Heart Failure - Pathophysiology

Introduction

The heart pumps deoxygenated blood from the venous circulation into the lungs, where it is oxygenated. Newly oxygenated blood travels via the pulmonary veins to the left atrium and left ventricle, where it is ejected via the aorta into the arterial circulation to supply oxygenated blood to peripheral tissue. Heart failure arises when structural or functional abnormalities prevent the heart adequately filling with or ejecting blood, resulting in the inability to meet metabolic needs of peripheral tissue. The cardiovascular system has a large reserve capacity, so overt clinical signs are only seen with severe disease when the heart cannot compensate for the decreased function.

The definition of heart failure is: a complex syndrome initiated by an inability of the heart to maintain a normal cardiac output at a normal filling pressure.

Heart failure can be further classified according to the cause, whether it leads predominantly to underperfusion or congestion (forward or backward failure) and whether the right or left side of the circulation is affected to a greater extent (right-sided failure or left-sided failure). In some cases, biventricular failure may occur.

• Forward failure (low output failure/cardiogenic shock): underperfusion of the arterial circulation at normal pressure
• Backward failure (congestive heart failure): adequate output at abnormal pressures, too much fluid in the venous circulation

The most basic equations relating to regulation of circulation are:

• Cardiac Output (CO) = Heart Rate (HR) x Stroke Volume (SV)
• Blood Pressure (BP) = Cardiac Output (CO) x Total Peripheral Resistance (TPR)
• Cardiac Output (CO) = Venous Return (VR)

The primary determinants of cardiac performance are:

• Preload: The volume of blood or hydrostatic pressure within the ventricles at the end of diastole.
• Afterload: The force that opposes ejection of blood into the peripheral arterial system, of which arterial blood pressure is the primary factor
• Contractility: The ability of the myocardium to function as a pump and eject blood

The Frank-Starling mechanism states that stroke volume increases in response to increased end-diastolic volume (preload) when all other factors remain constant. Therefore, if a larger volume of blood flows to the ventricle, there is greater wall stretch, causing greater expansion during diastole, which in turn increases the force of contraction and therefore stroke volume (quantity of blood that is pumped into the aorta during systole).

Mechanisms of failure

Myocardial failure : Failure of myocardial contraction (systolic dysfunction) e.g. Dilated Cardiomyopathy

Volume overload : Chronic increase in the amount of blood that must be pumped by a given chamber, due to shunting of blood (PDA, VSD), regurgitation of blood ( Degenerative Mitral Valve Disease), anaemia or increased metabolic demands (Hyperthyroidism).

Pressure overload : Increased resistance to chamber emptying. This may be as a result of systemic or pulmonary hypertension, or an outflow obstruction such as Aortic Stenosis or Pulmonic Stenosis.

Abnormal rate/rhythm : Compromised cardiac output due to an increased or decreased heart rate. Abnormally fast heart rates (tachycardias) result a shorter diastole, therefore impaired filling and reduced stroke volume. Abnormally slow heart rates (bradycardias) limit cardiac output as a direct consequence of reduced heart rate (CO = HR x SV).

Diastolic failure : Impaired ventricular filling with normal systolic function. Examples include cardiac tamponade in Pericardial Effusion, Constrictive Pericarditis and Hypertrophic Cardiomyopathy or Restrictive Cardiomyopathy

Clinical Signs

Forward-Low Output Failure

Decreased blood supply to the lungs and other organs. Left failure results in decreased blood returning to the right and so both sides fail simultaneously and vice versa. There will be low systemic blood pressure, exercise intolerance, pallor, tachycardia, weak femoral pulses and pre-renal failure and azotaemia.

Backward-Congestive Failure

Clinical signs are different for each side. In left-sided failure signs include dyspnoea and tachypnoea. There may also be pulmonary crackles on ausculatation due to pulmonary oedema and a cough due to left cardiomegaly compressing the left mainstem bronchus. In right-sided failure there may be jugular distension, hepatomegaly and splenomegaly, ascites, positive hepato-jugular reflux (Press firmly over the liver and abdomen. A positive test is distension of the jugular vein indicating right sided heart failure.) and pleural effusion.

Compensatory Mechanisms

Sympathetic Nervous System

In heart disease, there is simultaneous a shift of autonomic balance from one of parasympathetic dominance to one of sympathetic dominance. A decrease in systemic blood pressure is detected by baroreceptors (pressure receptors) and mechanoreceptors (stretch receptors) in the carotid sinus, aortic arch and atrial walls. A drop in signals from these receptors in response to perceived hypoperfusion leads to an increase in sympathetic activity (and noradrenaline production) and a reduction in parasympathetic activity. Increased adrenergic activity is mediated via cardiac beta and vascular alpha effects. Elevated sympathetic nervous system activity results in tachycardia, increased contractility, peripheral vasoconstriction and activation of the renin-angiotensin-aldosterone system (RAAS).

These effects are initially beneficial, as they act to increase cardiac output and systemic blood pressure. However, over time chronic activation of the sympathetic nervous system becomes detrimental. Noradrenaline stores become depleted, cardiac beta adrenergic receptors become downregulated and uncoupled and myocyte loss results from ischaemia and necrosis.

Renin-angiotensin-aldosterone system

Causes sodium and water retention by the kidney as well as vasoconstriction. Angiotensin is also recognised as a substance that causes modification and growth in cardiac myocytes and fibroblasts, influencing myocardial remodelling and hypertrophy.

Myocardial hypertrophy

Chronic increase in cardiac work results in a geometric alteration of the chambers involved. Remodelling of the ventricular myocardium occurs in two forms: concentric and eccentric hypertrophy. Factors implicated in the development of hypertrophy include adrenergic stimulation, angiotensin II and increased intracellular calcium.

Concentric hypertrophy develops in response to pressure overload (increased afterload). Increased afterload causes replication of sarcomeres in parallel, resulting in an increase in wall thickness and a decrease in internal diameter with no overall change in the external diameter of the chamber. This is better understood by considering the Laplace law, which states that ventricular wall stress is elevated by increased pressure and increased chamber diameter; whereas wall stress decreases as the ventricular wall thickens. Therefore concentric hypertrophy occurs as a compensatory mechanism to normalise ventricular wall stress in the face of pressure overload.

Eccentric hypertrophy develops in response to volume overload (increased preload). The sarcomeres replicate in series, leading to elongation of the myocytes, an increase in internal diameter and an approximately normal wall thickness with an overall increase in external diameter of the chamber.

Although initially compensatory, increased myocardial mass associated with hypertrophy eventually leads to an increase in myocardial oxygen demand. The increase in oxygen demand outstrips the ability of the coronary circulation to provide sufficient oxygen, which results in myocardial ischaemia. This can result in damage to the myocardium (myocardial necrosis) with replacement by scar tissue (fibrosis), further compromising cardiac function.

Natriuretic Peptides

Natriuretic peptides include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The main site of manufacture, storage and release is the myocardium. Under normal circumstances, ANP and BNP are both manufactured by the atrial myocardium. In heart disease, BNP is manufactured predominantly in the ventricular myocardium. Both are released in response to increased chamber wall stress. These hormones counter regulate many of the above mechanisms, causing vasorelaxation and increased sodium loss. However, in congestive heart failure this counter regulatory system is overwhelmed by other vasoconstrictive and sodium retaining mechanisms.

Natriuretic peptides are useful biomarkers of cardiac disease, as levels are elevated in patients with clinically significant disease.

Antidiuretic Hormone (ADH)

Release of ADH from the posterior pituitary gland increases absorption of free water in the collecting duct of the nephron. ADH is usually involved in regulation of osmolality and plays less of a role in regulation of circulating fluid volume. In heart failure, there are increased circulating levels of ADH. The stimulus for this 'non-osmotic' release of ADH is probably a marked drop in blood pressure. Therefore increased ADH occurs in late stage or severe heart failure.

Excess ADH leads to fluid retention, contributing to congestive heart failure, and dilutes total body sodium and chloride leading to hypo-osmolarity. The finding of hyponatraemia and hypochloraemia on blood tests from patients with cardiac disease indicate an advanced stage of disease. Dilutional hyponatraemia (excess free water, rather than a reduction in sodium) is a poor prognostic sign.

Classification

Modified New York Heart Association Classification

Classification of congestive heart failure modified from human medicine. This is problematic, as cardiac debilitation is not the only factor governing exercise tolerance. This is particularly difficult to apply to cats, which tend to lead a sedentary lifestyle. Furthermore, a normal level of activity is clearly defined for humans (e.g. ability to walk a certain distance), but in veterinary medicine this may be influenced by the breed and lifestyle of the dog.

• Class I: Heart disease with no clinical signs
• Class II: Exercise intolerance
• Class III: Marked exercise intolerance and dyspnoea
• Class IV: Cannot exercise, dyspnoea at rest

American Heart Association (AHA and American College of Cardiology (ACC)

• Stage A: Predisposition for developing cardiac disease
• Stage B: Structural heart disease, no clinical signs
• Stage C: Structural heart disease, current or prior clinical signs
• Stage D: Refractory heart failure

International Small Animal Cardiac Health Council (ISACHC)

The only veterinary-specific clinical classification.

• Class Ia: Structural heart disease, no radiographic or echocardiographic evidence of cardiac enlargement
• Class Ib: Structural heart disease,radiographic or echocardiographic evidence of cardiac enlargement
• Class II: Mild clinical signs
• Class IIIa: Overt clinical signs, death or severe debilitation likely without immediate therapy but homecare possible
• Class IIIb: Overt clinical signs, death or severe debilitation likely and hospitalisation required

Sample Book Chapters
Publisher	Free chapter	Book	Authors

Congestive Heart Failure in the Dog (part of Congestive Heart Failure in the Cat)

Small Animal Emergency and Critical Care Medicine

Elizabeth Rozanski, John Rush

Buy book

References

Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition) W.B. Saunders Company

Ettinger, S.J, Feldman, E.C. (2005) Textbook of Veterinary Internal Medicine (6th edition, volume 2) W.B. Saunders Company

Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition) Mosby Elsevier

Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition) Merial

Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier

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