Distribution of Left Ventricular Ejection Fraction in Patients With Ischemic and Hypertensive Heart Disease and Chronic Heart Failure

      The clinical manifestations and eventual outcomes of chronic heart failure (HF) are not closely related to the left ventricular ejection fraction (EF). This has contributed to the single syndrome hypothesis of HF that assumes a continuum, with the EF evolving and decreasing as the ventricle remodels and dilates. Such a continuum might be expected to be manifest as a unimodal distribution of EF in populations with chronic HF. We examined the distribution of EF in 2 populations of patients with HF (EF range 0.10 to 0.85), and we tested the hypothesis that the EF distribution is unimodal. In both populations, the distribution histogram was bimodal. This result is consonant with the 2 different patterns of cardiac structural and functional remodeling seen in patients with HF and normal and depressed EF. It is also consonant with published differences in response to the inhibition of the renin-angiotensin system in these 2 groups. In conclusion, the observed bimodal distribution of EF in patients with chronic HF is a reflection of 2 HF phenotypes with different underlying pathophysiologic features.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aurigemma G.P.
        • Gaasch W.H.
        Diastolic heart failure.
        N Engl J Med. 2004; 351: 1097-1105
        • Sanderson J.E.
        Heart failure with normal ejection fraction.
        Heart. 2007; 93: 155-158
        • Paulus W.J.
        • Tschope C.
        • Sanderson J.E.
        • Rusconi C.
        • Flachskampf F.A.
        • Rademakers F.E.
        • Marino P.
        • Smitseth O.H.
        • DeKeulenaer G.
        • Leite-Moreira A.F.
        • Borbely A.
        • Edes I.
        • Handoko M.L.
        • Heymans S.
        • Pezzali N.
        • Pieske B.
        • Dickstein K.
        • Fraser A.G.
        • Brutsaert D.L.
        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
        • Solomon S.D.
        • Anavekar N.
        • Skali H.
        • McMurray J.J.V.
        • Swedberg K.
        • Yusuf S.
        • Granger C.B.
        • Michelson E.L.
        • Wang D.
        • Pocock S.
        • Pfeffer M.A.
        Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients.
        Circulation. 2005; 112: 3738-3744
        • Gaasch W.H.
        • Delorey D.E.
        • Zile M.R.
        Patterns of structural and functional remodeling of the left ventricle in chronic heart failure.
        Am J Cardiol. 2008; 102: 459-462
        • Bourge R.C.
        • Abraham W.T.
        • Adamson P.B.
        • Aaron M.F.
        • Aranda J.M.
        • Magalski A.
        • Zile M.R.
        • Smith A.L.
        • Smart F.W.
        • O'Shaughnessy M.A.
        • Jessup M.L.
        • Sparks B.
        • Naftel D.L.
        Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure.
        J Am Coll Cardiol. 2008; 51: 1073-1079
        • Silverman B.W.
        Density Estimation for Statistics and Data Analysis.
        in: Chapman and Hall, London1986: 48
        • Hartigan J.A.
        • Hartigan P.M.
        The dip test of unimodality.
        Ann Stat. 1985; 13: 70-84
        • Bhatia R.S.
        • Tu J.V.
        • Lee D.S.
        • Austin P.C.
        • Fang J.
        • Haouzi A.
        • Gong Y.
        • Liu P.P.
        Outcome of heart failure with preserved ejection fraction in a population–based study.
        N Engl J Med. 2006; 355: 260-269
        • Fonarow G.C.
        • Stough W.G.
        • Abraham W.T.
        • Albert N.M.
        • Gheorghiade M.
        • Greenberg B.H.
        • O'Connor C.M.
        • Sun J.L.
        • Yancy C.W.
        • Young J.B.
        Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry.
        J Am Coll Cardiol. 2007; 50: 768-777
        • Baicu C.F.
        • Zile M.R.
        • Aurigemma G.P.
        • Gaasch W.H.
        Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure.
        Circulation. 2005; 111: 2306-2312
        • Van Heerebeek L.
        • Borbely A.
        • Niessen H.W.M.
        • Bronzwaer J.G.F.
        • van der Velden J.
        • Stienen G.J.M.
        • Linke W.A.
        • Laarman G.J.
        • Paulus W.J.
        Myocardial structure and function differ in systolic and diastolic heart failure.
        Circulation. 2006; 113: 1966-1973
        • Borbely A.
        • van der Velden J.
        • Papp Z.
        • Bronzwaer J.G.F.
        • Edes I.
        • Stienen G.J.
        • Paulus W.J.
        Cardiomyocyte stiffness in diastolic heart failure.
        Circulation. 2005; 111: 774-781
        • LeWinter M.M.
        Titin isoforms in heart failure: are there benefits to supersizing.
        Circulation. 2004; 110: 109-111
        • Spinale F.G.
        Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function.
        Physiol Rev. 2007; 87: 1285-1342
        • Hunt S.A.
        • Abraham W.T.
        • Chin M.H.
        • Feldman A.M.
        • Francis G.S.
        • Ganiats T.G.
        • Jessup M.
        • Konstam M.A.
        • Mancini D.M.
        • Michl K.
        2009 Focused update incorporated into the ACC/AHA guidelines for the diagnosis and management of heart failure in adults.
        J Am Coll Cardiol. 2009; 53: 1-90
        • Yusuf S.
        • Pfeffer M.A.
        • Swedberg K.
        • Granger C.B.
        • Held P.
        • McMurray J.J.
        • Michelson E.L.
        • Olofsson B.
        • Ostergren J.
        Effects of candisartan in patients with chronic heart failure and preserved left ventricular ejection fraction: the CHARM-preserved trial.
        Lancet. 2003; 362: 777-781
        • Cleland J.G.
        • Tendera M.
        • Adamus J.
        • Freemantle N.
        • Polonski L.
        • Taylor J.
        The perindopril in elderly people with chronic heart failure (PEP-CHF) study.
        Eur Heart J. 2006; 321: 215-218
        • Massie B.M.
        • Carson P.E.
        • McMurray J.J.
        • Komajdam M.
        • McKelvie R.
        • Zile M.R.
        • Anderson S.
        • Dionovan M.
        • Iverson E.
        • Staiger C.
        • Ptaszynska A.
        Irbesertan in patients with heart failure and preserved ejection fraction.
        N Engl J Med. 2008; 359: 2456-2467
        • Smith G.
        • Masoudi F.A.
        • Vaccarino V.
        • Radford M.D.
        • Krumholz H.M.
        Outcome in heart failure patients with preserved ejection fraction.
        J Am Coll Cardiol. 2003; 41: 1510-1518
        • Vasan R.S.
        • Levy D.
        Defining diastolic heart failure: a call for standardized diagnostic criteria.
        Circulation. 2000; 101: 2118-2121
        • Yturralde F.R.
        • Gaasch W.H.
        Diagnostic criteria for diastolic heart failure.
        Prog Cardiovasc Dis. 2005; 47: 314-319
        • Davis B.R.
        • Kostis J.B.
        • Simpson L.M.
        • Black H.R.
        • Cushman W.C.
        • Einhorn P.T.
        • Farber M.A.
        • Ford C.E.
        • Levy D.
        • Massie B.M.
        • Nawaz S.
        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
        • Little W.C.
        • Brucks S.
        Therapy for diastolic heart failure.
        Prog Cardiovasc Dis. 2005; 47: 380-388

      Linked Article

      • Ejection Fraction in Heart Failure
        American Journal of CardiologyVol. 105Issue 12
        • Preview
          I was interested to read the report by Gaasch et al1 on the distribution of left ventricular (LV) ejection fractions (EFs) in patients with chronic heart failure (HF). Specifically, they used trial data to test whether there is a continuum of HF from patients with normal EFs (HF with normal EF [HFNEF]) to those with reduced EFs (HF with reduced EF [HFREF]). Because the investigators found that the EF distribution was suggestive of a bimodal distribution, they concluded that there is no continuum.
        • Full-Text
        • PDF