Current mortality-reducing therapies target progressive neurohormonal, maladaptive responses


  1. Kemp CD, et al. Cardiovasc Pathol. 2012;21:365-371.
  2. Hartupee J, et al. Nat Rev Cardiol. 2017;14:30-38.
  3. Mann DL, et al. Heart failure and cor pulmonale. In: Longo DL, et al, eds. Harrison’s Principles of Internal Medicine. Vol II. 18th ed. New York, NY: McGraw-Hill; 2012:1901-1915.
  4. 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.
  5. Mann DL, et al. Circulation. 2005;111:2837-2849.
  6. van Bilsen M, et al. Eur J Heart Fail. 2017;19:1361-1378.
  7. Katz AM, et al. Eur Heart J. 2016;37:449-454.
  8. Rumsfeld JS, et al. Circulation. 2013;127:2233-2249.
  9. Wang Y, et al. J Am Heart Assoc. 2019;8:e012272. doi:10.1161/JAHA.119.012272
  10. Langenickel TH, et al. Drug Discov Today: Ther Strategies. 2014:e2-e9.
  11. Ma TK, et al. Br J Pharmacol. 2010;160:1273-1292.
  12. Shah A, et al. P T. 2017;42:464-472.
  13. Crowley SD, et al. Proc Natl Acad Sci U S A. 2006;103:17985-17990.
  14. Brown DA, et al. Nat Rev Cardiol. 2017;14:238-250.
  15. Tamargo J. Eur Cardiol. 2019;14:23-32.
  16. Sano M. J Cardiol. 2018;71:471-476.
  17. Volpe M, et al. Int J Mol Sci. 2019;20:2092. doi:10.3390/ijms20092092
  18. O’Connell J, et al. Int J Clin Cardiol Res. 2018;2:053-057.
  19. Sulfi S, et al. Int J Clin Pract. 2006;60:222-228.
  20. Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  21. Yancy CW, et al. J Am Coll Cardiol. 2016;68:1476-1488.
  22. Kayani W, et al. Neurohormonal Blockade in Heart Failure. In: Baliga RR, et al, eds. Color Atlas and Synopsis of Heart Failure. New York, NY: McGraw-Hill; 2019.
  23. McMurray JJV, et al. N Engl J Med. 2019. doi:10.1056/NEJMoa1911 303. [Epub ahead of print].

Various drug classes target different circulating hormones in HFrEF.1,12,13

Myotropes are a class of molecules that directly target the myosin and actin within the cardiac sarcomere through calcium-independent mechanisms

Current guidelines-directed drug therapy addresses specific effects of neurohormonal activation.1

The current SoC treatments for patients with HFrEF target maladaptive compensatory systems, but residual risk remains Caution needs to be used when prescribing If channel blockers to patients with low HR, and care must be taken to monitor HR, BP, and clinical status throughout therapy When treating patients with beta-blockers, vital signs and symptoms need to be closely monitored during initiation and up-titration to rapidly detect and manage any emergent AEs Confounding factors, such as the inability to tolerate therapy, concerns about side effects, and overlapping drug side effects, limit the ability to achieve guideline-directed medication goals Patients with HFrEF who are older or female, and those with hyperkalemia, low BP, or renal insufficiency, are more likely to be undertreated Despite benefits of guideline-directed medical therapy (GDMT), a significant portion of eligible HFrEF patients remains untreated, and many patients do not receive recommended, evidence-based GDMT Early intervention with GDMT in patients with HFrEF improves outcomes; 32,080 HF-related deaths in the US could potentially be prevented each year with the implementation of guideline-recommended therapies

Foundational therapies for HFrEF that target circulating hormones improve outcomes, however significant gaps in therapy remain.20-23

Confounding factors limit the ability to achieve guideline-directed medication goals
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