Heart failure develops as a response to all of the conditions, either acute as in myocardial infarction or chronic as in hypertension, that damage the heart’s muscle during one’s lifetime.  Normal cardiac performance can be compromised by two mechanisms:

  • Progressive deterioration of myocardial contractile function, known as forward failure or systolic dysfunction.1
  • Inadequate venous return to the heart arising from an inability of the heart chamber to relax, expand, and fill sufficiently during diastole (when the heart backward failure or diastolic dysfunction.1s at rest), know as backward failure or diastolic dysfunction.1


The heart relies upon a variety of compensatory mechanisms to maintain a circulation that is adequate to meet the basal metabolic requirements of the body. The manner in which the body responds to the decreased cardiac output of heart failure is very much like the natural response to hemorrhagic shock. The primary compensatory mechanisms are:

  • Increased sodium and fluid retention via the renin-angiotensin-aldosterone system (RAAS). The RAAS is the body’s most important long-term regulator of sodium, extracellular fluid volume, vascular resistance, and ultimately, arterial blood pressure.2;3
  • Increased sympathetic nervous system (SNS) activity.2;3
  • Extensive remodeling of the myocardium occurs at both the molecular and structural level with alterations in the size and shape (hypertrophy) of the affected heart chambers, most frequently the left ventricle.2;3

It is the pathophysiologic consequences of the compensatory mechanisms that lead to the development of the congestive heart failure syndrome. The transition from a clinical setting of chronic stable heart failure (compensated) to one of decompensated heart failure, characterized by a worsening of symptoms, is often a result of compensatory mechanisms becoming too excessive.4;5


Sodium and Fluid Retention – Activation of the RAAS, under normal physiological conditions, is advantageous for offsetting the effects of hemorrhage or other acute blood loss and will help to restore blood volume and maintain arterial blood pressure. On the other hand, the activation of RAAS is fundamental to the development of the complex pathophysiological symptoms that characterize congestive heart failure. The balance between sodium intake and sodium excretion is crucial in the control of extracellular fluid volume. A variety of physiologic signals related to reduced arterial pressure and blood volume causes renin to be released from the kidneys. Renin converts angiotensinogen to angiotensin I which is rapidly converted to angiotensin II by angiotensin converting enzyme. Angiotensin II then initiates a cascade of biological responses aimed at preserving arterial blood pressure and maintaining perfusion of the vital organs. Angiotensin II reduces renal sodium excretion and, as a result, blood volume is increased because water is passively retained as a consequence of the sodium retention. Excessive fluid and sodium retention leads to the well-recognized edematous state of congestive heart failure which impedes tissue perfusion and reduces the vasodilatory capacity of the blood vessels. Edema of the gastrointestinal tract impairs the absorption of nutrients, contributing to the development of cardiac cachexia. If the pressure in the pulmonary circulation becomes sufficiently high, fluid may move from the plasma into the alveoli causing pulmonary edema. Pulmonary edema causes the characteristic symptoms of shortness of breath and reduced exercise tolerance, interferes with the exchange of oxygen for carbon dioxide across pulmonary membranes, and suppresses the mechanics of ventilatory muscles.6-8

Angiotensin II also stimulates the release of aldosterone from the adrenal cortex which causes vasoconstriction with a consequent increase in peripheral resistance that supports blood pressure.6;9


Sympathetic Nervous System (SNS) – The SNS plays an important role in the regulation of the cardiovascular system in both health and disease. Activation of the SNS in the cardiovascular system results in vasoconstriction, increased heart rate (positive chronotropism), and increased contractile strength of both atria and ventricles (positive inotropism). Whereas this activation may be beneficial in the short-term, chronic and disproportionate activation of the SNS triggers a variety of pathological changes, including ventricular hypertrophy, further retention of sodium and fluid via the enhanced activation of the RAAS, and excessive vasoconstriction which imposes a higher afterload (the force against which a ventricle contracts which is largely dependent upon aortic pressure. As a consequence, cardiac pump function deteriorates and the clinical status of the heart failure patient substantially worsens. The cardiovascular changes evoked by activation of the SNS are better suited for short-term regulation of the cardiovascular system, typically lasting minutes to hours, not the long-term chronic activation that lasts for weeks to months characteristic in heart failure.7;10-13



Reference List

1.   Leonard BL, Smaill BH, LeGrice IJ. Structural Remodeling and Mechanical Function in Heart Failure. Microscopy and Microanalysis 2012;18:50-67.

2.   Seixas-Cambao M, Leite-Moreira AF. Pathophysiology of chronic heart failure. Rev Port Cardiol 2008;28:439-471.

3.   Grassi G, Seravalle G, Quarti-Trevano F, Dell’Oro R. Sympathetic activation in congestive heart failure: evidence, consequences and therapeutic implications. Current Vascular Pharmacology 2009;7:137-145.

4.   Dube P, Weber KT. Congestive heart failure: pathophysiologic consequences of neurohormonal activation and the potential for recovery: Part I. American Journal of the Medical Sciences 2011;342:348-351.

5.   Dube P, Weber KT. Congestive heart failure: pathophysiologic consequences of neurohormonal activation and the potential for recovery: Part II. American Journal of the Medical Sciences 2011;342:503-506.

6.   Mendzef SD, Slovinski JR. Neurohormones and heart failure. Nursing Clinics of North America 2004;39:845-861.

7.   Lee CS, Tkacs NC. Current concepts of neurohormonal activation in heart failure. AACN Advanced Critical Care 2008;19:364-385.

8.   Chaney E, Shaw A. Pathophysiology of fluid retention in heart failure. Contrib Nephrol 2010;164:46-53.

9.   Struthers AD. Pathophysiology of heart failure following myocardial infarction. Heart 2005;91:ii14-ii16.

10.   Adams J. Pathophysiologic role of the renin-angiotensin- aldosterone and sympathetic nervous systems in heart failure. American Journal of Health-System Pharmacy 2004;61:S4-S13.

11.   Summers RL, Amsterdam E. Pathophysiology of acute decompensated heart failure. Heart Failure Clin 2009;5:9-17.

12.   Floras JS. Sympathetic Nervous System Activation in Human Heart Failure: Clinical Implications of an Updated Model. J Am Coll Cardiol 2009;54:375-385.

13.   Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J 2012;33:1058-1066.