Philip R. Fox, DVM, MSc, DACVIM, DECVIM (Cardiology), ACVECC
Cardiomyopathy is a structural or functional heart muscle abnormality. Idiopathic (primary) cardiomyopathy describes the myocardium as the sole source of heart disease when etiology cannot be identified. Secondary cardiomyopathy relates the myocardial disorder to an identifiable systemic or metabolic disease. Categorization is facilitated by clinical, pathologic, or physiologic data. Many cases have overlapping features.
HYPERTROPHIC CARDIOMYOPATHY (HCM)
Etiology. Hypertrophic cardiomyopathy is a common disorder with heterogeneous morphologic expression. A heritable form of HCM suggesting autosomal dominant mode of inheritance has been reported in Maine Coon cats with 100% penetrance, and with the stillborns representing lethal homozygotes that die in utero.
Pathophysiology. Although morphologically heterogeneous, HCM is a disease characterized by diastolic dysfunction and a hypertrophied, nondilated left ventricle. There are a number of phenotypes. The principal pathophysiologic consequence is elevated left ventricular end-diastolic pressure in the face of a normal or reduced end-diastolic volume. Global left ventricular diastolic function is adversely affected through several interrelated abnormalities. A decrease in early rapid diastolic filling results from reduced ventricular distensibility (i.e., compliance) and prolonged (or incomplete) relaxation. Increased muscle stiffness may be caused by fibrosis or myocardial cell disorganization, while ventricular chamber stiffness and muscle mass (hypertrophy). Mitral regurgitation develops from distortional changes in the mitral valve apparatus (resulting from ventricular hypertrophy or from interference with normal mitral value closure due to anterior motion of the mitral valve during mid-systole. The left atrium dilates in response to increased end-diastolic pressures, and pulmonary venous pressures eventually become elevated.
Clinical Findings. There is a wide age range of affected cats (5 months to 17 years; mean age, 4.8 to 7 years). Domestic short-hair cats are most frequently reported followed by the domestic longhair. Maine coon cats have a heritable basis and the Persian breed may be similarly predisposed. Males are more commonly affected.
The predominant clinical sign is acute dyspnea associated with pulmonary edema or biventricular failure. Anorexia and vomiting may precede clinical signs by 1 or 2 days. Paresis of a front leg or posterior paralysis may result form thromboembolic disease. Sudden death occasionally occurs. Auscultation may disclose a diastolic gallop rhythm (fourth heart sound, S4) crackles, soft systolic murmur (I to II/VI) over the mitral and/or tricuspid valve areas and arrhythmias.
ECG abnormalities have been recorded in 35 to 70 percent of affected cats. The most commonly reported findings are conduction disturbances of which only left anterior fascicular block is most consistent. Left ventricular enlargement patterns (QRS > 0.04 sec; R11 > 0.9 mV) are present in some cats but are not diagnostic for HCM. Arrhythmias occur in ¼-1/2 of affected cats with ventricular premature complexes predominating.
Thoracic radiography may show mild to moderate LV enlargement with moderate to severe LA enlargement. Pulmonary venous congestion, interstitial and/or alveolar pulmonary densities (suggesting pulmonary edema), and occasionally slight pleural effusion occur most commonly. Pulmonary edema in cats may be patchy and focally distributed. With chronic or advanced HCM, cardiomegaly may be generalized and accompany extracardiac signs of severe biventricular failure (e.g., pleural, pericardial or abdominal effusion, hepatomegaly, and pulmonary edema.
Echocardiography will characterize a broad range of phenotypic patterns of LV hypertrophy ranging from localized and relatively mild wall thickening involving any one particular wall segment, to diffuse and pronounced hypertrophy of all portions of the left ventricle. No single pattern can be considered "classic" or characteristic of the disease. In cases of dynamic LV outflow tract obstruction, there is systolic anterior motion (SAM) of the mitral apparatus and mid-systolic aortic valve closure; narrowed LV outflow tract; a fibrous plaque on the basal ventricular septum corresponding to point of systolic anterior mitral valve contact; and thickening of the anterior mitral valve leaflet. Mitral regurgitation is common. With dynamic LV outflow tract obstruction, the maximal LV outflow tract velocity is increased. In addition, increased RV outflow tract gradients may occur. Mitral inflow Doppler waveforms may be normal or indicate a relaxation abnormality indicative of diastolic dysfunction. Occasionally, a mid-left ventricular gradient may be present.
Pathology. The principal pathologic feature is abnormal left ventricular hypertrophy and increased ventricular muscle mass in absence of a causative systemic or cardiac disease. Ventricular septal disorganization occurs in up to 1/4 of affected cats. Fibrous connective tissue may be present. Narrowed small intramural coronary arteries are common.
THERAPY OF HCM
There are several possible circumstances where cardiac structural and functional derangement could promote high risk, and justify Therapy as follows.
Myocardial infarction. Cats suspected with myocardial infarction may potentially benefit from beta-adrenergic blockers and ACE inhibitors. ACE inhibitors (enalapril or benazepril [0.25-0.5mg sid] or ramipril [0.25-0.5mg/kg sid]) have been used based upon their potential ability to reduce ventricular remodeling and improve hemodynamics. contraindication for combination ACE inhibitors/beta-blocker therapy is hypotension.
Tachyarrhythmia. Ventricular arrhythmias are usually associated with some degree of myocardial necrosis, fibrosis or ischemia. Atrial tachyarrhythmias are associated with left atrial enlargement. Therefore, antiarrhythmic therapy is advocated particularly when the ventricular rate is rapid.
Massive Left Ventricular Hypertrophy (Severe HCM). Morbidity and mortality is generally increased with greatly increased left ventricular mass (maximal diastolic septal or left ventricular wall thickness > 7mm). Beta- blockers have been the historic drug of choice; calcium antagonists (diltiazem, 7.5 mg bid-tid or Dilacor, 30-60mg sid) may directly improve ventricular diastolic relaxation and filling. Beta-blockers (propranolol, 5mg bid-tid; atenolol, 6.25-12.5mg sid-bid) are the best agents to reduce or abolish dynamic left ventricular outflow tract obstruction. ACE inhibitors may blunt neuroendocrine activation and prevent deleterious remodeling.
"Malignant" Family History (High Risk Genotype). Pedigrees are occasionally identified with heritable patterns of HCM and associated high morbidity and mortality, such as in Maine coon cats. In such animals, early intervention with beta-blockers or calcium channel blockers might be warranted.
Spontaneous Echo Contrast ("Smoke") and Stasis. These echocardiographic findings in the left atrium or left ventricle are associated with blood stasis and is considered to presage thromboembolism.
Syncope. Recurrent cardiovascular syncope can be associated with dynamic LV outflow tract obstruction, hypertrophy, tachyarrhythmia, altered baroreflexes, and ischemia. Negative inotropic drugs that reduce or eliminate obstruction usually decreases or abolishes dynamic outflow obstruction and syncope.
Symptomatic Cats (Congestive Heart Failure)--Initial Therapy (Fist 24-48 Hours)
Goals for acute cardiovascular emergencies are: 1) eliminate congestion (edema, effusions) and associated clinical signs; 2) suppress or abolish serious tachyarrhythmias; 3) improve ventricular relaxation and filling (diastolic function); 4) manage arterial thromboembolism and its consequences; and 5) eliminate syncope or exercise intolerance associated with dynamic LV outflow tract obstruction or tachyarrhythmia. In the severely dyspneic cat, care must be taken to avoid stress.
Furosemide is administered (1.1-2.2 mg/kg PRN, usually q1-4h). The dose is individually titrated to effect to quickly reduce preload and resolve dyspnea. Peak diuresis occurs within 30 minutes of IV administration. Resolution of severe pulmonary edema may be enhanced by adding the preload reducer, 2% nitroglycerin ointment (¼-½ inch q 6-8h cutaneously to the inside of the pinna) [12 hours on, 12 hours off] for the first 24 to 36 hours. Supplemental oxygen (40 to 60 percent oxygen-enriched inspired gas) may improve pulmonary gas exchange. Respiratory distress due to severe pleural effusion requires thoracocentesis.
Symptomatic Cats (Congestive Heart Failure)--Maintenance Therapy
Chronic therapies are optimized to maintain cardiac compensation; prevent arterial thromboembolism; halt, slow, or reverse myocardial dysfunction (theoretically); promote enhanced quality of life; and prolong survival. Underlying conditions and risk factors (e.g., arrhythmias, arterial hypertension, taurine deficient diets, hyperthyroidism, anemia) are treated.
As soon as congestion is reduced and breathing improves, furosemide is changed from IV or IM to the lowest effective oral dose (typically, 6.25-12.5 mg q 12-24h PO).Diuretic dosages can be expediently increased by owners (typically by 1-2 mg/kg) to control acute exacerbations dyspnea due to recurrent pulmonary congestion or pleural effusion. Cats with advanced, chronic CHF presenting for acute exacerbations of congestion are likely to benefit from parenterally administered furosemide which has higher bioavailability, or to the addition of two or more diuretics to furosemide, such as hydrochlorothiazide and/or spironolactone (2mg/kg/day).
Prolonged activation of the sympathetic nervous system may lead to cardiovascular injury that exacerbates disease progression, causes arrhythmias, or stimulates vasoconstriction and secondary tissue anoxia. By decreasing heart rate, ß-blockers prolong diastole and increase passive ventricular filling and ventricular compliance. Prolonged diastolic filling allows more time for coronary blood flow and reduces myocardial ischemia. Dynamic LV outflow tract obstruction and related pressure gradient is often reduced or abolished. Propranolol (5-10 mg q8-12h PO) and atenolol 6.25-12.5 mg q12-24h PO are commonly used.
Calcium Channel Blockers
Calcium antagonists may reduce heart rate (verapamil much more so than diltiazem) and blood pressure; exert a mild negative inotropic effect (reducing myocardial oxygen consumption); and improve rapid diastolic ventricular filling. Conventional diltiazem (Cardizem, 1mg/kg PO tid), long-acting diltiazem (Cardizem CD, 10mg/kg q 24h), and Dilacor XR (30 mg q 24h)are used.
Angiotensin Converting Enzyme (ACE) Inhibitors
Because neurohormonal activation plays an important role in heart failure, disruption of neurohormonal activation should provide therapeutic rationale for using ACE inhibitors. Many clinicians combine an ACE inhibitor (usually enalapril) with furosemide and either a ß-blocker or calcium channel blocker when: right-sided heart failure is present; if pulmonary edema reoccurs; or if progressive atrial enlargement is detected. Enalapril (0.25-0.5 mg/kg q24h PO) and benazepril (0.25-0.5 mg/kg q24h PO) are clinically well tolerated in cats.
RESTRICTIVE CARDIOMYOPATHY (RCM)
Restrictive cardiomyopathy is defined as heart muscle disease that results in impaired diastolic ventricular filling; normal or decreased ventricular diastolic volume; generally normal systolic function; and normal to increased ventricular wall thickness. It represents a spectrum of conditions and as such presents diverse phenotype. From a pathophysiological perspective, the diagnosis of RCM requires Doppler echocardiographic evidence of LV restrictive physiology or LV relaxation abnormality coupled with severe left atrial enlargement, absence of severe LV hypertrophy, and absence of severe left-sided volume overload (e.g., mitral regurgitation). When Doppler echo evidence of diastolic dysfunction is lacking, a presumptive diagnosis of RCM is based upon cardiac morphology, which closely conforms to classic phenotypes of RCM (see echocardiography), and excludes HCM and other cardiomyopathies. A diagnosis of RCM is not tenable in the presence of significant left ventricular dilation.
MYOCARDIAL FAILURE (DILATED CARDIOMYOPATHY)
Systolic dysfunction, myocardial failure or pump failure denotes myocardial disease associated with reduced contractility. In the classic condition of dilated cardiomyopathy (DCM), all four cardiac chambers are dilated, cardiac output is severely reduced, end-systolic and end-diastolic ventricular volumes are increased, and myocardial wall tension is elevated. More commonly, one encounters cardiomyopathies with variable degrees of chamber enlargement and myocardial failure ranging from mild to severe. Congestive heart failure results from both depressed contractility and failure (or overcompensation) of neuroendocrine and other compensatory mechanisms. Prognosis is not simply related to indices of contractility.
ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC)
ARVC is a newly recognized primary myocardial disease in the cat. Pathogenesis is incompletely resolved. This disorder is characterized by progressive atrophy of the RV myocardium with fibrous and/or fatty replacement. Some authors have used dysplasia (i.e., ARVD), a term that implies abnormal tissue growth and differentiation, to describe this disease, but consensus terminology favors ARVC. Many cases of ARVC are misdiagnosed as tricuspid valve dysplasia.
Some myocardial diseases have features that do not fit into a discrete category of HCM, RCM, DCM, or ARVC, or- display characteristics of more than one type of cardiomyopathy. In such cases the term "unclassified cardiomyopathy" is appropriate. This description should be embellished by including a statement to describe the status of systolic function (i.e., normal vs myocardial failure), and if possible, Doppler echocardiographic assessment of trans-mitral filling (i.e., relaxation abnormality, etc).
1. Fox PR. Feline Cardiomyopathies. In Fox PR, Sisson DD, Moise NS (eds): Textbook of Canine and Feline Cardiology Principles and Clinical Practice. 2nd Ed, WB Saunders, Philadelphia, 1999, p621.