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Introduction ...Description...Etiology....Pathophysiology...Clinical Signs...Diagnosis...Treatment

.The author wishes to acknowledge VIN cardiology message board and library as well as the publication by John E. Rush, DVM, MS in: Veterinary Clinics of North America, Nov. 1998, pp1459 for much of the information displayed on this page.

Feline cardiomyopathies are of several kinds. Dilated and Hypertrophic Cardiomyopathies are the most common. Dilated cardiomyopathy has been linked to nutritional deficiencies (e.g. taurine) and today is much less common than the Hypertrophic or variants of Hypertrophic Cardiomyopathy. Idiopathic Restrictive (and Endomyocarditis-related, excessive moderator band-related and endomyocarditis-related) Cardiomyopathy is uncommonly diagnosed (or misdiagnosed) and can results from distortions of papillary muscle and/or chordae tendonae, either of which may become fused and/or distorted due to inflammatory cell infiltration and fibrous adhesions. Signs of left atrial dilatation and ventricular hypertrophy may mimic those of hypertrophic (and dilated) cardiomyopathies. In addition to the above specific cardiomyopathies, cats can also develop valvular disorders, some of which are idiopathic in etiology. .

Hypertrophic Cardiomyopathy, (HCM) may be primary (idiopathic) or secondary to other (metabolic) causes (excess cathecholamines, hyperthyroidism, acromegaly, hypertension). The remainder of this discussion will focus on the anatomical and physiological manifestations, the diagnosis and proposed treatment of Feline Hypertrophic Cardiomyopathy. However, there will be some discussion of the other disorders introduced above, particularly as they may relate to complications in the diagnosis (or misdiagnosis) and/or treatment of HCM.

Description: Feline Idiopathic Hypertrophic Cardiomyopathy (HCM) is present when there is left ventricular cardiac free wall, interventricular septum with or without papillary muscle hypertrophy due to no identifiable cause. Secondary hypertophic cardiomyopathy can…and does …occur in cats with systemic hypertension (secondary to renal, adrenal, pituitary or thyroid illness) or valvular (aortic) stenosis. Muscle hypertrophy is most often concentric, but can be predominantly of the free wall or the interventricular septum (Figure 1). In the latter instance, there may be protrusion of septum and mitral valve leaflets into the outflow tract (Figure 2).

Etiology : The idiopathic form of HCM may have a heritable basis, possibly aberrant genes encoding for altered sarcomeric proteins. Evidence suggesting this is based upon limited studies in Main Coon, Persian and American Shorthair breeding populations.

Pathophysiology : The interrelationship of events in the pathophysiology of HCM is schematically represented in the a somewhat crude way below:

When selective interventricular septal thickening causes partial left outflow obstruction, ejection through the narrowed outflow tract results in turbulence that, in essence, "sucks" the anterior mitral valve leaflet into the ejection flow; this further impedes ejection and exacerbate mitral regurgitation and its effects (Figure 2).

Clinical Signs:

Presenting signs are variable and can be subtle or profound. The owner may simply describe a shy ("hiding a lot"), lethargic, anorectic animal…or… an animal in the throws of acute congestive heart failure (CHF). In the latter instances, severe or moderate respiratory distress (tachypnea, dyspnea), apparent paresis/paralysis, syncope, anorexia and vomition are possible. Occasionally, an animal in which HCM is present is assymptomatic ; in these either HCM is in the early stages or positive compensatory hemodynamic changes are active.

The routine physical exam may reveal a murmur and/or gallop rhythm with a prominent apex beat in an assymptomatic patient…and/or…if CHF is present, pulmonary crackles (edema), muffled heart sounds (effusions), cyanosis, apparent paresis associated with cold extremities (arterial thromboemboli) and vocalization (pain). If right-sided involvement is present, mild ascites, mild to severe pleural effusion, hepatomegaly and jugular distension may be found.

Diagnosis of Primary HCM:

1. Rule out secondary causes of cardiomyopathy

• Systemic blood pressure is normal
• T_{4 ..}is normal

2. Ascertain presence of characteristic echocardiogram

• Interventricular septum and left ventricular free wall thickness' in normal cats are each 0.55-0.6cm. In cats with HCM these are often > 0.9cm

• Doppler (or color flow doppler) may reveal turbulence in the left ventricular outflow tract and in the proximal aorta due to:

1. Partial outflow obstruction and increased pressure gradient secondary to thickened septum, and to
2. Systolic anterior motion….this is descriptor for motion of anterior mitral valve leaflet into the left ventricular outflow tract during systole

• Left atrial enlargement (there is increasing risk of turbulence and arterial thrombus with increasing size; this is visualized as "swirling" or "smoke" on the echocardiogram)

• A normal aortic diameter of ~ 1.0cm;

1. A small aorta is indicative of either severe forward heart failure (which should be accompanied by corresponding clinical signs) or a congenital defect (e.g. aortic stenosis).
2. When a small aorta is present, compensatory left ventricular hypertrophy may occur which could be confused with primary HCM.

3. Radiographic Findings

• Enlarged left atrium

• Enlarged pulmonary artery/vein (on dorso-ventral position)

• Tortuous pulmonary vein from caudal lobes…as visualized on lateral view.

• Pulmonary edema, effusion(s).

4. Electrocardiography

• Many (or no) arrythmias may be detected: ventricular & supraventricular tachycardias, atrial fibrillation, atrioventricular block
• Bradycardia can be found in hypothermic animals
• Left axis shift, Bundle-Branch blocks

Treatment Options: Remember that the goals of therapy are:

• Treat Congestive Heart Failure if present; treat/prevent thromboembolization
• Improve diastolic (and to some extent, systolic) function via pharmacological intervention. The principal approach towards this end is to slow the heart rate to permit greater diastolic filling.

1. ß-Blockers:

• Propanolol: is ß₁ & ß₂ blocker

  Additional Benefits

  Decreases heart rate, supraventricular and ventricular arrythmias

  Decreased inotropy--> reduced outlow turbulence and exacerbation of obstructopathy

  Other Considerations

  Is non-selective ß-blocker & may have negative effects on ß₂ airway and vascular receptors

  Requires TID dosing

  Dose: 2.5-5mg (sometimes up to 10mg)/cat TID

• Atenolol: is selective ß₁ receptor blocker

Additional Benefits

as for propanolol but without potential ß₂ blockade and associated respiratory and vascular side effects.

Only requires SID dosing

Dose: 6.25mg (up to 12.5mg, rarely)/cat SID..titrate to effect.

2. Calcium Channel Blockers

• Calcium Channel Blockers: Many to choose from

Additional Benefits

Coronary vasodilation results in increased myocardial perfusion

Mildly negative inotrope…theoretically reduces the probability of ventricular outflow turbulence and exacerbation of obstructopathy.

Other Considerations

Theoretically, though, vasodilation and reduced afterload could increase the probability of ventricular outflow turbulence, with concomitant increase in systolic anterior mitral valve displacement

Some forms require TID dosing

 

Drug Examples:

• Diltiazem (Cardiazem^®); Dose is 0.5-1.5mg /kg TID

• Diltiazem Extended Release Capsules (Dilacor XR^®): Note that each capsule contains four 60mgtabs; Dose is 1/2 of 60mg tab (30mg) BID (NOT SID as sometimes recommended).

• Verapamil : there appears to be minimal clinical experience with this drug in the treatment of feline cardiomyopathies.

• Additional Therapeutic Considerations in the Managment of HCM and Heart Failure

 

1 Diet: Low sodium diet

2 Heart Rate Control: Dr. Rush prefers either Diltiazem or Atenolol. Dilacor is the extended release version of Diltiazem..the dosages have been previously given.

3 Diuretic: Furosamide is the diuretic of choice..at least initially in the treatment of congestive heart failure (CHF). If in acute, severe CHF, 4mg/kg IV qhr can be given to effect. However it is essential to reduce the dose of this drug in the long term management, especially if there is concurrent employment of an ACE inhibitor,such as enalapril. That is because there is tremendous potential for electrolyte disturbances (e.g. potassium, calcium depletion), hypovolemia and/or azotemia with overzealous use of this type of diuretic. Dr. Rush suggests dosages of 6.25mg every other day to 6.25mg q12-24hr (the higher dose more likely required whenthere is pleural effusion). When used with an ACE inhibitor, consider lowering the dose to 0.25mg/kg q12-24hr, and monitoring renal parameters such as BUN, Creatinine a couple of times at 2-3 day intervals after beginning and/or adjusting the doses of these medications. If furosmide is causing electrolyte embalances, with resultant refractory heart failure consider changing or adding another diuretc such as spironolactone or hydrochlorothiazide.

4 Thrombus Prevention:

• Any time there is enlargement of left atrium, there is increased risk of thromboembolization.

• In assymptomatic animal with mild left atrial enlargement the use of low-dose aspirin may be appropriate prophylactic "antithrombolinergic". Some doubt the efficacy of aspirin for this purpose and there is anecodotal reports thay once there is a history of thrombus formation, aspirin is not useful in altering the probability of recurrence.

• Sodium Warafarin/ Coumadin blocks the Vitamin K-dependent clotting factor synthesis.Considered more potent than heparin, it is used in cats where there is either a history of recurrent throboembolizarion or there is severe left atrial enlargement...and thus considerable risk of ocurrence. Initiation of therapy should be concurrent with heparin for at least 48 hr. Recommended dosages are 0.25mg/cat q48hr to 0.5mg/cat q24-48hr. Again, monitor PT after initiating or changing doses of the drug every few days for 2-3 weeks, then weekly for a month then monthly. Additionally, it is imperative that treated cats be indoor-only and that anytime a cat is judged to be "ain't doin' right" (lethargic, weakness) by the owner the veterinarian should assume the worst case scenerario (i.e. hemorrage) and treat the situation as a potential emergency.

 

5 ACE Inhibitor: To be discussed shortly...based on recent (April 11th) roundtable on Feline Hyperthyroidism sponsored by Daniels Pharmaceuticals and on information obtained from other roundtable discussions of HCM and from the veterinary database on the Veterinary Information Network (VIN).....

6 Thrombus Treatment...Acute:

• Ideally, goals should be to increase collateral circulation, prevent further thromboembolization and to reduce or eliminate existing thombi.

• It is believed that during distal aortic embolus formation there release of a serotonin intermediate that effects nearby vasoconstriction and secondarily loss of function of the rear limbs. However some drugs which have been used for their vasodilatory properties....e.g. Acepromazine, actually make matters worse, as often there is secondary hypotension and worsening of perfusion of the distal tissues as well as other tissues and organs. Though theoretically sound, there is presently no data to support the use of any drug specifically to enhance the collateral circulation via vasodilation.

• Prevention of further thrombus formation or thrombus enlargement is most commonly affected by therapeutic heparin administration. If used without additional (e.g. thrombolytic) drugs, Dr. Rusch suggests that high doses, 200IU-300IU/kg, be administered every 6-8hr subcutaneously or intravenously in the cranial i/2 of the body. Ideally, this treatment results in PT times that are no more than 1 1/2 to 2 times the baseline (determined before initiation of heparin treatment) value. The PT should be monitored every 24 hours (Dr. Rush feels that if the lower end of the dose range is used, frequent monitoring of PT is unnecessary).

• Thrombolytic Agents: these include streptokinase and tissue plasminogen activator. With either agent reperfusion injury (from severe metabolic acidosis and hyperkalemia ...with effects on metabolic and electro-cardiovascular parameters) resulting in death is likely! With streptokinase, there is non-specific activation of all plasminogen to plasmin with resultant non-specific degradation of fibrin into fibrin split products. This drug has the potential to cause life-threatenting systemic hemorrhage. Tissue plasminogen activator differs from streptokinase in that it specifically activated fibrin-bound fibrinogen only. Thus there is considerably less risk of a hemorrhagic diathesis. However with both streptokinase and tissue plasminogen activator, the effects of reperfusion are frequently devastating (= or > 50% of cats die when treated with these drugs) and in the case of the "safer" drug (the tissue plasminogen activator) the cost is usually prohibitive anyway.

7 Long-Term Thrombus Prevention: The use of aspirin or warfarin, as descibed above is based upon perceived risk (e.g. size of left atrium, recurrence of aortic thrombi).

More information and a downloadable, anatomical/physiological descriptions of the disease can be obtain here