Canine myxomatous mitral valve disease diagnosis and treatment

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The disease and the dogs it affects

The consensus panel lists endocardiosis and degenerative or chronic valvular heart disease as other names for MMVD [1]. The panel describes changes to collagen and proteoglycans in the valve leaflets and chordae tendineae. These changes gradually distort the valve until the leaflets no longer meet. Blood then leaks back into the left atrium, and the heart responds by enlarging the atrium and ventricle [1].

The Merck Veterinary Manual reports how lesions are distributed among affected dogs [2]:

• About 60% have only mitral involvement.
• About 30% have both mitral and tricuspid lesions.
• Fewer than 10% have tricuspid disease alone.

The consensus reports the following patterns [1]:

• The disease is about 1.5 times more common in males.
• It is more common in dogs under 20 kg.
• Up to 85% of small-breed dogs show the valve lesion by 13 years of age.
• Cavalier King Charles Spaniels develop it young, but they do not appear to progress to heart failure much faster than other small breeds.
• Large dogs tend to progress faster and carry a more guarded prognosis.

Merck describes the disease as inherited in Cavalier King Charles Spaniels and Dachshunds [2]. A 2017 review in Veterinary Sciences notes that some small breeds have a lifetime incidence approaching 100% [4].

Clinical presentation

Merck describes no clinical signs in the early and middle stages apart from a systolic murmur loudest at the left apex [2]. Once regurgitation becomes severe, pulmonary edema causes tachypnea, dyspnea, and sometimes cough, and syncope can occur. Sudden death is rare but may occur after rupture of the left atrium or a primary chord [2]. The consensus notes that most dogs have a recognizable murmur for years before heart failure begins [1]. Merck estimates that only about 30% of dogs with mitral regurgitation ever develop congestive heart failure (CHF) [2].

Merck reports these ECG findings [2]:

• Dogs with mild to moderate disease show sinus rhythm or sinus arrhythmia.
• When CHF develops, sinus arrhythmia is often lost and sinus tachycardia appears.
• Left atrial enlargement predisposes dogs to atrial premature complexes and atrial fibrillation.

Diagnosis and testing pitfalls

For dogs in stage B, the consensus recommends three steps [1]:

• Thoracic radiographs for all dogs, partly so that baseline films exist before any cough develops.
• Blood pressure measurement for all dogs.
• Echocardiography by an experienced operator to confirm the cause of the murmur and measure chamber size.

The 2017 review adds that echocardiography provides the definitive diagnosis, because dogs with mild disease may have no audible murmur [4].

The sources point to several traps.

• Airway disease is common in the same population. The panel cautions that a typical murmur in a coughing dog does not by itself mean CHF [1].
• The panel considers obese dogs with no weight loss, and dogs with marked sinus arrhythmia and slow heart rates, less likely to be in heart failure [1].
• A low-velocity E wave on pulsed-wave Doppler before treatment argues strongly against left-sided heart failure, according to the consensus [1].
• Merck advises against judging severity from the size of the color-flow jet and calls left atrial size the more reliable estimate [2].
• Merck notes that when acute heart failure results from ruptured chordae tendineae, the left atrium is not severely enlarged [2].
• Normal VHS values vary with breed and thoracic conformation, which the panel says calls for caution when radiographs are used without echocardiography [1].

For dogs in heart failure, the consensus calls for the following as soon as practical: PCV, total protein, creatinine, urea nitrogen, electrolytes, and urine specific gravity. The panel singles out impaired renal function as an important comorbidity [1].

Staging under the 2019 ACVIM consensus

The panel writes that "ideally, all these criteria should be met before initiating treatment," and it considers echocardiographic enlargement the most reliable way to identify B2 [1]. When echocardiography is unavailable, the panel accepts either of two substitutes: a general-breed VHS of 11.5 or more, or accelerating enlargement on serial imaging. It adds that VLAS (vertebral left atrial size) values of 3 or more "likely identify Stage B2 MMVD" [1].

Dogs in stage C remain in stage C after their signs resolve. Reclassification to stage B is reserved for dogs that undergo successful surgical valve repair [1].

Treatment by stage

Stages A and B1

The panel recommends no drug or diet treatment at these stages. It advises that dogs used for breeding stop being bred if a murmur or mitral regurgitation is found before 6 to 8 years of age [1].

Stage B2

The consensus recommends pimobendan "at a dosage of 0.25-0.3 mg/kg PO q12h" as a Class I recommendation with strong evidence [1]. The panel also recommends mild dietary sodium restriction with a palatable diet that supplies enough protein and calories (Class IIa) [1].

On ACE inhibitors the panel split, with 5 of 10 panelists recommending them [1]. The 2017 review was written while the 2009 guidelines were under revision. It described ACE inhibitors at this stage as not recommended by a consensus of the panelists [4]. The panel does not recommend beta blockers or routine spironolactone at this stage [1].

The pimobendan recommendation rests largely on EPIC, a prospective, randomized, placebo-controlled, blinded, multicenter trial of 360 dogs [3]. The trial reported these results [3]:

• The hazard ratio for the primary endpoint was 0.64.
• Median all-cause survival was 1059 days on pimobendan versus 902 days on placebo.
• Adverse events did not differ between groups.

The authors addressed several limits:

• Enrollment was restricted to dogs weighing 4.1 to 15 kg. The authors said this reflected the tablet sizes available and that extrapolation to dogs of any body weight is likely but not proven [3].
• The trial was stopped early after a planned interim analysis [3].
• The trial was funded by Boehringer Ingelheim Animal Health GmbH, and the authors acknowledged industry funding as a potential source of bias [3].

The authors also stated that treating every dog with a compatible murmur "would not be justified on the basis of the findings of this study" [3].

Stage C, in hospital

The consensus recommends furosemide 2 mg/kg IV or IM, repeated hourly until breathing improves or a total of 8 mg/kg has been given over 4 hours [1]. Alongside it, the panel lists pimobendan, oxygen, free access to water once diuresis starts, and sedation. Butorphanol 0.2 to 0.25 mg/kg IM or IV was the narcotic panelists most often used [1]. The panel describes dobutamine and nitroprusside as options for dogs that respond poorly [1].

Stage C, at home

The panel's chronic regimen includes [1]:

• Oral furosemide, commonly 2 mg/kg q12h.
• An ACE inhibitor such as enalapril or benazepril at 0.5 mg/kg PO q12h.
• Spironolactone at 2.0 mg/kg PO q12-24h.
• Continued pimobendan.

The panel advises against starting a beta blocker while signs of CHF are active (Class IV) [1]. For atrial fibrillation, it recommends diltiazem, often combined with digoxin, with a target mean heart rate below 125 beats per minute [1]. Dietary guidance includes about 60 kcal/kg of body weight daily, adequate protein, and modest sodium restriction from all food sources [1].

Stage D

By the consensus definition, stage D dogs need more than 8 mg/kg of furosemide per day alongside standard doses of the other drugs [1]. Options the panel describes include:

• Torsemide for dogs no longer adequately responsive to furosemide.
• Afterload reduction with hydralazine or amlodipine.
• Sildenafil when pulmonary hypertension is present.
• An off-label third daily dose of pimobendan, which the panel says should be explained to and approved by the client.

The 2017 review described torsemide as usually reserved for dogs with recurrent CHF despite furosemide at 4 mg/kg/day or more [4]. The 2019 consensus defines stage D by a furosemide requirement above 8 mg/kg per day [1].

Surgery

The consensus rates mitral valve repair as Class I for stage C dogs at centers with low complication rates [1]. Merck describes the only successful program as being in Japan and calls it expensive. It reports that valve replacement is "almost uniformly unsuccessful" [2].

Monitoring and prognosis

For stage B1, the panel suggests repeat echocardiography, or radiography if echocardiography is unavailable, in 6 to 12 months [1]. The consensus lists several factors that are at least moderately predictive of progression [1]:

• Age.
• Enlargement of the left atrium and ventricle.
• Higher E-wave velocities.
• Higher NT-proBNP.
• Higher resting heart rate.

In EPIC's multivariable analysis, LA:Ao, LVIDDN, and reduced appetite were independently linked to reaching the endpoint sooner [3]. The 2017 review cites an estimated systolic pulmonary pressure above 55 mmHg as an independent predictor of poor outcome in stage B2 and C dogs [4].

For stage C, the consensus recommends checking creatinine, urea nitrogen, and electrolytes 3 to 14 days after starting furosemide, and creatinine and electrolytes 3 to 14 days after starting an ACE inhibitor. It flags a creatinine rise of 30% or more from baseline as a concern for acute kidney injury [1]. The EPIC authors note that median survival in stage C is under 1 year despite recommended treatment [3].

Merck says some dogs live more than a year but cautions that survival varies too much for firm estimates. It advises reassessing the diagnosis if a dog has been treated for left heart failure for more than 2 years [2].

Points for client conversations

The consensus supports several topics for client conversations:

• Small breeds should have yearly auscultation [1].
• Pimobendan at stage B2 "represents a lifelong commitment" [1].
• Among home-monitored variables, the panel identifies a rise in resting respiratory rate above baseline as having the best predictive value for impending decompensation [1].
• Cachexia, meaning loss of muscle or lean body mass with or without weight loss, has substantial negative prognostic implications. The panel says it is much easier to prevent than to treat [1].
• The panel recommends asking about anorexia and recording body condition score and weight at every clinic visit [1].

Before using any dose aboveVerify against the current label/formulary and the patient's full clinical picture.