Hypertrophic cardiomyopathy (HCM) represents the most common myocardial disease in cats. Other variants of cardiomyopathy, including restrictive and dilated cardiomyopathy, account for only 30% of cases seen in this species. Aortic thromboembolism is one of the most serious and difficult-to-manage complications of feline cardiac disease. Most, but not all, cats presenting with signs of aortic thromboembolism are found to have underlying cardiac disease at the time of presentation. In most cases no underlying disease has been diagnosed prior to presentation with paresis/paralysis and profound anxiety. Many of the proposed treatments are themselves associated with a high morbidity rate and long term clinical trials are required to make comparative risk-to-benefit ratio assessments of these different options. In cats which do survive the initial treatment, clinicians are still faced with the perplexing problem of long term thrombus prevention, as a majority of cats have been shown to re-embolise despite prophylaxis.
HCM is characterized by increased cardiac mass associated with a hypertrophied, non-dilated left ventricle and is commonly seen as a primary genetic disease in young cats and secondary to hyperthyroidism in older cats. HCM is an inherited disease of cats, seen more often in Persian, Maine coonRagdoll, Devon rex, American shorthair and British cats. 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.
The mode of inheritance for HCM is not fully understood. In the Maine Coon, HCM is inherited as an autosomal dominant trait with variable penetrance. This means that all affected cats will eventually show the trait, or disease (no silent carriers). However, since the gene has variable penetrance not all cats will have the same severity and some may have only very mild disease that can be only be identified by echocardiography. The cause for hypertrophy is probably related to genetic alteration of the ß-myosin heavy chain. An association with increased levels of growth hormone concentration has also been found. Histologically, there is myocardial fibre disarray and diffuse myocardial fibrosis. HCM is usually limited to the left ventricle but in some cases, concurrent right ventricular hypertrophy is present. The development of left ventricular hypertrophy is associated with altered intracellular calcium regulation. This results in the development of relaxation abnormalities during diastole.
HCM has historically been most common in middle-age male cats, but clinical signs occur in cats in a wide range of ages. Cats with milder disease may be asymptomatic for years. This is not surprising, because there is also a wide range of clinical expression of the disease in people with HCM, even within the same kindred. Many hypertrophic hearts in cats look normal on X-ray.
Echocardiographically, there are two distinct varieties of HCM, a non-obstructive form and an obstructive form. The non-obstructive form results primarily in diastolic dysfunction due to delayed or decreased myocardial relaxation. The obstructive form is caused by anterior motion of the mitral valve during systole, which obstructs the left ventricular outflow tract. This results in decreased cardiac output at faster rates, in addition to abnormal diastolic function. The outflow obstruction may contribute to the presence of ventricular concentric hypertrophy.
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.
HCM most commonly occurs in middle-aged cats. 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 oedema), 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 colour 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.
Symptomatic cats are most often presented for respiratory signs of variable severity or signs of thromboembolism. Respiratory signs include tachypnea, panting associated with activity, dyspnea, or, rarely, coughing (which can be misinterpreted as vomiting). Disease onset may seem acute in sedentary cats, even though pathologic changes have developed gradually. Occasionally lethargy or anorexia is the only evidence of disease. Some cats have syncope or sudden death in the absence of other signs. Stresses such as anaesthesia, surgery, fluid administration, systemic illnesses (e.g., fever or anaemia), and even boarding can precipitate heart failure in an otherwise compensated cat. Asymptomatic disease may be discovered by detecting a murmur or gallop sound on auscultation.
- 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 oedema can be initially manifested as an increased interstitial pattern in the lungs that coalesces into an alveolar pattern as CHF worsens. In many cats it develops ventrally or is distributed into multifocal, patchy areas of oedema rather than in the classic hilar regions. Pleural effusion can be seen in association with hepatomegaly and enlargement of the caudal vena cava. However, X-rays are not always useful in diagnosing this disease.
Systolic murmurs indicative of either mitral regurgitation or left ventricular outflow tract obstruction are common. A diastolic gallop sound (usually S4) may be heard, especially if heart failure is evident or imminent. Cardiac arrhythmias are not uncommon. Femoral pulses are usually strong, unless distal aortic thromboembolism has occurred. A vigorous precordial impulse is often palpable. Prominent lung sounds, pulmonary crackles, and sometimes cyanosis accompany severe pulmonary oedema; pleural effusion usually attenuates ventral pulmonary sounds. The physical examination findings can be normal, especially if paroxysmal arrhythmias are the only disease manifestation.
It is not uncommon for HCM to be diagnosed in cats presented with thromboembolism (a common sequela of this disease) or even during a routine examination. Also, because of a compromised circulation and the subsequent immunosuppression associated with HCM, some cats can have concurrent illness, including FIP and cat flu.
Hypertrophic cardiomyopathy (HCM) is an adult onset, primary heart muscle disease. Occasionally other disease processes, like hyperthyroidism and systemic hypertension can lead to the development of hypertrophy (or thickening) of the walls of the left side of the heart. This can result in findings on an ultrasound or at autopsy that look similar to HCM. However, hypertrophic cardiomyopathy is a primary heart muscle disease that is not caused by other systemic diseases.
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.
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 colour 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.
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 oedema, pleural effusion, hepatomegaly and pericardial effusion may be present in cats with congestive heart failure. Histologic changes may include myofibril 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.
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 oedema. 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 oedema 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.
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.
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 hyperglycaemia, mild hepatic enzyme elevations due to chronic passive congestion, and prerenal azotemia may occur. Prerenal azotemia 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.
- Congenital heart disease including VSD, ASD, PDA
- Dilated cardiomyopathy
- Restrictive cardiomyopathy
- Intrathoracic masses, e.g. mediastinal lymphoma
- Asthma or chronic bronchitis
- Chylous effusions
Natriuretic peptide markers
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are hormones synthesized by cardiomyocytes released into the circulation as a result of cardiac wall stretching and play a role in electrolyte-fluid homeostasis by inducing diuresis, natriuresis, and peripheral vasodilation. These members of the natriuretic peptide family, which also includes C-type natriuretic peptide, share similar amino acid sequences and a 17–amino acid ringlike structure resulting from the presence of an internal disulfide bond. Because ANP and BNP messenger RNA (mRNA) are mainly produced by the heart tissue and correlate with increases in circulating peptide levels, besides their hormonal function these peptides also have been indicated as potential markers for cardiac disease, such as congestive heart failure, dilated cardiomyopathy, and hypertrophic cardiomyopathy1. The use of natriuretic peptides in the diagnosis of HCM in cats is still experimental but shows promise as a diagnostic tool in future veterinary medicine.
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 oedema, high doses of furosemide are needed (4 mg/kg IV q 1 hour). Nitroglycerin is often used in the setting of acute severe pulmonary oedema. 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.
Because thromboembolism (clots) are a high risk outcome of HCM, aspirin therapy (5mg per cat every 2nd day) is advised as a prophylaxis.
1. A. W. Biondo, E. J. Ehrhart, D. D. Sisson, B. J. Bulmer, H. S. A. De Morais and P. F. Solter Immunohistochemistry of Atrial and Brain Natriuretic Peptides in Control Cats and Cats with Hypertrophic Cardiomyopathy Vet Pathol 40:501-506 (2003)