30/07/2021
Heart Failure
By Mark D. Kittleson , DVM, PhD, DACVIM (Cardiology), School of Veterinary Medicine, University of California, Davis
Last full review/revision Apr 2015 | Content last modified Apr 2015
Heart failure is a clinical syndrome that occurs secondary to severe, overwhelming cardiac disease. It occurs because the heart is no longer able to maintain normal venous/capillary pressures, cardiac output, and/or systemic blood pressure. It is most commonly caused by a chronic disease that results in a severe decrease in myocardial contractility, severe regurgitation or shunting, or severe diastolic dysfunction. However, it is common to have all three abnormalities present simultaneously (but with one predominating). By far, the most common clinical manifestations seen with heart failure are directly due to edema and effusion (congestive or backward heart failure). Much less commonly, animals present because of signs referable to a decrease in cardiac output (forward heart failure). Very rarely, they present in cardiogenic shock (low blood pressure due to decreased cardiac output). This occurs because the cardiovascular system operates under a system of priorities. Its three primary functions are to maintain a normal blood pressure and normal cardiac output, both at a normal venous/capillary pressure. When the system is overwhelmed, it allows venous/capillary pressure to increase first (and so allows edema or effusion to form) and then allows cardiac output to fall. Only after cardiac output has fallen remarkably does cardiogenic shock occur. In acute heart failure, before any compensation has occurred, cardiogenic shock may predominate, but even in this situation, acute chordal rupture is the most common cause of acute heart failure in animals and results in an increased left atrial pressure and thus pulmonary edema.
Initial changes in cardiac chamber dimension (volume) or wall thickness that occur are best understood in relation to preload (the tension imposed by venous return on the ventricular walls at end-diastole) and afterload (the tension imposed on the ventricular walls at end-systole). Alterations in preload or afterload may be caused by structural cardiac abnormalities, systemic compensatory mechanisms, or both. Volume overload states, such as those that occur with chronic valvular disease/valvular insufficiencies, patent ductus arteriosus, atrial or ventricular septal defects, peripheral left-to-right shunts, anemia, or hyperthyroidism, cause an increase in preload that leads to ventricular growth and chamber enlargement (euphemistically called dilation) via eccentric myocyte hypertrophy. Pressure overload states, such as those that occur with pulmonary or systemic hypertension, and pulmonic or aortic stenosis, cause an increase in afterload (systolic intraventricular pressure) that leads to ventricular wall thickening via concentric hypertrophy. Neither volume nor pressure overload is synonymous with heart failure; either state may result in heart failure, depending on the severity of the overload and the degree of compensation.
Systolic Dysfunction
Systolic function is a broad classification of cardiac function that encompasses all of the entities in systole that are capable of altering blood flow into the aorta. It includes (but is not limited to) heart rate, myocardial contractility, preload, afterload, hypertrophy (volume and pressure overload), leaks, and shunts. Diseases that alter systolic cardiac function can become severe enough to overwhelm the ability of the cardiovascular system to compensate for the systolic dysfunction (primarily renal sodium and water retention, leading to hypervolemia, leading to increased venous return to the heart, leading to increased stretch on the myocardium, leading to myocardial growth and a larger left ventricular chamber [eccentric or volume overload hypertrophy]) and thus cause heart failure. The most common disease that alters systolic function is mitral regurgitation. Here, in systole, a portion of the blood flow that should be ejected into the aorta is ejected backward through the mitral valve from the left ventricle into the left atrium. When the regurgitation is mild (75% backward flow), the compensatory mechanisms may become overwhelmed, resulting in an increase in left atrial pressure and so pulmonary edema. The classic example of systolic dysfunction is dilated cardiomyopathy (DCM), in which an inherent myocardial disease results in a decrease in myocardial contractility (myocardial failure). The decrease in myocardial contractility results in an increase in the end-systolic diameter/volume of the left ventricular chamber (muscle is weaker and cannot contract down as far in systole) and a decrease in myocardial contraction (the amount of wall motion [shortening fraction or fractional shortening] seen on an echocardiogram). Again, the left ventricle grows larger to compensate for this disease, but when the myocardial failure is severe, compensation can no longer maintain a normal diastolic pressure in the left ventricle (kidneys continue to retain sodium and water) and this increased pressure backs up into the left atrium, pulmonary veins, and pulmonary capillaries, creating pulmonary edema.
Diastolic Dysfunction
Diastole can be roughly divided into early myocardial relaxation and late filling that is altered primarily by compliance (1/stiffness). Most ventricular diastolic dysfunction severe enough to cause heart failure is due to myocardial fibrosis, thus due to a decrease in ventricular compliance (an increase in stiffness). When a ventricle is less compliant or stiffer than normal, for any given volume of blood that fills the chamber in diastole, the pressure is higher. This increase in diastolic pressure (when the AV valves are open) is transmitted back up into the atrium, veins, and capillary beds behind the affected ventricle, resulting in transudation of fluid and signs referable to edema or effusion. The classic example of a disease that primarily causes heart failure due to diastolic dysfunction is hypertrophic cardiomyopathy. Diastolic function is compromised to some degree by the thickening of the myocardium itself but more so by the myocardial fibrosis that builds up over time when severe disease is present. Restrictive cardiomyopathy is another classic example of diastolic dysfunction, but it is much less common. Diastolic dysfunction also occurs in pericardial diseases that cause cardiac compression (pericardial effusion, constrictive pericarditis). With pericardial disease, right heart failure (eg, ascites) predominates because systemic (eg, hepatic) capillaries leak more easily (leak profusely at a pressure of 10 mmHg) than pulmonary capillaries (which can generally withstand a pressure up to 20 mmHg without leaking).
CHF may also occur if a tumor or other anatomic obstruction impedes venous return to one or both atria. Pericardial disease or effusion leading to decreased ventricular filling may also be thought of as an extracardiac cause of CHF. Iatrogenic volume overload (ie, aggressive IV fluid therapy) can lead to edema formation in the absence of primary heart disease.
Compensatory Mechanisms
Systemic blood pressure and blood flow (and thus oxygen delivery to peripheral tissues and organs) is under strict neuroendocrine control. Compensatory mechanisms act rapidly to correct any decreases in blood flow and/or pressure. Acute compensatory mechanisms, such as increased sympathetic tone, are generally short-lived and useful only for situations that demand an acute change in cardiac function (eg, hypovolemia). Chronic mechanisms of cardiac compensation generally take over within days of the onset of a cardiac disease and are viable for years. They are responsible for the heart's ability to compensate for chronic disease. These remarkable mechanisms allow for an animal to compensate for mild, then moderate, and then even severe disease, often for years. Only at the very end of a chronic disease do they contribute to the formation of heart failure and require medical intervention.
When a decline in stroke volume occurs secondary to cardiac dysfunction, cardiac output decreases. The acute response is an increase in sympathetic tone leading to peripheral vasoconstriction, increased heart rate, and increased cardiac contractility that serve to restore cardiac output and maintain systemic blood pressure. This effect fades within days as events such as β-receptor down-regulation occur. Chronically, the renin-angiotensin-aldosterone system (RAAS) is activated. Activation is initiated by events such as decreased renal perfusion, leading to decreased sodium delivery to the macula densa (which interacts with the juxtaglomerular apparatus). The juxtaglomerular cells release renin, which converts angiotensinogen (synthesized in the liver) to angiotensin I. Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, chiefly in the lungs. A separate tissue RAAS exists in the brain, vascular, and myocardial tissues, which can generate angiotensin II independently of the renal, or systemic, RAAS.
Angiotensin II has widespread effects, including stimulation of aldosterone synthesis and release from the adrenal glands, increased thirst via stimulation of antidiuretic hormone (ADH) release, increased norepinephrine and endothelin release, and stimulation of cardiac hypertrophy. Aldosterone forces the renal distal tubules to retain sodium and water. This, plus the effect of ADH, causes an increase in circulating blood volume. The increased blood volume leads to an increase in venous return to the affected ventricle. This chronic increase in preload stimulates the myocytes to add in new sarcomeres (contractile elements), leading to the growth of longer myocytes. This creates a larger ventricle (larger chamber with normal wall thickness [volume overload or eccentric hypertrophy]).
In response to these compensatory mechanisms, counter-regulatory systems are in place such as the release of atrial natriuretic peptide (ANP) from the atria, and B-type natriuretic peptide (BNP) from the atria and ventricles. ANP and BNP are released in response to stretch of the atrial and ventricular chambers. Both hormones serve to increase natriuresis (with subsequent diuresis) and decrease systemic vascular resistance, thus countering the effects of the RAAS. The effects of ANP and BNP are greatly outweighed by those of the RAAS and other systems in animals with chronic disease. Again, this is beneficial up until the end, when the RAAS continues to force sodium and water retention despite the presence of edema and effusion.
In situations when the heart must deal with higher than normal systolic intraventricular pressures (eg, subaortic stenosis, pulmonic stenosis, systemic arterial hypertension), the affected ventricle must contract against a greater force. Much like skeletal muscle when it is forced to lift a heavier weight, cardiac muscle undergoes concentric or pressure overload hypertrophy. In this situation, sarcomeres again replicate within cardiac myocytes but in parallel (side by side), to grow a wider myocyte and a thicker ventricular wall.
Cardiac Biomarkers
A biomarker is a measurable characteristic that reflects the severity or presence of some disease state. Blood pressure, cholesterol, gamma-glutamyl transferase, and BUN are all biomarkers. Studies in dogs and cats have shown that increased blood concentrations of BNP (most commonly N-terminal pro-B-type natriuretic peptide [NT-proBNP]), ANP, and endothelin-1 are indicators of cardiac disease that increase proportionately with progressive cardiac disease and CHF. Cardiac troponin I (cTnI), which is released after cardiomyocyte death, has also been evaluated as a biomarker for cardiac disease but found to be less sensitive than those mentioned above. ANP, BNP, and cTnI have also been evaluated as screening tools for occult DCM (before onset of CHF) in dogs. Increased levels of BNP were found to be highly sensitive for the detection of occult DCM, whereas ANP and cTnI were relatively less sensitive. NT-proBNP is cleaved from BNP in equal amounts in response to increased cardiac filling pressures (myocardial stretch) and ischemia, and its greater stability and longer half-life make it more suitable for use as a diagnostic biomarker. Several studies have demonstrated the usefulness of NT-proBNP in differentiating between cardiac and primary respiratory causes of dyspnea in dogs and cats. A rapid assay is available for this use in cats. Biomarkers such as NT-proBNP and troponin I should never be evaluated in isolation, because they are not 100% accurate. Instead, they should be used in concert with other diagnostic modalities.
Clinical Manifestations
The hemodynamic changes that occur in heart failure are relatively limited, as are the clinical syndromes resulting from these changes. Much depends on the location(s) of cardiac chamber failure, as well as on species differences.
Left Heart Failure:
The pulmonary veins drain into the left atrium. Left atrial pressure increases as left heart diseases worsen (eg, from regurgitant blood flow and increased circulating blood volume). An increase in left atrial pressure is transmitted to the pulmonary veins and to the pulmonary capillaries. Pulmonary capillary hydrostatic pressure continues to increase, promoting the transudation of fluid out of the capillaries and first into the lung interstitium and then into the alveoli as the pressure increase becomes more severe. Simply put, pulmonary edema develops and becomes worse as heart failure progresses. In animals, this first causes tachypnea and then dyspnea. Most owners do not notice the tachypnea and so do not seek veterinary attention until dyspnea is present. This often makes it look like the onset of the heart failure was acute, when, in fact, it was chronic.
Some dogs and a few cats and horses will cough with cardiogenic pulmonary edema. Cough is a much more common manifestation of primary lung disease in all species. Coughing is always present in dogs with chronic bronchitis. One manifestation of chronic bronchitis is airway collapse (tracheomalacia and bronchomalacia) on radiographs. Bronchomalacia appears to be evidence of chronic bronchitis in dogs. When the left atrium is enlarged, a collapsed left mainstem bronchus can often be seen above the left atrium, because the large left atrium highlights this finding. It does not appear that the large left atrium actually compresses this bronchus.
Animals with heart failure may also be exercise intolerant due to lower than normal cardiac output during exercise and/or hypoxemia, which is caused by pulmonary edema or pleural effusion. This is a rare presenting complaint in cats, because they usually do not exercise. The same is true for many dogs. In dogs, most true exercise intolerance (fatigue with marked tachypnea or dyspnea) is due to respiratory failure rather than heart failure. However, most "exercise intolerance" ends up being due to something else and is not true exercise intolerance. Instead, it is frequently an unwillingness to exercise because of other conditions, such as orthopedic disease or obesity. A dog that is truly exercise intolerant looks and sounds "out of breath." A severe decrease in cardiac output results in cold extremities (paws, ears) and can lead to total body hypothermia, especially in cats. Although syncope (transient loss of consciousness due to a transient decrease in cerebral metabolic substrate, most commonly oxygen) is not a sign of or directly due to heart failure, it may also be noted in dogs in heart failure, especially in small-breed dogs with chronic valvular disease. In many instances, the cause is unknown. However, syncope often improves once pulmonary edema is treated. In some, it is associated with coughing and is most likely a vagally mediated event (transient asystole). The syncope is frightening to the owner, but sudden death is rare unless associated with DCM or subaortic stenosis.
Left heart failure, radiograph, dog
Left heart failure, radiograph, dog
COURTESY OF DR. MARK D. KITTLESON.
The diagnosis of congestive left heart failure (cardiogenic pulmonary edema) in dogs is classically made radiographically. However, the inability to take a radiograph during a deep inspiration is a diagnostic obstacle. Consequently, the caudodorsal lung fields on a lateral radiograph, where cardiogenic pulmonary edema is usually identified, often have an interstitial density that is either mistaken for pulmonary edema or hides pulmonary edema. This is exacerbated in older dogs. Most dogs with severe pulmonary edema can be identified radiographically, but those with mild to moderate edema are often problematic. In these dogs, it is often beneficial to send the dog home (if it is stable) to have the owner count the dog's sleeping respiratory rate (SRR). The owner must be taught how to count respiratory (breathing) rate and then count the rate preferably while the dog is sound asleep and in a cool environment. A normal dog has an SRR
