Controlling Ventricular Arrhythmias In Boxers

An Ohio State University study on ARVC has helped determine ways to deal with ventricular arrhythmias in boxers.

This column is based on abstracts presented at the 24th annual ACVIM Forum in Louisville (2006).

Ventricular arrhythmias in boxers are quite common. Many dogs can have minimal signs though some can have syncopal episodes or die suddenly.

A familial basis for the arrhythmias has been previously identified and the results published.1 These arrhythmias may be linked to a disease called arrhythmogenic right ventricular cardiomyopathy (ARVC). This disease has been found in humans and cats as well, but only in humans and boxers is it associated with a significant risk of sudden death.

A study at the Ohio State University obtained cardiac workups including 24-hour ambulatory ECGs on  239 boxers. Of these, 23 dogs with substantial ectopy or sudden death were necropsied.2 The necropsy study confirmed that these dogs had heart changes consistent with ARVC.

ARVC is associated with progressive remodelling of the heart predominantly affecting the right atrium and right ventricle, though the left side of the heart can also become involved. Normal heart tissue is replaced with a fatty or fibrofatty infiltrate. Myocarditis is also commonly present.

In many boxers, arrhythmias can be present for many years before signs of heart failure develop, if they do at all. Various treatments have been proposed for these often severe arrhythmias. A commonly used drug is sotalol, which has been shown to be superior to a variety of other drugs.3

The drugs tested included sotalol as a sole agent, procainamide, atenolol or the combination of atenolol and mexilitine. The combination was also very effective at controlling arrhythmias.

Researchers from the University of Florida and the Animal Heart Centers in Miami compared the efficacy of sotalol to the combination of sotalol and mexiltine in 16 boxers.4 A variety of parameters were assessed, including total number of VPCs, ventricular tachycardia, R on T, and syncope.

To be included the dogs had to have at least 500 VPCs in 24 hours and/or a severe arrhythmia (R on T, ventricular tachycardia). In seven of eight dogs treated with the combination, a 85 percent or greater reduction in VPCs was noted; this occurred in only two of seven dogs.

The combination was also 100 percent effective in eliminating ventricular tachycardias and R on T; this only happened in 33 percent of the dogs treated with standalone sotalol. Significant differences in syncope were not noted.

This is a relatively small study, but it does suggest that the combination of mexilitine and sotalol is more effective that sotalol as a sole agent. One downside to mexilitine is that administration generally is recommended three times daily.

It would, of course, be of great interest to carry this study out in more dogs to see if treatments affect syncope and prevent sudden death in these boxers.

Transdermal Atenolol in Cats

Atenolol is a beta blocker that is commonly used in cats with cardiomyopathy. Atenolol has become more popular than propranolol because dosing is less frequent. Unfortunately, in some cats giving pills, even only once daily, is virtually impossible.

Compounding pharmacies have marketed transdermal formulations of many medications, most of which have no efficacy data. Transdermal methimazole can be effectively used, but there is significant variation in the amount of drug needed to control hyperthyroidism in comparison to oral administration.

Researchers from Auburn University and the Massachusetts College of Pharmacy and Health Sciences in Boston looked at plasma concentrations and pharmacodynamic effects of transdermal atenolol in seven healthy cats.5 The cats received either 6.25 mg of atenolol orally or transdermally for one week, and after at least a one week washout period the other formulation. Blood was drawn two and 12 hours after drug administration. An ECG was obtained before and while blood count was obtained to assess the effectiveness of beta blockade.  

Oral and transdermal atenolol lowered resting heart rate at the two-hour mark after being medicated, but not at 12 hours. Stress-associated increases in heart rate were blunted by oral atenolol at the two and 12 hour marks, whereas transdermal atenolol only did this at the two-hour mark.

An equivalent dose of atenolol given transdermally resulted in a plasma atenolol concentration at two and 12 hours after dosing that was only between a third and a fourth that achieved by oral administration.

This study shows that an equivalent dose of atenolol given transdermally is significantly less effective than the same dose given orally. Currently it is unknown what dose of transdermal atenolol is needed to achieve adequate beta blockade in cats.

Spironolactone in Healthy Cats

Spironolactone has commonly been used as a diuretic in dogs and cats. In many instances it is used when diuretics such as furosemide no longer give adequate diuresis.

There also has been some resurgence in interest in this diuretic based on human studies that show it can prolong lifespan in patients with cardiac disease at dosages that have no diuretic effect. A major concern and advantage of spironolactone is that it is a potassium-sparing diuretic.

The combination of an ACE inhibitor and spironolactone could potentially lead to hyperkalemia, especially if the diet is supplemented with potassium.

Investigators from Virginia Tech looked at the effects of spironolactone in nine healthy cats.6 The mean dosage used was 2.7 mg/kg BID for seven to nine days. This dose that would have a diuretic effect is at the upper dosage range suggested.

Significant increases were found in potassium, calcium, creatinine, phosphorus and total protein concentration. In six of the nine cats, potassium concentration exceeded the upper limit of the reference range, but only minimally. Plasma concentrations of spironolactone and its main metabolite were detected after administration of spironolactone.

This study does reveal some interesting information. Spironolactone is absorbed and metabolism does occur. Potassium values do increase and clearly, a cat on this medication should not receive potassium supplementation.

Monitoring of serum chemistries is indicated when using this drug, especially if other drugs are being given that can also increase potassium such as an ACE inhibitor.
Anthony Carr, DVM, Dipl. ACVIM, is an associate professor at the Western College of Veterinary Medicine in Saskatoon, Saskatchewan, Canada.

References

1. Meurs KM, Spier AW, et al. Familial ventricular arrhythmias in Boxers. JVIM 13;437-439:1999.
2. Basso C, Fox PR, et al. Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in Boxer dogs: a new animal model of human disease. Circulation 109;1180-1185: 2004.
3. Meurs KM, Wright NA, et al. Comparison of the effects of four antiarrhythmic treatments in famial ventricular arrhythmias in Boxers. JAVMA 221; 522-527: 2002.
4. Pro_ek R, Estrada A, Adin D. Comparison of sotalol and mexilitine versus stand alone sotalol in treatment of Boxer dogs with ventricular arrhythmias. JVIM 20; 748:2006.
5. MacGregor JM, Rush JE, et al. Transdermal atenolol in cats: plasma concentration and pharmacodynamic effects. JVIM 20; 776: 2006.
6. Abbott JA, Saker KE. Serum chemisty variables of healthy cats receiving spironolactone. JVIM 20; 776-777: 2006.

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