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Pathophysiology
highlights
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2. Heart failure pathophysiology Silent underlying neurohormonal imbalance results in continued disease progression
In patients with heart failure, left ventricular remodeling leads to changes in cardiac volume and wall thickness.
The abnormality in cardiac structure or function contributes to1:
Inadequate cardiac output
Poor organ perfusion
Activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS)
Activation of the RAAS gives rise to1,2:
Vasoconstriction
Increased sodium and water retention
Fibrosis
Hypertrophy
Increased blood pressure
Activation of the SNS leads to2:
Increased heart rate and myocardial contractility
Sodium retention
Renin release
Natriuretic peptides help counter the effects of the RAAS and SNS in chronic heart failure but this balancing effect is diminished as heart failure progresses. Sustained overactivation of the RAAS and SNS with attenuation of the effects of the natriuretic peptide system leads to neurohormonal imbalance in heart failure.2-4
1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 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; 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; Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; 2015.

3. Heart failure pathophysiology Underlying neurohormonal imbalance results in continued disease progress
ARE CHRONIC HEART FAILURE PATIENTS SILENTLY PROGRESSING?
Even when heart failure symptoms are stabilised by current treatments and it may seem that patients are doing well, the neurohormonal imbalance underlying heart failure is still silently occurring, resulting in sustained progression of cardiac structure and function abnormalities.1
MYOCARDIAL INJURY
Worsening systolic dysfunction and cardiac remodeling1
RAAS and SNS are overactivated to support heart function1
PROGRESSION OF HEART FAILURE
Sustained neurohormonal imbalance leads to ongoing decline1
Beneficial compensatory effects of NPs are
diminished2-4
RAAS = Renin-angiotensin-aldosterone system
SNS = Sympathetic nervous system
NPs = Natriuretic peptides
1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 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; 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; Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; 2015.

4. HEART FAILURE IS A PROGRESSIVE DISEASE2
Heart failure pathophysiology Underlying neurohormonal imbalance results in continued disease progress
Heart failure is a complex deteriorating condition driven by neurohormonal imbalance, leading to a spiral of worsening disease and punctuated by acute episodes that result in poor outcomes for patients.1
HEART FAILURE IS A PROGRESSIVE DISEASE2
Chronic decline
CARDIAC FUNCTION
Hospitalisations for acute decompensation episodes
DISEASE PROGRESSION
From Gheorghiade M, et al. Am J Cardiol
1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 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.

5. Heart failure pathophysiology Underlying neurohormonal imbalance results in continued disease progress
Natriuretic peptides may potentially be an important therapeutic target due to their ability to counterregulate the RAAS and SNS.2,3
PHYSIOLOGY OF THE THREE MAIN TYPES OF NATRIURETIC PEPTIDES IN HEART FAILURE3,4,6*
BNP = B-type natriuretic peptide
ANP = Atrial natriuretic peptide
CNP = C-type natriuretic peptide
CNS = Central nervous system
NT-proBNP = N-terminal-proBNP
TGF = Transforming growth factor
*Neprilysin is the major enzyme responsible for degrading the natriuretic peptides ANP, BNP, and CNP.3
1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 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; 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; Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; Gheorghiade M, De Luca L, Fonarow GC, et al. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol ;96(6A):11G-17G. 6. Goetze JP, Friis-Hansen L, Rehfeld JF, Nilsson B, Svendsen JH. Atrial secretion of B-type natriuretic peptide. Eur Heart J. 2006;27(14):

6. Heart failure pathophysiology Underlying neurohormonal imbalance results in continued disease progress
Natriuretic peptides may potentially be an important therapeutic target due to their ability to counterregulate the RAAS and SNS.2,3
PHYSIOLOGY OF THE THREE MAIN TYPES OF NATRIURETIC PEPTIDES IN HEART FAILURE3,4,6*
BNP = B-type natriuretic peptide
ANP = Atrial natriuretic peptide
CNP = C-type natriuretic peptide
CNS = Central nervous system
NT-proBNP = N-terminal-proBNP
TGF = Transforming growth factor
*Neprilysin is the major enzyme responsible for degrading the natriuretic peptides ANP, BNP, and CNP.3
1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 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; 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; Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; Gheorghiade M, De Luca L, Fonarow GC, et al. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol ;96(6A):11G-17G. 6. Goetze JP, Friis-Hansen L, Rehfeld JF, Nilsson B, Svendsen JH. Atrial secretion of B-type natriuretic peptide. Eur Heart J. 2006;27(14):