ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-to-date information on the pathophysiology, diagnosis, and treatment of clinically important animal diseases. The ACVIM Board of Regents oversees selection of relevant topics, identification of panel members with the expertise to draft the statements, and other aspects of assuring the integrity of the process. The statements are derived from evidence-based medicine whenever possible and the panel offers interpretive comments when such evidence is inadequate or contradictory.A draft is prepared by the panel, followed by solicitation of input by the ACVIM membership which may be incorporated into the statement. It is then submitted to the Journal of Veterinary Internal Medicine, where it is edited prior to publication. The authors are solely responsible for the content of the statements.AbstractThis report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed. K E Y W O R D S canine, congestive heart failure, evidence-based treatment, mitral Abbreviations: ACEI, angiotensin converting enzyme inhibitors; Ao, aorta; BW, body weight; CHF, congestive heart failure; CRI, constant rate infusion; IM, intramuscularly; LA, left atrium; LOE, level of evidence; LV, left ventricle; LVIDD, left ventricular end diastolic diameter; LVIDd, left ventricular end diastolic diameter in diastole; LVIDdN, left ventricular end diastolic diameter normalized for body weight; MMVD, myxomatous mitral valve disease; MR, mitral regurgitation; NT-proBNP, N-terminal pro-B-type natriuretic peptide; VHS, vertebral heart score; VLAS, vertebral left atrial size.

# | introduction
The panel adopted the following scheme, adapted from the American Heart Association, [bib_ref] ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of..., Yancy [/bib_ref] to rate the strength of the recommendations in these guidelines. The recommendation class designation appears with each recommendation, along with a second term that independently rates the quality of the evidence upon which the recommendation was based.

## | 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 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.

## | levels of evidence
The methods of assessing the quality of the scientific evidence that supports clinical decision making are evolving. The panel chose to use a hybrid of the American Heart Association and Veterinary Emergency Critical Care RECOVER evidence grading criteria, as outlined below. 1,2

## | strong
High-quality evidence is from 1 randomized controlled trial, or a moderate-quality randomized controlled trial, corroborated by a highquality observational study or other moderate-quality trials. These prospective clinical studies were performed in dogs and either randomly allocated subjects to an intervention or control group or used concurrent controls (ie, controls recruited at the same time as the experimental subjects) without randomization. Strong evidence also could have been obtained from prospectively enrolled, controlled, observational clinical studies in dogs with spontaneously occurring mitral valve disease. These studies asked clinically relevant questions, were considered to be adequately powered, and did not experience excessive loss of subjects to follow up in any group, generating a clear and statistically valid result.

## | moderate
Moderate-quality evidence is from 1 well-designed, well-executed nonrandomized studies, observational studies, or registry studies, or meta-analyses of such studies. Evidence rated as "moderate" by the panel was generated from controlled, retrospective studies in dogs (ie, studies in which dogs with mitral valve disease [or appropriate controls] were selected from a previous period in time). Moderate evidence also could have been generated from blinded and controlled laboratory studies that were performed in experimental dogs.

## | weak
Weak-quality evidence is from randomized or nonrandomized observational or registry studies with limitations of design or execution, but performed in dogs with clinical myxomatous mitral valve disease (MMVD), or physiological, mechanistic, or experimental studies performed in research dogs. Evidence rated as "weak" by the panel was generated from uncontrolled clinical case reports or case series in dogs with mitral valve disease, as well as by experimental or clinical studies that were not performed in dogs with MMVD. These could include experimental models of mitral valve disease in other species, as well as high-quality studies in humans (such as meta-analyses, randomized controlled trials, and clinical studies with concurrent controls, including observational studies) with spontaneous mitral valve disease.

## | expert opinion
Expert opinion based on clinical experience, common sense, or physiologic or mechanistic studies performed in species other than dogs is considered the weakest LOE.

## | incidence, pathology, and pathogenesis of mmvd
It is estimated that approximately 10% of dogs presented to primary care veterinary practices have heart disease, and MMVD is the most common heart disease of dogs in many parts of the world, accounting for approximately 75% of heart disease cases seen in dogs by veterinary practices in North America.
The pathology of MMVD has been relatively recently reviewed, [bib_ref] Pathology of myxomatous mitral valve disease in the dog, Fox [/bib_ref] and some progress in understanding the genetics and pathophysiology of the disease has been reported. [bib_ref] Evaluation of genes associated with human myxomatous mitral valve disease in dogs..., Meurs [/bib_ref] [bib_ref] Identification of 2 loci associated with development of myxomatous mitral valve disease..., Madsen [/bib_ref] Myxomatous mitral valve disease most commonly affects the left atrioventricular or mitral valve, although in at least 30% of cases, the right atrioventricular (tricuspid) valve also is involved. [bib_ref] Historical review, epidemiology and natural history of degenerative mitral valve disease, Borgarelli [/bib_ref] The disease is approximately 1.5 times more common in males than in females. Prevalence is also higher in smaller (<20 kg) dogs, although large breeds sometimes are affected, and larger dogs also often experience faster disease progression with more apparent myocardial dysfunction, and have a more guarded prognosis. [bib_ref] Comparison of primary mitral valve disease in German shepherd dogs and in..., Borgarelli [/bib_ref] In small breed dogs, the disease generally is slowly but at times unpredictably progressive. Most dogs experience the onset of a recognizable murmur of mitral valve regurgitation years before the clinical onset of heart failure.
Cavalier King Charles Spaniels notably are predisposed to developing MMVD at a relatively young age, although the time course of their disease progression to heart failure does not appear to be markedly different from that of other small breed dogs. [bib_ref] Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy, Borgarelli [/bib_ref] [bib_ref] An update on treatment and prognostic indicators in canine myxomatous mitral valve..., Haggstrom [/bib_ref] Although the cause of MMVD remains unknown, the disease has an inherited component in some breeds, 5,10 and the severity of the disease may have a genetic component in other breeds. The disease consistently is characterized by changes in the cellular constituents as well as the intercellular matrix of the valve apparatus (including the valve leaflets and chordae tendineae). [bib_ref] Pathology, protein expression and signaling in myxomatous mitral valve degeneration: comparison of..., Aupperle [/bib_ref] [bib_ref] Distribution of myofibroblasts, smooth muscle-like cells, macrophages, and mast cells in mitral..., Han [/bib_ref] These changes involve both the collagen content and the alignment of collagen fibrils within the valve. Expansion of the spongiosa layer is characterized by changes in the proteoglycan content of this layer. Dysregulation of the extracellular matrix appears to be central to these changes. Valvular interstitial cells, possibly with posttranscriptional regulation from microsatellite ribonucleic acids, acquire properties of activated myofibroblasts, and activated myofibroblasts increase proteolytic enzymes, including matrix metalloproteinases, which degrade collagen and elastin faster than they can be produced by unactivated valvular interstitial cells. [bib_ref] Circulating exosome micro-RNA associated with heart failure secondary to myxomatous mitral valve..., Yang [/bib_ref] [bib_ref] Myxomatous degeneration of the canine mitral valve: from gross changes to molecular..., Markby [/bib_ref] [bib_ref] Comparative transcriptomic profiling and gene expression for myxomatous mitral valve disease in..., Markby [/bib_ref] Endothelial cell changes and subendothelial thickening also occur, [bib_ref] Identification of surface morphologic changes in the mitral valve leaflets and chordae..., Corcoran [/bib_ref] [bib_ref] Structural and cellular changes in canine myxomatous mitral valve disease: an image..., Han [/bib_ref] [bib_ref] Molecular changes in fibrillar collagen in myxomatous mitral valve disease, Hadian [/bib_ref] but these changes do not appear to put dogs with MMVD at increased risk for either arterial thromboembolism or infective endocarditis. Mitral valve prolapse is a common finding in dogs with myxomatous valve degeneration and represents a prominent echocardiographic feature of MMVD in some breeds. [bib_ref] Epidemiology and inheritance of mitral valve prolapse in dachshunds, Olsen [/bib_ref] [bib_ref] Assessment of mitral regurgitation in dogs: comparison of results of echocardiography with..., Sargent [/bib_ref] [bib_ref] Echocardiographic mitral valve prolapse in Cavalier King Charles Spaniels: epidemiology and prognostic..., Pedersen [/bib_ref] Progressive deformation of the valve structure eventually prevents effective coaptation, allowing regurgitation (valve leakage). Progressive valvular regurgitation increases cardiac work, leading to ventricular remodeling (eccentric hypertrophy of both the atrium and ventricle, and intercellular matrix changes), and eventually to ventricular dysfunction.
It has been hypothesized that abnormal numbers or types of mitogen receptors (ie, any of the subtypes of serotonin, endothelin, or angiotensin receptors) on fibroblast cell membranes in the valves of affected dogs play a role in the pathophysiology of acquired valvular lesions. [bib_ref] Increased endothelin-receptor density in myxomatous canine mitral valve leaflets, Mow [/bib_ref] [bib_ref] Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with..., Cremer [/bib_ref] [bib_ref] Insights into serotonin signaling mechanisms associated with canine degenerative mitral valve disease, Oyama M A [/bib_ref] Systemic or local metabolic, neurohormonal, or inflammatory mediators (eg, endogenous catecholamines, inflammatory cytokines) also may influence progression of the valve lesion or the subsequent myocardial remodeling and ventricular dysfunction that accompany long-standing, hemodynamically important valvular regurgitation. The interactions of these factors, as well as the impact of changes in mitral valve annular geometry and mechanical stress on the pathogenesis and progression of MMVD, are incompletely understood. [bib_ref] Pathology, protein expression and signaling in myxomatous mitral valve degeneration: comparison of..., Aupperle [/bib_ref] [bib_ref] Distribution of myofibroblasts, smooth muscle-like cells, macrophages, and mast cells in mitral..., Han [/bib_ref] [bib_ref] Circulating exosome micro-RNA associated with heart failure secondary to myxomatous mitral valve..., Yang [/bib_ref] [bib_ref] Mitral valve morphology assessed by three-dimensional transthoracic echocardiography in healthy dogs and..., Menciotti [/bib_ref] The prevalence of MMVD increases markedly with age in small breed dogs, with up to 85% showing evidence of the valve lesion by 13 years of age. [bib_ref] Chronic valvular disease (endocardiosis) in dogs, Buchanan [/bib_ref] The presence of the pathologic lesion of MMVD in an individual does not necessarily identify a dog that will develop clini- failure. [bib_ref] Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease, Sargent [/bib_ref] [bib_ref] Associations between N-terminal procollagen type III, fibrosis and echocardiographic indices in dogs..., Hezzell [/bib_ref] [bib_ref] Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of..., Peddle [/bib_ref] [bib_ref] Prediction of first onset of congestive heart failure in dogs with degenerative..., Reynolds [/bib_ref] The rate of change of echocardiographic and radiographic variables also may identify animals at increased risk of heart failure or death from cardiac cause. [bib_ref] Radiographic heart size and its rate of increase as tests for onset..., Lord [/bib_ref] [bib_ref] Selected echocardiographic variables change more rapidly in dogs that die from myxomatous..., Hezzell [/bib_ref] Development of truly predictive (sensitive and specific) risk stratification schemes, however, awaits further refinement.

## | classification of heart disease and heart failure
The term heart disease is used synonymously with cardiac pathologyin 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. [bib_ref] Guidelines for the diagnosis and treatment of canine chronic valvular heart disease, Atkins [/bib_ref] 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, hospitalbased 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 Left ventricular internal diameter in diastole, normalized for body weight (LVIDDN) 1.7 [fig_ref] Table 1 ,: tions for chronic dietary management [/fig_ref] breed-adjusted 47-53 radiographic vertebral heart score (VHS) >10.5.
- Ideally, all these criteria should be met before initiating treatment, because treatment represents a lifelong commitment. Of these criteria, echocardiographic evidence of left atrial and ventricular enlargement meeting or exceeding these criteria is considered to be the most reliable way to identify dogs expected to benefit from treatment.
- Although studies to identify reliable radiographic markers of Stage For dogs weighing between 1 and 20 kg (BW, left hand column), the left ventricular end diastolic diameter (LVIDD) meeting this criterion must be more than or equal to the dimension (in cm) in the right hand column. In the referenced clinical trial, the end-diastolic LV dimension was obtained from a 2D short-axis-guided M-mode echocardiogram of the chamber. [bib_ref] Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables..., Boswood [/bib_ref] The formula for normalizing LVIDD to BW is LVIDdN = LVIDd (cm)/weight (kg) 0.294 .
[Correction added on 24-April-2019, after first online publication: in the legend for - 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. [bib_ref] The pathophysiology of cardiac cachexia, Freeman [/bib_ref] [bib_ref] Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats, Freeman [/bib_ref] (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. [bib_ref] Dietary patterns of dogs with cardiac disease, Freeman [/bib_ref] - 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. [bib_ref] Combination therapy with digoxin and diltiazem controls ventricular rate in chronic atrial..., Gelzer [/bib_ref] (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. [bib_ref] Sildenafil citrate therapy in 22 dogs with pulmonary hypertension, Kellum [/bib_ref] 

# Off-label antimicrobial declaration
Authors declare no off-label use of antimicrobials.

## Institutional animal care and use committee (iacuc) or other approval declaration
Authors declare no IACUC or other approval was needed.

## Human ethics approval declaration
Authors declare human ethics approval was not needed for this study.

## Orcid
[fig] : Small breed dogs, including breeds with known predisposition to develop MMVD (eg, 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. (Class I, LOE: expert opinion)  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. (Class I, LOE: expert opinion) 6.1.2 | Recommendations for treatment of Stage A (unchanged from 2009)  No drug treatment recommended for any patient. (Class I, LOE: expert opinion)  No dietary treatment recommended for any patient. (Class I, LOE: expert opinion)  Potential breeding animals should no longer be bred if a murmur or echocardiographic evidence of mitral regurgitation (MR) is identified early, during the normal breeding age range (<6-8 years of age). (Class I, LOE: moderate) Myxomatous mitral valve disease typically is recognized during a screening or routine health examination by auscultation of a heart murmur typical of mitral valve regurgitation.  Thoracic radiography is recommended in all patients to assess the hemodynamic relevance of the valve disease and to obtain baseline thoracic radiographs at a time when the patient is asymptomatic for MMVD. Patients with MMVD frequently have concurrent tracheal or bronchial diseases and having baseline radiographs at a time when the dog is asymptomatic can enhance the ability to radiographically differentiate cardiac from noncardiac causes of cough in the face of future clinical signs. (Class I, LOE: expert opinion).  Blood pressure measurement is recommended for all patients to identify or rule out concurrent systemic hypertension and to establish baseline blood pressure. (Class I, LOE: expert opinion)  Echocardiography, performed by an experienced operator, is recommended to definitively identify the cause of the murmur, answer specific questions regarding the severity of cardiac chamber enlargement, and identify comorbidities. A specialist's examination might identify hemodynamic abnormalities including pulmonary hypertension or increased left atrial pressure. Echocardiographic identification of mild left atrial or ventricular enlargement can be challenging, and comparisons to breed-specific normal values may be required (Class I, LOE: Moderate). 35-41 In addition to short axis basilar views, recently described 2-dimensional, long-axis echocardiographic ratios (left ventricle (LV)/aorta (Ao), LA/Ao, and LA/LV) have proven to be effective for identifying left atrial and ventricular enlargement in dogs with MMVD. 42 (Class I, LOE: strong)  The panel recognizes that it is sometimes necessary to use thoracic radiography in the absence of echocardiography to further refine Stage B. Under these circumstances, the clinician must be cautious because of marked variation in thoracic conformation and breed differences in normal vertebral heart scales; the use of the vertebral left atrial size (VLAS) (details below) may be beneficial. (Class I, LOE: moderate) 6.3 | Stage B1: Asymptomatic dogs with mitral valve regurgitation caused by MMVD that is not severe enough to meet criteria used to trigger the use of medical treatment to delay the onset of heart failure. Stage B1 dogs are characterized by a spectrum of imaging findings ranging from those with radiographically and echocardiographically normal left atrial [LA] and ventricular [LV] dimensions with normal LV systolic function and normal radiographic vertebral heart or Recommendations for treatment and monitoring of Stage B1 (both pharmacologic and dietary, small and large breed dogs) remain unchanged from the 2009 recommendations Treatment is not recommended in these dogs because at this early stage of disease, progression to heart failure is uncertain, unlikely to occur within the recommended evaluation interval, and there is no evidence that medication is effective at this stage. To summarize,  No drug or dietary treatment is recommended (Class I, LOE: expert opinion)  Reevaluation by echocardiography is suggested (or radiography if echocardiography is unavailable) in 6-12 months, depending on the imaging results (some panelists recommend more frequent follow-up in large dogs). (Class I, LOE: expert opinion) 6.4 | Stage B2: Asymptomatic MMVD causing MR severe enough to result in cardiac remodeling (LA and LV enlargement) sufficient to recommend treatment before the onset of clinical signs based on the results of a clinical trial. 43,44 Dogs in this category should meet the current criteria outlined below.  Stage B2 criteria for heart enlargement identify dogs that are likely to benefit substantially from treatment before the onset of clinical signs of heart failure. (Class I, LOE: Strong): murmur intensity 3/6; echocardiographic LA : Ao ratio in the right-sided short axis view in early diastole 1.6 (Figure 1) 45 ; [/fig]
[fig] : B2 cardiac remodeling and enlargement in MMVD are underway, definitive criteria for the radiographic identification of this stage are currently not available. In the absence of echocardiographic measurements, clear radiographic evidence of cardiomegaly (eg, a "gen-eral breed" VHS 11.5, or a comparable "breed-adjusted" VHS in cases where breed-specific VHS normal values are available) or evidence of accelerating (increasing) interval change in radiographic or echocardiographic cardiac enlargement patterns 42 can substitute for quantitative echocardiography to identify Stage B2. (Class I, LOE: expert opinion) A newer index of radiographic left atrial enlargement, the VLAS, provides a quantitative method of estimating left atrial size. Measured on either the right or left lateral radiograph by drawing a line from the center of the most ventral aspect of the carina to the most caudal aspect of the LA where it intersects with the dorsal border of the caudal vena cava, that line then is transposed to the cranial edge of the 4th thoracic vertebral body. 54 Studies are ongoing to determine a VLAS value that accurately predicts B2 remodeling, but in the absence of echocardiography, VLAS values of 3 likely identify Stage B2 MMVD. (Class 1, LOE: moderate) 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: 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 used 60 (Class IIb, LOE: expert opinion). [/fig]
[table] Table 1 ,: tions for chronic dietary management. Some patients in Stage C may have life-threatening clinical signs and require more extensive acute treatment than is considered standard. These acute care patients tem- [/table]