Pathological Responses Associated with HF
HF is a progressive syndrome with multiple pathological processes that affect the heart and cause stress on the body.1
Neurohormonal systems activate, providing some benefit by compensating for cardiac dysfunction; however, this can ultimately lead to progressive damage and worsening HF.1‑4





SNS AND RAAS







NP SYSTEM





NO-sGC-CGMP SYSTEM




Where care stands today
Several drug classes target compensatory responses to HF.1 Confounding factors, such as the inability to tolerate therapy and concerns about side effects or overlapping drug side effects, limit the ability to achieve guideline-directed medication goals.10‑13



BETA BLOCKERS/HR MODULATORS (SNS)
INHIBIT OVERACTIVE SNS, AND ALSO AFFECT:2




SGLT2is (SNS)
REDUCE SNS ACTIVITY, AND ALSO AFFECT:15



ACEis, ARBs, ARNis, MRAs (RAAS)
INHIBIT RAAS, AND ALSO AFFECT:2,5,7,19



NEPis, ARNis (NP SYSTEM)
AUGMENT NP SYSTEM ACTIVATION, AND ALSO AFFECT7



sGC STIMULATORS (sGC SENSITIVITY)
ENHANCE SGC SENSITIVITY TO ENDOGENOUS NO IN AN NO-INDEPENDENT MANNER, MAY ALSO AFFECT:8,9


The ACC Expert Consensus acknowledges
Comorbidities such as abnormal renal function and/or hyperkalemia are common barriers to initiation and titration of GDMT22
ACC, American College of Cardiology; ACEi, angiotensin‑converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ARNi, angiotensin receptor‑neprilysin inhibitor; CGMP, cyclic guanosine monophosphate; GDMT, guideline‑directed medical therapy; HF, heart failure; HR, heart rate; MRA, mineralocorticoid receptor antagonist; NEPi, neprilysin inhibitor; NO, nitric oxide; NP, natriuretic peptide; RAAS, renin‑angiotensin‑aldosterone system; sGC, soluble guanylate cyclase; SGLT2i, sodium‑glucose cotransporter‑2 inhibitor; SNS, sympathetic nervous system.
References:
1. Mann DL, et al. Heart failure and cor pulmonale. In: Longo DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. McGraw‑Hill; 2012:1901‑1915. 2. Kemp CD, et al. Cardiovasc Pathol. 2012;21:365‑371. 3. Brown DA, et al. Nat Rev Cardiol. 2017;14:238‑250. 4. Malik FI, et al. J Mol Cell Cardiol. 2011;51:454‑461. 5. Hartupee J, et al. Nat Rev Cardiol. 2017;14:30‑38. 6. Ma TKW, et al. Br J Pharmacol. 2010;160:1273‑1292. 7. Volpe M, et al. Clin Sci (Lond). 2016;130:57‑77. 8. Emdin M, et al. J Am Coll Cardiol. 2020;76:1795‑1807. 9. Gheorghiade M, et al. Heart Fail Rev. 2013;18:123‑134. 10. Fitzgerald AA, et al. J Card Fail. 2011;17:664‑669. 11. Steinman MA, et al. Am J Geriatr Pharmacother. 2010;8:583‑594. 12. Ferdinand KC, et al. J Am Coll Cardiol. 2017;69:437‑451. 13. Marti CN, et al. Eur J Heart Fail. 2019;21:286‑296. 14. Shah A, et al. P T. 2017;42:464‑472. 15. Saad M, et al. Drugs Context. 2018;7:212549. doi:10.7573/dic.212549. 16. Verma S, et al. Diabetologia. 2018;61:2108‑2117. 17. McMurray JJV, et al. N Engl J Med. 2019;381:1995‑2008. 18. Lytvyn Y, et al. Circulation. 2017;136:1643‑1658. 19. Oliveros E, et al. Cardiorenal Med. 2020;10:69‑84. 20. Cooper LB, et al. Circ Cardiovasc Qual Outcomes. 2017;10:e002946. doi:10.1161/CIRCOUTCOMES.116.002946. 21. Yancy CW, et al. J Am Coll Cardiol. 2017;70:776‑803. 22. Maddox TM, et al. J Am Coll Cardiol. 2021;77:772‑810.