Treatment of Feline Myocardial Diseases
World Small Animal Veterinary Association World Congress Proceedings, 2013
Fiona E. Campbell, BVSc (Hons), PhD, MANZCVSc, DACVIM (Cardiology)
Veterinary Specialist Services, Carrara, QLD; School of Veterinary Science, University of Queensland, Gatton Campus, QLD, Australia

Amongst adult cats, myocardial disease (cardiomyopathy) is the most common form of heart disease. Hypertrophic cardiomyopathy (HCM) is identified in over 60% of cardiomyopathic cats, with the rest attributable to dilated cardiomyopathy, restrictive cardiomyopathy (endomyocardial or myocardial), arrhythmogenic right ventricular cardiomyopathy, and "unclassified" cardiomyopathy.

The criteria by which each form of cardiomyopathy is defined are based on echocardiographically-derived parameters; however, there is some overlap between categories, which results in controversy over the classification of some individuals. Of greater importance for these individuals is correct identification of the type of functional abnormality (e.g., systolic dysfunction, diastolic dysfunction, or both), as this has direct implications for patient management.

While pathophysiology of the feline cardiomyopathies differs, affected cats are at risk for the same three adverse sequelae: congestive failure, thromboembolic event, and sudden death. With the exception of taurine supplementation to cats with taurine-deficient dilated cardiomyopathy,1 there are no therapies that are proven to delay or reduce the risk of adverse events. There are few placebo-controlled clinical drug trials in cardiomyopathic cats, and as such, treatment recommendations are often based on theoretical benefit and anecdotal success.

Treatment of Congestive Heart Failure

Diuretics

Diuretics are indicated for cats with congestive failure irrespective of the classification of cardiomyopathy, to reduce total circulating fluid volume, thereby attenuating the outward transudation of fluid from capillaries that precipitates pulmonary oedema, pleural effusion, and rarely, ascites.

Loop Diuretics (e.g., Furosemide)

Furosemide should be the first-choice diuretic for all cats with congestive heart failure, both chronically PO and acutely via parenteral administration. It acts at the thick ascending Loop of Henle, a region of the nephron that resorbs the greatest proportion (25%) of filtered sodium and water, so it is able to elicit a potent diuresis. In cats with early pulmonary oedema, a dose of 1–2 mg/kg PO SID–BID is often appropriate. This dose can be gradually increased when clinical signs of congestion recur to a total daily dose of 4 mg/kg PO TID. Once maximal doses are achieved, increasing the dose administered orally will not achieve greater diuresis, and a second diuretic is indicated. The exception to this is acute decompensation, whereby parenterally administered furosemide will still be efficacious because of increased bioavailability and likely the additional venodilation properties when given intravenously.2

Thiazide Diuretics (e.g., Hydrochlorothiazide, Chlorothiazide)

The next most potent diuretics available are the thiazide diuretics. These act on the distal tubule and so augment the diuresis produced by furosemide by sequential nephron blockade. Hydrochlorothiazide (HCTZ: 2–4 mg/kg PO BID) or chlorothiazide (20–40 mg/kg PO BID) can be added and titrated upward as indicated by recurrence of congestive signs.

Potassium-Sparing Diuretics (e.g., Spironolactone, Amiloride)

Spironolactone (2–4 mg/kg PO BID) or amiloride can be administered to patients with recurrent congestive signs receiving maximal loop and thiazide diuresis, and these diuretics can be up-titrated as necessary. Although spironolactone will have an additional diuretic effect in patients receiving furosemide and thiazide diuretics through its aldosterone antagonistic effect in the collecting tubules, it is the weakest diuretic,3 and the onset of action is usually 2–3 days. Any theoretical attenuation of myocardial fibrosis that may be mediated by spironolactone's antialdosterone effects has not been demonstrated in cats with HCM, and cats are also at risk of developing ulcerative facial dermatitis with chronic spironolactone administration.4

Thiazide-Potassium Sparing Diuretic Combinations

Aldactazide tablets (hydrochlorothiazide 25 mg and spironolactone 25 mg) or Moduretic tablets (hydrochlorothiazide 50 mg and amiloride 5 mg) are a convenient way to chronically administer combined diuretic therapy. The patient should be dosed according to the hydrochlorothiazide component against a background of maximal furosemide therapy.

Thoracocentesis

Thoracocentesis is the single most important approach to a cat with dyspnoea due to pleural effusion. Thoracocentesis can be performed repeatedly as indicated by recurrence of pleural effusion sufficient in volume to produce dyspnoea. However, in some cats with repeated thoracocentesis, pleural fibrosis will limit lung expansion post-centesis, and tears in the visceral pleura can result in iatrogenic pneumothorax. In my experience, this occurs very rarely, and cats will tolerate repeated thoracocentesis surprisingly well. Each time thoracocentesis is performed, and if the patient is not markedly azotemic, the dose of diuretic should be increased (or a second or third diuretic added) to attempt to delay recurrence.

Thoracocentesis Method

1.  Equipment

a.  21-gauge butterfly catheter

b.  1 X 3-way tap

c.  1 X short IV extension set (75 cm or less); a clean, used IV line can be used and cut short

d.  20-mL syringe

e.  Measuring jug or kidney dish

2.  Technique

a.  Lightly restrain the cat in sternal recumbency. Often dyspnoeic and orthopnoeic cats will squat sternally, and thoracocentesis can readily be performed in the cat in this position if the forelimb is extended slightly forward. Sedation is rarely necessary.

b.  Clip the coat over the ventrolateral thorax.

c.  Use ultrasound guidance to choose a region ventrally where there is a large anechoic space or blindly select a region between the 6th–9th rib in the ventral 1/3rd of the thorax and sterilize with alcohol.

d.  To the 3-way tap, attach the butterfly catheter, the 20-mL syringe, and the extension set. Tape the end of the extension set to the inside of a measuring jug or kidney dish.

e.  Insert the butterfly catheter into the thorax at 45–90 degrees to the thoracic wall with the bevel facing into the chest. Insert right up to the hub and tip the butterfly wings dorsally until they lay against thorax. Local anesthetic is not necessary.

f.  Remove all the fluid possible. Typically, 150 mL or more must be removed to ease dyspnoea in a cat with pleural effusion. The mediastinum in cats is fenestrated, so repeating thoracocentesis on the other side is not usually necessary.

Inotropic Agents

Atenolol (6.25–12.5 mg/cat PO BID) is commonly used in cats with hypertrophic cardiomyopathy (HCM). It may be considered for patients with HCM that have high resting heart rate, moderate-severe left ventricular outflow tract obstruction, ventricular arrhythmias, or atrial fibrillation. By increasing diastolic time and attenuating dynamic left ventricular outflow tract obstruction, atenolol aims to delay onset of congestive failure and, for congestive patients, it may minimize diuretic requirement. As a class II antiarrhythmic, atenolol may also reduce risk of sudden arrhythmogenic death. However, these theoretical benefits remain unproven in clinical patients (Fox P. Unpublished abstract. ACVIM Forum; 2002).

Diltiazem (7.5 mg/cat PO TID) can be used in those rare individuals with concurrent asthma where atenolol may be problematic (beta2-adrenergic cross-reactivity may cause bronchoconstriction). However, diltiazem will not control ventricular arrhythmias, and it may precipitate undesirable gastrointestinal side effects in some individuals.5

Pimobendan (0.625–1.25 mg/cat PO BID) is not registered for use in cats, but it can safely be used off-label for cats that have developed congestive heart failure associated with systolic dysfunction.6

Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are indicated in patients with congestive heart failure to blunt the neurohormonal activation exacerbated by diuretic reduction in circulating fluid volume. While an ACE-inhibitor is not a diuretic, it does antagonize aldosterone-mediated sodium and hence, water retention. Several studies have assessed the use of ACE inhibitors in cats with congestive heart failure with varied results reported.7-9 No benefit has been demonstrated in long-term administration of ACE inhibitors to cats with pre-congestive hypertrophic cardiomyopathy.10

Amlodipine

Amlodipine is a vascular-specific calcium channel blocker that is an effective orally administered vasodilating agent. It is indicated for cats with hypertrophic heart disease that are hypertensive (systolic blood pressure > 160 mm Hg), whereby the reduction in afterload aims to reduce the stimulus for compensatory concentric hypertrophy. It should be dosed at 0.625 mg or 1.25 mg/cat SID PO. Due to slow onset of action, upward titration should be performed at weekly intervals as guided by repeated blood pressure measurement. The goal is to reduce systolic blood pressure below 150 mm Hg.11,12

Feline Aortic Thromboembolism (FATE)

Systemic thromboembolism develops in 20–40% of cats with cardiomyopathy. Emboli form in the dilated left atrium where a combination of stagnating blood in the dilated left auricular appendage together with disease of the endomyocardium and hypercoagulability facilitate thrombus formation. Systemic embolization of the thrombus is typically to the aortic trifurcation, producing sudden onset of hind-limb paralysis.

Palliative/Supportive Care

Analgesia is important in the immediate post-FATE period, and narcotic agents should be employed. Sensory nerve lesions become complete within several hours of the ischaemic event, so pain relief more than 48 hrs after the event is unlikely to be warranted. Monitoring in the acute post-FATE period is necessary to identify common fatal complications, including congestive heart failure and reperfusion hyperkalaemia. Continuous ECG monitoring is optimal, because it allows rapid identification of worsening hyperkalaemia (more so than intermittent serum K+ determination), facilitating treatment to reduce serum K+ (insulin, glucose) and cardio-protect (calcium gluconate); however, the success of such aggressive monitoring is typically limited to ICU referral facilities. Thoracic radiographs should be performed in any tachypnoeic patient that is presumed to be pain-controlled, to identify those cats developing pulmonary oedema during hospitalization.

Definitive Treatment

There have been many treatments/interventions aimed at removing the aortic thromboembolism, but none have proven superior to conservative management. This is likely because thrombolytics (e.g., tissue plasminogen activator, streptokinase) and mechanical clot removal methods (e.g., balloon embolectomy, thrombectomy, rotor embolectomy/thrombosuction) pose the risk of fatal reperfusion injury when thrombus removal facilitates perfusion of necrotic myocytes and acute severe hyperkalaemia. Mechanical techniques also necessitate high-risk general anesthesia, and streptokinase poses a risk of systemic haemorrhage. Furthermore, these methods all fail to attenuate underlying cardiac disease, and survivors remain at imminent risk of recurrent event.13,14

Anticoagulant/Antiplatelet Therapy

Fractionated heparins (dalteparin and enoxaparin) administered to normal cats have proven efficacy at clotting factor inhibition with superior safety compared to unfractionated heparin. However, these drugs have not been trialed in feline patients with cardiomyopathy, so studies of clinical efficacy are currently lacking. Their disadvantages are cost (> $AUD200 per week/cat) and the need for injection by the owner subcutaneously up to four (enoxaparin) to six (dalteparin) times daily.15,16 The author primarily recommends fractionated heparin for cats that have already experienced a thromboembolic event and are at known risk for repeat event.

Clopidogrel is a platelet ADP-receptor inhibitor. Pharmacodynamic studies in healthy cats demonstrate its ability to impair platelet aggregation without the unwanted side effects associated with aspirin.17 Dosed at 18.75 mg/cat SID, it costs around $AUD50/month to the owner. The FATCAT trial is a large multicentre study currently underway in North America that aims to assess the efficacy of this medication at reducing the risk of recurrent thromboembolism in affected cats. At this time, the author prescribes clopidogrel for all cats with moderate-severe left atrial enlargement and for all post-FATE cats in conjunction with fractionated heparin.

References

1.  Pion PD, Kittleson MD, Rogers QR, Morris JG. Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science. 1987;237:764–768.

2.  de Berrazueta JR, Gonzalez JP, de Mier I, Poveda JJ, Garcia-Unzueta MT. Vasodilatory action of loop diuretics: a plethysmography study of endothelial function in forearm arteries and dorsal hand veins in hypertensive patients and controls. J Cardiovasc Pharmacol. 2007;49:90–95.

3.  Jeunesse E, Woehrle F, Schneider M, Lefebvre HP. Effect of spironolactone on diuresis and urine sodium and potassium excretion in healthy dogs. J Vet Cardiol. 2007;9:63–68.

4.  MacDonald KA, Kittleson MD, Kass PH, White SD. Effect of spironolactone on diastolic function and left ventricular mass in Maine Coon cats with familial hypertrophic cardiomyopathy. J Vet Intern Med. 2008;22:335–341.

5.  Wall M, Calvert CA, Sanderson SL, Leonhardt A, Barker C, Fallaw TK. Evaluation of extended-release diltiazem once daily for cats with hypertrophic cardiomyopathy. J Am Anim Hosp Assoc. 2005;41:98–103.

6.  Macgregor JM, Rush JE, Laste NJ, et al. Use of pimobendan in 170 cats (2006–2010). J Vet Cardiol. 2011;13:251–260.

7.  Rush JE, Freeman LM, Brown DJ, Smith FW Jr. The use of enalapril in the treatment of feline hypertrophic cardiomyopathy. J Am Anim Hosp Assoc. 1998;34:38–41.

8.  Amberger CN, Glardon O, Glaus T, et al. Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy results of a prospective, open-label, multicenter clinical trial. J Vet Cardiol. 1999;1:19–26.

9.  Taillefer M, Di Fruscia R. Benazepril and subclinical feline hypertrophic cardiomyopathy: a prospective, blinded, controlled study. Can Vet J. 2006;47:437–445.

10. MacDonald KA, Kittleson MD, Larson RF, Kass P, Klose T, Wisner ER. The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure. J Vet Intern Med. 2006;20:1093–1105.

11. Brown S, Atkins C, Bagley R, et al. Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med. 2007;21:542–558.

12. Snyder PS, Sadek D, Jones GL. Effect of amlodipine on echocardiographic variables in cats with systemic hypertension. J Vet Intern Med. 2001;15:52–56.

13. Reimer SB, Kittleson MD, Kyles AE. Use of rheolytic thrombectomy in the treatment of feline distal aortic thromboembolism. J Vet Intern Med. 2006;20:290–296.

14. Pion PD. Feline aortic thromboemboli and the potential utility of thrombolytic therapy with tissue plasminogen activator. Vet Clin North Am Small Anim Pract. 1988;18:79–86.

15. Alwood AJ, Downend AB, Brooks MB, et al. Anticoagulant effects of low-molecular-weight heparins in healthy cats. J Vet Intern Med. 2007;21:378–387.

16. Van De Wiele CM, Hogan DF, Green HW 3rd, Sederquist KD. Antithrombotic effect of enoxaparin in clinically healthy cats: a venous stasis model. J Vet Intern Med. 2010;24:185–191.

17. Hogan DF, Andrews DA, Green HW, Talbott KK, Ward MP, Calloway BM. Antiplatelet effects and pharmacodynamics of clopidogrel in cats. J Am Vet Med Assoc. 2004;225:1406–1411.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Fiona E. Campbell, BVSc (Hons), PhD, MANZCVSc, DACVIM (Cardiology)
Veterinary Specialist Services
Carrara, QLD, Australia


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