ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs (Part 1 of 2). To view Part 2 of 2 click here.

6.4.1 Recommendations for treatment of Stage B2

• Pimobendan is recommended at a dosage of 0.25-0.3 mg/kg PO q12h.44, 55 (Class I, LOE: strong)
• Dietary treatment is recommended. Principles guiding dietary treatment at this stage include mild dietary sodium restriction and provision of a highly palatable diet with adequate protein and calories for maintaining optimal body condition.56 (Class IIa, LOE: weak)
• Angiotensin converting enzyme inhibitors (ACEI): For patients in Stage B2 on either initial examination, or in which the LA has increased markedly in size on successive monitoring examinations, 5 (of 10) panelists recommend treatment with ACEI.57-59 (Class IIa in geographic regions where ACEI are low cost, LOE: weak)

Clinical trials addressing the efficacy of ACEI for treatment of dogs in Stage B have shown mixed results.

• Beta blockade is not recommended routinely to delay the onset of heart failure in dogs in Stage B2, regardless of heart enlargement. Clinical trials addressing the efficacy of beta blockers for the treatment of dogs in Stage B2 have shown no benefit to date. (Class III, LOE: weak)
• Spironolactone also is not recommended for routine use to delay the onset of heart failure in dogs. Clinical trials addressing the efficacy of spironolactone for the treatment of dogs in Stage B2 have not been published as of this writing (2019), although a pilot study suggests this approach should be used60 (Class IIb, LOE: expert opinion).
• No other pharmacologic treatments for Stage B were recommended by a majority of panelists. A few panelists considered the use of the following medications for patients in advanced Stage B2 under specific circumstances: beta blockers, amlodipine. These treatment strategies require further investigation to assess their efficacy and safety in this patient population before definitive recommendations can be made. (Class III, LOE: expert opinion)
• Some panelists find the use of cough suppressants useful in occasional patients in advanced Stage B2 when their cough is thought to be the result of pressure from cardiac enlargement (without pulmonary edema) on adjacent bronchi. (Class IIa, LOE: expert opinion)
• Surgical intervention in advanced Stage B2 is possible and recommended by some panelists for clients who can afford and access mitral valve repair at the few centers demonstrating evidence of acceptably low complication rates and effective, durable results.61-63 (Class IIa, LOE: moderate)

6.5.1 Recommendations for diagnosis of Stage C

The signalment, history, and physical examination can be helpful in determining the pretest probability of heart failure as a cause of clinical signs in patients with MMVD. For example, obese dogs with no history of weight loss are less likely to be in heart failure secondary to MMVD; dogs with marked sinus arrhythmia and relatively slow heart rates also are less likely to have clinical signs attributable to MMVD than are those with similar clinical signs (eg, cough, dyspnea) with sinus rhythm or sinus tachycardia. (Class I, LOE: expert opinion)

• The typical dog in Stage C from MMVD presents with clinical signs of left-sided CHF and a history that can include tachypnea, restlessness, respiratory distress, or cough. Because of the relatively high prevalence of chronic tracheobronchial disease in the population most at risk for MMVD, the presence of a typical left apical regurgitant quality murmur in a coughing dog does not necessarily mean that clinical signs are the result of CHF. A clinical database (including thoracic radiographs and ideally an echocardiogram) should be obtained. Additionally, basic laboratory tests, including at a minimum PCV as well as serum total protein, creatinine, urea nitrogen and electrolyte concentrations, and urine specific gravity) should be obtained as soon as practical in dogs with heart failure. Impaired renal function in particular represents an important comorbidity in dogs with heart failure. (Class I, LOE: expert opinion)
• Echocardiography with Doppler studies also is useful in the diagnosis of dogs with MMVD that have advanced to Stages C and D. Cardiac ultrasound examination can confirm the presence of MMVD, quantify chamber enlargements and cardiac function, provide general estimates of LV filling pressures, and identify comorbidities and complications of chronic MR. These might include pulmonary hypertension, acquired atrial septal defect, and pericardial effusion from an atrial tear or unrelated cardiac tumor. As an example, a pretreatment finding of a low-velocity E-wave on pulsed-wave Doppler strongly argues against a diagnosis of left-sided heart failure. Conversely, most dogs in Stages C and D have high-velocity early filling waves. In dogs with evidence of symptomatic pulmonary hypertension (eg, exertional fatigue, collapse or syncope, ascites from right-sided CHF), spectral Doppler findings can substantiate the diagnosis and help guide therapeutic decision-making.
• Serum NT-proBNP concentrations (obtained using a commercially available test) can add useful adjunct evidence when determining the cause of clinical signs in dogs with MMVD, especially when the NT-proBNP concentration is normal or nearly normal in a symptomatic animal. As a group, dogs with clinical signs caused by heart failure have higher serum NT-proBNP concentrations than do dogs in which clinical signs are caused by primary pulmonary disease, although the positive predictive value of any single specific NT-proBNP concentration has not been adequately characterized. A normal or near normal NT-proBNP concentration in a dog with clinical signs of cough, dyspnea, or exercise intolerance strongly suggests that heart failure is not the cause of the clinical signs.64, 65 (Class I, LOE: moderate)
• Most symptomatic dogs with MMVD are middle-aged or older, and it is prudent to complete the clinical database with a blood pressure assessment, CBC, serum biochemical profile, and urinalysis, especially if treatment for CHF is anticipated. (Class I, LOE: expert opinion)

6.5.2 Recommendations for acute (hospital-based) treatment of Stage C

• Furosemide 2 mg/kg administered IV (or intramuscularly [IM]), followed by 2 mg/kg IV or IM hourly until the patient's respiratory signs are substantially improved (ie, respiratory rate and effort are decreased) or a total dosage of 8 mg/kg has been reached over 4 hours. (Class I, LOE: expert opinion)
• For life-threatening pulmonary edema (ie, expectoration of froth associated with severe dyspnea, radiographic white-out lung, poor initial response to furosemide bolus with failure of respiratory effort and rate to improve over 2 hours), furosemide also may be administered as a constant rate infusion (CRI) at a dosage of 0.66-1 mg/kg/hour after the initial bolus.66, 67 (Class IIa, LOE: weak)
• Allow the patient free access to water once diuresis has begun. (Class I, LOE: expert opinion; humane considerations apply)
• Pimobendan, 0.25-0.3 mg/kg administered PO q12h. Although the clinical trial evidence supporting the chronic use of pimobendan in the management of Stage C heart failure from MMVD is stronger than for the acute presentation, the recommendation to use pimobendan in acute heart failure treatment is strongly supported by hemodynamic and experimental evidence68 as well as the anecdotal experience of the panelists. In many countries outside of the United States, pimobendan for IV administration is available. (Class I, LOE: weak)
• Oxygen supplementation, if needed, can be administered via a humidity and temperature-controlled oxygen cage or incubator or via a nasal oxygen cannula. (Class I, LOE: expert opinion)
• Mechanical treatments (eg, abdominal paracentesis, thoracentesis) are recommended to relieve effusions judged sufficient to impair ventilation or cause respiratory distress. (Class I, LOE: expert opinion)
• Sedation-anxiety associated with dyspnea should be treated. Narcotics, or a narcotic combined with an anxiolytic agent, most often are used by panelists. Care must be taken to monitor the blood pressure and respiratory response to narcotics and tranquilizers in the setting of acute heart failure. No specific treatment or dosage regimen was used by all panelists. Butorphanol 0.2 to 0.25 mg/kg administered IM or IV was the narcotic most often utilized for this purpose; combinations of buprenorphine (0.0075-0.01 mg/kg) and acepromazine (0.01-0.03 mg/kg IV, IM, or SC) as well as other narcotics, including morphine and hydrocodone, also were suggested. (Class I, LOE: expert opinion)
• Provide optimal nursing care, including maintenance of appropriate environmental temperature and humidity, increase of the head on pillows, and placement of sedated patients in sternal posture. (Class I, LOE: expert opinion)
• Dobutamine (2.5-10 μg/kg/min as a CRI, starting at 2.5 μg/kg/min and increasing the dosage incrementally) may be used in addition to the above treatments to improve the left ventricular function in patients that fail to respond adequately to diuretics, pimobendan, sedation, oxygen, and comfort care measures. Continuous ECG monitoring is recommended where available during dobutamine infusion, with dosage reduction indicated if tachycardia or ectopic beats occur. (Class I, LOE: expert opinion)
• Constant IV infusion of sodium nitroprusside at dosages ranging from 1 to 15 μg/kg/min) for up to 48 hours often is useful for life-threatening, poorly responsive pulmonary edema69; this medication is currently (2018) expensive in the United States. The use and PO titration of additional arterial dilators (eg, hydralazine or amlodipine, specific dosing recommendations also in Class D below) also may be useful in patients when administration of nitroprusside is not feasible. (Class I, LOE: weak)
• ACEI, for example, enalapril or benazepril, 0.5 mg/kg PO q12h. Although treatment with an ACEI is a Class I recommendation for chronic Stage C heart failure (see below) and some panelists also treat acute heart failure with ACEI, the evidence supporting ACEI efficacy and safety in acute treatment, when combined with furosemide and pimobendan, is less clear. There is, however, clear evidence that the acute administration of enalapril plus furosemide in acute heart failure results in significant improvement in pulmonary capillary wedge pressure when compared with the administration of furosemide alone.70 (Class IIb, LOE: weak)
• Nitroglycerin ointment, approximately half an inch paste/10 kg BW, applied to an unhaired or shaved area of skin, can be used for the first 24 to 36 hours of hospitalization.71, 72 Some panelists recommend administering the ointment at intervals (12 hours on, 12 hours off). Other panelists do not use nitroglycerin in this setting. (Class IIb, LOE: weak)

6.5.3 Recommendations for chronic (home-based) treatment of Stage C

• Continue PO furosemide administration to effect, commonly at a dosage of 2 mg/kg administered q12h, or as needed to maintain patient comfort. Some panelists now choose to substitute torsemide for furosemide at 1/10-1/20 or approximately 5% to 10% of the furosemide dosage, or approximately 0.1-0.3 mg/kg q24h73 for home care in animals in which hospitalized CHF management using furosemide was difficult or met with limited success. (Class I, LOE: moderate)
• Chronic PO furosemide dosages ≥8 mg/kg q24h in any dosing regimen (or the equipotent torsemide dosage) needed to maintain patient comfort in the face of appropriate dosages of pimobendan, an ACEI, and spironolactone indicate disease progression to Stage D. Consideration of known causes of diuretic resistance, including noncompliance (ie, not receiving the drug), high sodium intake, slow absorption (eg, gut edema), impaired secretion into the renal tubular lumen (eg, chronic kidney disease, advanced age, concurrent nonsteroidal anti-inflammatory drug use), hypoproteinemia, hypotension, nephron remodeling, and neurohormonal activation is warranted. (Class I, LOE: weak)
• Measurement of serum creatinine, blood urea nitrogen, and electrolyte concentrations 3-14 days after initiating furosemide treatment is recommended for animals with Stage C heart failure. (Class I, LOE: weak)
• Continue or start ACEI (eg, enalapril or benazepril, 0.5 mg/kg PO q12h) or an equivalent dosage of another ACEI, if approved for this use. Measurement of serum creatinine and electrolyte concentrations 3-14 days after beginning an ACEI is recommended for animals with Stage C heart failure. Concern for development of acute kidney injury is warranted should serum creatinine concentrations increase by ≥30% of the baseline concentration. (Class I, LOE: weak)
• Spironolactone (2.0 mg/kg PO q12 - 24 h) is recommended as an adjunct for chronic treatment of dogs in Stage C heart failure. The primary benefit of spironolactone in this situation is thought to be aldosterone antagonism.74, 75 (Class I, LOE: moderate)
• Continue pimobendan, 0.25-0.3 mg/kg PO q12h.76, 77 (Class I, LOE: strong)
• Panelists recommend against starting a beta blocker in the face of active clinical signs of CHF (eg, cardiogenic pulmonary edema) caused by MMVD. (Class IV, LOE: weak)
• None of the panelists routinely use nitroglycerin in the chronic treatment of Stage C heart failure. (Class III, LOE: expert opinion)
• Participation in a structured, home-based extended care program to promote ideal BW, appetite, respiratory and heart rate monitoring while providing client support to enhance medication regimen adherence and dosage adjustments in patients with heart failure is encouraged. (Class I, LOE: expert opinion)

Of these variables, identification of increases in resting respiratory rate above normal baseline has the best predictive value for impending clinical decompensation.78, 79 (Class I, LOE: moderate).

• In centers with low complication rates, Stage C patients benefit from surgical intervention to repair their mitral valve apparatus.61, 63 (Class I, LOE: moderate)
• In cases complicated by atrial fibrillation, diltiazem, often in combination with digoxin (see below), is recommended to control ventricular rate. Multiple preparations of diltiazem are available; treatment should be started at a modest dosage for the preparation chosen and titrated to achieve heart rate control. Ideally, mean heart rate as measured by Holter monitoring in dogs with well-controlled signs of CHF receiving stable drug dosage regimens should be close to normal or at least <125 beats per minute.80, 81 (Class I, LOE: moderate)
• Digoxin 0.0025-0.005 mg/kg, administered PO q12h to achieve a target steady-state plasma concentration (approximately 8 hours post-pill) of 0.8-1.5 ng/mL. For the chronic management of Stage C heart failure, panelists recommended the addition of digoxin only in cases complicated by persistent atrial fibrillation to slow the ventricular response rate. In these cases, digoxin generally is used in combination with diltiazem. Digoxin may not be tolerated in patients with factors known to put animals at risk for adverse effects or toxicity (eg, increases of serum creatinine concentration above normal, ventricular ectopy, concerns over owner adherence, or chronic gastrointestinal disease resulting in frequent or unpredictable bouts of vomiting or diarrhea).82 (Class IIb, LOE: moderate)
• In patients receiving a beta blocker before the onset of Stage C heart failure, the majority of panelists continue beta blockade; some panelists consider dosage reduction if needed clinically because of clinical signs of low cardiac output, hypothermia, or bradycardia. (Class IIB, LOE: expert opinion)
• Some panelists find the use of cough suppressants useful in occasional patients in Stage C heart failure from MMVD. (Class IIa, LOE: expert opinion)
• Some panelists find the use of bronchodilators useful in occasional patients in Stage C MMVD patients. (Class IIb, LOE: expert opinion)

6.5.4 Recommendations for dietary treatment for Stage C

• Cardiac cachexia is defined as a loss of muscle or lean body mass associated with heart failure, with or without clinically relevant accompanying weight loss. Cachexia has substantial negative prognostic implications and is much easier to prevent than to treat.83, 84 (Class I, LOE: moderate)
• Maintain adequate calorie intake (maintenance calorie intake in Stage C should be approximately 60 kcal/kg BW) to minimize weight loss that often occurs in CHF.85, 86 Simple culinary strategies to improve appetite may be beneficial in accomplishing this goal (eg, warming food, mixing wet food with dry food, offering a variety of foods). (Class I, LOE: moderate)
• Specifically address and inquire about the occurrence of anorexia and make efforts to treat any drug-induced or other identifiable causes of anorexia that occur. (Class I, LOE: expert opinion)
• Record body condition score and accurate weight of the patient at every clinic visit and investigate the cause of clinically relevant changes in body condition, weight gain or loss. (Class I, LOE: expert opinion)
• Ensure adequate protein intake and avoid low-protein diets designed to treat chronic kidney disease, unless severe concurrent renal failure is present.83 (Class I, LOE: moderate)
• Modestly restrict sodium intake, taking into consideration sodium from all dietary sources (including dog food, treats, table food, and foods used to administer medications) and avoid any processed or other salted foods.87, 88 (Class I, LOE: moderate)
• Monitor serum electrolyte concentrations and supplement the diet with potassium from either natural or commercial sources only if hypokalemia is identified. The panel's anecdotal experience is that hypokalemia is much more common in animals receiving torsemide. (Class I, LOE: expert opinion)
• Hyperkalemia is relatively rare in patients treated for CHF with diuretics, even in those concurrently receiving ACEI in combination with spironolactone. Diets and foods with high potassium content should be avoided when hyperkalemia is present. (Class I, LOE: expert opinion)
• Consider monitoring serum magnesium concentrations, especially as heart failure progresses and in dogs with arrhythmias. Supplement with magnesium in cases in which hypomagnesemia is identified. (Class IIa, LOE: expert opinion)
• Consider supplementing with omega-3 fatty acids, especially in dogs with decreased appetite, muscle loss, or arrhythmia.86 (Class IIa, LOE: moderate)

CLASSIFICATION OF HEART DISEASE AND HEART FAILURE (see original article or click here)

The term heart disease is used synonymously with cardiac pathology—in this case, myxomatous degenerative changes of the mitral valve. Heart disease, depending on its nature, rate of progression, and patient age and condition may or may not lead to heart failure. The term “heart failure” refers to clinical signs caused by heart dysfunction. Heart failure is caused by heart disease that affects heart function such that either venous pressures increase so severely that fluid accumulates in the lungs or a body cavity (congestive heart failure [CHF], sometimes called “backward heart failure because the heart fails to drain the veins adequately), or the heart's pumping ability is compromised such that it cannot meet the body's needs either during exercise or at rest, in the face of either normal or increased venous pressures (sometimes called “forward heart failure”)....

CLASSIFICATION OF RECOMMENDATIONS (see original article or click here)

The recommendation classification and level of evidence (LOE) upon which that recommendation was based were independently determined by the panel (ie, any class of recommendation may be paired with any LOE).

original article: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15488 to view Part 2 of 2 click here