7. EXTRACARDIAC DISEASE AND THE HEARTRebecca E. Gompf, DVM., M.S.

1. How can systemic diseases affect the heart?Systemic diseases can directly or indirectly affect the heart. Disease processes that alter elec­

trolytes, acid-base balance, or neurohormonal balance of the body can have a direct effect on theelectrical and mechanical functions of the heart. Some diseases directly affect the heart by caus­ing the release of cardiac stimulant or cardiac depressant factors. The heart can also be indirectlyaffected when disease imposes abnormally great demands on the cardiovascular system, such ascan occur in chronic and severe anemia.

2. Which diseases will cause electrolyte imbalances that may affect the heart?The primary electrolyte changes that affect the heart usually involve hypokalemia, hyper­

kalemia, hypocalcemia, or hypercalcemia. Hypoadrenocorticism (Addison's disease), primary al­dosteronism (Conn's syndrome), diabetes mellitus, gastric dilation and volvulus, septic shock,and renal disease can all influence electrolyte balance in the body. Depending on the severity andthe rate at which the electrolyte imbalance develops, the heart may be adversely affected.

Other diseases can result in vomiting and diarrhea, which can affect the electrolyte balance.However, the changes are usually gradual and primary cardiac events are unusual.

3. What is hypoadrenocorticism (Addison's disease) and how does it affect the heart?Addison's disease is a deficiency of either cortisol or mineralocorticoid secretion from the

adrenal gland. Cortisol has many effects that are noncardiac. Its cardiac effects include its effecton systemic vasculature and on calcium.

Cortisol helps to maintain blood pressure by preserving vascular integrity and responsive­ness to circulating vasoconstrictors; it therefore contributes to the maintenance of vascular tone.The decrease in vascular tone and intravascular volume associated with the lack of cortisol con­tributes to the hypotension found in patients with Addison's disease.

Cortisol also helps to maintain the normal calcium levels in the body by affecting the renalexcretion of calcium. About one third of dogs with Addison's disease are hypercalcemic. The el­evated levels of calcium are mild (12.0-14.9 mg/dl) and are correlated with the severity of theirdehydration and potassium elevation. Cardiac problems resulting from the elevated calciumlevels have not been reported.

Mineralocorticoids maintain the sodium, potassium, and chloride balances in the body. Theprimary mineralocorticoid is aldosterone. Aldosterone promotes the renal reabsorption of sodiumand chloride in exchange for potassium and hydrogen ions. Water is reabsorbed with the sodiumand chloride. A lack of aldosterone results in the loss of sodium, chloride, and water. One resultis hypovolemia, which in tum reduces cardiac output and contributes to hypotension. One of theclassic findings on thoracic radiographs in a patient with Addison's disease is a small heart.

Sodium is necessary for both excitation and contraction in the heart. The low sodium levelassociated with Addison's disease does affect the heart's normal functions; however, its cardiaceffects are overshadowed by the effects of the hyperkalemia and are not recognized as specificclinical signs associated with the heart.

Hyperkalemia due to Addison's disease is potentially life threatening. Its primary effects areon electrical conduction throughout the myocardium and on the strength of contraction.

The severity of the hyperkalemia can be monitored with an electrocardiogram (ECG). Whenthe serum levels of potassium are mildly elevated (5.5-6.5 mEqlL), the ECG may show brady­cardia with tall, peaked T-waves. With moderate hyperkalemia (6.6-8.5 mEq/L), the ECG canshow decreased P-wave height, and prolonged QRS-, P-wave, and PR-interval duration. When

40

Extracardiac Disease and the Heart 41

the potassium levels exceed 8.5 mEqlL, the P waves generally disappear (atrial standstill occursand the atria are not contracting). When potassium levels exceed II mEq/L, death can occur dueto ventricular asystole or ventricular fibrillation. In clinical cases, the correlation of serum potas­sium levels to electrocardiographic appearance is imperfect; however, the ECG is an excellentway to monitor the clinical consequences of moderate and severe hyperkalemia.

The overall cardiac effects of Addison's disease include decreased cardiac wall motion, de­creased cardiac output, decreased heart rate, and decreased peak left-ventricular work. Most ofthese changes are due to hypovolemia and hyperkalemia. Stress can cause cardiac collapse anddeath but congestive heart failure does not occur.

4. How does hyperadrenocorticism (Cushing's disease) affect the heart?Cushing's disease in people has caused congestive heart failure secondary to the severe hy­

pertension that it causes. The hypertension results from the retention of sodium and water fromactivation of the renin-angiotensin system, and from the increased sensitivity to vasopressors,which causes vasoconstriction. Fifty percent of dogs with Cushing's disease are hypertensive, butcongestive heart failure caused by the hypertension is rare.

It is likely that the only dogs with Cushing's disease that develop congestive heart failure arethose with underlying heart disease. Most of the dogs that develop Cushing's disease are thosebreeds that are also prone to mitral valve endocardiosis. The increased fluid retention inCushing's disease could result in problems if the dog has significant preexisting heart disease.

The most common side effect of Cushing's disease that indirectly affects the heart is pul­monary embolism. See Chapter 47 for a discussion of this problem.

5. What is primary aldosteronism (Conn's syndrome) and how does it affect the heart?Primary aldosteronism is an excessive secretion of aldosterone from the adrenal glands,

which results in hypernatremia, hypokalemia, and severe systemic hypertension in man. As aresult of the hypertension, the left ventricle will hypertrophy and can eventually fail. Also, ar­rhythmias can occur.

While cardiovascular abnormalities have been observed in small animals with Conn's syn­drome, it should be recognized that this disorder is very uncommon, having been reported in onlyone dog and two cats.

6. How can diabetes mellitus affect the heart?In people, diabetes mellitus causes hypertension, arrhythmias, and coronary atherosclerosis.

As a result, myocardial infarcts (heart attacks) are common in diabetics and result in high mor­bidity and mortality. Diabetic cardiomyopathy has also been reported in people and is associatedwith severe, prolonged coronary microvascular disease caused by the diabetes.

Dogs with diabetes have an increased risk of hypertension. However, dogs and cats rarelydevelop coronary artery disease. Diabetic dogs may develop mildly impaired systolic myocardialfunction but congestive heart failure is not a problem in diabetic dogs and cats.

Dogs and cats that are being treated for ketoacidotic diabetes may develop profound hy­pokalemia. Atrioventricular conduction disturbances have been observed in association withsevere hypokalemia. However, and perhaps most importantly, hypokalemia predisposes to the de­velopment of ventricular arrhythmias including ventricular premature complexes, ventriculartachycardia, and potentially ventricular fibrillation.

7. How does gastric dilation/volvulus (GDV) affect the heart?GDV affects the heart in several different ways. In experimental GDV, it was found that

GDV reduced cardiac output, contractility, mean arterial pressure, total peripheral resistance,coronary perfusion, and myocardial oxygen consumption. After gastric decompression most ofthese variables return to normal except that the cardiac output and mean arterial pressure remainlow. Myocardial contractility increases due to sympathetic stimulation. However, cardiac outputremains low because of arrhythmias, decreased preload, and increased afterload.

42 Extracardiac Disease and the Heart

Most of the above effects are secondary to the hypovolemia that occurs when the enlargedstomach occludes flow in the hepatic portal vein and posterior vena cava. However, endotoxinsfrom congestion of the abdominal viscera activate many inflammatory mediators such as hista­mines, prostaglandins, and leukotrienes. Also, there is a release of a vasoactive peptide from thepancreas that decreases myocardial contractility and contributes to decreased cardiac output andmyocardial hypoperfusion.

Arrhythmias develop in about 40% of the dogs with GDY. Most of these tend to occur one­half to three days after presentation. Ventricular arrhythmias are the most common. They areprimarily due to myocardial hypoxia from the hypovolemia and decreased cardiac output. Reper­fusion injury, which is caused by the release of accumulated neutrophils and reactive hydroxylradicals resulting in superoxide radicals plus hypochlorite ions, may also contribute to the ven­tricular arrhythmias. The hypokalemia, acidosis, and hypoxia that are also associated with theGDV facilitate the ventricular arrhythmias and make them resistant to antiarrhythmic therapy.

8. How do endotoxins from septic shock affect the heart?Many different factors, including gastric torsion, can contribute to septic shock in animals.

In people with septic shock, tumor necrosis factor and interleukin-l cause myocardial depres­sion. These inflammatory substances cause myocardial depression by causing nitric oxide syn­thesis, which in turn forms nitric oxide in the myocardium. This same mechanism of myocardialdepression is thought to exist in animals with septic shock. Besides myocardial depression, thetoxins may also result in atrial and/or ventricular arrhythmias.

9. Do animals with renal failure have cardiac problems?Toxins that accumulate due to renal failure may have a direct cardiotoxic effect. In man, an

uremic cardiomyopathy has been documented, but it has not been documented in animals.Most of the cardiac complications of renal disease in humans are the results of coronary ath­

erosclerosis, hypertension, lipid abnormalities, and the complications of chronic hemodialysis.These complications can result in congestive heart failure.

Dogs with protein-losing nephropathies are at risk for pulmonary thromboembolism andsystemic hypertension can be associated with canine renal disease. However, congestive heartfailure resulting from either of these problems has not been reported in the dog or cat.

People with acute or chronic uremia have been reported to have pericardial inflammation,which is probably secondary to the accumulation of uremic toxins causing a pericardial serositis.Uremic pericarditis usually results in the accumulation of a small amount of hemorrhagic peri­cardial effusion and a few patients develop cardiac tamponade.

Pericardial effusions do occur in animals with renal disease but the effusions are usually smalland cardiac tamponade has not been reported. Those animals with pericardial effusion may have apericardial friction rub on auscultation and a small amount of effusion may be detected on echocar­diogram. Other than these findings, there is no other evidence of cardiac disease in these animals.

Cats with lower urinary obstruction can develop significant hyperkalemia. The obstructedeat's ECG is similar to a dog's with hyperkalemia (see Addison's disease above).

10. Do animals develop hypertension and what effect does it have on the heart?Systemic hypertension is a sustained elevation in systemic arterial pressure. While animals

can develop primary, or essential, hypertension, it is more commonly associated with other disor­ders such as renal disease, hyperadrenocorticism, hyperthyroidism, and diabetes mellitus.

The clinical signs associated with hypertension are those of the underlying disease process.However, with chronic hypertension, other organs such as the retinas, kidneys, and heart canbecome damaged.

Hypertension causes a chronic pressure overload of the left heart. As a result, the left heartwill hypertrophy, but the hypertrophy is seldom severe and heart failure appears to be uncom­mon. The increased afterload can increase the severity of mitral regurgitation in patients withpreexisting heart disease.

Extracardiac Disease and the Heart 43

11. What is synchronous diaphragmatic flutter and what causes it?Synchronous diaphragmatic flutter occurs when the diaphragm contracts with every heart­

beat.The animal appears to be shaking or twitching and auscultation confirms that the twitchescorrespond to the heart rate. Fluoroscopy can provide radiographic confirmation of the diagnosis.

The flutter is believed to be caused by excitation of the pericardial segment of the phrenicnerve by the electrical activity of the heart. This problem occurs most commonly in dogs withpersistent vomiting. This problem is felt to be the result of either the alkalosis associated with thepersistent vomiting or hypocalcemia resulting in hyperirritability of the phrenic nerve. Oncethese underlying problems are corrected, the flutter disappears.

12. How does a pheochromocytoma affect the heart?Most of the cardiac problems associated with a pheochromocytoma, which is a functional

tumorof the adrenal medulla, are due to the invasion of the tumor into the caudal vena cava or totheeffects of increased levels of catecholamines. Neoplastic invasion of the caudal vena cava canobstruct blood returning to the heart, which can cause ascites.

The increased levels of catecholamines cause sinus tachycardia, which is the most commonECG finding; it is observed in 15-54% of the cases. Catecholamines can also sensitize the heartto arrhythmias such as atrial and ventricular premature beats. Ventricular arrhythmias may causesuddendeath. Also, 50% of the dogs whose blood pressure is measured are hypertensive, and leftventricular and left atrial enlargement is common in dogs. In one report, 2 out of 15 dogs showedsigns of congestive heart failure.

13. How does hypothyroidism affect the heart?Thyroid hormones have a direct effect on the heart and will increase contractility, stimu­

late myocardial hypertrophy, and increase the myocardial sensitivity to adrenergic simulation.When hypothyroidism occurs, the number of beta receptors in the heart decreases, whichmeans that the heart cannot respond well to sympathetic stimulation. This results in a brady­cardia and decreased contractility. A decrease in the rate of myocardial relaxation may also beobserved.

In people, a myxedematous heart is the result of chronic hypothyroidism. The myxedema­tous heart has the same appearance as the heart with dilated cardiomyopathy, except that withthyroid supplementation the myxedematous heart returns to normal. In dogs, chronic hypothy­roidism has not been shown to cause dilated cardiomyopathy. However, some breeds such as theDoberman pinscher, golden retriever, Irish setter, Great Dane, Old English sheepdog, and cockerspaniel are prone to having both problems. By treating the hypothyroidism in dogs with dilatedcardiomyopathy, the dogs feel better and their heart disease may be easier to manage.

The common cardiac signs associated with hypothyroidism are bradycardia, weak cardiacapex beat, and arrhythmias. In humans there is an increased incidence of hypertension. Withsevere hypothyroidism, the dog's ECG may show sinus bradycardia and low-voltage QRS com­plexes. In experimental dogs, the PR interval is prolonged, which may indicate a problem in theatrioventricular node secondary to the hypothyroidism. Some hypothyroid dogs have had atrialfibrillation or other arrhythmias,

Echocardiographic changes include thinning of the left ventricular posterior wall, decreasedshortening fraction due to decreased left ventricular wall excursion, alterations in the systolic anddiastolic time intervals, and mildly increased left ventricular systolic diameter.

The cardiac manifestations of canine hypothyroidism are generally of little clinical conse­quence and resolve after replacement therapy. There have been anecdotal reports of thyroid sup­plementation causing dogs with dilated cardiomyopathy and hypothyroidism to go back intocongestive heart failure by starting them at their normal level of thyroid replacement. Studies inhumans have not found any problems with thyroid supplementation at normal levels in peoplewith dilated cardiomyopathy and hypothyroidism. Until such studies are done in dogs with bothdiseases, dogs with hypothyroidism and dilated cardiomyopathy should be monitored closely forthe first few weeks of thyroid supplementation.

44 Extracardiac Disease and the Heart

14. Can dogs have heart attacks?Heart attacks in people are caused by the sudden blockage of blood flow through one or

more coronary arteries, resulting in hypoxia and death of the areas of the heart perfused by theblocked vessel(s). The underlying cause of the heart attacks is usually atherosclerosis, which isthe accumulation of cholesterol plaques that causes gradual obstruction of the vessel(s).

In dogs, atherosclerosis is uncommon but it can occur secondary to chronic hypothyroidism.A major heart attack can occur but is uncommon. More commonly the dog has arrhythmias anddecreased contractility of the area of the wall affected by atherosclerosis.

Since major arteriosclerosis causing a heart attack is rare in the dog, the practitioner shouldrefrain from telling a client that an animal has suffered or died from a "heart attack." When car­diac disease is indeed responsible, it is much more likely that the dog died of heart failure or asudden arrhythmia.

15. What is an arteriovenous (AV) fistula and how does it affect the heart?An arteriovenous (AV) fistula is an abnormal connection between an artery and a vein in

which the blood does not pass through a capillary bed. These shunts can be congenital or ac­quired. Acquired AV fistulas are usually the result of trauma or perivascular injection of an irri­tating substance, or are associated with the presence of a neoplasm. Most AV fistulas involvesingle vessels but occasionally more than one AV fistula can be present in an area.

An AV fistula can be located anywhere in the body, but it is usually located in an extremity.The AV fistula allows oxygenated blood from an artery to enter the venous system directly. Thiscan cause proliferation of the affected vessels, which can increase the number or size of the AVfistulas. The affected area may also be painful and may become edematous due to the increasedblood flow. Occasionally the area can develop necrosis and ulceration and sometimes the area de­velops abnormal pigmentation.

Depending on the size or number of AV fistulas in an area, a continuous murmur may be aus­cultated over the area. Also, the murmur sometimes can be felt as a "thrill" over the affected area.

If the AV fistula is large and a significant volume of blood flows from the artery into thevein, it can cause a volume overload of the entire heart. On radiographs there is generalized car­diomegaly. Echocardiography confirms generalized cardiomegaly and may show an increasedfractional shortening due to the volume overload. In very large shunts, there is an increase in end­diastolic pressure, which can lead to congestive heart failure.

Diagnosis of AV fistulas can be difficult and may require angiography to outline the AV fis­tula. Once the AV fistula has been identified, surgery is done to ligate it. Once the AV fistula hasbeen ligated, the circulation in the area will return to normal if all of the fistulas have been lo­cated and ligated. The heart will also return to normal size and function.

16. How can anemia affect the heart?In people, anemia is an important cause of high cardiac-output states. The low oxygen-carry­

ing capacity of the blood stimulates a sequence of reactions that results in increased heart rate, in­creased volume of blood pumped by the heart, and increased cardiac output. The increased volumeof blood pumped by the heart is similar to the volume overload due to leaky heart valves or con­genitalleft-to-right shunts such as a patent ductus arteriosus (PDA). The heart will dilate and hy­pertrophy. Radiographs of an animal with chronic anemia may show generalized cardiomegaly.

Clinical complications of anemia only occur with chronic, severe anemia (packed cellvolume less than 20%). Most animals will have a soft systolic murmur. Occasionally an animalmay have a gallop rhythm. Many times the precordial impulse of the heart is stronger thannormal.

In people, anemia can cause high-output cardiac failure and signs of congestion. In animals,cardiac failure is rare unless the animal has underlying heart disease that is potentiated by theanemia. The symptoms and treatment of the heart disease will depend on which disease is pre­sent in those animals with both heart disease and anemia. Heart disease is not a cause of anemiain animals.

Extracardiac Disease and the Heart 45

17. What causes polycythemia and how does it affect the heart?Polycythemia, or erythrocytosis, refers to a pathologic increase in red blood cell mass; it

must be distinguished from elevations in packed cell volume (PCV) that result from hemocon­centration. The two major causes of polycythemia in small animals are right-to-left cardiacshunts (such as tetralogy of Fallot) and idiopathic polycythemia vera. Chronic congestive heartfailure can lead to increases in red cell mass, but this is typically offset by the increase in in­travascular volume that results from salt and water retention; thus, the packed cell volume (PCV)in most patients with chronic heart failure is normal.

Pathologic polycythemia (PCV over 60% in dogs) causes an increase in the amount ofoxygen carried by the blood, an increase in blood volume, and potentially an increase in cardiacoutput despite an increase in ventricular afterload. High-output cardiac failure can occur, but israre in animals. The animals have brick-red mucous membranes. Their other clinical signs andexamination findings depend on the cause of their disease. Some animals will present for seizuresdue to the slow movement or sludging of blood in the brain.

18. How does pancreatitis affect the heart?When pancreatitis occurs, a myocardial depressant factor is released that can depress my­

ocardial function. Clinically this rarely is significant in animals.Pancreatitis has also been associated with ventricular arrhythmias in animals. The cause of

ventricular arrhythmias in this syndrome has not been identified, although inflammatory media­tors, myocardial depressant factor, electrolyte derangements, and acid-base disturbances couldpotentially have a role in arrhythmogenesis.

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