Canine Degenerative Mitral Valve Disease Christian Weder DVM, MS, DACVIM (Cardiology) Great Lakes Veterinary Conference

Canine Degenerative Mitral Valve Disease Christian Weder DVM, MS, DACVIM (Cardiology) Great Lakes Veterinary Conference Introduction Degenerative mitral valve disease (DMVD) is the most common form of acquired cardiovascular disease in dogs and accounts for approximately 75% of cases of heart disease in the species.1 It is also referred to as chronic valvular heart disease (CVHD), endocardiosis, and myxomatous mitral valve disease (MMVD) in the veterinary literature. While the disease is more commonly diagnosed in small breeds, it can also occur in large dogs. DMVD primarily affects the mitral valve, although approximately 30% of cases have concurrent disease of the tricuspid valve and a smaller proportion have lesions of the aortic valve.2 Males are 1.5 times more likely to develop the disease and often have a younger age of onset.3 DMVD is a form of acquired heart disease that often develops in dogs older than 5 years of age. With that said, Cavalier King Charles Spaniels are predisposed to developing DMVD at a younger age.4 The cause of DMVD is unknown, however, there is undoubtedly a heritable component in many breeds. It is typically recognized by the presence of a systolic heart murmur over the left cardiac apex. The disease progression is generally slow, although the exact clinical course is often variable and difficult to predict. As dogs age, the prevalence of DMVD increases, with 85% of small breeds showing evidence of valvular lesions by 13 years.5 Classification In 2009, guidelines for the diagnosis and treatment of DMVD were published in the Journal of Veterinary Internal Medicine.2 An update to these guidelines was published in 2019.1 The guidelines provide a useful consensus and structure for the management of DMVD in practice. The staging system outline by the consensus panel describes 4 basic stages of DMVD in dogs and is summarized below. Stage A Patients with stage A DMVD are at higher than average risk for developing heart failure but do not have any apparent structural abnormality at the time of examination. These patients are identified by the absence of an audible heart murmur. For example, every Cavalier King Charles without a murmur is classified into this stage of DMVD. While the author does not find this stage to be particularly useful, it may justify more frequent screenings and careful auscultation, particularly with increasing age. Dog shows and other breed sponsored events with a board-certified cardiologist provide additional screening opportunities for these patients. As these dogs have no evidence of overt disease, no drug therapy or dietary modifications are recommended for stage A DMVD. Repeat screenings should be considered every 6-12 months. Stage B Stage B refers to dogs with a structural abnormality typical of DMVD but that have never had clinical signs of heart failure. These are patients with a typical left apical systolic murmur but do not have a history of a cardiogenic cough and have a normal respiratory history. Stage B DMVD is typically recognized during routine health exams. Because of the importance of this stage, it is subclassified into B1 and B2, as outlined below. Thoracic radiographs, blood pressure measurement, and echocardiography are recommended in all patients, once a heart murmur is identified. If the client is unable to pursue an echocardiogram, thoracic radiography can be used as the primary diagnostic tool in these patients. Stage B1: Patients with a hemodynamically insignificant amount of valvular regurgitation as assessed through thoracic radiography and/or echocardiography. Stage B1 is characterized by a spectrum of findings that can range from normal left ventricular and left atrial dimensions to evidence of mild chamber enlargement that does not meet the criteria outlined for stage B2. If thoracic radiographs are performed, the vertebral heart score (VHS) should be used to establish a normal cardiac silhouette size.6 If using the VHS, always remember to check for breed specific reference ranges. If no clear cardiac enlargement is established on diagnostics, no drug therapy or dietary modifications are recommended. Recheck imaging is recommended in 6-12 months to primarily assess for progressive cardiomegaly. Stage B2: Patients with a hemodynamically significant amount of valvular regurgitation. Dogs with stage B2 DMVD are asymptomatic but have severe enough valvular regurgitation to cause significant enough cardiac remodeling that justifies treatment. These patients have murmur intensities of a grade 3 or higher, moderate left ventricular and left atrial enlargement, as well as an increased VHS. There are specific cut- offs for the left ventricular and left atrial dimensions that have been published in the EPIC trial.7 If these specific criteria are met, treatment with pimobendan is recommended at a dosage of 0.25-0.3mg/kg PO q12. There is no clear consensus on the use of angiotensin converting enzyme inhibitors (ACEi) in dogs prior to the onset of congestive heart failure. The author tends to use ACEi in the presence of concurrent systemic hypertension and/or progressive increase in the left atrial dimension on successful monitoring exams. Recheck imaging is recommended every 6-9 months or at the time clinical symptoms develop. Stage C Stage C DMVD refers to patients that have current or past clinical signs of congestive heart failure (CHF) but are not refractory to standard therapy. Common clinical signs of include coughing, tachypnea, dyspnea, and restlessness. It is important to note that not every dog that is coughing with a murmur typical of DMVD is in congestive heart failure. Therefore, it is important to differentiate coughing that is due to CHF from that which is due to a primary respiratory etiology (tracheal disease, bronchitis, etc.). Thoracic radiography is the test of choice for definitively determining the presence or absence of pulmonary edema secondary to CHF. While echocardiography is helpful in supporting the diagnosis of CHF and can identify comorbidities, it does not allow for definitive assessment of the pulmonary parenchyma. Basic laboratory testing is indicated in all patients, primarily to evaluated renal function prior to the use of diuretics. Treatment recommendations for stage C can be classified into acute (hospital-based) and chronic (home-based) strategies. Acute Treatment: For the acute treatment of congestive heart failure, the acronym FONS+P can be used. F refers to furosemide, the primary medication used to clear pulmonary edema. The author typically uses a starting bolus of 2mg/kg (range 1-4mg/kg), ideally given via the IV route (or IM). Repeat 2mg/kg boluses can be administered hourly, however, a total dosage of great than 8mg/kg in 4-hour period should be avoided. For life-threatening pulmonary edema, a constant rate infusion of furosemide (0.66-1mg/kg/hr) can also be used following the initial bolus. Supplemental oxygen (O), if needed, should be administered. Although less commonly used, vasodilatory agents can also be considered. Nitroglycerin (N) is a venodilator that can be administered as a paste (1/2” paste per 10kg BW on pinna of ear) to decrease preload. Nitroprusside is a veno- and arteriodilator that is typically reserved for dogs with profound concurrent systemic hypertension. Anxiety associated with dyspnea should be treated with sedation (S). The author typically administers butorphanol at 0.2mg/kg IV, however, other agents such as buprenorphine, morphine, and low dose acepromazine can be used. Finally, if the patient can take oral medications, pimobendan (P) should also be administered in the acute setting (0.25-0.3mg/kg PO). Proper and optimal nursing care is also important to maintain patient comfort and temperature during treatment. Mechanical treatments (abdominocentesis and/or thoracocentesis) should be performed, as needed to relieve effusions Chronic Treatment: Once a patient has been successfully treated for CHF acutely (if necessary), they should be transitioned to oral medications for home-based care. Furosemide should be administered to effect, but the author typically uses a starting dose of 2mg/kg BID. For recurrent episodes of CHF, dose increases in furosemide are recommended. An ACE inhibitor should be started or continued. The author typically uses enalapril 0.5mg/kg BID, although benazepril is also commonly prescribed. Pimobendan should also be started or continued (0.25-0.3mg/kg BID). Finally, spironolactone (2 mg/kg SID-BID) should also be started after the onset of congestive heart failure. Recheck bloodwork (primarily renal values and electrolytes) is imperative and should be performed 3-14 days after initiating therapy (exact time depends on baseline renal function). If significant alternations in renal values are noted, dose reduction(s) should be considered. Stage D Stage D DMVD refers to patients with clinical signs that are refractory to standard therapy for stage C. Dogs with this stage of disease typically require a total daily dose of furosemide greater than 8mg/kg/day, in addition to the other standard medications outlined above. Any arrhythmia that is present (i.e. atrial fibrillation, etc.) should be controlled prior to deeming a patient to be refractory. Three times daily dosing of furosemide and pimobendan should be considered in this stage. Torsemide, a potent long-acting loop diuretic, is becoming more common and can replace furosemide in dogs that have become refractory to its effects. Torsemide is approximately 10x as potent as furosemide and, therefore, is typically dosed at approximately 5-10% of the current total daily dose of furosemide.8 Careful monitoring of renal values is recommended as the risk of developing azotemia increased with higher dose diuretic use. Other treatments for patients with stage D DMVD include more vigorous afterload reduction using amlodipine, sildenafil for pulmonary hypertension, and the addition of hydrochlorothiazide for sequential nephron blockade. Cavitary centesis should also be performed, as indicated, to maintain patient comfort. Adjunct therapy for residual coughing can also be considered (see section below).

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