Definitions and Historical Considerations – The Misleading Role of Ejection Fraction
Chronic heart failure (CHF) is a heterogeneous syndrome with a complex pathophysiology. Although many different definitions for heart failure exist, we prefer the following: “a clinical syndrome characterised by symptoms and signs of increased tissue/organ water and decreased tissue/organ perfusion. Regardless of its aetiology, symptoms and signs may be related either to impaired left ventricular (LV) relaxation, suction and filling (predominantly diastolic pump dysfunction/failure) or to impaired output of the cardiac compression pump (predominantly systolic pump dysfunction/failure) but almost always to a combination of both.”1
This definition of heart failure refrains from including any notion of LV ejection fraction. However, mostly driven by clinical trial design, heart failure has been dichotomised according to ejection fraction as ‘preserved’ (heart failure with preserved ejection fraction [HFpEF]) or ‘reduced’ (heart failure with reduced ejection fraction [HFredEF]). Recently, epidemiological surveys have revealed that the incidence of HFpEF has been steadily increasing over the past 25 years.2 Currently, the LV ejection fraction is found to be preserved in >50% of cases of heart failure. Patients with HFpEF appear to be older and are more likely to be female, have a history of hypertension and have less coronary artery disease. Once hospitalisation for ‘decompensation’ has occurred, the cardiovascular mortality and overall prognosis is as poor as for HFredEF.2,3
Erroneously, the pathophysiology of HFpEF and HFredEF were considered to be genuinely different. Whereas HFredEF was correlated with mere ‘systolic abnormalities’, these abnormalities were believed to be absent in HFpEF. Instead, when ejection fraction was preserved, heart failure was correlated with ‘diastolic abnormalities’, and was thought to occur without abnormalities in systole. Inevitably, the connotations ‘systolic’ and ‘diastolic’ heart failure were introduced as they were estimated to reflect distinct diseases. However, recent observations have neglected to refine this view.4,5 Most importantly, it is now generally recognised that in systolic heart failure LV diastolic abnormalities are profound, and predict a patient’s symptoms better than systolic (dys)function.6 In contrast, in diastolic heart failure there are marked, previously overlooked LV systolic abnormalities, as revealed by novel cardiac imaging techniques.7 In fact, CHF, irrespective of ejection fraction (even when preserved), is emerging as a syndrome in which many pathophysiological processes interact.
- Brutsaert DL, Cardiac dysfunction in heart failure: the cardiologist’s love affair with time, Prog Cardiovasc Dis, 2006;49:157–81.
- Owan TE, Hodge DO, Herges RM, et al., Trends in prevalence and outcome of heart failure with preserved ejection fraction, N Engl J Med, 2006;355:251–9.
- Fonarow GC, Stough WG, Abraham WT, et al., OPTIMIZE-HF Investigators and Hospitals. Characteristics, treatments and outcomes of patients with preserved systolic function hospitalized for heart failure, J Am Coll Cardiol, 2007;50: 768–77.
- De Keulenaer GW, Brutsaert DL, Systolic and diastolic heart failure: different phenotypes of the same disease, Eur J Heart Fail, 2007;9:352–6.
- Brutsaert DL, De Keulenaer GW, Diastolic heart failure: a myth, Curr Opin Cardiol, 2006;21:240–48.
- Skaluba SJ, Litwin SE, Mechanisms of exercise intolerance: insights from tissue Doppler imaging, Circulation, 2004;109: 972–7.
- Sanderson JE, Heart failure with a normal ejection fraction, Heart, 2007;93:155–8.
- Maurer MS, Burkhoff D, Fried LP, et al., The cardiovascular health study: Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction, J Am Coll Cardiol, 2007;49:972–81.
- Kawaguchi M, Hay I, Fetics B, Kass DA, Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations, Circulation, 2003;107:714–20.
- Kitzman DW, Little WC, Brubaker PH, et al., Pathophysiological characterization of isolated diastolic heart failure in comparison of systolic heart failure, JAMA, 2002;288:2144–50.
- Prestle J, Dieterich S, Preuss M, et al., Heterogeneous transmural gene expression of calcium-handling proteins and natriuretic peptides in the failing human heart, Cardiovasc Res, 1999;43:323–31.
- van Heerebeek L, Borbély A, Niessen HW, et al., Myocardial structure and function differ in systolic and diastolic heart failure, Circulation, 2006;113:1966–73.
- De Keulenaer GW, Brutsaert DL, Molecular Mechanisms of Diastolic Dysfunction. In: Smiseth O, Tendera M (eds), Diastolic Heart Failure, Springer, 2008;3–21.
- Paulus WJ, Tschöpe C, Sanderson JE, 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;28:2539–50.
- Borlaug BA, Melenovsky V, Russell SD, et al., Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction, Circulation, 2006:114:2138–47.
- Yusuf S, Pfeffer MA, Swedberg K, et al., Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial, Lancet, 2003;362:777–81.
- Cleland JG, Tendera M, Adamus J, et al., PEP-CHF Investigators. The perindopril in elderly people with chronic heart failure (PEP-CHF) study, Eur Heart J, 2006;27:2338–45.
- Flather MD, Shibata MC, Coats AJ, et al., SENIORS Investigators, Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS), Eur Heart J, 2005;26:215–25.