The Role of Ejection Fraction In Heart Failure

Chronic Heart Failure and Acute Heart Failure:

Heart failure syndrome consists of chronic compensated heart failure with associated periods of acute decompensation triggered by a variety of different factors such as hypertension, acute coronary syndrome (ACS), arrhythmias, infections, renal dysfunction, medication or dietary nonadherence, and medications.1

Ejection fraction (EF) measurement and heart failure patient types: Is the pattern changing?

The American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines recommend measuring ejection fraction by echocardiography, nuclear testing, or magnetic resonance imaging (MRI) for assessment of left ventricular function and structure.2

Heart failure with reduced ejection fraction (HFrEF)

Often referred to as systolic heart failure, the definition of HFrEF varies; however, current guidelines define HFrEF as occurring in patients with heart failure and EF ≤40%. Studies using this definition have found a prevalence of approximately 50% in patients hospitalized for heart failure. 2,5,6

While there are established therapeutic options to treat HFrEF, morbidity and mortality rates remain high2

Ejection fraction classifications.

*A subset of patients with HFpEF previously had HFrEF

Heart failure with preserved ejection fraction (HFpEF)

Often referred to as diastolic heart failure, HFpEF has been defined using several different criteria and has been variably classified as ejection fraction (EF) >40%, >45%, >50%, and ≥50%. Some studies suggest that the prevalence of HFpEF is increasing.2,5

  • It reportedly accounts for nearly 40% or more of heart failure patients, and may be underreported for varying diagnostic criteria5,6
  • It is identified by signs and symptoms of heart failure accompanied by diastolic dysfunction and a normal or not markedly reduced ejection fraction in most cases2
  • It is a disorder of myocardial relaxation such that the ventricle does not fill effectively3
  • It is more likely to develop in older women with a history of hypertension2

Which assessments and cardiac biomarker tests may help detect, diagnose, and evaluate the severity of heart failure?

The assessment of patients with suspected heart failure should include a thorough medical history and physical examination; routine laboratory tests, imaging examinations, and biomarkers determine the type and severity of heart failure. Some of the more common evaluations are estimates of jugular venous pressure, tests for peripheral edema, chest x-rays, echocardiograms, Doppler flow studies, and sometimes nuclear tests or MRI.2

Natriuretic peptides are one of the most important counterregulatory systems activated in heart failure. American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines recommend the use of biomarkers B-type natriuretic peptide (BNP) or N-terminal pro–B-type natriuretic peptide (NT-proBNP) in the initial diagnosis of ambulatory patients with dyspnea and in episodes of acutely decompensated heart failure, and additionally, to establish prognosis of chronic or acute heart failure. Elevated BNP and NT-proBNP levels may be useful in the diagnosis of heart failure.1,2

While the results of BNP or NT-proBNP are useful in the diagnosis of heart failure, they should always be used to supplement clinical judgment and should not replace it. Elevation of these peptides may occur not only with left ventricular systolic dysfunction, but also with age, renal failure, and with other conditions such as valvular heart disease, pulmonary hypertension, ischemic heart disease, and atrial arrhythmias. US guidelines do not provide a cut point for interpretation of specific BNP or NT-proBNP values; however, pivotal studies used results of BNP and NT-proBNP for diagnosis as follows1:

  • Breathing Not Properly study: BNP concentration of 100 pg/mL was highly accurate in the diagnosis of acutely decompensated heart failure1
  • ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study: NT-proBNP cutoff value of 900 pg/mL was comparable in performance to a BNP of 100 pg/mL1
  • International Collaborative of NT-proBNP (ICON) study: NT-proBNP concentration below 300 pg/mL was useful to exclude acutely decompensated heart failure1

In evaluation of ambulatory patients, the optimized cut-off values from emergency department studies should not be used; lower values are mandatory, optimized for their negative predictive value to exclude—rather than to identify—heart failure. Age stratification of values may also be valuable. Please note that BNP and NT-proBNP levels may vary by lab.1,7

Although some trials suggest there may be value to using BNP or NT-proBNP to monitor a patient's progress, current recommendations state that the usefulness of serial measurement of BNP or NT-proBNP to reduce hospitalization or mortality in patients with heart failure is not well established.2

A large National Institutes of Health (NIH) trial, GUIDE-IT, is currently underway to determine the effectiveness of a biomarker-guided therapeutic strategy with serial measurement of NT-proBNP in high-risk patients with left ventricular systolic dysfunction.8

Treatment strategies combining multiple biomarkers may ultimately be beneficial in guiding heart failure therapy.2

As a response to cardiac stress, cardiomyocytes synthesize the prohormone, pro-BNP, which is then proteolytically cleaved by furin into two components: NT-proBNP, a biologically inactive N-terminal fragment, and BNP, a biologically active peptide.1


  1. Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; 2015.
  2. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128(16):e240-e327.
  3. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.
  4. Gheorghiade M, De Luca L, Fonarow GC, Filippatos G, Metra M, Francis GS. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol. 2005;96(6A):11G-17G.
  5. Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126(1):65-75.
  6. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355(3):251-259.
  7. Wu AHB. Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: The role of biologic variation in the interpretation of results. Am Heart J. 2006;152(5):828-834.
  8. US National Institutes of Health. Guiding evidence based therapy using biomarker intensified treatment (GUIDE-IT). Study record detail. Updated July 1, 2014. Accessed September 29, 2014.