Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden
The discovery of cardiomyopathy in a cat often means that the veterinarian and the owner have to make a decision how to manage the condition. Preferably, this decision should be based on results from clinical trials. Unfortunately, therapeutic clinical trials in cats are few and this means that decisions and treatment recommendations are often based on extrapolation of results from human clinical trials, expert opinion, and own experience. In the absence of clinical trials, treatment strategies are bound to be controversial, and this is certainly the case for feline cardiomyopathy, particular in managing cats with subclinical cardiomyopathy. This presentation will outline the most commonly instituted treatments of cats with subclinical and clinical cardiomyopathy.
Feline cardiomyopathy is often discovered in clinically healthy cats as an incidental finding or as a consequence of screening for hypertrophic cardiomyopathy (HCM). Chronic therapy is often initiated in these cats to reverse or slow the progression of hypertrophy, in case of HCM, because there is a pressure on the veterinarian to do something, because of theoretical benefit, because an absence of evidence of efficacy is not the same as evidence of inefficacy, and because the rate of unwanted side reactions for the most common treatment choices are low. The drugs that are most commonly used in this setting are beta-blockers, ACE-inhibitors and calcium channel blockers, but pimobendan has gradually become more frequently used. A finding of an enlarged left atrium with or without an atrial thrombus or spontaneous echocardiographic contrast (smoke) means that antithrombotic therapy is indicated.
Several reasons have been suggested for using beta receptor blockers in subclinical HCM. The tendency for veterinary specialists to introduce beta-blockade in subclinical disease increases if systolic anterior motion (SAM) of the mitral valve is present. This phenomenon leads to a dynamic subaortic stenosis and mitral regurgitation, and it is a common finding in cats with HCM. Beta-receptor antagonism leads to a reduction of the dynamic outflow obstruction and a slowed heart rate. Beta-blockers may be indicated in HCM for its antiarrhythmic properties. The most commonly used beta-receptor antagonists used in veterinary medicine include: atenolol (6.25–12.5 mg/kg/cat q12h PO) and propranolol (0.4–1.2 mg/kg q8h PO). A recent study reported no long-term (5 years) benefit of atenolol on pro longing the pre-clinical period or survival compared to no treatment.
The rationale for using an ACE-inhibitor in subclinical HCM is to pharmacologically suppress the activity of the renin-angiotensin-aldosterone system (RAAS), and by doing so, counteract progressive myocyte hypertrophy and fibrosis. It has been shown that circulating levels of components of RAAS is increased in cats with HCM, especially after the onset of congestive heart failure. This data provides a theoretical background for efficacy of ACE-inhibitors in subclinical HCM, and ACE-inhibitors are widely used in this setting. The clinical studies concerning the effect of ACE-inhibitors on degree of hypertrophy in cats with HCM shows conflicting results, and there is no published study showing a beneficial effect of ACE-inhibitors on quality of life variables and survival.
Calcium Channel Blockers
Diltiazem is a drug with failing popularity among veterinary cardiology specialists. The rationale for using calcium-channel blockers is subclinical HCM is that diltiazem has been suggested to lessen edema formation and decrease wall thickness in cats with HCM. Furthermore, calcium channel blockers have been suggested to improve diastolic function (improved relaxation) and reducing ischemia. Exactly how these drugs cause an improved diastolic function is currently not completely understood. However, both the systolic and diastolic abnormalities may be related to abnormal calcium kinetics, and drugs that block the inward transport of calcium over the myocardial cell membrane may be able change this abnormality in a positive way. The most commonly used calcium-channel blocker in cats is diltiazem, which is also available as a slow-release product. The pharmacokinetics has been described for both formulations. The doses described in cats are diltiazem 7.5 mg/cat q8h PO and sustained release diltiazem (Dilacor XR) 30 mg/cat q12h PO and (Cardizem CD) 10 mg/ kg q24h PO. In many European countries, diltiazem is only available in 60 mg tablets, which is very impractical.
The pharmacokinetics of oral pimobendan has been studied in cats, and the drug appears to have longer elimination half-time and higher maximal drug concentrations in cats compared to dogs. The dose most frequently used is 0.625–1.25 mg PO q12h. The drug does produce similar cardiovascular effects; i.e., increased inotropy and a reduction in systemic arterial resistance, in cats as in other species. The drug has become more frequently used, particularly in cardiomyopathic non-obstructed cats. One case series report of worsening of syncopal episodes in severely obstructed cats receiving pimobendan. To the contrary, another retrospective study showed a significant survival benefit in pimobendan treated cats versus those receiving other treatments. There is one placebo controlled clinical trial completed in cats with cardiomyopathy, but the results are not yet published.
Cats with clinical signs of CHF should be managed symptomatically. The required dose of furosemide depends on the severity of dyspnea. In the acute phase, cats often require an approximate dose of 2–3 mg/kg IV, SC or IM q2–6h to reduce the resting respiratory rate to less than 50/min. Oxygen supplementation is often required, and cats with significant pleural effusion may require thoracocentesis. It is important that cats with significant dyspnea is not stressed, for example struggling during acquisition of thoracic radiographs. These procedures should preferably wait until the condition has stabilized. Some cats may need sedation with a low dose of acepromazine (0.05 to 0.1 mg/kg IV) to produce anxiolysis. Once the condition has stabilized, the furosemide dose should be reduced as much as possible to avoid dehydration, electrolyte disturbances and renal failure, which should all be monitored. Should the cat be severely de hydrated, small volumes of intravenous fluid may be administered, but with caution because of the significant risk of aggravating the pulmonary edema. Oftentimes the maintenance dose of furosemide is approximately 1–4 mg/kg q8–24h PO or lower. It is useful to instruct the owner to count the respiratory rate at home in order to monitor the cat. It is controversial which other drugs that could be added to the furosemide treatment: beta-blocker, calcium-channel blocker, ACE-inhibitor or pimobendan. There is currently one, unpublished study, comp rising 118 cats receiving one of atenolol, diltiazem, enalapril or placebo together with furosemide. Study end-points were recurring heart failure and death. The results showed no significant benefit of any of these 3 treatments over furosemide treatment alone. However, there was a trend for a worse prognosis for cats receiving beta-blocker together with furosemide did worse than the other 3 groups, a finding that drastically reduced the use of beta-blockers in cats with signs of CHF. Again, pimobendan has become an increasing popular choice of treatment, particularly in non-obstructed cats. With aggravating heart failure, the addition of a second diuretic, such as spironolactone 1–2 mg/kg PO q12–24h, or hydrochlorothiazide 1–4 mg/ kg PO q12h, could be considered. At this stage, it is common for cats to be mildly dehydrated and mildly to moderately azotemic, as a consequence of the disease and the diuretic therapy, but otherwise act normally and eat and drink. However, it is often not possible to lower the diuretic dose because that would lead to recurrence of pulmonary edema. Potassium supplementation should be considered in cases where clinical signs are present that could indicate clinically significant hypokalemia.
The level of evidence for different treatments of cats with cardiomyopathy is low, and there is a general lack of large prospective placebo-controlled clinical trials. Treatment is therefore often based on opinions and own experiences. For the adjunctive treatments to furosemide, beta-blockers and calcium channel blockers are less frequently used, whereas pimobendan has become more popular. Cats in CHF should be handled gently, to minimize stress, be administered furosemide and have pleural effusion evacuated (if present).
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