Heart failure with reduced ejection fraction (HFrEF) is a significant burden on healthcare, and unmet need remains


  1. Benjamin EJ, et al. Circulation. 2019;139:e56-e528.
  2. Cook C, et al. Int J Cardiol. 2014;171:368-376.
  3. Ponikowski P, et al. ESC Heart Fail. 2014;1:4-25.
  4. Savarese G, et al. Card Fail Rev. 2017;3:7-11.
  5. Cowie MR, et al. ESC Heart Fail. 2014;1:110-145.
  6. James SL, et al. Lancet. 2018;392:1789-1858.
  7. Heidenreich PA, et al. Circ Heart Fail. 2013;6:606-619.
  8. Bahit MC, et al. JACC Heart Fail. 2018;6:179-186.
  9. Gerber Y, et al. Circ Heart Fail. 2016;1:e002460. doi:10.1161/CIRCHEARTFAILURE.115.002460
  10. American Heart Association/RTI International. Projections of cardiovascular disease prevalence and costs: 2015–2035. November 2016.
  11. Adams KF, et al. Am Heart J. 2005;149:209-216.
  12. Chen J, et al. JAMA. 2011;306:1669-1678.
  13. Dunlay SM, et al. J Am Coll Cardiol. 2009;54:1695-1702.
  14. Mesquita ET, et al. Int J Cardiovasc Sco. 2017;30:81-90.
  15. Kemp CD, et al. Cardiovasc Pathol. 2012;21:365-371.
  16. Ma TK, et al. Br J Pharmacol. 2010;160:1273-1292.
  17. Hasenfuss G, et al. Pathophysiology of heart failure. Zipes DP, et al, eds. In: Braunwald’s Heart Disease. 11th ed. Philadelphia, PA: Elsevier Inc; 2019;442-461.
  18. Ambrosy AP, et al. Eur J Heart Fail. 2013;34:835-843.
  19. Arrigo M, et al. Eur Heart J Sup. 2016;18:G11-G18.
  20. Guglin M, et al. Int J Clin Pract. 2012;66:1224-1229.
  21. Kitzman DW, et al. Cardiol Clin. 2011;29:461-477.
  22. Nilsson KR, et al. Curr Cardiol Rev. 2008;4:92-100.
  23. Jaarsma T, et al. Curr Opin Support Palliat Care. 2010;4:233-237.
  24. Rumsfeld JS, et al. Circulation. 2013;127:2233-2249.
  25. Ambrosy AP, et al. Euro Heart J. 2016;18:306-313.
  26. Gnanasakthy A, et al. Value Health. 2017;20:420-429.
  27. Green CP, et al. J Am Coll Cardiol. 2000;35:1245-1255.
  28. Joseph SM, et al. Circ Heart Fail. 2013;6:1139-1146.
  29. Kosiborod M, et al. Circulation. 2007;115:1975-1981.
  30. Gallagher AM, et al. ESC Heart Fail. 2019;6:3-9.
  31. Reddy YNV, et al. Eur J Heart. 2019;0:1-17.
  32. Basuray A, et al. Circulation. 2014;129:2380-2387.
  33. Florea VG, et al. Circ Heart Fail. 2016;9:e003123. doi:10.1161/CIRCHEARTFAILURE.116.003123
  34. Lucas C, et al. Am Heart J. 2000;140:840-847.
  35. Greene SJ, et al. J Am Coll Cardiol. 2018;72:351-366.
  36. Steinman MA, et al. Am J Geriatr Pharmacother. 2010;8:583-594.
  37. Berthelot E, et al. Health Care: Current Rev. 2018;6. doi:10.4172/2375-4273.1000221
  38. Ferdinand KC, et al. J Am Coll Cardiol. 2017;69:437-451.
  39. Hickling JA, et al. Br J Gen Pract. 2001;51:615-618.
  40. Yancy CW, et al. Circulation. 2013;128:e240-e327.
  41. Fonarow GC, et al. JAMA Cardiol. 2016;1:714-717.

The vicious cycle of HFrEF leads to progressive decline.15

Heart failure with reduced ejection fraction (HFrEF) is a significant burden on healthcare, and unmet need remains

The pathophysiology of HFrEF induces organ dysfunction and clinical manifestations.19

HF is responsible for a high volume of hospital visits in the US: there were 481,000 emergency department visits in 2015 and 900,000 hospital discharges in 2014

There is a lack of correlation between severity of symptoms and objective measures of HF (hemodynamic, echocardiographic, laboratory, and reduced exercise tolerance).20

Decreased cardiac output causes skeletal muscle hypoperfusion, a potent stimulus for early anaerobic metabolism. Subsequent generation of muscle lactate and other metabolites produce the sensation of peripheral and central fatigue, which reduces exercise tolerance.21

HF is associated with skeletal muscle abnormalities that impair oxygen uptake and utilization and contribute to exercise intolerance.22

In patients with HF, a flattening VO2 trajectory is a strong predictor of cardiac death

Progressive HFrEF leads to symptoms associated with HF, which affect patients’ functional status and HRQoL.23,24

For US patients with HFrEF in the GWTG-HF (Get With The Guidelines® - Heart Failure) registry, the HF-related readmission rate was 49% at 5 years

Patients with HFrEF often have impaired HRQoL, which increases the complexity of care. Patient-reported outcomes (PROs) are becoming more accepted by regulatory agencies and are being incorporated in clinical trial designs.25,26 One such validated PRO is the Kansas City Cardiomyopathy Questionnaire (KCCQ).27

Lower HRQoL scores are associated with a higher risk of death in patients with HF

Worsening health status (categorized by the KCCQ score) = risk of death or hospitalization.28,29

HF lowers HRQoL in many areas, including physical, cognitive, psychological, social, and financial

HRQoL and exercise capacity are important assessments for current standard management and outcomes measures in HFrEF.30

References Back to Top