Myxomatous mitral valve disease (MMVD) is a chronic degenerative condition of typically the mitral valve, however other valves may also be involved. Valvular insufficiency leads to increased atrial pressures and congestive heart failure (CHF). Chronic volume overload results in myocardial failure. Atrial and ventricular stretch may result in arrhythmias. Ruptured chordae tendineae and atrial tears are not infrequent complications of this disease.
In order to rationally select appropriate therapy and provide an accurate prognosis, it is advantageous to stage the degree of heart failure. A system for staging heart failure in animals was recently developed by the International Small Animal Cardiac Health Council. The three stages and their criteria are as follows:
The asymptomatic patient--heart disease is detectable but there are no clinical signs. A cardiac murmur, arrhythmia and radiographic changes may be present.
Mild to moderate heart failure--clinical signs of heart failure are evident at rest or with mild exercise.
Advanced heart failure--there are critical clinical signs including respiratory distress, marked ascites, and profound exercise intolerance.
With each advancing stage the prognosis worsens and the need for treatment increases. There has been considerable controversy in recent years as to which drug to use at the different stages of the disease.
ISACHC Stage 1
The SVEP trial and the VetProof trial looked at the use of angiotensin converting enzyme (ACE) inhibitors versus placebo in the treatment of dogs with slight to moderate MMVD without signs of heart failure; in both trials the results showed no significant difference between the groups in the primary end point, time to onset of congestive heart failure. The dogs in the SVEP trial were all cavalier King Charles spaniels (CKCSs), in the VetProof trial there were a variety of dog breeds.
There is considerable interest in the early use of beta receptor antagonists in this stage of the disease. A recent study looked at the time to onset of clinical signs in ten CKCSs in ISACHC stage 1 treated with carvedilol, a third generation beta receptor antagonist. The results were compared to the results of the SVEP trial and the time to onset of clinical signs was found to be shorter with carvedilol. There has also been speculation in the veterinary literature as to the early use of spironolactone, an aldosterone inhibitor, because of the role of aldosterone in cardiac remodelling. However no clinical trials have been undertaken to date using this drug at this stage of the disease.
A recent trial in a small number of beagle dogs comparing benazepril to pimobendan at this stage of the disease suggested pimobendan may have an adverse affect, however further trials are required to validate these findings.
Thus, at the moment, no treatment has been shown to delay the onset of clinical signs in this group of dogs.
ISACHC Stages 2 and 3--Long Term Management
The traditional therapy of dogs with MMVD in CHF before the 1990s was based on the use of diuretics to decrease preload and cardiac glycosides for their negative chronotropic and positive inotropic effects.
ACE inhibitors were introduced for the treatment of CHF in dogs in the 1990s. ACE inhibitors result in vasodilation, decreased sodium retention, decrease in fluid retention and decrease in sympathetic tone. Clinical trials have supported the efficacy of ACE inhibitors in the treatment of CHF in dogs with MMVD. They have shown improved clinical score of severity of heart failure when added to other heart failure therapy. They have also been shown to decrease treatment failure, whether due to death, euthanasia or worsening heart failure in dogs in CHF with MMVD.
In recent years pimobendan has been used as an adjunctive therapy in the treatment of CHF in dogs. It is an inodilator, combining positive inotropic and vasodilator effects through selective inhibition of phosphodiesterase 111 and V and sensitization of contractile proteins to calcium. It also is lusitropic, suppresses platelet aggregation and decreases plasma levels of cytokines. Initial clinical trials focused on the use of pimobendan in dogs with dilated cardiomyopathy, however in recent years there has been considerable focus on the use of pimobendan in dogs with MMVD in CHF.
A six month trial undertaken at the University of Edinburgh showed a significant decrease in adverse events (death, euthanasia or withdrawal) in MMVD dogs in CHF treated with pimobendan and frusemide compared to dogs treated with ramipril and frusemide. The Vetscope trial, a prospective double blinded, positive controlled, randomised multi-centre trial of pimobendan versus benazepril in MVD dogs in CHF has shown a significant decrease in ISACHC grade and increased survival in the pimobendan group compared to the benazepril group. The results of the recently completed Quest trial comparing benazepril and pimobendan should be available in the near future.
There is mounting evidence for the use of pimobendan in the treatment of dogs with MMVD in CHF. What is missing from the literature at the moment is the long term effect of combination therapy with ACE inhibitors and pimobendan in this group of dogs.
Heart Rate Control
Heart rate control is important in heart failure, as heart rate appears to be a major contributor to myocardial remodelling and systolic function. Traditionally digoxin has been used for its combined negative chronotropic and positive inotropic properties in dogs with MMVD in CHF. More recently attention has focused on the use of beta receptor antagonists to control heart rate and in the long term improve systolic function. Beta receptor antagonists are poorly tolerated in the presence of CHF and the dose has to be titrated up carefully. A recent study has shown improved quality of life and functional classification score in dogs treated with carvedilol however no effect on heart rate was found. At the moment digoxin still remains the drug of choice for heart rate control in MMVD dogs in CHF.
Diuretics and Diet
Frusemide is a powerful natriuretic and remains the diuretic of choice in the treatment of CHF. Frusemide stimulates aldosterone release even in the presence of ACE inhibitors and thus in recent years there has been considerable interest in the use of spironolactone as an additional diuretic. Controversy remains as to when this drug should be introduced into the treatment regime. In end stage MMVD, studies have shown that there is reduced activity of the renin angiotensin aldosterone system, so earlier introduction of spironolactone may be more appropriate. Torasemide is a novel loop diuretic presently under investigation which may have advantages over frusemide in the treatment of congestive heart failure.
Sodium restricted diets have been used in the management of CHF. The optimal time to initiate a cardiac diet and the ideal sodium levels relative to the severity of heart disease are areas which still require further research.
ISACHC Stage 3--Acute Decompensation and Refractory Cases
Acute decompensation is frequently due to ruptured chordae tendineae and results in acute increase in left atrial pressure and pulmonary oedema. Intravenous frusemide, cage rest and oxygen remain the cornerstones of therapy. Recent work has shown that constant rate infusions of frusemide may be more potent than intermittent intravenous boluses.
Percutaneous glyceryl trinitrate causes venodilation and has been used to decrease left atrial pressures and relieve signs of pulmonary congestion. No clinical trials have been undertaken to demonstrate efficacy in dogs however there are numerous anecdotal reports of response. In severe refractory CHF the combination of nitroprusside with dobutamine constant rate intravenous infusions may be life saving, however both these drugs require intensive monitoring.
Once stabilized the challenge is to successfully wean animals onto oral medication. In addition to the therapies mentioned earlier (frusemide, spironolactone, digoxin, ACE inhibitor, pimobendan) hydralazine and amlodipine have been also used in selective cases to further decrease mitral regurgitation. Hydralazine is a potent arterial vasodilator and dose rate needs to be titrated up cautiously or profound hypotension may occur. Persistent pleural effusion may be a problem in some refractory cases and repeated thoracocentesis may be indicated. Severe ascites may also compromise respiration and on rare occasions abdominocentesis may be indicated. It is very important that abdominocentesis should only be used after every effort has been made to stabilize the dog medically first, in order to avoid unnecessary protein loss which will further contribute to the cachexia, that inevitably occurs in the end stage patient.