PathophysiologyBMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7228.167 (Published 15 January 2000) Cite this as: BMJ 2000;320:167
- G Jackson,
- C R Gibbs,
- M K Davies,
- G Y H Lip
Heart failure is a multisystem disorder which is characterised by abnormalities of cardiac, skeletal muscle, and renal function; stimulation of the sympathetic nervous system; and a complex pattern of neurohormonal changes.
Developments in our understanding of the pathophysiology of heart failure have been essential for recent therapeutic advances in this area
Myocardial systolic dysfunction
The primary abnormality in non-valvar heart failure is an impairment in left ventricular function, leading to a fall in cardiac output. The fall in cardiac output leads to activation of several neurohormonal compensatory mechanisms aimed at improving the mechanical environment of the heart. Activation of the sympathetic system, for example, tries to maintain cardiac output with an increase in heart rate, increased myocardial contractility, and peripheral vasoconstriction (increased catecholamines). Activation of the renin-angiotensin-aldosterone system (RAAS) also results in vasoconstriction (angiotensin) and an increase in blood volume, with retention of salt and water (aldosterone). Concentrations of vasopressin and natriuretic peptides increase. Furthermore, there may be progressive cardiac dilatation or alterations in cardiac structure (remodelling), or both.
Chronic heart failure is associated with neurohormonal activation and alterations in autonomic control. Although these compensatory neurohormonal mechanisms provide valuable support for the heart in normal physiological circumstances, they also have a fundamental role in the development and subsequent progression of chronic heart failure.
Stimulation of the renin-angiotensin-aldosterone system leads to increased concentrations of renin, plasma angiotensin II, and aldosterone. Angiotensin II is a potent vasoconstrictor of the renal (efferent arterioles) and systemic circulation, where it stimulates release of noradrenaline from sympathetic nerve terminals, inhibits vagal tone, and promotes the release of aldosterone. This leads to the retention of sodium and water and the increased excretion of potassium. In addition, angiotensin II has important effects on cardiac myocytes and may contribute to the endothelial dysfunction that …