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

6.6.1 Recommendations for the diagnosis of Stage D (refractory heart failure)

• Because Stage D heart failure patients are, by definition, refractory to the standard treatments for Stage C patients, defining refractory CHF involves the same diagnostic steps outlined for Stage C plus the finding of failure to respond to treatments outlined in the Stage C guidelines.

6.6.2 Recommendations for acute (hospital-based) treatment of Stage D

• In the absence of severe renal insufficiency (eg, serum creatinine concentration >3 mg/dL), additional furosemide can be administered to dyspneic patients diagnosed with refractory heart failure as an initial 2 mg/kg IV bolus followed by either additional bolus doses or a furosemide CRI at a dosage of 0.66-1 mg/kg/h, until respiratory distress (rate and effort) has decreased, or for a maximum of 4 hours. (Class I, LOE: expert opinion)
• Torsemide, a potent long-acting loop diuretic may be used to treat dogs no longer adequately responsive to furosemide (0.1-0.2 mg/kg q12h-q24h or approximately 5%-10% of the current furosemide dosage to deliver a furosemide-equivalent dose).28 It appears that the diuresis induced by torsemide produces less renin-angiotensin-aldosterone system activation than more frequent doses of furosemide, similar to what has been shown in dogs and horses with the diuresis induced by furosemide CRI.89, 90 Clinicians should continue to allow patients free access to water, once diuresis has begun. (Class I, LOE: expert opinion)

• Cavitary centesis (abdominal paracentesis, thoracentesis), as needed to relieve respiratory distress or discomfort. (Class I, LOE: expert opinion)

  • In addition to oxygen supplementation as in Stage C (above), mechanical ventilatory assistance may be useful in making the patient comfortable, in allowing time for medications to have an effect, and in providing time for left atrial dilatation to accommodate sudden increases in mitral valve regurgitant volume in patients with acute exacerbation of MMVD (eg, chordae tendineae rupture with severe cardiogenic pulmonary edema) and impending respiratory failure.91 (Class I, LOE: weak)

• In patients that can tolerate it, more vigorous afterload reduction (arterial vasodilation) is recommended, with close monitoring of arterial blood pressure. In cases in which mechanical ventilation and IV vasodilator or inotropic support is needed, arterial pressure monitoring via peripheral arterial catheterization is preferred over noninvasive blood pressure monitoring when possible. In dogs judged to be too sick to wait for the effects of PO afterload reduction or inotropic support (eg, pimobendan with or without hydralazine or amlodipine), the administration of a CRI IV of sodium nitroprusside (for afterload reduction) or dobutamine (for inotropic support, especially in hypotensive patients) or both is recommended by a majority of panelists.69 Both are started at dosages of 1.0 μg/kg/min and up-titrated every 15-30 minutes to a maximum of approximately 10-15 μg/kg/min. These rates may be used for 12-48 hours to improve hemodynamic status and control refractory cardiogenic pulmonary edema. Continuous ECG and blood pressure monitoring are recommended to minimize the potential risks of this treatment. (Class IIa, LOE: weak)
• Potentially beneficial PO drugs that decrease afterload in this situation include hydralazine (0.5-2.0 mg/kg PO, starting at a low dosage and titrating to effect as described above with nitroprusside, but with hourly dosage increases or amlodipine (approximately 0.05-0.1 mg/kg PO, also to effect, although maximal drug effect does not occur for approximately 3 hours, mandating a slower titration). (Class I, LOE: expert opinion)

These drugs are recommended in addition to an ACEI and pimobendan. Vigilance is needed to avoid serious, prolonged hypotension (monitor blood pressure closely, maintaining arterial systolic blood pressure >85 mm Hg, or mean arterial blood pressure >60 mm Hg). Serum creatinine concentration should be reevaluated no more than 24 to 72 hours after initiating these drugs.

The panel emphasized that because afterload reduction may increase cardiac output substantially in the setting of severe MR and heart failure, administration of an effective arterial dilator drug in this setting does not necessarily compromise blood pressure. (Class IIa, LOE: expert opinion).

• Sildenafil, (starting at 1-2 mg/kg PO q8h, and titrating if needed) is used by panelists to treat Stage D heart failure from MMVD that is complicated by clinically relevant estimated pulmonary hypertension. Pulmonary hypertension is recognized as an increasingly frequent complication of MMVD, either as a direct consequence of severe mitral valve regurgitation or as an independent comorbidity that can be responsible for clinical signs including syncope, cough, and shortness of breath (dyspnea), and sometimes radiographically evident pulmonary infiltrates.92, 93 (Class I, LOE: moderate) The occurrence of ascites or jugular distension in patients with primarily left-sided heart disease is suggestive of pulmonary hypertension and should prompt an attempt to conclusively diagnose and identify patients that may benefit from sildenafil. (Class IIa, LOE: weak)
• Pimobendan dosage may be increased (off-label use) to include a third 0.3 mg/kg daily PO dose (ie, 0.3 mg/kg PO q8h); some panelists administer an additional dose of pimobendan on admission to Stage D patients with acute pulmonary edema regardless of the timing of the last dose given at home. This dosage recommendation is outside the US Food and Drug Administration–approved labeling for pimobendan (off-label use), and this use of the drug should be explained to and approved by the client. (Class IIa, LOE: expert opinion)
• Some panelists recommend adjunctive treatment with bronchodilators in treating cardiogenic pulmonary edema in hospitalized patients. (Class IIb, LOE: expert opinion)

6.6.3 Recommendations for chronic (home-based) Stage D treatment

• Furosemide (or torsemide) dosage should be increased as needed to decrease the accumulation of pulmonary edema or body cavity effusions, if not limited by renal dysfunction (indicators of which generally should be monitored 12-48 hours after dosage increases). Inappetence may increase the risk of development of azotemia associated with medications for heart failure. The specific strategy and magnitude of dosage increase (eg, same dosage divided q8h instead of 2 higher doses, substituting 1 SC dose for a PO dose q4h, or flexible SC dose supplementation, based on BW or girth measurements) varied widely among the panelists. See Stage C recommendations (above) for a brief discussion of diuretic resistance. (Class IIa, LOE: expert opinion)
• Torsemide, a potent and longer-acting loop diuretic, may be used to treat dogs no longer adequately responsive to furosemide (torsemide beginning dosage of 0.1-0.2 mg/kg PO, or approximately 5%-10% of the current furosemide dosage, up to approximately 0.6 mg/kg, divided q12h if necessary).94 (Class I, LOE: moderate)
• Spironolactone, if not already started as recommended in Stage C, is indicated for chronic treatment of Stage D patients.74 (Class I, LOE: moderate)
• Beta blockers generally should not be initiated at this stage, unless they are being used as an adjunct to control heart rate in atrial fibrillation. (Class IV, LOE: expert opinion)
• Hydrochlorothiazide was recommended by several panelists as adjunctive treatment to furosemide or torsemide, utilizing various dosing schedules (including intermittent use every 2nd-4th day). Some panelists warned of the risk of acute kidney insufficiency and marked electrolyte disturbances, based on personal experience. (Class IIb, LOE: expert opinion)
• Pimobendan dosage is increased by some panelists to include a third 0.3 mg/kg daily dose (off-label use; routine explanations and cautions to the owner apply as in hospital care described above) or an even higher dosage when repeated rescue is necessary. (Class IIa, LOE: expert opinion)
• Additional afterload reduction, using either amlodipine or hydralazine (see dosages and cautions above), may provide additional hemodynamic benefit and decrease cough frequency.
• Digoxin, at the same (relatively low) dosages recommended by some panelists for Stage C heart failure with atrial fibrillation, is recommended for the treatment of atrial fibrillation in Stage D patients lacking a concrete contraindication.82 (Class IIb, LOE: moderate)
• Digoxin, at the same (relatively low) dosages recommended by some panelists for Stage C heart failure with atrial fibrillation, also is recommended by some panelists for all Stage D patients, including those in sinus rhythm, lacking a concrete contraindication. (Class IIb, LOE: expert opinion)
• Sildenafil (1-2 mg/kg PO q8h) may be useful in the management of patients with clinical signs related to exertion and in management of ascites when there is echocardiographic evidence of moderate to severe pulmonary hypertension.95 (Class IIa, LOE: weak)
• Beta blockade may be useful in decreasing the ventricular response rate in atrial fibrillation after stabilization and digitalization, but caution should be used because of the negative inotropic effects of beta blockers. (Class IIb, LOE: expert opinion)
• The majority of panelists felt that beta blockade initiated previously should not be stopped, but that dosage reduction may be needed if shortness of breath cannot be controlled by the addition of other medications or if bradycardia, hypotension, or both were present. (Class IIb, LOE: expert opinion)
• Cough suppressants are recommended to treat chronic, intractable cough in Stage D home care patients by some panelists. (Class IIa, LOE: expert opinion)
• Bronchodilators are recommended to treat chronic, intractable coughing in Stage D home care patients by some panelists. (Class IIb, LOE: expert opinion)

6.6.4 Recommendation for chronic (home-based) dietary treatment for Stage D

• All of the dietary considerations for Stage C (above) apply.
• In patients with refractory fluid accumulations, attempts should be made to further decrease dietary sodium intake if it can be done without compromising appetite or renal function. (Class IIa, LOE: expert opinion)

CLASSIFICATION OF HEART DISEASE AND HEART FAILURE

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”).

In 2009, the consensus panel adapted a staging system for heart disease and heart failure, and sought to link the severity of morphologic changes and clinical signs to appropriate treatments at each stage.32 According to this approach, patients are expected to advance from 1 stage to the next stage, unless progression of the disease is altered by corrective treatment (such as surgery). This staging system, applied to dogs with MMVD, remains useful, although recent clinical trial results necessitate a more critical clinical evaluation of dogs in Stage B to facilitate sound therapeutic decision making.

This staging system for MMVD describes 4 basic stages of heart disease and heart failure:

• Stage A identifies dogs at high risk for developing heart disease but that currently have no identifiable structural disorder of the heart (eg, every Cavalier King Charles Spaniel or other predisposed breed without a heart murmur).

• Stage B identifies dogs with structural heart disease (eg, the typical murmur of mitral valve regurgitation, accompanied by some typical valve pathology, is present), but that have never developed clinical signs caused by heart failure. In a change from the 2009 recommendations, strong evidence now supports initiating treatment to delay the onset of clinical signs of heart failure in a subset of stage B patients with more advanced cardiac morphologic changes (outlined below).

  • Stage B1 describes asymptomatic dogs that have no radiographic or echocardiographic evidence of cardiac remodeling in response to their MMVD, as well as those in which remodeling changes are present, but not severe enough to meet current clinical trial criteria that have been used to determine that initiating treatment is warranted (see specific criteria below).
  • Stage B2 refers to asymptomatic dogs that have more advanced mitral valve regurgitation that is hemodynamically severe and long-standing enough to have caused radiographic and echocardiographic findings of left atrial and ventricular enlargement that meet clinical trial criteria used to identify dogs that clearly should benefit from initiating pharmacologic treatment to delay the onset of heart failure (specific criteria detailed below).

   

• Stage C denotes dogs with either current or past clinical signs of heart failure caused by MMVD. Because of important treatment differences between dogs with acute heart failure requiring hospital care and those in which heart failure can be treated on an outpatient basis, these issues have been addressed separately by the panel. It is important to note that some dogs presented with heart failure for the first time may have severe clinical signs requiring aggressive treatment (eg, with additional afterload reducers or temporary ventilatory assistance) that more typically would be reserved for those patients refractory to standard treatment (see Stage D below).
• Stage D refers to dogs with end-stage MMVD, in which clinical signs of heart failure are refractory to standard treatment (defined later in this consensus statement). Such patients require advanced or specialized treatment strategies to remain clinically comfortable with their disease, and at some point, treatment efforts become futile without surgical repair of the valve. As with Stage C, the panel has distinguished between dogs in Stage D that require acute, hospital-based treatment and those that can be managed as outpatients.

This staging system emphasizes that there are known risk factors and structural prerequisites for the development of heart failure caused by MMVD. Accordingly, the classification system is designed to aid in:

• developing screening programs for the presence of MMVD in dogs known to be at risk;
• implementing interventions that may (now and in the future) decrease the risk of disease development or progression;
• identifying asymptomatic dogs with MMVD early in the course of their disease, comparable to in situ cancer, so they can be more effectively managed medically as chronic disease patients, or possibly be treated surgically;
• identifying symptomatic dogs with MMVD so that these patients can be managed medically as chronic disease patients or possibly treated surgically; and
• identifying symptomatic dogs with advanced heart failure caused by MMVD refractory to conventional medical treatment. These patients require aggressive or new treatment strategies, possibly including surgery, or potentially palliative or hospice-type end-of-life care.

CLASSIFICATION OF RECOMMENDATIONS

Class I recommendations are strong, reflecting the panel's conviction that the recommended action appears to have definite benefit for most patients, outweighing the risk to most patients.

Class I recommendations can be summarized as “benefit >>> risk”.

Class IIa recommendations are moderately strong, reflecting the panel's belief that the recommended action should benefit most patients, probably outweighing the risk to most patients.

Class IIa recommendations can be summarized as “benefit >> risk”.

Class IIb recommendations are weak, reflecting the belief that the recommended action possibly benefits some patients and may outweigh the risk of taking the proposed action in most patients.

Class IIb recommendations can be summarized as “benefit > risk”.

Class III is used to describe recommendations in which the panel believes that the potential risk and benefit of the proposed action are essentially equal, such that these actions should probably not be pursued under most circumstances.

Class III recommendations can be summarized as “benefit = risk”.

Class IV recommendations indicate the panel's belief that the proposed action is more likely to cause harm than benefit to most patients, such that Class IV designates actions that the panel believes are contraindicated under most circumstances.

Class IV recommendations can be summarized as “risk >> benefit”.

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).

The panel acknowledges that future evidence may change the strength of any of these recommendations, as well as the quality of the evidence on which they are based. Many important clinical questions addressed in the guidelines have not yet been adequately addressed by clinical trials. At times, the panel has made strong recommendations based on more than the available evidence—thus weak or even absent evidence does not necessarily accompany a weak recommendation. Although randomized clinical trial evidence may be unavailable, a clear clinical consensus that a particular test or treatment is useful may exist.

original article: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15488 or to view Part 1 of 2 click here.