According to Virginia Luis Fuentes of the Royal (Dick) School of Veterinary Studies, University of Edinburgh, the prognosis for Cavaliers with Mitral Valve Disease (MVD) appears to be poorer than for other breeds affected with MVD. In addition to the onset being earlier, the progression also seems to be faster. The time from first detection of a murmur to death from heart failure is variable.

Slow Progression – Some Cavaliers may develop a murmur but remain asymptomatic for many years. If the progression is slow enough, these dogs may die of other diseases before they die of heart failure. This is the usual pattern seen in most other breeds of dogs affected with MVD.

Gradual Progression – Most Cavaliers will show a gradual progression in the loudness of the murmur, and in the symptoms shown. Symptoms may appear in as little as two years after the appearance of a murmur, depending on the stage at which a murmur was first detected. These symptoms may include a cough, or sometimes just ascites, which is an abnormal accumulation of fluid in the peritoneal cavity. Cavalier owners may notice that a dog’s appetite has become pickier, and/or the abdomen is increasing in size. Drugs may help to minimize symptoms, so that the animal may survive for many months after the first episode of problems.

Sudden Deterioration – Some dogs will progress suddenly from being previously stable. They may develop sudden onset breathing difficulties, as the lungs rapidly fill with fluid. This often occurs following the rupture of a chordae tendineae (the rupture of a chord is always a problem). Sudden decompensation can occur in any Cavalier with MVD, especially in those that are already in an advanced disease state. Death may follow despite treatment, although sometimes aggressive therapy can resolve symptoms (at least for a while). The outlook for these dogs is very poor.

The classes of drugs used to treat heart failure and described in this article include:

• diuretics

• vasodilators

• angiotensin converting enzyme inhibitors (ACEs)

• positive inotropes

• negative inotropes

• antidysrhythmics

• beta blockers

• calcium channel blockers

• angiotensin II receptor blockers

Some of these classes are overlapping. It is important to consider the class of drug therapy most beneficial with each pathophysiologic state. Do not memorize the present day drugs but consider only the classes of drugs and then review the most current veterinary literature (i.e. Current Veterinary Therapy XXII if appropriate) and find the best representative drug of that class at the time.

Diuretics cause the kidneys to excrete more fluid than normal. Fluid is drawn out of the lungs, and passed out through the kidneys. Therefore they are the mainstay therapy of animals with pulmonary edema. They consequently make the dog thirstier than normal, as well as causing increased urination. A dog on diuretic therapy must always have access to fresh water to drink, and may need to be let out more frequently to avoid losing bladder control.

Of the several types of diuretics available, the loop diuretics such as furosemide (brand name, Lasix) are most commonly used. The dose and frequency of furosemide required is dependent on the severity of pulmonary edema present and the degree of respiratory distress. The usual recommendation is for the veterinarian to find the lowest dose of furosemide that will control pulmonary edema and its clinical signs of cough and respiratory distress, as diuretics can have some disadvantages. It is also important that the dog continue to eat in order to avoid one of the potential consequences of furosemide therapy, the loss of too much potassium.

For a Cavalier weighing 8 kg (17.6 pounds), Lasix dosage ranges might be:

Maintenance: 10 mg one or two times a day orally;

More intervention required because the dog is symptomatic: 15-30 mg, two or three times a day (by injection or orally);

To remain free of respiratory distress, as much as 30 mg of Lasix four times a day (spaced out every 6 hours, for example 6 a.m., 12 n, 6 p.m., 12 m.n.) may be required – give this amount with veterinary recommendation;

In severe pulmonary edema (admitted to a vet hospital): intravenous therapy as determined by the veterinary specialist, either at a constant rate of infusion or as needed.

If it is clear the dog is close to the end of her/his life, the overriding goal may be to keep the breathing as comfortable as possible, and holding to a daily upper limit may be of less concern. There has been one Cavalier who was given 40 mg of Lasix orally every 5 hours (200 mg/24 hours) for two days prior to being euthanized. It was also reported that by giving a Doberman a huge amount of Lasix orally at home (higher than recommended), an owner reduced the pulmonary edema and the dog had another eight months of life.

Another diuretic occasionally used is spironolactone (an aldosterone antagonist) in addition to furosemide. According to Dr. Michael O’Grady’s internet site, since the elevation of aldosterone plays an important role in the pathophysiology of heart failure, this class of drug may serve to direct therapy to the "heart" of one of the problems. Cavalier dosage would be about 8-16 mg two times a day. The combined drug use can be very powerful and should be very closely monitored. O’Grady says, "One must strive to find the least dose required to achieve your goal."

Vasodilators - Vasodilators are classified as: purely venodilators, purely arterial vasodilators, and mixed vasodilators. While classified as so-called pure veno- or arterial vasodilators, all of these agents have some mixed vasodilator features while affecting primarily the venous or arterial tree, respectively. Whenever vasodilator therapy is added to diuretic therapy the potential for hypotension is greatly increased.

Venodilators - Venodilator therapy reduces preload by trapping blood in the venous circulation; this effectively shifts blood from the central circulation (heart and lungs) into the peripheral circulation. This effectively reduces pulmonary edema. Common venodilators are nitroglycerin ointment (applied to the chest wall while person applying wears latex gloves; can drop human blood pressure too) – ¼ - ½ inch three-four times a day (only with veterinary supervision and/or direct monitoring); and isosorbide dinitrate (average Cavalier dosage 2-8 mg two times a day, orally). If a more moderate approach is not successful in alleviating acute congestive heart failure, the veterinary specialist may suggest trying sodium nitroprusside. This drug must be administered as a constant rate infusion (by IV), and can cause both arterioles and veins to dilate and blood pressure to drop. Careful blood pressure monitoring is required.

Arterial vasodilators – There are actually several different types, such as arterial smooth muscle relaxant (hydralazine), alpha receptor blocker (example, acepromazine), and calcium channel blocker. However, the ones that Cavalier owners have heard the most about are the angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors are indicated in the treatment of mild to severe left-sided CHF in the dog. They block production of angiotensin II (a potent arterial constrictor) and block production of aldosterone (which contributes to fluid overload). By reducing vasoconstriction and excessive systemic vascular resistance, ACE inhibitors improve cardiac output and reduce regurgitant fraction when mitral insufficiency is present. ACE inhibitors have been shown to improve survival time of dogs as compared to placebos, which do not.

Enalapril’s (Vasotec, Cardiovet) therapeutic usefulness was documented in a recent multicentre study involving 211 dogs with congestive heart failure. The addition of enalapril to conventional therapy resulted in an improvement in heart failure scores, a decrease in heart rate, frequency of cough, and degree of pulmonary edema. Side effects occurred with equal frequency in the placebo treated group, the most common being anorexia or lack of appetite, vomiting, and azotemia, which is abnormal and means the presence of nitrogen-containing compounds in the blood (28.7% of enalapril treated dogs, 25.9% of placebo treated dogs). Hypotension (low blood pressure) is rare (1.1%) and typically occurs when aggressive ACE inhibition is initiated in a volume depleted (dehydrated) animal. Clinically, the most significant concern is the development of azotemia secondary to reduced kidney bloodflow. Although the risk is low, it is recommended to ascertain kidney function prior to starting ACE inhibitor therapy. It is also advisable to decrease the diuretic dose by approximately 25%, and to monitor kidney function by doing BUN and creatinine blood studies 5-7 days after initiating ACE inhibitor therapy. If azotemia develops or worsens, it is recommended to decrease the diuretic dose. If azotemia persists despite diuretic dose adjustment, the frequency of enalapril administration should be decreased to once daily rather than twice a day. It is prudent to monitor kidney function periodically in older animals receiving enalapril and a diuretic. Enalapril should be initiated at 0.5 mg/kg once daily (Cavaliers, 5 mg). The dose will probably be increased to twice daily if there is an inadequate response, and maintained on a twice daily basis.

Benazepril (Fortekor) has recently been approved for use in dogs with heart failure. Only benazapril and enalapril have been approved for use in dogs. Benazapril offers the advantage of being a once daily formulation whereas enalapril should be used twice daily in most dogs with heart failure. There is currently some controversy as to whether benazepril should be given twice daily as well. Studies are ongoing. At the recommended dose (of once daily), benazapril is considerably less expensive than enalapril (Cavaliers, about 3 mg once a day). Unlike enalapril and captopril, benazepril is excreted by the liver as well as the kidney, and may be useful in animals with heart failure and kidney insufficiency. The theoretical benefit is attributed to duo route excretion (via kidney and liver), in that the dog may not become toxic on the medication. The dose may not have to be reduced as much because of the kidney insufficiency. However, a dog with kidney insufficiency already present may be at risk being medicated with either enalapril or benazepril.

Positive inotropes - These agents increase cardiac contractility and are indicated when myocardial function, specifically contractility, is impaired. Advanced degenerative valve disease is one of the common indications in small animal practice. The digitalis glycosides are the most often used positive inotropic agents. Digoxin (Lanoxin) and digitoxin increase the intracellular concentration of calcium causing a modest increase in cardiac contractility. Digoxin is the most commonly used digitalis glycoside, and is available in tablet, elixir, and intravenous form. Digoxin has what is called a narrow therapeutic index, and side effects are common. These include depression, anorexia, vomiting, diarrhea, and abnormal cardiac rhythms. Digoxin is excreted by the kidneys and should be used with caution if the dog already has kidney failure, if at all. Dr. O’Grady cautions, "There has been considerable controversy as to the efficacy of digitalis in the setting of heart failure with a normal sinus rhythm." He suggests in light of evidence in people in which digoxin failed to improve survival, digoxin may have little use in veterinary cases.

Negative inotropes - Negative inotropes are divided into two general categories: beta-adrenergic blockers and calcium channel blockers. Among their uses, they reduce myocardial oxygen demand; they treat particular types of abnormal heart rhythms called supraventricular arrhythmias (including atrial fibrillation) and sinus tachycardia (a negative chronotropic function); and beta blockers (carvedilol) and some calcium channel blockers (amlodipine) improve survival in people with congestive heart failure due to reduced contractility (systolic dysfunction). Prescribing these medications is best left to the veterinary cardiologists because they can be poorly tolerated in some patients.

Beta blockers – Selective beta blockers are metoprolol and atenolol; propranolol is a non-selective beta blocker (average Cavalier dose would be 5 mg twice a day). Beta blockers can increase survival in people with heart failure. They can protect against arrhythmic death (sudden death). They have disadvantages as well, including low blood pressure, bronchospasm, and slowing the heart rate. Beta blockers should only be prescribed by the specialists.

As described by Virginia Luis Fuentes:

Early MVD – A murmur is noted at routine check-up; the animal is symptom-free; and there is a minimal enlargement of the heart on X-ray/scan. Treatment - At this stage, there is no real need for treatment. Dogs which are overweight should be put on a weight-reducing diet. Extremes of exertion should probably be avoided.

Moderate MVD – The murmur may have become louder; the animal may show increased breathlessness on occasions; there may be occasional coughing; there is clear enlargement of the heart on X-ray/scan, with some fluid present in the lungs.

Treatment – Treatment will be necessary at this stage, but can usually be given in tablet form on an out-patient basis. To remove fluid from the lungs, furosemide (Lasix) can be given. One of the ACE inhibitors can be started to prevent fluid retention and to reduce demands on the heart. Reducing exercise will help to reduce the workload of the heart, and when the dog first starts showing signs, it is worth cutting back on exercise.

Severe MVD – The murmur may have become much louder (or may even be difficult to hear if the deterioration has been sudden); the dog may have breathing difficulties at rest; and even minimal exercise may not be tolerated. There are some dogs who are diagnosed with severe MVD who are well compensated, and may only display symptoms with more strenuous exercise.

Treatment – The urgency of treatment will vary slightly according to the severity of signs – some animals with sudden severe flooding of the lungs may be close to death, whilst others with a more gradual onset may be treated less aggressively. Ensure the animal has enough oxygen - an oxygen cage or use of nasal prongs to deliver oxygen may be required. Cage rest – the dog should not exert itself in any way. Remove fluid from the lungs – diuretics should be given by injection, as this will be faster-acting. Reduction of pressure in the left atrium can be achieved by diuretics and use of the venodilators. Use of the ACE inhibitors can help reduce the load on the heart and reduce the pressure in the arteries. If the heart muscle is so weakened that it does not contract properly, digoxin (Lanoxin) may be prescribed.

Cardiovascular Disease, Veterinary Heart Institute, Principles of Heart Disease, http://www.vetheart.com/diseases.html.

Fuentes, Virginia Luis, Royal (Dick) School of Veterinary Studies, University of Edinburgh, "The Diagnosis and Treatment of Mitral Valve Disease in Cavaliers", presentation to The Cavalier King Charles Spaniel Club, Saturday 2 November 1996.

O’Grady, Dr. Michael, Cardiology Concepts, Therapy of Heart Failure, http://www.ovcnet.uoguelph.ca/ClinStudies/Courses/Public/Cardiology/Concepts/.

IMPORTANT INFORMATION: PLEASE NOTE:

Dr. Sandra Minors, D.V.M., D.V.Sc., Dip. A.C.V.I.M. (Cardiology), is one of two veterinary cardiologists located in southern Ontario. Dr. Minors has been one of two investigators for the CKCSCC Mitral Valve Disease natural progression study since its inception. During 1999, Dr. Minors is providing cardiology services for the University of Guelph’s Veterinary Teaching Hospital while Dr. Michael O’Grady is on sabbatical leave. She also sees patients in private practice. Dr. Minors has agreed to come to meet with us during our 1999 specialty weekend, to provide more information on the pathophysiology of mitral valve disease and congestive heart failure. She will also talk with us about the importance of understanding more about how best to treat and manage the clinical symptoms of heart disease in Cavaliers, and the advantages of our participation in a drug trial study. Please plan on attending this very important session, once the specialty weekend schedule is known.

Disclaimer: Your veterinarian is the most qualified person to answer all of the questions you have about your pet's health. Nothing in this article should be construed as medical advice regarding any individual animal’s condition.