John E. Rush, DVM, MS, Diplomate ACVIM, Diplomate ACVECC

Key Points

Hypertrophic cardiomyopathy is the most common form of feline heart disease. Affected cats have concentric or asymmetric left ventricular hypertrophy without identifiable cause. While the cause of HCM in the cat has not been conclusively identified, there is good evidence to suggest that an abnormality in the genes encoding for sarcomeric proteins is the cause in at least some cats.

Pathology of feline hypertrophic cardiomyopathy

Concentric hypertrophy of the left ventricle and ventricular septum is evident in most cases, the papillary muscles of the left ventricle are typically hypertrophied, and the ratio of heart weight to body weight is increased. Asymmetric hypertrophy involving either the interventricular septum or the left ventricular free wall is identified in some cases. Left atrial enlargement is usually evident, and variable right heart enlargement or hypertrophy may be noted. In cases with profound hypertrophy of the interventricular septum and narrowing of the left ventricular outflow tract, the anterior mitral valve leaflet may be thickened. Pulmonary edema, pleural effusion, hepatomegaly and pericardial effusion may be present in cats with congestive heart failure. Histologic changes may include myofiber disarray within the interventricular septum. An increase in fibrous connective tissue may be present, and the conduction system may be affected. Intramural coronary arteries may be narrowed.

Pathophysiology - Hypertrophic cardiomyopathy can negatively impact cardiac performance through a number of mechanisms. Classically, the hypertrophy of the left ventricle leads to a small left ventricular internal dimension, and this impedes diastolic filling. The hypertrophied muscle can become stiff, and the fibrous tissue replacement seen in some cats can contribute to the impediment to diastolic filling. Since the duration of diastole is inversely proportional to the heart rate, tachycardia further compromises diastolic function. When tachycardia is superimposed upon a cat with stable hypertrophic cardiomyopathy, decompensation commonly occurs and the result is usually an acute onset of congestive heart failure, classically severe pulmonary edema. Catecholamine stimulation causes tachycardia and can further impede diastolic filling. The resulting compromise in diastolic filling results in elevations of left ventricular diastolic pressure and necessitates progressive increases in left atrial pressures to effectively fill the left ventricle with blood. Eventually, left atrial pressure rises high enough that the pressure is transmitted back through the pulmonary veins to the pulmonary capillaries and left-sided congestive heart failure with pulmonary edema results. In some cats, chronic elevation of left atrial pressure can be transmitted back through the pulmonary vascular circuit and can lead to pulmonary hypertension with eventual right heart failure. Intravenous or subcutaneous fluids, long acting corticosteroids, and megestrol acetate can precipitate congestive heart failure in previously asymptomatic cats. In cats with hypertrophy of the interventricular septum, the hypertrophy of the septum causes an impediment to the ejection of blood through the left ventricular outflow tract. The left ventricle must generate higher pressures to overcome this obstruction, which may further contribute to the left ventricular hypertrophy. Blood is ejected through the narrowed outflow tract at greater velocity than normal, and this increase in velocity often creates a Venturi effect that pulls the mitral valve leaflet into the left ventricular outflow tract. As the previously closed anterior mitral valve leaflet is pulled away from the mitral orifice during systole, secondary mitral regurgitation results. Mitral regurgitation further increases left atrial size and contributes to the development of left-sided congestive heart failure.

Etiology - Molecular studies have determined that the genetic alterations that cause hypertrophic cardiomyopathy in humans include mutations in the genes that encode for several proteins in the sarcomere. These include mutations for ß-myosin heavy-chain, cardiac troponin T, a-tropomyosin, myosin binding protein C and myosin light chains. The formation of these abnormal myocardial proteins leads to the inappropriate ventricular hypertrophy in affected individuals. A genetic cause is suspected based on breeding studies on a colony of Maine coon cats and on other work done with American shorthair cats and Persian cats.

History - Clinical signs in cats with congestive heart failure often include lethargy, hiding, reluctance to interact with the owner, and anorexia. Many owners do not recognize tachypnea, dyspnea or respiratory distress until it is at an advanced stage. Coughing occurs in some cats with pleural effusion but is an uncommon sign of CHF in the cat. Syncope occasionally occurs; many cats with CHF have anorexia and/or an episode of vomiting just prior to presentation.

Physical examination - Physical examination can be normal in up to 30% of cats with HCM. During the course of routine examination a cardiac murmur (esp. near the sternal border) and/or cardiac gallops are often identified in affected cats. Physical exam findings can include increased respiratory rate and effort, loud pulmonary crackles (pulmonary edema), lung sounds may be muffled ventrally (pleural effusion), and jugular vein distension or hepatomegaly (esp. in cats with pleural effusion). Arterial pulses may be normal or weak, mucous membrane color may be normal or somewhat cyanotic, and capillary refill time may be delayed. A prominent cardiac apex beat is often noted on the left side of the chest. Hypothermia is common in cats with CHF and the heart rate in these cats may seem inappropriately low. Arterial thromboembolism to the rear legs results in the acute onset of posterior paresis or paralysis. Most cats cannot use their rear limbs and vocalize, presumably as a result of pain. The pulses are usually absent to both rear legs, although there may be reduced flow or weak pulses in only one limb. The nail beds of the affected limb(s) are cyanotic when compared to the nail beds of the normal limbs. The affected limbs are usually colder than the normal limbs. The gastrocnemius muscles are usually firm in the affected rear limb(s). Most cats retain the ability to move their tail and retain anal tone, and many retain some ability to flex their hip.

Electrocardiography - The electrocardiogram can be normal. Sinus tachycardia is common; however sinus bradycardia is often seen in hypothermic cats with CHF. Deep S waves in lead II signal the presence of an axis shift, which is usually a left axis shift or a left anterior fascicular block. Many arrhythmias can be seen including ventricular arrhythmias, supraventricular tachycardia, atrial fibrillation and atrioventricular block.

Thoracic radiographs - Cardiomegaly is identified on the thoracic radiographs of most cats with hypertrophic cardiomyopathy. The classic finding of biatrial enlargement, or a valentine-shaped heart on the dorsoventral (DV) or ventrodorsal (VD) view, is present in some affected cats, but can also be seen in cats with other forms of cardiomyopathy. Most cats with significant left atrial enlargement will also have enlargement of both pulmonary artery and vein on the DV view. On the lateral view, a bulge is often noted on the caudodorsal aspect of the cardiac silhouette and cats with chronic left atrial enlargement often have a tortuous pulmonary vein returning to the left atrium from the caudal lung lobes. Pulmonary edema can be initially manifested as an increased interstitial pattern in the lungs that coalesces into in alveolar pattern as CHF worsens. In many cats it develops ventrally or is distributed into multifocal, patchy areas of edema rather than in the classic hilar regions. Pleural effusion can be seen in association with hepatomegaly and enlargement of the caudal vena cava.

Echocardiography - Classic echocardiographic findings seen in cats with HCM include hypertrophy of the interventricular septum and left ventricular wall (<0.55 to 0.6 cm in diastole in normal cats). Additionally, the systolic dimensions of the interventricular septum and left ventricular freewall are typically greater than 0.9 cm in affected cats. The earliest indicator of hypertrophic cardiomyopathy may be hypertrophy of the papillary muscles. Left ventricular outflow obstruction often occurs due to septal hypertrophy. The thickened septal tissue protrudes into the outflow tract, and turbulent blood flow can be identified in the left ventricular outflow tract or proximal aorta. Doppler studies often identify increased aortic flow velocity indicating a significant transvalvular pressure gradient resulting from the outflow tract obstruction. Systolic anterior motion of the mitral valve results from the previously described motion of the septum into the outflow tract during systole. In many of these cases, when color flow Doppler is performed, there is a distinct jet of mitral regurgitation which travels above the surface of the posterior mitral valve leaflet towards the distal wall of the left atrium. Significant left atrial enlargement is often present. In cats with long standing left atrial enlargement and secondary pulmonary hypertension, the pulmonary artery is often enlarged and bigger than the aorta and these cats often have accompanying right-sided heart failure. Pericardial effusion resulting from congestive heart failure may be identified in some cats, however, pericardial effusion infrequently results in cardiac tamponade. Thrombus formation can be identified echocardiographically in some cats (esp. in the left auricular appendage) and swirling, spontaneous echo contrast or "smoke" in the left atrium is also judged to be a marker of a cat at increased risk for arterial thromboembolism.

Ancillary testing - Since hyperthyroidism can result in cardiac changes that mimic hypertrophic cardiomyopathy, a T4 should be obtained on all cats that are six years of age or older. Systemic arterial hypertension results in secondary concentric left ventricular hypertrophy so a normal arterial blood pressure reading should be obtained to exclude a diagnosis of systemic hypertension. A complete blood count is rarely helpful. The serum biochemistry profile is usually normal in the asymptomatic cat. Stress hyperglycemia, mild hepatic enzyme elevations due to chronic passive congestion, and prerenal azotemia may occur. Prerenal azotemia and nd is much more common in cats that have been treated with diuretics. Prerenal azotemia, metabolic alkalosis, hyponatremia, hypokalemia, hypochloremia, and hypomagnesemia can all result from high dose furosemide therapy.

Controlling Heart Rate and Improving Diastolic Function

Hypertrophic cardiomyopathy is a disease of diastolic dysfunction, and the core therapeutic strategy is to improve diastolic function. Since the duration of diastole is inversely related to heart rate, core drug therapies are those that will decrease heart rate.

The theoretical benefits of treatment with calcium channel blockers includes improved diastolic function secondary to decreased heart rate, improved myocardial perfusion secondary to coronary arterial vasodilation, and other myocardial effects of calcium channel blockade that improve diastolic function. Diltiazem is the calcium channel blocker most frequently used for management of cats with hypertrophic cardiomyopathy. The dose (0.5 to 1.5 mg/kg q 8 H) usually translates into a starting dose of one quarter of a 30 mg tablet three times per day. This dose can be increased up to 15 mg PO q 8 H. To limit non-compliance, an extended-release formulation of diltiazem (Dilacor) is often preferred. Dilacor is available in 240 mg capsules, and inside each 240 mg capsule there are four 60 mg tablets. These 60 mg tablets can be cut in half for a dose of 30 mg. This 30 mg/cat dose is administered either q 12 H or q 24 H. Cardizem CD can also be used at a dose of 10 mg/kg q 24 H.

ß blockers have theoretical benefit of reducing heart rate, reducing myocardial oxygen demand and controlling both ventricular and supraventricular arrhythmias. By decreasing inotropic state, ß blockers may reduce the left ventricular outflow gradient in some cats. In general, when using ß blockers, the initial low dose is selected and the dose is titrated upward until the desired effect of heart rate reduction or arrhythmia control is achieved. Propranolol is a non-specific ß blocker that blocks both ß-1 and ß-2 receptors. Due to the short half-life of propranolol in cats (T ½ = 0.49 hours), this drug should usually be given at least three times per day. A low starting dose is initiated (2.5 mg q 8 h) and the dose is titrated upward to as high as 10 mg three times a day. Atenolol is a hydrophilic ß1-specific ß blocker that has been successfully used to treat cats with hypertrophic cardiomyopathy. The drug has been used successfully by some authors using a once a day dosing schedule, however pharmacologic studies and heart rate monitoring indicate that twice a day dosing is preferable. Pharmacologic testing in normal cats defined the half-life of atenolol as approximately 3.5 hours and the duration of heart rate reduction as at least 12 hours. Based on this information, it appears that twice a day dosing of atenolol is preferable in cats. In most cats, an initial dose of 6.25 mg per cat q 24 hours is titrated up to as high as 12.5 mg per cat q 12 hours until adequate therapeutic response is achieved. Some pharmacies are now formulating transcutaneous methods for drug delivery, however these have not been well studied and the efficacy and drug absorption properties of the various formulations remain to be established.

Treatment of Congestive Heart Failure

Thoracocentesis should be performed on any cat with a moderate or large volume of pleural effusion. Low sodium diets are not necessary for asymptomatic animals, however a restriction from certain high sodium foods should be recommended to the owner. Once heart failure develops, feeding a moderate to severely restricted sodium diet is more important. These diets are rarely crucial in the initial management of heart failure. Cats with CHF should be tolerating their cardiac medications well and have a good appetite for their normal diet before any sodium restricted diet is introduced. Stress reduction can be an important aspect to management of CHF in cats with HCM. As an example, restricting an outdoor cat from going outdoors may place greater stress on the cat and can be counterproductive, despite the potential benefit of being able to watch the cat for recurrence of signs of CHF.

Furosemide is the diuretic that forms the backbone of therapy of congestive heart failure in cats with hypertrophic cardiomyopathy. In cases of acute and severe congestive heart failure with pulmonary edema, high doses of furosemide are needed (4 mg/kg IV q 1 hour). Nitroglycerine is often used in the setting of acute severe pulmonary edema. For chronic management of heart failure, a much lower dose of furosemide is used. In many cats, furosemide administration at 6.25 mg per cat every other day is sufficient to control signs of congestion, and the vast majority of cats can be effectively treated with 6.25 mg per cat twice a day or less. Cats with pleural effusion seem more likely to require high furosemide doses during chronic therapy. When combined with an angiotensin- converting enzyme inhibitor, a low dose of furosemide is essential to avoid side effects. Side effects of ACE inhibitors can include dehydration, azotemic, weakness, hypotension, and anorexia. Azotemia is more likely to occur in cats that are dehydrated, those that have received high doses of diuretics, and those with pre-existing renal dysfunction. In most cases, a reduction in diuretic dose will improve renal function and restore blood pressure to normal.

Summary

Successful management of hypertrophic cardiomyopathy in the cat often includes used of drugs to control tachycardia, can include use of drugs to treat congestive heart failure, and in selected cases also includes the use of antithrombotic drugs in an attempt to reduce the risk of arterial thromboembolism. Dietary management can also be important in cats with congestive heart failure.