Pathophysiology of Chronic Heart Failure

Heart failure is a progressive disorder that is initiated after an event either damages the heart muscle, with resultant loss of functioning cardiac myocytes, or disrupts the ability of the myocardium to contract normally. This event may have an abrupt onset, as in the case of a myocardial infarction; a gradual onset, as in the case of hemodynamic pressure or volume overloading; or it may be hereditary.1

The neurohormonal imbalance associated with chronic heart failure is a contributing factor to the progression of the disease. Overactivation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), as well as other systems, contributes to cardiac remodeling and decline in heart function; the normal counterregulatory beneficial effects of the natriuretic peptide system (NPS)—one of the most important counterregulatory neurohormonal systems—are diminished in heart failure.1-4

In addition, emerging research suggests that inflammation may play a role in the progression of structural heart failure and cardiac remodeling. Circulating levels of proinflammatory cytokines including TNF and IL-6 are increased in patients with heart failure and correlate with adverse patient outcomes.1

Are chronic heart failure patients "stable" or silently progressing?

*Other compensatory mediators include adrenomedullin, prostaglandin E, bradykinin, etc.1

References:

  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. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.
  3. Boerrigter G, Costello-Boerrigter L, Burnett JC Jr. Alterations in renal function in heart failure. In: Mann DL, ed. Heart Failure: A Companion to Braunwald's Heart Disease. 2nd ed. St. Louis: Saunders; 2011.
  4. McMurray J, Komajda M, Anker S, Gardner R. Heart failure: epidemiology, pathophysiology and diagnosis. In: Camm AJ, Lüscher TF, Serruys PW, eds. ESC Textbook of Cardiovascular Medicine. 2nd ed. New York: Oxford University Press; 2009.
  5. Roig E, Perez-Villa F, Morales M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J. 2000;21(1)53-57.
  6. Cicoira M, Zanolla L, Francheschini L, et al. Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002;89(4):403-407.
  7. MacFadyen R.J. Lee A.F. Morton J.J. Pringle S.D. Struthers A.D. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart 1999 82 57 61.
  8. Riegger GAJ, Elsner D, Kromer EP. Circulatory and renal control by prostaglandins and renin in low cardiac output in dogs. Am J Physiol. 1989;256(4):H1079-1086.
  9. Suga S, Nakao K, Komatsu Y, et al. Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-β. Possible existence of "vascular natriuretic peptide system." J Clin Invest. 1992;90(3):1145-1149.
  10. Barrett KE, Boitano S, Barman SM, Brooks HL. Cardiovascular regulatory mechanisms. In: Barrett KE, Boitano S, Barman SM, Brooks HL, eds. Ganong's Review of Medical Physiology. 24th ed. New York: McGraw-Hill; 2012.
  11. Stephenson SL, Kenny AJ. Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes. Biochem J. 1987;241(1):237-247.
  12. Abassi ZA, Tate JE, Golomb E, Keiser HR. Role of neutral endopeptidase in the metabolism of endothelin. Hypertension. 1992;20(1):89-95.
  13. Lisy O, Jougasaki M, Schirger JA, Chen HH, Barclay PT, Burnett JC Jr. Neutral endopeptidase inhibition potentiates the natriuretic actions of adrenomedullin. Am J Physiol. 1998;275(3):F410-414.
  14. Moro C, Crampes F, Sengenes C, et al. Atrial natriuretic peptide contributes to the physiological control of lipid mobilization in humans. Faber J. 2004;18(7):908-910.
  15. Fujita S, Shimojo N, Terasaki F, et al. Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade. Heart Vessels. 2013;28(5):646-657.
  16. Miller WL, Phelps MA, Wood CM, et al. Comparison of mass spectrometry and clinical assay measurements of circulating fragments of B-type natriuretic peptide in patients with chronic heart failure. Circ Heart Fail. 2011;4(3):355-360.
  17. Niederkofler EE, Kiernan UA, O'Rear J, et al. Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure. Circ Heart Fail. 2008;1(4):258-264.
  18. Edvinsson ML, Uddman E, Edvinsson L, Andersson SE. Brain natriuretic peptide is a potent vasodilator in aged human microcirculation and shows a blunted response in heart failure patients. J Geriatr Cardiol. 2014;11(1):50-56.