Hypertrophic Cardiomyopathy:
What’s new and relevant in 2002?
Clarke E. Atkins, DVM, Diplomate, ACVIM
College of Veterinary Medicine
North Carolina State University, Raleigh, NC
ETIOLOGY AND PATHOPHYSIOLOGY
Hypertrophic cardiomyopathy (HC) is the most prevalent feline cardiac disorder, its relative importance having increased with the decline in the incidence of dilated cardiomyopathy (DC). It is a disease of middle-aged cats (average 6.5 years), but all ages are affected. There is a male predisposition, with > 75% of cases being male. In humans, there is an important hereditary predisposition for HC in 55% of cases. In people, this disorder may be congenital or acquired, and probably represents a group of diseases. Although the etiology of feline HC is unknown, the Persian and Maine coon cat have appeared to be predisposed in some case series, suggesting a genetic influence. A controlled study in our laboratory showed a trend toward a predisposition for Maine coon cats to HC. Interesting work by Kittleson and associates suggests a potential etiologic role for excessive growth hormone secretion in some cases. As is the case with systemic hypertension, hyperthyroidism, and aortic stenosis, HC is associated with marked left ventricular hypertrophy, but in this instance, no underlying cause can be identified.
Cardiac lesions are typified by severe left ventricular concentric hypertrophy and secondary left atrial dilatation. Asymmetric septal hypertrophy (ASH), present in the majority of dogs and humans with HC, is present in only 30% of cats with HC. Histological cardiac myofiber disarray is reported in 27% of affected cats and only in those with asymmetric septal hypertrophy. Other histological features of feline HC include myocardial and endocardial fibrosis and narrowed coronary arteries. Dynamic aortic outflow obstruction, secondary mitral insufficiency, myocardial ischemia, and systemic arterial embolism (SAE) may complicate this syndrome. The left heart is predominately affected and clinical signs manifested as sudden death or, more commonly, acute left heart failure due to diastolic dysfunction. Systolic function is usually adequate or enhanced. Tilley and Lord demonstrated an elevated resting left ventricular end diastolic pressure (LVEDP) in feline HC. With the administration of isoproterenol, mimicking endogenous, stress-related sympathoadrenal activity, the LVEDP pressure doubled. Left ventricular end diastolic pressure is indicative of pressures in the left atrium and pulmonary veins, which reflect the tendency for the development of pulmonary edema. In addition, during stressful situations, acceleration of the heart rate reduces cardiac filling time and myocardial perfusion. The former further diminishes cardiac volume and the latter results in relative myocardial ischemia in a rapidly beating heart with high oxygen needs, thereby, aggravating diastolic dysfunction. Stressful incidents, such as a car ride, restraint for an ECG, confrontation with a dog, or an embolic event may precipitate in left heart failure and pulmonary edema.CLINICAL SIGNS
With the aid of ECG, thoracic radiographs, and echocardiography, a high percentage of cases of HC are diagnosed prior to the onset of symptomatology. Suspicion is raised in such instances when the attending clinician discovers a murmur, gallop, or arrhythmia. At the other end of the spectrum, cats may die unexpectedly with no prior signs. The most common clinical sign is the sudden onset of dyspnea, with or without evidence of SAE (the prevalence of which has ranged from 16 to 48%, in clinical and autopsy studies, respectively). Physical examination typically reveals a well-fleshed, dyspneic cat with audible pulmonary crackles, murmur (50% of cases) typically loudest at the left apex, gallop (40%, usually S4), and/or arrhythmia (25 to 40% of cases). Heart sounds may be muffled. The oral mucosa is ashen, the pulses normal, weak, or absent (SAE), the apex beat may be hyperdynamic, and the liver may rarely be palpably enlarged. Cats with HC are generally not hypothermic, providing information useful in differentiation from DC.DIAGNOSIS
Diagnosis of HC is not difficult, but does require special testing to confirm clinical suspicions. Without the aid of echocardiography, dilated and restrictive (RC) cardiomyopathies can be difficult to distinguish from HC. This distinction is especially important in the case of DC, because it requires an entirely different therapeutic approach and prognosis. Other disorders that produce left ventricular and septal hypertrophy, such as hyperthyroidism, systemic hypertension, and aortic stenosis, must also be ruled out. The ECG is abnormal in 35 to 70% of cases and can provide useful diagnostic information. Many ECG findings are not specific, but left axis deviation and left anterior fascicular block are strongly suggestive of HC, but also may be recognized in RC, hyperkalemia, hyperthyroidism, and, rarely, DC. Other ECG abnormalities include P-mitrale and P-pulmonale (10% and 20%, respectively), tall R waves (40%), wide QRS complexes (35%), conduction disturbances (50%, including left axis deviation in 25% and left anterior fascicular block in 15%), and arrhythmias (55%, usually ventricular in origin). Thoracic radiographic findings suggestive of HC include cardiomegaly with a prominent left ventricle and atrium, and pulmonary congestion and/or edema. In the ventrodorsal projection, the heart may appear "valentine-shaped," reflecting the concentric ventricular hypertrophy and enlarged left auricle. Additionally, the apex is often shifted to the right. On the lateral view, the heart is enlarged with increased sternal contact, left atrial prominence, left ventricular convexity, and a prominent caudal cardiac waist. Pleural effusion may be noted in 25 to 33% of cases in heart failure, but is usually of much less volume than that noted in DC. Nonselective angiography is of less risk in HC than in DC. This procedure typically reveals normal or enhanced circulation, pulmonary venous tortuosity, left atrial enlargement, small left ventricular lumen, thickening of the left ventricular wall, and papillary muscle enlargement. The diagnosis of SAE (usually located at the aortic trifuracton: saddle thrombus) can be confirmed by the finding of an abrupt termination of the dye column in the aorta at its trifurcation. Echocardiography is extremely useful for distinguishing HC from DC, but, because of overlap of echocardiographic reference values, differentiation of normal from asymptomatic HC and HC from RC may be difficult. Concentric left ventricular hypertrophy and left atrial enlargement are features useful in confirming the diagnosis of HC. Cardiac function is normal to exaggerated, due to diminished afterload and possibly hypercontractility. Systolic anterior mitral valve motion may be evident, suggesting dynamic aortic outflow obstruction. If present, ASH, left atrial thrombi, pleural effusion, and/or pericardial effusion may be evident. In the case of sudden death, the diagnosis is made at necropsy by disclosure of typical gross and histologic cardiac pathology. Other laboratory findings, with the exception of hypotaurinemia, are similar to that described for feline DC. Differential diagnoses are also similar with the addition of restrictive pericarditis and emphasis of systemic hypertensive and hypertrophic thyrotoxic heart disease.THERAPY
The treatment of HC is different than that of DC and entails the goals of reducing LVEDP, abolishing sinus tachycardia and other arrhythmias, improving myocardial oxygenation, and alleviating and preventing pulmonary edema. Positive inotropic agents are not needed and generally contraindicated because they may increase LVEDP and aggravate outflow obstruction. The latter precaution should be exercised in the use of arterial vasodilators and, to a lesser degree, preload reducing agents (diuretics and mixed or venodilators). Diuretic therapy is indicated to eliminate pulmonary edema. Furosemide is the diuretic of choice in emergencies because it reduces LVEDP and, hence, left atrial, and pulmonary venous pressures through diuresis and venodilation. In the emergency situation, treatment with parenteral furosemide (2-4 mg/kg IV or IM) is accompanied by the use of topical nitroglycerin (1/8-1/4 inch tid-qid for first 24 hours, then “8 hours on, 8 off” only if necessary) and oxygen supplementation (40%). Although furosemide diuresis is usually successful, the addition of enalapril (.25-.5 mg/kg sid) is indicated in refractory cases or when biventricular failure (pleural effusion) ensues. Drugs that enhance ventricular relaxation and slow the heart include the beta adrenergic (atenolol), and calcium channel (diltiazem) blockers. Such therapy is indicated in treatment of the diastolic failure of HC. Beta blockers improve diastolic indirectly, enhancing ventricular filling by reducing heart rate and improving myocardial perfusion. Traditionally, beta-blockers have been administered orally after stabilization (24 to 36 hours after institution of diuretic therapy) to reduce and prevent elevations in LVEDP, to lower systolic pressure gradients and myocardial oxygen requirements, to prevent stress-induced tachycardia and reduce resting heart rate, and for its antiarrhythmic effects. When arrhythmias are present, this drug may be initiated earlier in the disease course. This is the author’s treatment of choice for asymptomatic HC, for cats with documented outflow obstruction (HOCM), and when tachycardia persists.. Calcium channel blocking agents have been effective in human HC by reducing heart rate, myocardial oxygen consumption, and diastolic dysfunction. In addition to directly enhancing myocardial relaxation, these drugs dilate peripheral and coronary arteries. Bright has demonstrated the utility of diltiazem (3-7.5 mg po tid) in the treatment feline HC, including those cases refractory to the beta-blocker, propranolol. Unfortunately, current packaging for human use, makes accurate feline dosing of diltiazem difficult. Long-acting diltiazem may be substituted and includes Cardizem CD (45 PO sid; requires disassembling capsules) or Dilacor (30 mg PO bid; requires disassembling capsules). Combining a calcium channel blocker and a beta blocker has theoretical advantages and is often done, using a long-acting form of each drug, one in the morning and one in the evening. A recent report by Rush, et al. demonstrated a reduction in wall thickness with the administration of enalapril to cats with HCM. This suggests a potential role for ACE-inhibitors in the treatment of HCM. These drugs are generally safe and do play a role in cases which are refractory or in which pleural effusion is present. In asymptomatic patients, it is logical that the renin-angiotensin-aldosterone system is not pathologically activated, and hence ACE-inhibitors would not be useful. The study referred to argues that they may play a role, however. Further studies are being planned. Enalapril is used at .5 mg/kg daily. Drugs other than those described above should be used sparingly and with caution (see section on DC). Digoxin, while generally contraindicated in HC, may be used when supraventricular arrhythmias are refractory to calcium channel and beta adrenergic blocking agents. Other therapies, including oxygen, aspirin, home confinement, and moderate salt restriction should be instituted as needed. Taurine supplementation is not necessary in the treatment of HC. In asymptomatic cats with HC, the author advises home confinement, moderate salt restriction, Beta- and/or calcium channel blockade, and aspirin indefinitely.PATIENT MONITORING
Cats with asymptomatic HC should be evaluated at 12 month intervals, while those with symptoms should ideally be seen more frequently until stabilized for a period of time. The prognosis for asymptomatic HC is guarded to good, with a median survival of over 5 years. Cats presented in heart failure survive a median of approximately 3 months (though 20% live longer than 3 years), while cats with emboli survive a median of approximately 2 months.