• IN SHORT
• IN DEPTH
• What It Is
• Symptoms
• Diagnosis
• -- auscultation (stethoscope)
• -- x-rays (radiography)
• -- respiratory rates
• -- ultrasound (echos)
• -- electrocardiograph (ECG)
• -- natriuretic peptides
• -- other cardiac biomarkers
• DNA Testing
• Progression & Prognosis
• Stages of MVD
• Treatment
• -- mild murmur
• -- moderate MVD
• -- severe MVD
• -- end stage of MVD
• -- slow the progression
• Surgery
• Breeders' Responsibilities
• Seminars
• Research News
• Related Links
• Veterinary Resources
• Page 2 of MVD

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IN SHORT:

Heart mitral valve disease (MVD) is the leading cause of death of cavalier King Charles spaniels throughout the world. MVD is a polygenetic disease which afflicts over half of all cavaliers by age 5 years and nearly all cavaliers by age 10 years, should they survive that long.

What It Is

MVD is a degeneration of the heart's mitral valve, one of four sets of valves in a dog's heart. As the mitral valve degenerates, the valve no longer fully closes after each pumping action, allowing some blood to flow backwards through them from the ventricle back into the atrium. As the condition worsens, more and more blood is able to backflow through the valve. In the final stages, the valve’s struts sometimes break, causing the valve to collapse completely. MVD results in congestive heart failure in the CKCS.

About 10% of all dogs suffer from some form of heart disease. Mitral valve disease is the most common heart disorder in older dogs of all breeds. However, in the cavalier King Charles spaniel, the prevalence of MVD is about 20 times that of other breeds. Also in cavaliers, the onset of the disease typically is much earlier in the life of the dog. It has been reported that, once diagnosed, mitral valve disease is much more rapid in cavaliers than in other breeds, possibly reaching a life-threatening stage within as little as 1 to 3 years, rather than the average 3 to 5 years. To a lesser extent, cavaliers also suffer from deterioration of their tricuspid valves. More►

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Diagnosis

All cavaliers should be screened for heart murmurs once a year beginning at age 1 year. Once MVD is detected, its progression can be monitored with stethoscopic examinations (auscultations), x-rays, echocardiograms, and color Doppler echocardiograms. If a heart murmur is detected, it should be confirmed in 3 to 6 months. If it still is detected, the dog is considered probable for MVD.   More►

Symptoms & Treatment

The progression of mitral valve disease can be rapid or slow. In most cavaliers, the disease shows a gradual progression in the loudness of the murmur and to more serious symptoms, in as little as 2 years after first detecting the murmur. Drugs may help to minimize the symptoms, but eventually the drugs may be unable to control them. The drugs prescribed for cavaliers with MVD can sometimes have severe adverse side effects, and blood chemistry should be done routinely to monitor their effects upon the kidneys, liver, and other internal organs. Severe symptoms of MVD in some cavaliers will appear more quickly, although previously having been stable. The ultimate consequence of the disease is heart failure.  More►

Breeders' Responsibilities

Due to the pervasiveness of MVD in the breed worldwide, cavalier King Charles spaniels under the age of five years should not be bred (with one limited exception -- see MVD Breeding Protocol). Also, no cavalier should be bred after age five years if it developed an MVD murmur before the age of five years. Any littermates of breeding stock having early-onset MVD (mitral valve murmurs before age 5 years) should be taken into very serious consideration. All CKCS breeding stock should be examined by board certified veterinary cardiologists at least annually and cleared by the veterinary specialists for MVD, the closer the examination to the breeding the better. It is recommended that all cavaliers, breeding stock or not, be examined annually by board certified veterinary cardiologists after age one year. See the current list of health clinics for upcoming cardiologist examinations.

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IN DEPTH:

Degenerative mitral valve disease (MVD)* is the leading cause of death of cavaliers. It is a highly-heritable, polygenetic acquired heart disease which, statistics show, afflicts over half of all cavalier King Charles spaniels by age 5 years and greater than 90% by age 10+ years, should they survive that long.

* MVD is also called cardiac valve disease (CVD) and medically known as endocardiosis, atrioventricular valve endocardiosis, chronic degenerative valvular disease, chronic valvular disease, chronic mitral valve insufficiency, myxomatous atrioventricular degeneration, chronic valvular fibrosis, acquired mitral regurgitation or insufficiency, and mitral valve defect.

Veterinary cardiologists began compiling statistics on cavaliers with MVD murmurs in the United Kingdom in 1990. Since then, cardiologists have examined the hearts of many thousands of cavalier King Charles spaniels at health clinics held by CKCS breed clubs in the UK, Canada, the USA, and elsewhere. From the data they have compiled, they have found that the percentage of CKCSs which develop MVD murmurs increases at a rate of about 10% per year. So, roughly 10% of cavaliers by age one year have MVD murmurs, and 20% aged between one and two years have murmurs, and so on for each age level. Specifically, the statistics show that more than half of all cavaliers aged five years have murmurs, and it is the very rare cavalier at age ten years which does not have, at the very least, a low grade MVD murmur.

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What It Is

Mitral valve disease is a uniquely serious, life-shortening problem for cavalier King Charles spaniels and is their leading cause of death. About 10% of all dogs suffer from some form of heart disease. MVD is the most common heart disorder in older dogs of all breeds. Several smaller breeds of dogs typically are predisposed to suffer from MVD. However, in most all breeds, MVD does not result in heart failure, causing death, because MVD does not develop early in a dog's life, and does not progress rapidly.

In the cavalier King Charles spaniel, statistics have shown that the prevalence of MVD is about 20 times that of other breeds of dog. Also in cavaliers, the onset of the disease typically is much earlier in the life of the dog, with over half of all CKCSs having developing MVD by their fifth birthday, as noted above. For most breeds, MVD is an old-age disease, and the age of onset is between 10 and 15 years of age.

It has been reported that, once diagnosed, MVD is much more rapid in cavaliers than in other breeds, possibly reaching a life-threatening stage within as little as 1 to 3 years, rather than the average 3 to 5 years. Studies of cavaliers have concluded that it has an hereditary basis and is "polygenetic", meaning that more than one gene can be the cause.

MVD is a degeneration and fibrosis of the heart's mitral valve, one of four sets of valves in a canine's (and a human's) heart. It is the valve which is designed to prevent the backflow of blood from the left ventricle into the left atrium. It consists of a set of double flaps, called "leaflets", that open and close like a set of one-way doors at appropriate times during each heart beat. Normal mitral valve leaflets are comprised of three layers of tissue (atrialis, fibrosa, and spongiosa) and are very thin and nearly transparent. They are connected by tendons (chordae tendineae) to the muscles of the left ventricle.

Blood flows through the pulmonary veins from the lungs into the left atrium, one of the chambers of the heart. The mitral valve is located between the left atrium and the left ventricle, another chamber in the heart. The valve's action is governed by the movement of blood as it is pumped from the atrium and into the ventricle. The leaflets of the mitral valve are controlled by the tendons, which serve as thin "struts" shaped much like the chords of a parachute.

As the diseased mitral valve degenerates, myxomatous transformation -- the development of excess connective tissue that thickens the spongiosa and separates collagen bundles in the fibrosa -- causes the valve to lose its flexibility, its leaflets thickening and shortening, its fibers stiffening, and its chordae tendineae elongating. The leaflets no longer fully close after each pumping action, allowing blood to jet backwards through them from the ventricle back into the atrium. As the condition worsens, advanced lesions cause the leaflets to fold, invert, and displace toward the left atrium. (In the photo at right, LA is the heart's left atrium, LV is the left ventricle, and in-between, the opening of the mitral valve shows thickened, shortened leaflets which no longer fully close.) More and more blood is able to backflow through the valve, causing both the left atrium and the left ventricle to enlarge. In the final stages, the valve’s chordae tendineae sometimes rupture, and if they are major chords, causing the valve to collapse completely.

Apart from the mitral valve itself, the disease has severe consequences for the rest of the heart and the lungs. The increased pressure in the left atrium decreases blood flow from the lungs to the heart, resulting in congestion in the pulmonary veins, ultimately causing fluid, called pulmonary edema, to leak out of the capillaries into the pleural cavity of the lungs. As the left atrium enlarges, cardiac output declines. The decrease in output forces the body to compensate by activating angiotensin-converting enzyme (ACE) to excessive levels, forming angiotensin II, which causes the veins and arteries to constrict. Angiotensin II also releases aldosterone, resulting in sodium and water retention. The left atrium enlarges first, followed by an enlarged left ventricle and the pulmonary veins. The heart enlargement may cause a tear in the left atrium, which usually results in immediate stoppage of blood flow.

To a lesser extent, cavaliers also suffer from deterioration of their tricuspid valves. For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

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Symptoms

For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

As MVD progresses towards congestive heart failure (CHF), early symptoms which may occur are exercise intolerance, breathlessness, a distended abdomen, lack of appetite, restlessness at night, weight loss, and fainting. Breathlessness is a most common sign, starting as excessive panting on exercise. As breathing difficulties become more severe, the dog may sit or stand, holding its elbows away from the chest, and it may be reluctant to sit down.

Productive coughing or a hacking cough can be an early symptom of CHF, due to the enlargement of the heart.

As greater quantities of blood leak through the damaged mitral valve from the left ventricle back into the left atrium of the heart, the atrium gradually begins to swell and enlarge (see x-ray of enlarged heart at right) -- called myocardial remodeling -- to accommodate the overload of blood, and there is a reduction in the ability of the ventricle to provide sufficient blood to meet the demands of the rest of the body. The heart then has to pump harder and faster, to meet those demands.

Also, due to the increasing lack of blood being pumped throughout the body, non-essential blood vessels begin to shut down, to conserve blood flow for vital organs, such as the brain and the heart itself, and reducing the flow to the skin and the kidneys. This causes the skin to pale and the kidneys to retain fluids in the circulation, because the circulation identifies the low cardiac output as dehydration. The excess fluid retention results in further stretching of the heart and greater mitral valve leakage.  If the tricuspid valve is also affected, the retained fluid, called ascites, is squeezed into other body tissues, the liver, chest, and peritoneal cavity of the abdomen. See photo below right of dog with ascites.

The shut-down of the distant blood vessels also has the effect of causing the left ventricle to beat against a higher resistance, causing another increase in mitral valve leakage.

The enlarged size of the heart fills the voids in the chest cavity and causes pressure on the main airway -- the left main bronchus, resulting in a dry, hacking cough and breathlessness. It may even cause the trachea to collapse.* However, in a June 2011 preliminary study report, researchers were unable to confirm an association between left atrial enlargement and airway collapse in dogs with MVD. The study suggested that airway inflammation was common in the affected dogs.

* Trachea collapse also may be due to Brachycephalic airway obstruction syndrome (BAOS).

Also, the overload of blood in the left atrium creates increased pressure back into the pulmonary veins, which drain into the left atrium from the lungs. When a critical pressure is reached, flooding of the lungs can occur, with pulmonary edema.

Cavaliers with murmurs of between Grade 3 and Grade 6 may display episodic weakness of the hindquarters, ataxia, or collapse, which is called presyncope, or combined with loss of consciousness, which is called syncope, due to a sudden decline in blood flow to the brain. See Syncope for a discussion of this disorder and its causes.

A loss of appetite, resulting in possibly severe weight loss (called cardiac cachexia), particularly of muscle mass, is another symptom of advanced MVD. There is a possibility that a dog will develop CHF without displaying any symptoms.

The ultimate consequence of mitral valve disease is heart failure. The median survival period for dogs once they develop severe congestive heart failure (CHF) due to MVD is approximately seven months, with 75% of the dogs dead by one year. For dogs with less severe CHF, the median survival period is one year, with 75% of the dogs dead by 21 months. However, the CKCS has a more accelerated version of MVD, and they typically progress more rapidly to heart failure.

As the cavalier nears death from MVD, often the dog will display a severe air hunger and uses all of its remaining energy just trying to breathe.

In a 2005 report, cardiac researchers at Tufts University's Cummings School of Veterinary Medicine devised a survey that may prove to be similarly useful in evaluating the quality of life for dogs with heart disease. Known as "FETCH" (Functional Evaluation of Cardiac Health), the survey asks the dogs' owners to rank aspects of their dog's health on a scale of 0 to 5. Veterinarians are then able to assess the animal's perceived quality of life, which may inform decisions about treatment, nutrition or even euthanasia. Researchers found that the FETCH scores correlated well to the International Small Animal Cardiac Health Council (ISACHC) classification for disease severity.

For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

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Diagnosis

Cavaliers should be screened for heart murmurs annually, beginning at age one year. Once mitral valve disease (MVD) is detected, its progression can be monitored with stethoscopic examinations (auscultations), x-rays, respiratory rates (breaths per minute while resting or asleep), echocardiograms, and color Doppler echocardiograms. If a cavalier's heart murmur is first detected by a general practice veterinarian, it should be confirmed within 3 to 6 months by a specialist, preferably a board certified veterinary cardiologist. If it still is detected, the dog has MVD.

 

Ask the cardiologist to use this standardized report form. A list of upcoming heart testing examination clinics is on our Health Clinic webpage.
 

 

In a 2009 "Consensus Statement" published by a panel of the board certified veterinary cardiologists of the American College of Veterinary Internal Medicine (ACVIM), they state:

"Consensus recommendations:

"Small breed dogs, including breeds with known predisposition to develop CVHD [chronic valvular heart disease] (e.g., Cavalier King Charles Spaniels, Dachshunds, Miniature and Toy Poodles) should undergo regular evaluations (yearly auscultation by the family veterinarian) as part of routine health care.

"Owners of breeding dogs or those at especially high risk, such as Cavalier King Charles Spaniels, may choose to participate in yearly screening events at dog shows or other events sponsored by their breed association or kennel club and conducted by board-certified cardiologists participating in an ACVIM-approved disease registry."

For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

-- auscultation (stethoscope)

The earliest indications of MVD are outwardly invisible and silent and can only be observed by echocardiography (ultrasound scanning). The first indication is the excessive bulging of the mitral valve leaflets into the left atrium, which is called mitral valve prolapse (MVP) (see illustration "C" at right above), followed by thickening of the leaflets, and then by the presence of a soft whistling sound, called a "murmur", which can be heard by a veterinarian using a stethoscope, which is called auscultation. The murmur sound is caused by the turbulent flow of blood jetting backwards through the damaged leaflets of the mitral valve from the left ventricle, into the left atrium (see illustration "D" at right above).

Listen to the sound of a Grade 3 MVD heart murmur here, on the website of the Cardiac Education Group.

Even if the veterinarian does not hear a murmur, he might report hearing a "systolic click" when he examines the dog with his stethoscope. Veterinary cardiologist Dr. James Buchanan of the University of Pennsylvania has stated that "systolic clicks occur twenty-five times more frequently in cavaliers than other breeds and may be a precursor to a murmur showing up a few years later."

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-- x-rays (radiography)

Radiography (x-ray) is used to determine if the heart is enlarged (particularly the left atrium and left ventricle), if the veins from the lungs to the heart are distended, or if fluid is beginning to develop in the lungs. Once MVD is diagnosed, annual x-rays are very useful in charting the progression of the disease. Mild to moderate heart enlargement indicates moderate progression, with the heart compensating for the effects of mitral valve disease by enlarging. When moderate to severe heart enlargement develops, early clinical signs such as breathlessness or rapid breathing would be expected. Severe heart enlargement indicates impending congestive heart failure.

Cardiologists use x-rays to evaluate the size and shape of the heart in order to assess the severity of MVD. They measure the the length and width of the heart and compare those dimensions to the number of veterbrae from T4 to T12, to calculate the Vertebral Heart Score (VHS). See this YouTube video for details. A diagram showing how the VHS is calculated is here. This is called the Buchanan VHS method, devised by Dr. James W. Buchanan, a pioneer in the research of MVD in cavaliers, in 1995. In a 2012 study, a team of Spanish researchers, issued a new VHS measurement, called Objective VHS.

Periodic x-rays of the cavalier's heart, showing the rate of its enlargement, are viewed by many cardiologists as an effective way to anticipating the onset of congestive heart failure (CHF). In a September 2011 study of 94 CKCSs*, an international team of cardiologists concluded that the difference in the vertebral heart scale per month was a useful measurement for detecting the onset of CHF.

* See follow up letters to editor by Dr. Mark A. Oyama and by the authors regarding this study.

The radiograph image at the right above shows vertebral heart scale measurements. View other radiographs of dogs with various stages of MVD here, on the website of the Cardiac Education Group.

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-- respiratory rates

An ever increasing respiratory rate, while the dog is asleep or resting, which approaches or exceeds 30 breaths per minute, is an indication that the dog is approaching congestive heart failure. Once a dog is diagnosed with MVD and the disease has been progressing, the treating veterinarian may ask the dog's owner to periodically count the number of breaths the dog takes per minute while asleep or resting, and to keep a record of those counts. In an October 2012 study, researching cardiologists found that healthy adult dogs generally have mean sleeping respiratory rates of less than 30 breaths per minute and rarely exceed that count.

While the dog is resting or sleeping (preferably sleeping), count the number of breaths the dog takes in 15 seconds. Then multiply that number by four to get the number of breaths per minute. If that respiratory rate increases by more than 20 percent over 2 to 3 days, or exceeds 30 breaths per minute, many treating veterinarians would advise the dog's owner to report to them.

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-- ultrasound (echocardiography)

Echocardiography (ultrasound scanning) is a beam of ultra-high frequency sound directed at the heart, and is used to evaluate heart size, function, and valve appearance. Echo scans can demonstrate the thickened valve leaflets and their abnormal movement, such as prolapse (MVP).

The echo image at right shows a dog's heart with MVD. LA-left atrium; LV-left ventricle; MV-mitral valve, septal leaflet. Note the thickened free end of the mitral valve leaflet at the left of the valve.

The color Doppler can evaluate the direction and velocity of blood flow, quantifying blood leakage. It can be used to distinguish MVD from benign murmurs in ambiguous cases. The Doppler may detect leakage before it is audible as a murmur. However, trivial regurgitation of blood through the mitral valve may be present in as many as 50% of normal dogs. In such cases, however, there is no MVP or valve thickening present.

During echo exams, the operator typically also will take measurements of the heart to determine if it has enlarged and the likely onset of congestive heart failure (CHF). See this 2002 report by Drs. Jens Häggström, Kjerstin Hansson, Clarence Kvart, and the 2012 PREDICT Cohort Study, for more information.

For cavaliers' hearts, it is recommended that ultrasound scanning be conducted by specialists, preferably board certified veterinary cardiologists.

As of December 2011, Drs. Julia Sargent, Virginia Luis Fuentes, and Holger Volk, of the Queen Mother Hospital for Animals at the Royal Veterinary College in the UK, have developed a new echocardiographic scoring system to grade the severity of mitral regurgitation in chronic mitral valve disease, based upon a number of different measurements that they believe can offer more reliable information on the severity of MVD. They are testing their new scoring system by comparing it to cardiac magnetic resonance imaging (cMRI), which is considered the most reliable test for quantifying valve disease in humans.

Due to the necessity of anaesthetizing the dogs for the cMRIs, the researchers are seeking to recruit dogs already scheduled for MRIs for other reasons, such as syringomyelia examinations. All dogs will undergo conventional echocardiography to assess their heart disease prior to anaesthesia and the MRI scan, and only dogs with stable heart disease will be recruited.

The researchers expect to be able to provide more accurate information for the individual dogs on the severity of their valve disease as a result of the MRI scan, and new echo score. They believe that the scoring system should be particularly useful for standardizing the severity of MVD at entry for clinical studies.

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-- electrocardiography (ECG or EKG)

Electrocardiography (ECG or EKG) is a diagnostic tool that measures and records the heart's electrical activity. Multiple, advanced resting electrocardiographic techniques have been applied to humans to detect cardiac diseases before onset of symptoms or changes in the standard ECG. In a June 2011 study by Slovenian and Danish researchers, they were able to use advanced ECG to predict the severity of mitral regurgitation in dogs with MVD.  They reported:

"Our results indicate that for a cut-off criteria of MR [mitral regurgitation] 50% jet the five selected ECG parameters could predict the severity of MR caused by MMVD in CKCSs with sinus rhythm with sensitivity 65% (78% with age inclusion) and specificity 98% (92% with age inclusion) (P < 0.05)."

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-- natriuretic peptides tests (ANP and BNP)

There has been much research into attempting to diagnose MVD, and more particularly, to diagnose the onset of congestive heart failure (CHF) in dogs by measuring "cardiac biomarkers", such as plasma concentrations of the natriuretic peptides: atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Natriuretic peptides are hormones manufactured and secreted by areas of the heart. A test of natriuretic peptides measures the quantity of the natriuretic peptides in the dog's blood. Elevated levels of these natriuretic peptides in the blood may be directly related to heart defects, and natriuretic peptides in the blood become elevated only after the heart has to pump harder to compensate for the disorder. In particular, BNP is secreted by the left ventricle in response to heart wall stretching or stress.

A 2003 study (conducted by Drs. Kristin A. MacDonald, Mark D. Kittleson, Coralie Munro, and Philip Kass of the University of California at Davis) has shown a positive correlation between BNP and heart disease and CHF in dogs. In that study, BNP increased with the progressively increased severity of mitral valve disease and CHF. For every 10-pg/mL increase in BNP, the 2003 study's dogs' mortality rate increased approximately 44% over the four months of the study. In a 2005 study, Drs. William E. Herndon, Justine A. Lee, Kenneth J. Drobatz, and Matthew J. Ryan concluded that "With further investigation, this new BNP assay may someday provide a widely available noninvasive diagnostic test with rapid turnaround time to help diagnose and/or treat heart disease and congestive heart failure in the dog."

However, in earlier studies (1994 and 1997) conducted by Drs. Jens Häggström, Kjerstin Hansson, Clarence Kvart, and others, the researchers have suggested that BNP levels in cavaliers with mitral regurgitation did not rise as dramatically as in humans, and that N-terminal (NT)-proANP (NT-proANP) may better reflect the severity of mitral regurgitation in cavalier King Charles spaniels than NT-proBNP tests.

Four trademarked names for NT-proBNP tests are Canine CardioCare (Veterinary Diagnostics Institute), Canine VetSign CardioSCREEN (Guildhay Ltd.), Cardiopet proBNP (IDEXX Laboratories), and Antech Cardio-BNP (Antech Diagnostics). There have been studies showing the effectiveness of these types of tests for dogs suffering from asymptomatic occult dilated cardiomyopathy (DCM), which is not the same disorder as MVD and is not known to be a genetic problem for cavalier King Charles spaniels.

Whichever test (NT-proBNP or NT-proANP) is found to be more accurate for detecting MVD, it is believed by some researchers that the test may be useful in assisting examining veterinarians in deciding whether or not detected heart murmurs are innocent or are pathologic in nature. However, in a 2007 study of 54 CKCSs by Drs. Tarnow, Pedersen, Kvart, and others from Denmark and Sweden, they found that "Natriuretic peptides are elevated in cavalier King Charles spaniels with congestive heart failure but not in dogs with clinically inapparent mitral valve disease."

In a May 2008 report by Drs. Mark A. Oyama, Philip R. Fox, John E. Rush, Elizabeth A. Rozanski, and Michael B. Lesser of 119 dogs, they found that "Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function." They concluded that, "For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure." And that, "Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease."

In a May 2009 report from Sweden, the researchers concluded: "Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size."

In a 2012 study of 1,134 dogs, including 37 cavaliers, Stephen J. Ettinger, Giosi Farace, Scott D. Forney, Michelle Frye, and Andrew Beardow concluded that "This biomarker [NT-proBNP] may be a useful tool for staging of cardiac disease and identifying cardiac-related coughing or dyspnea in this species."

In a 2013 study of 36 dogs, none being CKCSs, a team of Japanese researchers concluded: "These results indicated that plasma ANP rose with an increase in the volume overload of the left side of the heart. Plasma ANP discriminated cardiomegaly from non-cardiomegaly caused by asymptomatic MMVD. We conclude, therefore, that plasma ANP concentrations may be a clinically useful tool for early diagnosis of asymptomatic MMVD in dogs."

In an April 2013 report, a team of German veterinary cardiologists studied 352 dogs and found that: "NPs [natriuretic peptides] in canine MMVD are useful to discriminate between asymptomatic dogs and dogs with CHF. Due to a large overlap of NP-concentrations between the groups, NPs do not seem to be useful to differentiate between dogs in stages B1 and B2. Interpretation of NT-proBNP and proANP values should include consideration of sex-specific differences."

Nevertheless, it appears that veterinary cardiologists and other cardio-specialists should be quite capable of detecting mitral valve prolapse (MVP) murmurs and distinguishing between them and flow murmurs or other innocent varieties of heart murmurs. Since BNP in the blood becomes elevated only after the heart has to pump harder to compensate for the disorder, the question then is: When does the heart start working so hard that BNP levels start to go up? In the cavalier King Charles spaniel's version of heart defects -- mitral valve disease due to deteriorating valve flaps -- there are no immediate external symptoms. It is not yet clear from research studies thus far, as to whether the heart becomes labored enough to produce increased levels of BNP before auscultation is able to detect the murmurs from minimal backflow of blood leaking through the mitral valve flaps. Advocates of BNP testing do represent that that studies of BNP and cardiomyopathy show that BNP is elevated before the onset of signs and murmur. But it does not yet appear that BNP testing is an any earlier warning system for MVD than auscultation.

Bolstering this viewpoint is the comment by Dr. Jennifer L. Garcia in "The NT-proBNP assay: A portent of heart health." in dvm360:

"For conditions such as mitral valve disease, this test may be of limited value because a diagnosis can be readily made by thorough auscultation and documentation of a heart murmur. In these cases, the assay also has limited utility in determining disease severity; thoracic radiography is preferred."

One possible uniquely valuable use for natriuretic peptides tests is if the dog is approaching congestive heart failure (CHF) without any symptoms. In that case, natriuretic peptides tests, combined with "Left Chambers on Aorta ratio" greater than 4,5, the veterinarian may begin administering ACE inhibitors, pimobendan, and other drugs immediately even though the dog is asymptomatic.  See Dr. Gerard Le Bobinnec's proposal in this report to the 2010 WSAVA Congress. See, also, the 2012 report of the PREDICT Cohort Study, which found that measurements of left heart size (using the "left atrial to aortic root dimension ratio [LA:Ao]") and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with MVD. It correctly predicted first-onset of CHF in 72.5% of cases out of 82 dogs, which included cavaliers.

Dr. Oyama has stated that natriuretic peptide tests may also be useful to properly diagnose a dog known to suffer from congestive heart failure and also is in respiratory distress. He said that, “When dogs come into veterinary hospitals in respiratory distress, it’s sometimes difficult to know if they are having a respiratory or heart problem. Such a test could speed effective treatment and also help decide if a dog should be referred to a veterinary cardiologist before undergoing more expensive testing.”

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-- other cardiac biomarkers

---cardiac troponin I (cTnI)

Other cardiac biomarkers include cardiac troponin I (cTnI), and high-sensitivity cardiac troponin I (hscTnI), and sodium-calcium exchanger (NCX-1), and leptin. Several studies of cardiac troponin I (cTnI) have shown increases in cTnI concentrations in dogs with poor prognoses, and that cTnI has potential in assessing the prognosis and severity of MVD and enlargement of the heart. See the 2009 study, the January 2010 study, the June 2010 study, and the April 2013 study. In a February 2012 study, high-sensitivity cardiac troponin I (hscTnI), in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, has been examined. The researchers concluded that:

"Survival times were shortest in dogs in which both serum hscTnI and NT-proBNP were increased. hscTnI and NT-proBNP increased more rapidly in dogs that died of cardiac disease. Conclusions and Clinical Importance: Serum hscTnI has prognostic value in dogs with DMVD. Measurement of NT-proBNP and hscTnI is prognostically superior to measuring either alone. Serial measurement strategies provide additional prognostic information."

---sodium-calcium exchanger (NCX-1)

Sodium-calcium exchanger (NCX-1) is being examined as an alternative to natriuretic peptides because NCX-1 appears to better differentiate between heart failure and renal failure.  See this 2010 South Korean report.  Also, leptin, a protein produced by fat tissues and associated with canine body fat, was found in an August 2011 UK report to be more highly concentrated in dogs with congestive heart failure.

---aldosterone concentration (UAC)

In a November 2012 report, researchers found that left ventricular heart enlargement in dogs with MVD is associated with a decrease in the serum concentration of a marker of collagen type III turnover, and an increase in urinary aldosterone concentration (UAC). They also reported that both serum N-terminal procollagen type III concentration and UAC were higher in cavalier King Charles spaniels than in other breeds when other measured variables were controlled for.

However, in an April 2013 study of 50 dogs (including 20 CKCSs), the researchers reported that:

"Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI [cardiac Troponin-I] concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases." (Emphasis added.)

---serum serotonin (serum 5HT)

In a November 2012 study of 120 dogs by an international team of cardiologists, the researchers found that cavaliers had higher concentrations of serum serotonin (serum 5HT) than other breeds not predisposed to mitral valve disease, and that serum 5HT concentrations decreased with increased left atrial enlargement. They concluded that, "the finding of higher serum 5HT concentrations in dogs predisposed to MMVD (CKCS) and dogs with mild MMVD suggests that alterations in 5HT signaling might play a role in progression of early stages of MMVD."

In a 2009 study, some of the same researchers found, "Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD."

In a January 2013 interview with AKC's Canine Health Foundation, board certified cardiologist Dr. Mark Oyama of University of Pennsylvania's veterinary school, said:

"Our research involving serotonin and other pathways involved in the development and progression of disease are ultimately targeted towards discovering the underlying abnormalities that produce mitral valve disease in dogs. If serotonin and other pathways contribute to disease formation blockade of these pathways could result in reduction in disease development and progression."

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DNA Testing

A team of veterinarians from Denmark, Sweden, Germany, England, and France reported in September 2011 that they have identified two specific locations on cavaliers' chromosomes CFA13 and CFA14 which are associated the breed's hereditary mitral valve disease. They grouped 139 cavaliers with early-onset MVD and 102 old CKCSs with no or mild signs of MVD as controls. Then they conducted a genome-wide association study to find specific locations associated with development of MVD. They also stated:

"We will initiate studies of the most promising candidate genes in the 2 candidate regions which hopefully will lead us to the mutations affecting the development of mitral valve disease."

However, in November 2011, a team of UK cardiologists and geneticists divided 36 CKCSs into groups of early and late onset MVD and assessed whether the distinction is determined by a small number of genetic factors. They report that they came up dry. They concluded:

"There were no regions of highly discrepant homo/heterozygosity in the two groups. Similarly, there was no evidence for loci associated with mitral valve murmur in a genome-wide association study. This analysis suggests that familial occurrence of mitral valve murmur in the CKCS breed is not due to a single major gene effect, indicating that breeding strategies to eliminate the disease cannot be based on genotype information at this time."

This seems to contradict the much more successful September 2011 report issued by the team of veterinarians from Denmark, Sweden, Germany, England, and France.

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Progression & Prognosis

The progression of mitral valve disease can be rapid or slow. In most CKCSs, the disease shows a gradual progression in the loudness of the murmur and to more serious symptoms, in as little as two years after first detecting the murmur. But, some cavaliers develop a mild murmur without any more serious symptoms for many years. If the progression is slow enough, the dogs may die of other causes before their hearts reach failure. This is the usual pattern of MVD in most other breeds affected with it.

Once the dog reaches the stage of congestive heart failure, the average time until death is nine months.

In the cavalier King Charles spaniel, some cardiologists have found prognostic value from the degree of mitral valve prolapse, the thickness of the leaflets, and whether ruptured tendinous chords are observed on the echocardiogram. In an April 2010 research article, Swedish cardiologists reported finding that cavaliers' left heart chambers increased in size rapidly only during the last year before the onset of congestive heart failure.

 Drugs may help to minimize the symptoms, but eventually the drugs may be unable to control them. Severe symptoms in some cavaliers will appear more quickly, although previously having been stable. If the tendinous chords rupture, and the valve leaflets cannot continue to open and close with each heart beat, death could be almost immediate.

A method which cavalier owners can use to determine if and when their dog reaches the stage of congestive heart failure is to count the dog's breaths per minute while sleeping. In an October 2012 study, researchers found that healthy adult dogs generally have a mean sleeping respiratory rate of less than 30 breaths per minute and rarely exceed that rate at any time. Some cardiologists recommend that their patient's owners periodically count their dog's respiratory rate, and when the average rate starts to creep up to the high twenties, to make an appointment for the dog to be re-examined by the cardiologist to see if the dog is approaching or has reached the stage of congestive heart failure.

Studies are being conducted into possibly slowing the progression of MVD. These studies, discussed in greater depth below at Drugs to Slow the Progression of MVD, involve the testing of medications.

For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

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Stages of MVD

In a 2009 "Consensus Statement" published by a panel of the board certified veterinary cardiologists of the American College of Veterinary Internal Medicine (ACVIM), they create a new classification of stages of MVD.

They state:

"The new system describes 4 basic stages of heart disease and failure:

Stage A identifies patients at high risk for developing heart disease but that currently have no identifiable structural disorder of the heart (e.g., every Cavalier King Charles Spaniel without a heart murmur).

Stage B identifies patients with structural heart disease (e.g., the typical murmur of mitral valve regurgitation is present), but that have never developed clinical signs caused by heart failure. Because of important clinical implications for prognosis and treatment, the panel further subdivided Stage B into Stage B1 and B2.

Stage B1 refers to asymptomatic patients that have no radiographic or echocardiographic evidence of cardiac remodeling [enlargement] in response to CVHD.

Stage B2 refers to asymptomatic patients that have hemodynamically significant valve regurgitation, as evidenced by radiographic or echocardiographic findings of left-sided heart enlargement.

Stage C denotes patients with past or current clinical signs of heart failure associated with structural heart disease. Because of important treatment differences between dogs with acute heart failure requiring hospital care and those with heart failure that can be treated on an outpatient basis, these issues have been addressed separately by the panel. Some animals presenting with heart failure for the 1st time may have severe clinical signs requiring aggressive therapy (eg, with additional afterload reducers or temporary ventilatory assistance) that more typically would be reserved for those with refractory disease (see Stage D).

Stage D refers to patients with end-stage disease with clinical signs of heart failure caused by CVHD that are refractory to 'standard therapy' (defined later in this document). Such patients require advanced or specialized treatment strategies in order to remain clinically comfortable with their disease. As with Stage C, the panel has distinguished between animals in Stage D that require acute, hospital-based therapy and those that can be managed as outpatients."

For an in-depth on-line seminar about the symptoms, diagnosis, progression, stages, and treatment of mitral valve disease, watch Dr. Andrew Beardow (right), with his terrific active graphics, explain MVD.

 

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Treatment

It is unrealistic to try to cure canine mitral valve disease. Replacement of the defective mitral valve is available in veterinary medicine. For example, Colorado State University's James L. Voss Veterinary Teaching Hospital has such a surgical program under the direction of Dr. E. Christopher Orton, whose cardiac surgery team has been replacing canines' heart valves since 1997. (See Surgery below for more information about various surgical techniques being used on dogs' mitral valves.) However, surgical replacement usually is cost-prohibitive and would require that the dog's renal system and other vital organs be in ideal condition. Therefore, MVD typically is treated by managing heart failure. The goals of the veterinary cardiologist are to improve the dog's quality of life and to increase the length of its life.

Studies are being conducted into possibly reducing the progression of MVD.  They are discussed below at Drugs to Slow the Progression of MVD.

Also, in 2008 in at least one pre-med research paper, the author suggests that injecting bone marrow stromal cells into the heart of a cavalier King Charles spaniel may stimulate stem cells to regenerate heart muscle and repair damage to the valve tissues.

The veterinarian tries to eliminate or reduce signs of fluid accumulation and congestion, and to maintain adequate cardiac output in order to provide needed blood flow. The degree of treatment will depend upon the stage of the disease. Early MVD is not treated in the same way as advanced MVD.

-- mild murmur (Stage B1)

A cavalier with early mitral valve disease has a mild murmur (Grade 1 or 2 out of 6) but otherwise is symptom-free (asymptomatic). This dog would be at Stage B1 of the ACVIM's 2009 Consensus Statement, although a dog with even a higher grade murmur (Grade 3 or 4) could meet the Stage B1 definition, if it is symptom-less and has no heart enlargement.  Cardiologists refer to this as the pre-clinical stage. There may be minimal enlargement of the heart, as shown by x-ray or ultrasound scan. At this stage, there is no need for treatment*, but heart size should be monitored by x-rays every 6 to 12 months. Overweight dogs should be put on a weight-reducing diet. Low salt diets have been suggested, to help reduce water retention. It would be prudent to avoid extreme exertion.

* The participating cardiologists in the ACVIM's 2009 Consensus Statement unanimously declined to recommend any drug or dietary therapy for Stage B1 dogs.

--- supplements

Also, the above-described supplements (Vitamin C and Vitamin E and CoQ10 and Udo's Choice Oil 3.6.9 Blend and fish oils) should be considered after MVD murmurs are detected, along with:

4Bio-Cardio, a Thorne Veterinary Products multi-vitamin, mineral, and herbal extract supplement (which includes Vitamin E, selenium, magnesium, potassium, L-Carnitine, L-Taurine, coenzyme Q-10, dimethylglycine [DMG], Hawthorne extract, desiccated bovine heart, and Siberian genseng extract).

4Canine Cardiac Support, and human-grade supplements, including Cardio-Plus, Cardiotrophin PMG, Cataplex E, and Vasculin, which are nutritional whole food supplements offered by Standard Process, Inc.

4Flavonex, a salvia and gingko extract herbal supplement made by Health Concern.

4(Natural supplements which may help to strengthen and energize the heart of a dog with severe MVD include D-Ribose (Corvalen Ribose or Pure Encapsulations Ribose), also known as alpha-D-ribofuranoside, which reportedly improves ventilatory efficiency in patients with congestive heart failure (CHF). See 2009 report. It also reportedly boosts the energy level of heart muscle cells, improving cardiovascular function and the flow of blood.)

Vitamins and food supplements such as these may be prescribed for all stages of mitral valve disease. Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained. A search webpage for finding holistic veterinarians in the United States is located here.

The participating cardiologists in the ACVIM's 2009 Consensus Statement unanimously declined to recommend any drug or dietary therapy for Stage B1 dogs. Nevertheless, studies of drugs have been conducted on dogs in Stage B1, and what follows is a discussion of the reports of those studies:

--- ACE-inhibitors

A 2002 study, sponsored by a drug manufacturer and involving 124 dogs of several breeds, suggests that dogs with only mild MVD murmurs and some enlargement of the heart but which otherwise are symptomless be prescribed angiotensin converting enzyme (ACE)-inhibitors (enalapril maleate [Enacard, Vasotec, Prilenal], benazepril hydrochloride [Lotensin, Fortekor, Benefortin, VetACE], imidapril [Tanatril], ramipril [Altace, Tritace, Vasotop], captopril, lisinopril) as therapy to postpone or prevent congestive heart failure. (See below for discussion of ACE-inhibitors' adverse side effects.) However, a 2002 Scandinavian study of 229 asymptomatic cavalier King Charles spaniels with mild MVD murmurs has shown that the such application of ACE-inhibitors had no significant affect upon the time from the initiation of ACE-inhibitor therapy to heart failure.

--- natural alternatives to ACE-inhibitors

A natural supplement as an alternative to ACE-inhibitors is a combination of active fish petides, including LKPNM, from the bonito fish (Sarda orientalis), such as Vasotensin, manufactured by Metagenics, Inc., and PeptACE by Natural Factors.  Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is located here.

--- alpha & beta blockers

Other drugs being used by some veterinary cardiologists are carvedilol (Coreg), and bisoprolol, both non-selective beta-and alpha-blockers with anti-oxidant effects which reduce the heart's rate and the force of its contraction, thereby reducing the work of the heart. Carvedilol and bisoprolol also cause the arteries to relax and the blood pressure to drop. Some cardiologists have begun to administer low doses of carvedilol and Bisoprolol early in the disease process, with the aim of causing MVD to progress at a slower rate than dogs not taking the medication. A less expensive alternative beta-blocker is atenolol (Tenormin, Tenoretic). However, atenolol lacks the vasodilatory and antioxidant properties of carvedilol.

Cardiologists often refer to these drugs as beta- (β-) adrenergic receptor antagonists (BARA).

--- pimobendan

Finally, pimobendan (Vetmedin, Cardisure), which has been prescribed for dogs with severe MVD, such as congestive heart failure, is the subject to research for treatment of dogs in the early stage of MVD. In October 2010, UK cardiologists began a study (the "EPIC Trial") giving pimobendan to cavaliers with low grade MVD murmurs to see if the drug will slow the progression of MVD to congestive heart failure. However, research reports are conflicting, and harmful side effects have been noted from early use of this drug. See the "A Few Words About Pimobendan" box below for details. As noted above, the members of the ACVIM panel who participated in its 2009 Consensus Statement unanimously refused to recommend prescribing pimobendan to Stage B1 dogs.

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-- moderate MVD (Stage B2)

Moderate MVD is indicated by a louder murmur, increased breathlessness on occasions, occasional dry, hacking coughing, and moderate to severe enlargement of the heart on x-rays or scan, with some fluid present in the lungs. At this stage, reducing exercise will help to reduce the heart's workload. This is a Stage B2 dog, according to the 2009 ACVIM Consensus Statement (although technically, Stage B2 would also include dogs with only heart enlargement and otherwise symptom-less).

A majority of the participating cardiologists in the ACVIM's 2009 Consensus Statement declined to recommend any drug or dietary therapy for Stage B2 dogs. Nevertheless, some cardiologists begin prescribing medications at this stage, and studies of drugs have been conducted on dogs in Stage B2. What follows is a discussion of the reports of those studies.

--- diuretics

Diuretics (furosemide [such as Lasix, Diuride, Frudix, Frusemide], hydrochlorothiazide [Dyazide], and co-amilozide, a combination of amiloride and hydrochlorothiazide), which are drugs which cause the kidneys to excrete more fluid than normal, may be used to remove fluid from the lungs. Side effects would be that the dog is thirstier than normal, and increased urination. Furosemide can severely affect the kidney by activating the renin-angiotensin aldosterone system (RAAS), as well as the liver and other bodily functions, and so the kidneys and liver should be evaluated before starting furosemide and should be monitored every three months thereafter.

In a 2009 study report which did not include CKCSs, veterinary cardiologists observed a three-fold increase in RAAS activity using furosemide.  Their conclusion was that "furosemide is not recommended for chronic use in the absence of concurrent therapy to blunt RAAS activity, such as ACE-I, aldosterone receptor blockers, or angiotensin II type I receptor blockers."

Medications approved to treat humans with congestive heart failure, such as the aquaretic (vasopressin receptor anatagonist = vaptans), (tolvaptan),  and another loop diuretic, torsemide (Demadex), are being empirically considered as alternatives to diuretics such as furosemide. In a 2012 report, researchers compared doses of torsemide and furosemide in treating dogs with stable congestive heart failure (Stage C). They found that "torsemide is equivalent to furosemide at controlling clinical signs of CHF in dogs and is likely to achieve greater diuresis vs. furosemide." Torsemide is approximately 10-times as potent as furosemide
in dogs and cats.

--- natural alternative diuretics

Natural diuretics include urea (AC Carbamide) by Standard Process, and Wu Ling San by Mayway and Alisma by Seven Forests, both traditional Chinese herbal medicines (TCM). Other Chinese herbal alternatives include Salvia Shou Wu, a Seven Forests patented supplement which consists of Salvia extract, and several other herbs and flowers. Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is locate here.

--- ACE-inhibitors

ACE-inhibitors (enalapril maleate [Enacard, Vasotec, Prilenal], benazepril [Lotensin, Fortekor, Benefortin, VetACE], imidapril [Tanatril], ramipril [Altace, Tritace, Vasotop]), captopril, lisinopril, may also be prescribed. ACE-inhibitors block the angiotensin converting enzyme, which is necessary to produce a substance that causes blood vessels to tighten. So, ACE-inhibitors serve to relax the blood vessels, thereby lowering the blood pressure and increasing the supply of blood and oxygen to the heart. The result is that they tend to blunt the enlargement of the heart and slow the progression of heart failure.

 In a 2007 U.S. study of 124 dogs, the researchers concluded that enalapril "modestly delays the onset of congestive heart failure in dogs with moderate to severe mitral regurgitation."

Recent studies have concluded that diuretics such as furosemide should be used only combined with ACE-inhibitors -- which also prevent fluid retention -- so that the diuretic dosage may be sharply reduced to avoid the worst of its negative side effects.

Researchers have found that extensive use of diuretics alone may contribute to renal dysfunction by activating the renin-angiotensin aldosterone system (RAAS) , as well as dehydration, azotemia (elevation of blood urea nitrogen [BUN]), and hypokalemia (low potassium).

--- natural alternatives to ACE-inhibitors

A natural supplement as an alternative to ACE-inhibitors is a combination of active fish petides, including LKPNM, from the bonito fish (Sarda orientalis), such as Vasotensin, manufactured by Metagenics, Inc., and PeptACE by Natural Factors.  Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is located here.

--- aldosterone antagonist

In a 2010 European study, spironolactone (Aldactone, Prilactone), an aldosterone antagonist (or mineralocorticoid receptor blocker -- MRB), when added to conventional cardiac therapy (such as an ACE inhibitor, plus furosemide and digoxin if needed) decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe mitral regurgitation caused by MVD.*

*But see a 2011 report indicating that spironolactone did not extend survival times of dogs with advanced heart failure.

Spironolactone has been approved within the European Union for use in dogs with clinical signs of CHF secondary to MVD, as adjunctive therapy. It typically acts as a comparatively weak diuretic, when
administered alone, but has synergistic effects when combined with other diuretics.

However, spironolactone, which is known as a potassium-sparing diuretic because, unlike some other diuretics, it does not cause the loss of potassium -- reportedly may lead to excessively high, life-threatening levels of potassium in the dog's blood, particularly when combined with ACE inhibitors. Some veterinary cardiologists recommend that potassium levels be carefully monitored when using spironolactone in combination with ACE inhibitors by drawing blood at regular intervals until it is evident that the potassium level is or is not going to be a problem.

Cardalis is a tablet which combines spironolactone with the ACE-inhibitor benazepril.

--- alpha & beta blockers

Carvedilol (Coreg), and bisoprolol, also are being prescribed for moderate MVD. They are non-selective beta-and alpha-blockers with anti-oxidant effects which reduce the heart's rate and the force of its contraction, thereby reducing the work of the heart. In a 2012 report, researchers studied the effect of carvedilol in treating cavaliers with Stage B2 MVD and found no adverse effects and median survival of 48.5 months.

Other beta blockers, also known as beta-adrenergic antagonists (BAA), include metoprolol (Lopressor, Toprol).

--- pimobendan

Pimobendan (Vetmedin, Cardisure), which has been prescribed for dogs with severe MVD, such as congestive heart failure, may be a new alternative to ACE inhibitors for dogs with only moderate MVD, based upon a 2006 study comparing the two medications. However, research reports are conflicting, and harmful side effects have been noted from early use of this drug. See the "A Few Words About Pimobendan" box below for details. A majority of the ACVIM panel who participated in its 2009 Consensus Statement did not recommend prescribing pimobendan to Stage B2 dogs.

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-- severe MVD (Stage C)

Severe MVD normally involves a murmur that has become much louder. However, the murmur can become more difficult to hear, if the heart's deterioration has been sudden. So a Grade 6 murmur later could be downgraded to a Grade 5, but that would not mean an improvement in the dog's condition. Also, the dog will have difficulty breathing while at rest, and may not be able to tolerate even minimal exercise. This is a Stage C dog, according to the 2009 ACVIM Consensus Statement. Pressure in the left atrium can be relieved by diuretics* and drugs which lower the pressure in the veins, called venodilators. Diuretics should be given by injection in severe cases. ACE inhibitors also have venodilating effects.

* See diuretics above. In a 2012 report, researchers compared doses of torsemide and furosemide in treating dogs with stable congestive heart failure (Stage C). They found that "torsemide is equivalent to furosemide at controlling clinical signs of CHF in dogs and is likely to achieve greater diuresis vs. furosemide."

Since the 2009 ACVIM Consensus Statement does not recommend any drug or dietary therapy for dogs before reaching Stage C, a method which cavalier owners can use to determine if and when their dog reaches the stage of congestive heart failure is to count the dog's breaths per minute while sleeping. In an October 2012 study, researchers found that healthy adult dogs generally have a mean sleeping respiratory rate of less than 30 breaths per minute and rarely exceed that rate at any time. Some cardiologists recommend that their patient's owners periodically count their dog's respiratory rate, and when the average rate starts to creep up to the high twenties, to make an appointment for the dog to be re-examined by the cardiologist to see if the dog is approaching or has reached the stage of congestive heart failure.

--- diuretics

Treatment will be necessary at this stage, usually in a tablet form. Since a dog with moderate MVD begins to retain fluid and salt, drugs which prevent fluid retention, or which increase fluid elimination, may be used. Diuretics (furosemide [such as Lasix, Diuride, Frudix, Frusemide], hydrochlorothiazide [Dyazide], and co-amilozide, a combination of amiloride and hydrochlorothiazide), which are drugs which cause the kidneys to excrete more fluid than normal, may be used to remove fluid from the lungs. Side effects would be that the dog is thirstier than normal, and increased urination. Furosemide can severely affect the kidney by activating the renin-angiotensin aldosterone system (RAAS), as well as the liver and other bodily functions, and so the kidneys and liver should be evaluated before starting furosemide and should be monitored every three months thereafter.

In a 2009 study report which did not include CKCSs, veterinary cardiologists observed a three-fold increase in RAAS activity using furosemide.  Their conclusion was that "furosemide is not recommended for chronic use in the absence of concurrent therapy to blunt RAAS activity, such as ACE-I, aldosterone receptor blockers, or angiotensin II type I receptor blockers."

Medications approved to treat humans with congestive heart failure, such as the aquaretic (vasopressin receptor anatagonist = vaptans), (tolvaptan),  and another loop diuretic, torsemide (Demadex), are being empirically considered as alternatives to diuretics such as furosemide. In a 2012 report, researchers compared doses of torsemide and furosemide in treating dogs with stable congestive heart failure (Stage C). They found that "torsemide is equivalent to furosemide at controlling clinical signs of CHF in dogs and is likely to achieve greater diuresis vs. furosemide." Torsemide is approximately 10-times as potent as furosemide
in dogs and cats.

--- natural alternative diuretics

Natural diuretics include urea (AC Carbamide) by Standard Process, and Wu Ling San by Mayway and Alisma by Seven Forests, both traditional Chinese herbal medicines (TCM). Other Chinese herbal alternatives include Salvia Shou Wu, a Seven Forests patented supplement which consists of Salvia extract, and several other herbs and flowers. Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is located here.

--- ACE-inhibitors

ACE-inhibitors (enalapril maleate [Enacard, Vasotec, Prilenal], benazepril [Lotensin, Fortekor, Benefortin, VetACE], imidapril [Tanatril], ramipril [Altace, Tritace, Vasotop]), captopril, lisinopril, usually also will be prescribed. ACE inhibitors block the angiotensin converting enzyme, which is necessary to produce a substance that causes blood vessels to tighten. So, ACE inhibitors serve to relax the blood vessels, thereby lowering the blood pressure and increasing the supply of blood and oxygen to the heart. The result is that they tend to blunt the enlargement of the heart and slow the progression of heart failure.

Recent studies have concluded that diuretics such as furosemide should be used only combined with ACE inhibitors -- which also prevent fluid retention -- so that the diuretic dosage may be sharply reduced to avoid the worst of its negative side effects. Researchers have found that extensive use of diuretics alone may contribute to renal dysfunction by activating the renin-angiotensin aldosterone system (RAAS) , as well as dehydration, azotemia (elevation of blood urea nitrogen [BUN]), and hypokalemia (low potassium).

--- natural alternatives to ACE-inhibitors

A natural supplement as an alternative to ACE-inhibitors is a combination of active fish petides, including LKPNM, from the bonito fish (Sarda orientalis), such as Vasotensin, manufactured by Metagenics, Inc., and PeptACE by Natural Factors.  Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is located here.

--- spironolactone, aldosterone antagonist

In a 2010 European study, spironolactone (Aldactone, Prilactone), an aldosterone antagonist (or mineralocorticoid receptor blocker -- MRB), when added to conventional cardiac therapy (such as an ACE inhibitor, plus furosemide and digoxin if needed) decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe mitral regurgitation caused by MVD.*

*But see a 2011 report indicating that spironolactone did not extend survival times of dogs with advanced heart failure.

Spironolactone has been approved within the European Union for use in dogs with clinical signs of CHF secondary to MVD, as adjunctive therapy. It typically acts as a comparatively weak diuretic, when
administered alone, but has synergistic effects when combined with other diuretics.

However, spironolactone, which is known as a potassium-sparing diuretic because, unlike some other diuretics, it does not cause the loss of potassium -- reportedly may lead to excessively high, life-threatening levels of potassium in the dog's blood, particularly when combined with ACE inhibitors. Some veterinary cardiologists recommend that potassium levels be carefully monitored when using spironolactone in combination with ACE inhibitors by drawing blood at regular intervals until it is evident that the potassium level is or is not going to be a problem.

Cardalis is a tablet which combines spironolactone with the ACE-inhibitor benazepril.

--- pimobendan & arteriolardilators

Reducing pressure in the arteries can make it easier for the heart to pump. ACE inhibitors reduce arterial pressure, as do arteriolardilators (hydrazaline [Apresoline], pimobendan (Vetmedin, Cardisure), and sodium nitroprusside. In advanced heart failure, the heart muscle may become weakened so that it does not contract properly. Digoxin (Lanoxin), a cardiac glycoside extracted from the foxglove plant (digitalis), may be used to improve heart muscle strength to help the heart contract more strongly. Pimobendan (Vetmedin, Cardisure) reportedly eases the resistance in the circulatory system by dilating blood vessels, and improves the efficiency with which the heart can function as a pump, thereby both improving cardiovascular function and the blood flow to major organs.

--- sildenafil (Viagra) and tadalafil (Cialis)

Also, sildenafil (Viagra) (a/k/a sildenifil) a phosphodiesterase (PDI) 5 inhibitor, is being prescribed to lower pulmonary hypertension by some cardiologists for dogs with congestive heart failure, often in combination with pimobendan. In an April 2006 French study report, tadalafil (Cialis), a long-acting PDI-5 inhibitor, belonging to the same family as sildenafil, has been shown to have decreased systolic pulmonary arterial pressure significantly. However, research by Dr. Rosemary A Henik, of the University of Wisconsin-Madison, has indicated that pulmonary venous hypertension due to left heart disease, is managed best with "afterload" reduction, and not sildenafil. More recently, a 2007 study by Drs. Joao S. Orvalho, William P. Thomas, and P. H. Kass found that "these data suggest that oral tadalafil, when added to conventional heart failure therapy, decreases the pulmonary artery pressure in this group of dogs."

--- natural alternatives

In addition to the natural alternatives to diuretics and ACE inhibitors and arteriolardilators described above, natural supplements which may help to strengthen and energize the heart of a dog with severe MVD include D-Ribose (Corvalen Ribose or Pure Encapsulations Ribose), also known as alpha-D-ribofuranoside, which reportedly improves ventilatory efficiency in patients with congestive heart failure (CHF). See 2009 report. It also reportedly boosts the energy level of heart muscle cells, improving cardiovascular function and the flow of blood.  Holistic supplements should be taken only if prescribed by a licensed veterinarian who also is holistically trained in TCM. A search webpage for finding holistic veterinarians in the United States is located here.

A good general health supplement for older dogs in congestive heart failure is N, N-Dimethylglycine (DMG). Vetri-DMG is a pure DMG product offered by Vetri-Science Laboratories of Vermont (www.vetriscience.com). DMG is said to support the immune system, promote oxygen utilization, improve cardiovascular function, support liver function, and support ocular health.

-- end stage of MVD (Stage D)

Follows the Pimobendan box just below.

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-- end stage of MVD (Stage D)

Often, the cavalier in the late stage of congestive heart failure suffers from a progressive deterioration of the quality of its life, which is due to the combination of an inability to comfortably keep the dog free from fluid congestion in its heart, lungs, and abdominal cavity, together with enlarged heart chambers, lethargy, collapse, and deterioration of its kidney and/or liver functions. Eventually diuretics, ACE inhibitors, other drugs, and even pimobendan, no longer are able to remove enough of the fluids and increase the supplies of blood and oxygen to the heart. This is a Stage D dog under the 2009 ACVIM Consensus Statement.

A good general health supplement for older dogs in congestive heart failure is N, N-Dimethylglycine (DMG). Vetri-DMG is a pure DMG product offered by Vetri-Science Laboratories of Vermont (www.vetriscience.com). DMG is said to support the immune system, promote oxygen utilization, improve cardiovascular function, support liver function, and support ocular health.

--- appetite stimulants

General nutrition is very important. cavaliers at this advanced stage may suffer severe weight loss, called progressive cardiac cachexia, and they should be fed any palliative food to maintain muscle mass. Cardiologists may prescribe an appetite stimulant, such as mirtazapine (Remeron) or meclizine (Antivert, Bonine, Dramamine II, Driminate II).

--- bronchial dialators

Dogs with severe flooding of the lungs should not be exerted in any way. Some cardiologists may prescribe a bronchial dialator, such as aminophylline, oxtriphylline, theophylline (Corvental, Apo-Theo-LA), or terbutaline (Brethine, Bricanyl) which are human grade prescription medications which relax and open air passages in the lungs, making breathing easier. A narcotic, hydrocodone bitartrate (Hydodan, Tussigon, Mycodone), may be prescribed to suppress the coughing by affecting the brain's cough centers.

The onset of acute pulmonary edema requires immediate recognition and therapy, including oxygen treatment, in order to save the dog's life. (See the Darcy's Daily Blog entry dated 8/25/06 for details of symptoms requiring oxygen treatment.) Retained fluids (ascites), which fill the peritoneal cavity of the abdomen due to tricuspid valve deterioration, may be removed periodically by aspiration with a hypodermic needle (abdominocentesis).

--- avoid vaccines

Some cardiologists recommend that dogs with advanced mitral valve disease not be vaccinated with the usual serums, including rabies, because of possible adverse reactions which might accelerate damage to the dogs' hearts. In such cases, the veterinarians will write letters to the county licensing authorities which require periodic vaccinations, and in many instances, the counties will accept the cardiologists' letters and excuse the dogs from having to be vaccinated. There is a large body of research, much of which may be found on the Internet, on the questions of vaccinosis and other health problems attributed to annual or other periodic vaccinations, particularly immune-mediated disorders.

--- euthanasia

At this stage of deterioration, inability to breathe, and suffering, the owner may elect euthanasia, rather than to allow the dog to continue to suffer.

For an in-depth on-line seminar about the symptoms, diagnosis, progression, and treatment of mitral valve disease, watch Dr. Andrew Beardow, with his terrific active graphics, explain MVD.

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-- diet and drugs to slow the progression of MVD

UK cardiologist Simon Swift noted at a 2010 symposium that:

"Interestingly, asymptomatic dogs fed a 'heart diet' had a reduction in heart size. The 'heart diet' included decrease sodium, increased levels of arginine, carnitine and taurine as well as supplementation with omega 3 fatty acids. Whether this translates into a delay before heart failure develops remains to be proven."

The Heart Diet was reported in a 2006 article by Drs. Lisa M. Freeman (board certified veterinary nutritionist) and John E. Rush (board certified veterinary cardiologist), and by Peter J. Markwell (senior veterinary nutritionist at a UK dog food company). They fed "a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine" for four weeks to fourteen dogs, including cavaliers, with asymptomatic mitral valve disease. Another fifteen asymptomatic dogs, including cavaliers, were fed a placebo. They found that the dogs on the heart diet had measurable reductions in heart size, including the left-atrial dimension and left-ventricular internal dimension.

A downside of this 2006 study was that the food fed in both diets consisted of "commercial, extruded, dry dog foods", i.e., kibble. Another downside is that the study was funded by Mr. Markwell's employer, a kibble manufacturer.

See a list of suggested heart-healthy supplements here.

Two studies are being conducted to find medications directed at the pathology of mitral valve disease and which may slow the progression of MVD.

--- serotonin blockers

One of the two studies involves blocking the cavalier's excessive production of serotonin. Research thus far has suggested that: (a) serotonin (5HT) activates growth activity in canine mitral valves; (b) dogs with MVD have more serotonin receptors in their valve cells than other dogs; (c) mitral valve cells have the capacity to make their own serotonin; and (d) cavaliers also have a higher level of serotonin in their bloodstream. See, e.g., this June 2011 report.

Researchers are exploring the possibility that if serotonin levels can be reduced, by blocking the receptors in the mitral valves, then the progression of the deterioration of the valves and their leaflets can be slowed.  One existing drug, approved for use by humans in Europe, is being tested on dogs with MVD to determine its effectiveness in reducing the level of serotonin and slowing the progression of MVD in cavaliers.

These drugs may include ketanserin, a 5HT-R2A receptor blocker, or GR55562, a 5HT-R1B receptor blocker, based upon suggestions made by Dr. Mark Oyama in his September 2009 report and January 2010 report.

See more information under Research News below.

--- beta blockers

The other study involves a beta blocker intended to slow the progression of MVD.  This study is being conducted at veterinary schools and some cardiology clinics throughout the United States.  The researchers need participating dogs.  See details below.

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Surgery

A few veterinary surgery centers have experimented with surgically repairing the mitral valves or replacing either the mital valve tendons (chordae tendineae) or the valve leaflets with implants, such as pig or cow heart valves or mechanical devices.

Other surgeons have replaced chordae tendineae and valve leaflets with polytetrafluoroethylene (PTFE) and expanded polytetrafluoroethylene (ePTFE) implants are made of a carbon and fluorine based synthetic polymer (Gore-Tex and SoftForm) that is biologically inert and non-biodegradable in the body. In a 2012 article, Japanese veterinary surgeons report that using ePTFE "has excellent tissue compatibility and durability and can be effectively used for canine mitral valve repair."

The box below lists locations where mitral valve surgeries have been performed, with details about their techniques, success rates, and costs.