Heart failure

Heart failure occurs when the heart is unable to circulate enough blood to meet the metabolic demands of the body. This can be due to regurgitation of blood back through diseased valves (chronic valvular heart disease, CVHD) or due to a weakened heart muscle (dilated cardiomyopathy, DCM). Compensatory mechanisms such as the renin-angiotensin-aldosterone system (RAAS) are activated in order to allow the failing heart to meet the body’s metabolic demands.  

Congestive heart failure (CHF) happens when the compensatory mechanisms are overwhelmed. Damming back of blood in the circulation behind the failing heart results in volume overload. Fluid backs up in the veins leading to raised pressure in the veins and fluid leakage into the tissues (oedema). Heart failure may affect either or both sides of the heart. If mainly the left side of the heart is failing (this is most common), oedema in the lungs develops, resulting in clinical signs such as exercise intolerance. If mainly the right side of the heart is failing (relatively rare), the liver becomes congested and there may be fluid in the abdomen (ascites).  

• Disease progression
• Regulatory mechanisms
• Activation of regulatory mechanisms

Disease progression

CHF is a progressive disease. The timing of the key changes that occur vary with each patient and with the underlying disease, therefore treatment should be tailored to each patient’s needs.

RAAS activation

• One of the first things to happen as heart disease progresses

Congestion (fluid build-up, oedema)

• The marker for the onset of CHF

Systolic dysfunction (myocardial failure, poor heart muscle contractility)

• CVHD: only occurs in later stages of the disease¹
• In large breeds it may occur earlier than in small breeds
• In one study three quarters of dogs <20kg with CVHD had normal systolic function at the time of diagnosis of CHF²
• DCM: occurs early in the disease

References: 1. M. Borgarelli et al. (2004) JVC, 6(2): 27-34. 2. de Madron E. Proc ACVIM 2009; 82.

Regulatory mechanisms

The cardiovascular system aims to maintain normal systemic blood pressure. This ensures adequate blood supply reaches body tissues to meet metabolic demands. As demands vary, the system regulates cardiac output to match demand. The maintenance of systemic blood pressure is achieved by:  

• Hormonal mechanisms 
• Cardiac responses
• Nervous system response

Hormonal mechanisms

The most important compensatory mechanism is the RAAS. Decreased blood pressure causes reduced renal perfusion (a drop in blood flow through the kidney), which triggers release of renin from an area of the kidney (the juxtaglomerular apparatus).

This triggers a cascade of events: 

• Renin causes conversion of angiotensinogen to angiotensin I 
• In the presence of angiotensin-converting enzyme (ACE), angiotensin I becomes angiotensin II  
• Angiotensin II triggers the release of aldosterone

Heart failure causes reduced cardiac output and hence decreased renal perfusion, therefore the RAAS is activated in all heart failure patients. This happens at a very early stage, even before the owner notices any clinical signs, and remains activated throughout the course of the disease.

Angiotensin II has many harmful effects in patients with heart failure:

• Activation of sympathetic nervous system
  - causes increased heart rate and vasoconstriction  

• Release of aldosterone from the adrenal glands
  - causes retention of sodium and water in the body (this increases the blood volume)

• Hypertrophy (thickening) of blood vessels
  -  makes the vessels narrower, thus increasing blood pressure 

• Cardiac remodelling
  - hypertrophy (thickening) of the heart muscle
  - the heart enlarges and changes shape in response to the additional workload

• Cardiac myocyte fibrosis and necrosis
  - the heart muscle cells become fibrosed (scarred) and may die 

ACE inhibitors like Fortekor® (benazepril hydrochloride) work by inhibiting the angiotensin-converting enzyme and hence blocking the formation of angiotensin II and thus its deleterious effects.

Cardiac responses

In the normal heart, the volume of blood pumped out of the heart during systole (contraction phase) is equal to the volume of blood entering the heart during diastole (relaxation phase). The heart adjusts the force of contraction to match the volume of blood entering the heart (higher volume = increased force of contraction).

In heart failure, the cardiac response mechanism may not work well. The heart is unable to pump out all of the blood returning to the heart so excessive blood remains in the heart, causing it to enlarge. 

Nervous system response

Regulation is carried out by the sympathetic nervous system (SNS). Receptors in the heart and blood vessels register a drop in blood pressure and stimulate the SNS, resulting in an increased heart rate, increased strength of cardiac contraction and peripheral vasoconstriction.

Activation of regulatory mechanisms

If there is a sudden drop in blood pressure, for example, due to acute haemorrhage, compensatory regulatory mechanisms are activated for only a short time, until the underlying problem is resolved, and thus have a beneficial effect. However, if these mechanisms are activated for a long period of time (as in heart failure), they have harmful effects and contribute to progression of the cardiac disease.

The net result of all these compensatory mechanisms (of which the RAAS is the most important) is an increased cardiac workload and less efficient cardiac function.