • Lindner D.
      • Kasner M.
      • Zietsch C.
      • Savvatis K.
      • Escher F.
      • et al.
      Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction.
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      References

        • Comroe Jr, J.H.
        Retrospectroscope. Insights into medical discovery.
        Von Gehr Press, Menlo Park, CA1977
        • Paulus W.J.
        • Tschoepe C.
        A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.
        J Am Coll Cardiol. 2013; 62: 263-271
        • Shah S.J.
        • Kitzman D.W.
        • Borlaug B.A.
        • van Heerebeek L.
        • Zile M.R.
        • Kass D.A.
        • et al.
        Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap.
        Circulation. 2016; 134: 73-90
        • Franssen C.
        • Chen S.
        • Unger A.
        • Korkmaz H.I.
        • De Keulenaer G.W.
        • Tschöpe C.
        • et al.
        Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction.
        JACC Heart Fail. 2016; 4: 312-324
        • Van Heerebeek L.
        • Hamdani N.
        • Falcão-Pires I.
        • Leite-Moreira A.F.
        • Begieneman M.P.V.
        • Bronzwaer J.G.F.
        • et al.
        Low myocardial protein kinase G activity in heart failure with preserved ejection fraction.
        Circulation. 2012; 126: 830-839
        • Westermann D.
        • Lindner D.
        • Kasner M.
        • Zietsch C.
        • Savvatis K.
        • Escher F.
        • et al.
        Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction.
        Circ Heart Fail. 2011; 4: 44-52
        • Gandhi S.K.
        • Powers J.C.
        • Nomeir A.M.
        • Fowle K.
        • Kitzman D.W.
        • Rankin K.M.
        • et al.
        The pathogenesis of acute pulmonary edema associated with hypertension.
        N Engl J Med. 2001; 344: 17-22
        • Vasan R.S.
        • Benjamin E.J.
        Diastolic heart failure—no time to relax.
        N Engl J Med. 2001; 344: 56-59
        • Zile M.R.
        • Baicu C.F.
        • Gaasch W.H.
        Diastolic heart failure-abnormalities in active relaxation and passive stiffness of the left ventricle.
        N Engl J Med. 2004; 350: 1953-1959
        • European Study Group on Diastolic Heart Failure
        How to diagnose diastolic heart failure.
        Eur Heart J. 1998; 19: 990-1003
        • Petrie M.
        • McMurray J.
        Changes in notions about heart failure.
        Lancet. 2001; 358: 432-434
        • McMurray J.
        • Pfeffer M.A.
        New therapeutic options in congestive heart failure: part II.
        Circulation. 2002; 105: 2223-2228
        • Paulus W.J.
        • van Ballegoij J.J.
        Treatment of heart failure with normal ejection fraction: an inconvenient truth!.
        J Am Coll Cardiol. 2010; 55: 526-537
        • Yusuf S.
        • Pfeffer M.A.
        • Swedberg K.
        • Granger C.B.
        • Held P.
        • McMurray J.J.V.
        • et al.
        Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.
        Lancet. 2003; 362 (for the; CHARM Investigators and Committees): 777-781
        • Pitt B.
        • Pfeffer M.A.
        • Assmann S.F.
        • Boineau R.
        • Anand I.S.
        • Claggett B.
        • et al.
        Spironolactone for heart failure with preserved ejection fraction.
        N Engl J Med. 2014; 370: 1383-1392
        • Persson H.
        • Lonn E.
        • Edner M.
        • Baruch L.
        • Lang C.C.
        • Morton J.J.
        • et al.
        Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence: results from the CHARM Echocardiographic Substudy-CHARMES.
        J Am Coll Cardiol. 2007; 49: 687-694
        • Pfeffer M.A.
        • Claggett B.
        • Assmann S.F.
        • Boineau R.
        • Anand I.S.
        • Clausell N.
        • et al.
        Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.
        Circulation. 2015; 131: 34-42
        • Sanderson J.E.
        HFNEF, HFpEF, HF-PEF, or DHF: what is in an acronym?.
        JACC Heart Fail. 2014; 2: 93-94
        • Paulus W.J.
        • Tschöpe C.
        • Sanderson J.E.
        • Rusconi C.
        • Flachskampf F.A.
        • Rademakers F.E.
        • et al.
        How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology.
        Eur Heart J. 2007; 28: 2539-2550
        • Gaasch W.H.
        • Zile M.R.
        Left ventricular structural remodeling in health and disease: with special emphasis on volume, mass, and geometry.
        J Am Coll Cardiol. 2011; 58: 1733-1740
        • Anand I.S.
        • Rector T.S.
        • Cleland J.G.
        • Kuskowski M.
        • McKelvie R.S.
        • Persson H.
        • et al.
        Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: findings from the I-PRESERVE trial.
        Circ Heart Fail. 2011; 4: 569-577
        • Shuai X.X.
        • Chen Y.Y.
        • Lu Y.X.
        • Su G.H.
        • Wang Y.H.
        • Zhao H.L.
        • et al.
        Diagnosis of heart failure with preserved ejection fraction: which parameters and diagnostic strategies are more valuable?.
        Eur J Heart Fail. 2011; 13: 737-745
        • Sanderson J.E.
        • Gibson D.G.
        • Brown D.J.
        • Goodwin J.F.
        Left ventricular filling in hypertrophic cardiomyopathy. An angiographic study.
        Br Heart J. 1977; 39: 661-670
        • Brutsaert D.L.
        • Housmans P.R.
        • Goethals M.A.
        Dual control of relaxation. Its role in the ventricular function in the mammalian heart.
        Circ Res. 1980; 47: 637-652
        • Grossman W.
        • Barry W.H.
        Diastolic pressure-volume relations in the diseased heart.
        Fed Proc. 1980; 39: 148-155
        • Gaasch W.H.
        • Zile M.R.
        • Hoshino P.K.
        • Weinberg E.O.
        • Rhodes D.R.
        • Apstein C.S.
        Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.
        Circulation. 1990; 81: 1644-1653
        • Sanderson J.E.
        Heart failure with a normal ejection fraction.
        Heart. 2007; 93: 155-158
        • Brutsaert D.L.
        • De Keulenaer G.W.
        Diastolic heart failure: a myth.
        Curr Opin Cardiol. 2006; 21: 240-248
        • Dunlay S.M.
        • Roger V.L.
        • Weston S.A.
        • Jiang R.
        • Redfield M.M.
        Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction.
        Circ Heart Fail. 2012; 5: 720-726
        • Lam C.S.
        • Roger V.L.
        • Rodeheffer R.J.
        • Bursi F.
        • Borlaug B.A.
        • Ommen S.R.
        • et al.
        Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota.
        Circulation. 2007; 115: 1982-1990
        • Linke W.A.
        • Hamdani N.
        Gigantic business: titin properties and function through thick and thin.
        Circ Res. 2014; 114: 1052-1068
        • Bull M.
        • Methawasin M.
        • Strom J.
        • Nair P.
        • Hutchinson K.
        • Granzier H.L.
        Alternative splicing of titin restores diastolic function in a HFpEF-like genetic murine model (TtnΔIAjxn).
        Circ Res. 2016; 119: 764-772
        • Krijnen P.A.J.
        • Meischl C.
        • Hack C.E.
        • Meijer C.J.L.M.
        • Visser C.A.
        • Roos D.
        • et al.
        Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction.
        J Clin Pathol. 2003; 56: 194-199
        • Packer M.
        Can brain natriuretic peptide be used to guide the management of patients with heart failure and a preserved ejection fraction? The wrong way to identify new treatments for a nonexistent disease.
        Circ Heart Fail. 2011; 4: 538-540
        • López B.
        • Ravassa S.
        • González A.
        • Zubillaga E.
        • Bonavila C.
        • Bergés M.
        • et al.
        Myocardial collagen cross-linking is associated with heart failure hospitalization in patients with hypertensive heart failure.
        J Am Coll Cardiol. 2016; 67: 251-260
        • Seferović P.M.
        • Paulus W.J.
        Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes.
        Eur Heart J. 2015; 36: 1718-1727
        • D'Elia E.
        • Vaduganathan M.
        • Gori M.
        • Gavazzi A.
        • Butler J.
        • Senni M.
        Role of biomarkers in cardiac structure phenotyping in heart failure with preserved ejection fraction: critical appraisal and practical use.
        Eur J Heart Fail. 2015; 17: 1231-1239
        • Davis B.R.
        • Kostis J.B.
        • Simpson L.M.
        • Black H.R.
        • Cushman W.C.
        • Einhorn P.T.
        • et al.
        Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.
        Circulation. 2008; 118: 2259-2267
        • Borlaug B.A.
        • Redfield M.M.
        • Melenovsky V.
        • Kane G.C.
        • Karon B.L.
        • Jacobsen S.J.
        • et al.
        Longitudinal changes in left ventricular stiffness: a community-based study.
        Circ Heart Fail. 2013; 6: 944-952
        • Wohlfahrt P.
        • Redfield M.M.
        • Lopez-Jimenez F.
        • Melenovsky V.
        • Kane G.C.
        • Rodeheffer R.J.
        • et al.
        Impact of general and central adiposity on ventricular-arterial aging in women and men.
        JACC Heart Fail. 2014; 2: 489-499
        • Gallet R.
        • de Couto G.
        • Simsolo E.
        • Valle J.
        • Sun B.
        • Liu W.
        • et al.
        Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation.
        JACC Basic Transl Sci. 2016; 1: 14-28
        • Heymans S.
        • Corsten M.F.
        • Verhesen W.
        • Carai P.
        • van Leeuwen R.E.
        • Custers K.
        • et al.
        Macrophage microRNA-155 promotes cardiac hypertrophy and failure.
        Circulation. 2013; 128: 1420-1432