Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease

This is the report of the American College of Veterinary Internal Medicine (ACVIM) Specialty of Cardiology consensus panel convened to formulate guidelines for the diagnosis and treatment of chronic valvular heart disease (CVHD, also known as endocardiosis and myxomatous valve degeneration) in dogs. It is estimated that approximately 10% of dogs presented to primary care veterinary practices have heart disease, and CVHD is the most common heart disease of dogs in many parts of the world, accounting for approximately 75% of canine cases of heart disease cases seen by veterinary practices in North America. CVHD most commonly affects the left atrioventricular or mitral valve, although in approximately 30% of cases the right atrioventricular (tricuspid) valve also is involved. The disease is approximately 1.5 times more common in males than in females. Its prevalence is also higher in smaller (<20 kg) dogs, although large breeds occasionally are affected.1 In small breed dogs, the disease generally is slowly but somewhat unpredictably progressive, with most dogs experiencing the onset of a recognizable murmur of mitral valve regurgitation years before the clinical onset of heart failure. When large breed dogs are affected by CVHD, the progression of the disease appears to be more rapid than that observed in small breed dogs.2 Cavalier King Charles Spaniels are predisposed to developing CVHD at a relatively young age, but the time course of their disease progression to heart failure does not appear to be markedly different from that of other small breed dogs except for the early age of onset.3,4 The cause of CVHD is unknown, but the disease appears to have an inherited component in some breeds studied.5,6 CVHD 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).7,8 These changes involve both the collagen content and the alignment of collagen fibrils within the valve.9,10 Endothelial cell changes and subendothelial thickening also occur,11 although affected dogs do not appear to be at increased risk for arterial thromboembolism or infective endocarditis. Mitral valve prolapse is a common complication of myxomatous valve degeneration and represents a prominent feature of CVHD in some breeds.6,12 Progressive deformation of the valve structure eventually prevents effective coaptation and causes regurgitation (valve leakage). Progressive valvular regurgitation increases cardiac work, leading to ventricular remodeling (eccentric hypertrophy and intercellular matrix changes) and ventricular dysfunction. Abnormal numbers or types of mitogen receptors (eg, any of the subtypes of serotonin, endothelin, or angiotensin receptors) on fibroblast cell membranes in the valves of affected dogs may play a role in the pathophysiology of the valvular lesions.13 Systemic or local metabolic, neurohormonal or inflammatory mediators (eg, endogenous catecholamines and inflammatory cytokines) also may influence progression of the valve lesion or the subsequent myocardial remodeling and ventricular dysfunction that accompany long-standing, hemodynamically significant valvular regurgitation. However, these factors are poorly understood at this time.14 The prevalence of CVHD increases markedly with age in small breed dogs (with up to 85% showing some evidence of the lesion at necropsy by 13 years of age), but the presence of the pathologic lesion does not necessarily indicate that a dog will develop clinical signs of heart failure. Like the underlying cause of the disease, the factors that determine the progression of the lesion remain unknown, although age, left atrial size, and heart rate have been shown to predict outcomes.15,16 Heart failure is a general term that describes a clinical syndrome that can be caused by a variety of specific heart diseases, including CVHD. Heart failure from any cause is characterized by cardiac, hemodynamic, renal, neurohormonal, and cytokine abnormalities. The classification systems for heart failure most familiar to veterinarians are the modified New York Heart Association (NYHA)17 and International Small Animal Cardiac Health Council18 functional classification systems, both of which were designed to provide a framework for discussing and comparing the clinical signs of patients in heart failure. These functional classification systems vary in their details, but both serve as semiquantitative schemes for judging the severity of a patient's clinical signs. Such categorization aids in teaching therapeutic protocols and constitutes a basis for stratification of subjects in clinical trials. The modified NYHA functional classification of heart failure can be summarized as follows: Class I describes patients with asymptomatic heart disease (eg, CVHD is present, but no clinical signs are evident even with exercise). Class II describes patients with heart disease that causes clinical signs only during strenuous exercise. Class III describes patients with heart disease that causes clinical signs with routine daily activities or mild exercise. Class IV describes patients with heart disease that causes severe clinical signs even at rest. Functional classification systems share a common problem in that they are based on relatively subjective assessments of clinical signs that can change frequently and dramatically over short periods of time. Furthermore, treatments may not differ substantially across the functional classes. A newer classification system that might more objectively categorize patients in the course of their heart disease has been developed, and this scheme was used by the panel for consensus recommendations. The goal was to link severity of signs to appropriate treatments at each stage of illness. In formulating these guidelines, the consensus panel adapted the 2001 American College of Cardiology/American Heart Association classification system for the treatment of heart disease and failure in human patients to the management of canine CVHD.19 In this approach, patients are expected to advance from 1 stage to the next unless progression of the disease is altered by treatment. The classification system presented below and used in these guidelines is meant to complement, not replace, functional classification systems. The new system describes 4 basic stages of heart disease and failure: Stage A identifies patients at high risk for developing heart disease but that currently have no identifiable structural disorder of the heart (eg, every Cavalier King Charles Spaniel without a heart murmur). Stage B identifies patients with structural heart disease (eg, the typical murmur of mitral valve regurgitation is present), but that have never developed clinical signs caused by heart failure. Because of important clinical implications for prognosis and treatment, the panel further subdivided Stage B into Stage B1 and B2. Stage B1 refers to asymptomatic patients that have no radiographic or echocardiographic evidence of cardiac remodeling in response to CVHD. Stage B2 refers to asymptomatic patients that have hemodynamically significant valve regurgitation, as evidenced by radiographic or echocardiographic findings of left-sided heart enlargement. Stage C denotes patients with past or current clinical signs of heart failure associated with structural heart disease. Because of important treatment differences between dogs with acute heart failure requiring hospital care and those with heart failure that can be treated on an outpatient basis, these issues have been addressed separately by the panel. Some animals presenting with heart failure for the 1st time may have severe clinical signs requiring aggressive therapy (eg, with additional afterload reducers or temporary ventilatory assistance) that more typically would be reserved for those with refractory disease (see Stage D). Stage D refers to patients with end-stage disease with clinical signs of heart failure caused by CVHD that are refractory to “standard therapy” (defined later in this document). Such patients require advanced or specialized treatment strategies in order to remain clinically comfortable with their disease. As with Stage C, the panel has distinguished between animals in Stage D that require acute, hospital-based therapy and those that can be managed as outpatients. This classification system emphasizes that there are risk factors and structural prerequisites for the development of heart failure in CVHD. The use of this classification system is meant to encourage veterinary clinicians to think about heart disease in a way analogous to the current clinical approach to cancer. This classification system is designed to aid in: Developing screening programs for the presence of CVHD in dogs known to be at risk. Identifying interventions that may (now or in the future) decrease the risk of disease development. Identifying asymptomatic dogs with CVHD early in the course of their disease, comparable to “in situ” cancer, so that they can perhaps be treated more effectively. Identifying symptomatic dogs with CVHD so that these patients can be treated medically and either potentially cured (interventionally or surgically) or managed with their chronic disease. Identify symptomatic dogs with advanced heart failure from CVHD and refractory to conventional therapy—these patients require aggressive or new treatment strategies or potentially hospice-type end-of-life care. In classifying dogs with CVHD according to their disease stage and clinical status and matching them with diagnostic, pharmacologic, and dietary treatment recommendations, the consensus panel considered both the quantity and quality of evidence available to inform the diagnostic and therapeutic decisions made in these patients. The heading “Consensus recommendation” preceding a diagnostic, therapeutic, or dietary recommendation indicates that the panelists were unanimous in their opinion that the combination of available clinical trial evidence, other published experimental or anecdotal evidence, clinical experience, and expert opinion indicate that the potential benefit of the approach under discussion clearly outweighs the potential risks to the patient and minimizes financial impact on the client. In situations in which the available evidence regarding the efficacy of a diagnostic or therapeutic maneuver was conflicting, weak, or absent and no consensus on a recommended course of action could be reached by the panelists based on the available evidence and their collective clinical experience, the panel's opinions and reasoning on clinically important issues are briefly summarized. These bulleted summary statements are grouped together and summarized under the heading “No consensus.” The panel recognized that there is considerable variation in the scientific quality of the evidence available to support clinical decision making, and sought to include topically relevant references. Whereas the status of a particular recommendation (consensus versus no consensus) reflects the collective judgment of the panel on each question addressed, no attempt was made to assign a specific scientific grade or value to each included citation. Stage A—Dogs at high risk for development of heart failure, but without apparent structural abnormality (no heart murmur is heard) at the time of examination. Consensus recommendations: Small breed dogs, including breeds with known predisposition to develop CVHD (eg, Cavalier King Charles Spaniels, Dachshunds, Miniature and Toy Poodles) by the as of routine care. of dogs or those at high as Cavalier King Charles Spaniels, may to in screening at dog or other by their breed or and by in an disease Consensus recommendations: therapy is recommended for any dietary therapy is recommended for any no be mitral regurgitation is during their age of Stage patients have a structural abnormality the presence of CVHD, but have never clinical signs of heart failure. These patients are generally recognized during a screening or routine with a heart murmur typical of mitral valve Consensus recommendations: is recommended in patients to the of the murmur and also to at a time the patient is asymptomatic for CVHD. is recommended for patients. In small breed dogs with typical is recommended to specific regarding either cardiac or the cause of the murmur those are not by and generally is in breed dogs the murmur of is more to be to other causes (eg, of and is in patients. Because their prognosis and therapy may differ asymptomatic patients with of mitral valve are further into based on the of the Stage (defined as or or or with heart on for Stage B1 and is for both small and large breed dogs. Consensus recommendations: Small and large breed or dietary therapy is is by either or with in approximately panelists more in large Stage significant with cardiac remodeling (defined as clearly or for Stage B2 and is and no consensus could be reached with currently available Small breed patients with clinically relevant left atrial on either or those in which the left has increased in dramatically on a of the panel of therapy with an the efficacy of for the treatment of dogs in Stage B2 have no or a small the onset of heart A of the panel no therapy for asymptomatic animals further clinical to the efficacy of therapy in this patients with clinically relevant left atrial on either or the left has increased in dramatically on a of the panel of therapy with a of a to the over a of approximately on the specific A of the panel no therapy for asymptomatic animals further clinical to the efficacy of therapy in this the efficacy of for the treatment of dogs in Stage B2 are in other treatments were recommended in Stage B2 by a of A panelists considered the use of the for patients in Stage B2 under specific and The panel in general that these treatment strategies additional into their efficacy and in this patient before a consensus recommendation could be treatment was recommended by a of panelists in Stage a of the panel recommended no dietary dietary treatment at this stage include mild dietary and of a with and for breed panelists recommended treatment in smaller breed dogs their the use of both and in breed dogs in Stage B2. treatment for breed dogs were the as those for small mild and and changes were Stage have a structural abnormality and current or clinical signs of heart failure caused by CVHD. Stage C patients that have an of clinical heart failure. Such patients in this stage of their clinical signs with therapy their clinical signs for are for both management of heart failure and for care management of heart failure, as well as for chronic dietary Some patients that in Stage C may have clinical and require more acute therapy than is considered These acute care patients may share some management strategies with dogs that have to Stage D heart failure, In Stage C, heart failure to CVHD, the panel not clinically relevant therapeutic between small and breed dogs for either acute or chronic both C and D patients with symptomatic heart the acute care of heart failure is on the patient's status by well as under clinical and heart and to cardiac decrease the of mitral valve regurgitation and clinical signs associated with either cardiac or increased The of chronic management are on these to the additional treatments at clinical signs of heart failure, and quality Consensus recommendations: Because of the relatively high prevalence of chronic disease in the at risk for CVHD, the presence of a typical left murmur in a dog does not necessarily that the clinical signs are the of CVHD. A clinical (including and an and basic be and to determine the cause of clinical signs in animals with CVHD. in the cause of clinical signs in dogs with CVHD. there is no as a dogs with clinical signs caused by heart failure have higher than those with clinical signs caused by primary disease, the value of any by a available has not been characterized at the time of this to a consensus recommendation with to The and can be in the of heart failure as a cause of clinical signs in patients with CVHD. dogs with no of are to be in heart failure to dogs with and relatively heart also are to have clinical signs to CVHD. of these dogs are or and is to the with a and therapy for is Consensus recommendations: specific of in a dog with be to the severity of clinical signs and the response to or higher (eg, may be appropriate in specific IV or a rate IV may be for poorly dogs. of associated with severe on response to with failure of and rate to over is as a rate at a of 1 the patient to has the clinical trial evidence the chronic use of in the management of Stage C heart failure from CVHD is than for the acute the recommendation to use in acute heart failure therapy is by and experimental as well as the anecdotal of the can be a and or or a treatments (eg, and are recommended to to or cause including of an appropriate and in the on and of patients in associated with be or a with an are most used by or IV was the most for this of and or as well as other including and also have been of for up to is for poorly to Class D below for specific consensus was reached on the acute care Stage C be to the and response to and in the of acute heart failure. specific treatment or was used by (eg, treatment with is a consensus recommendation for chronic Stage C heart failure and a of panelists also acute heart failure with the evidence efficacy and in acute therapy with and is evidence that the acute of in acute heart failure in in with the of approximately for Some panelists the in (eg, panelists do not use in this Consensus recommendations: to commonly at a of The daily for dogs with is and can be as as to The be to patient and with to on and to patient in the of appropriate therapy indicates disease progression to Stage or (eg, or of for The of is most panelists at the of this of and an is recommended for animals with Stage C heart failure. a in the of clinical signs of heart failure (eg, caused by CVHD. of the panelists use in the chronic treatment of Stage C heart failure. in a care to and heart rate support to and in patients with heart failure is consensus was reached regarding the treatment strategies in Stage was recommended by a of panelists as an for the chronic therapy of dogs in Stage C heart failure. The primary of in this is to be clinically relevant be This treatment is in at a of with of the chronic management of Stage C heart failure, a of panelists recommended the of in cases by atrial to the ventricular response Some panelists also at this for patients in Stage C heart failure in the of as as no to is evident (eg, increased ventricular over chronic disease in or of or heart failure signs have a has been and the patient is and a of panelists a of a is no clinical trial evidence in dogs to support this there is no consensus regarding which specific to use or is the most frequently The of in this is to potential on myocardial and These have been in some experimental and in with heart failure, but not in clinical trials. The presence of atrial the for the ventricular response to atrial for those panelists recommended a In patients a before the onset of Stage C heart failure, the of panelists some panelists would clinically of clinical signs of cardiac or Some panelists of are some for chronic heart rate in atrial Some panelists in patients in Stage C heart failure from CVHD. Some panelists in patients in Stage C heart failure from CVHD. Cardiac is as the of of the patient's not including associated with the of or the of has and is to that to Consensus recommendations: in Stage C provide approximately to that in and about the of and to any or other identifiable causes of that the of the patient at every and the cause of or and designed to chronic disease, unless severe failure is into from dietary (including dog and used to and any or other and the with from either or is is relatively in patients treated for heart failure with even in those an in combination with and with high content be has been consensus was reached on the dietary therapy for Stage as and in animals with with in cases in which is with in dogs with or Stage have clinical signs of failure refractory to treatment for Stage C heart failure from CVHD, as Stage D heart failure patients be the recommended of an and as in the Stage C guidelines and to or the ventricular response to atrial in a heart rate of also be used before a patient is considered refractory to there have been clinical efficacy and in this patient This patients with heart failure refractory to conventional therapy with a variety of treatment Because of the of clinical trial evidence and the clinical of patients with end-stage heart failure, development of consensus guidelines regarding the and of and dietary treatment strategies for Stage D patients As with Stage C, guidelines for treatment are for both and for care management of heart failure, and for chronic dietary therapy are also Because Stage D heart failure patients by refractory to the treatments for Stage C refractory heart failure the diagnostic for Stage C the of failure to to treatments in the Stage C Consensus recommendations: In the of severe additional is IV as a at a of by either additional or a at a of 1 and has or for a of 4 As the or is a and higher or may be appropriate for a to patient to has (eg, as to or In to as in Stage C ventilatory may be to the patient more to time for to have an and to provide time for left atrial to increases in mitral valve in patients with acute of CVHD (eg, chordae with severe and failure. afterload in patients that can arterial potentially include at or be at a and clinical by a decrease of approximately in is These are recommended in to an and The be that any in will also on specific are rapid onset with but with is to and arterial or arterial be before and of these in Stage D have heart failure, and a trial of additional afterload is The panel that afterload may cardiac substantially in the of severe and heart failure, of an arterial in this does not necessarily decrease consensus was reached regarding the acute care Stage D recommendations: may be increased to include a daily Some panelists an additional of on of Stage D patients with acute Because this recommendation is of the for this use of the be to and by the client. In animals to be to for the of afterload or support (eg, with or without or afterload in or support of the be by can be at of and every to a of approximately These either separately or in can be used for to status and refractory and is recommended to the potential risks of this is used by a of panelists to acute of Stage D heart failure caused by CVHD, even in the of are recommended as an therapy in in patients by a of Consensus recommendations: be increased as to decrease or use is not by dysfunction generally be The specific and of (eg, increased to times versus higher 1 for a or based on or the not in Stage C, is for chronic treatment of Stage D patients. generally not be at this stage unless clinical signs of heart failure can be as in Stage consensus was reached regarding the chronic Stage D therapeutic recommendations: was recommended by panelists as therapy with (including only use every Some panelists of the risk of acute failure and based on is increased by some panelists to include a daily and as for at the recommended by some panelists for Stage C heart failure, was recommended for treatment of atrial for patients in Stage with the in Stage C at the recommended by some panelists for Stage C heart failure, also was recommended by a of panelists for patients in Stage D in no was is used by some panelists to Stage D heart failure caused by CVHD or to advanced CVHD by The of panelists that at an stage of heart failure in CVHD not be but that may be of could not be by the of other or or both were may be to decrease the ventricular response rate in atrial and are recommended by a of panelists to in Stage D patients care. are recommended by a of panelists to in Stage D patients Consensus recommendations: of the dietary for Stage C In patients with refractory be made to further decrease dietary can be without or