ACVIM Consensus Statement
Guidelines for the Diagnosis and Treatment of Canine Chronic
Valvular Heart Disease
C. Atkins, J. Bonagura, S. Ettinger, P. Fox, S. Gordon, J. Haggstrom, R. Hamlin, B. Keene (Chair),
V. Luis-Fuentes, and R. Stepien
Key words: Cardiology; Cardiovascular; Heart
This is the report of the American College
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 (o20 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.
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
publication. The authors are solely responsible for the content of the statements.
From the Department of Clinical Sciences, North Carolina State
University, Raleigh, NC (Atkins, Keene); Department of Veterinary
Clinical Sciences (Bonagura), Department of Veterinary Biosciences
(Hamlin), The Ohio State University, Columbus, OH; California
Animal Hospital, Los Angeles, CA (Ettinger); Department of
Medicine, Animal Medical Center, New York, NY (Fox); Department
of Small Animal Clinical Science, Texas A&M University,
College Station, TX (Gordon); Department of Clinical Sciences,
University of Agricultural Sciences, University of Uppsala, Uppsala,
Sweden (Haggstrom); Royal Veterinary College, VCS, University of
London, London, UK (Luis-Fuentes); and Department of Medical
Sciences, University of Wisconsin-Madison, Madison, WI (Stepien).
Corresponding author: Bruce Keene, Department of Clinical Science,
4700 Hillsborough Street, North Carolina State University,
Raleigh, NC 27606; e-mail: email@example.com.
Submitted June 12, 2009; Revised August 7, 2009; Accepted
August 17, 2009.
Copyright r 2009 by the American College of Veterinary Internal
ACEI angiotensin converting enzyme inhibitors
ACVIM American College of Veterinary Internal Medicine
CRI constant rate infusion
CVHD chronic valvular heart disease
LA left atrium
LV left ventricle
MR mitral regurgitation
J Vet Intern Med 2009;23:1142–1150
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
Classification of Heart Disease and Heart Failure
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
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
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
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
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 cli-
Canine Chronic Valvular Heart Disease 1143
nicians 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
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
these patients can be treated medically and either potentially
cured (interventionally or surgically) or
managed with their chronic disease.
Identify symptomatic dogs with advanced
from CVHD and refractory to conventional therapy—
these patients require aggressive or new treatment strategies
or potentially hospice-type end-of-life care.
Evaluating the Evidence for Efficacy and Safety
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
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.
Guidelines for Diagnosis and Treatment of CVHD
Stage A—Dogs at high risk for development of heart
failure, but without apparent structural
(no heart murmur is heard) at the time of examination.
Diagnosis for Stage A
Small breed dogs, including breeds with
predisposition to develop CVHD (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.
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.
Therapy for Stage A
No drug therapy is recommended for any patient.
No dietary therapy is recommended for any
Potential breeding stock should no longer
if mitral regurgitation (MR) is identified early,
during their normal breeding age of o6–8 years.
Stage B—These patients have
a structural abnormality
indicating the presence of CVHD, but have never had
clinical signs of heart failure. These patients
recognized during a screening or routine health
examination with a heart murmur typical of mitral
Diagnosis for Stage B
Thoracic radiography is recommended in all
to assess the hemodynamic significance of the
murmur and also to obtain baseline thoracic radiographs
at a time when the patient is asymptomatic
Blood pressure measurement is recommended
In small breed dogs with typical murmurs,
is recommended to answer specific
questions regarding either cardiac chamber enlargement
or the cause of the murmur if those
questions are not answered adequately by
auscultation and thoracic radiography.
Echocardiography generally is indicated
breed dogs because the murmur of MR is more
likely to be related to other causes (eg, dilated
Basic laboratory work (a minimum of hematocrit,
total protein concentration, serum creatinine concentration,
and urinalysis) is indicated in all patients.
Because their prognosis and therapy may differ substantially,
asymptomatic patients with murmurs of
1144 Atkins et al
mitral valve insufficiency are further subcategorized into
2 groups based on the results of the above evaluation:
Stage B1: Hemodynamically
insignificant MR (defined
as radiographically or echocardiographically normal or
equivocally enlarged LA, LV, or both, with normal LV
systolic function; normal vertebral heart score on radiography;
normotensive, normal laboratory results).
Therapy for Stage B1 (both pharmacologic
is identical for both small and large breed dogs.
Small and large breed dogs:
No drug or dietary therapy is recommended.
Re-evaluation is suggested by either radiography
or echocardiography with Doppler studies in approximately
12 months (some panelists recommend
more frequent follow-up in large dogs).
Stage B2: Hemodynamically significant
MR with cardiac
remodeling (defined as clearly enlarged
or both); normotensive.
Therapy for Stage B2 (both pharmacologic
is controversial, and no consensus could be
reached with currently available evidence.
Small breed dogs:
Angiogensin converting enzyme inhibitor
For patients with clinically relevant left atrial enlargement
on either initial examination, or those
in which the left atrium has increased in size dramatically
on successive monitoring examinations, a
majority of the panel members recommend initiation
of therapy with an ACEI. Clinical trials
addressing the efficacy of ACEI for the treatment
of dogs in Stage B2 have had mixed results—either
no effect or a small positive effect delaying the onset
of congestive heart failure.20–22
A minority of
the panel members recommend no therapy for
asymptomatic animals pending further clinical trials
to examine the efficacy of therapy in this setting.
b blockers: For patients with clinically relevant left
atrial enlargement on either initial examination, or
when the left atrium has increased in size dramatically
on successive monitoring examinations, a
minority of the panel members recommend initiation
of therapy with a low dosage of a b blocker,
titrating to the highest tolerated dose over a period
of approximately 1–2 months depending on the
specific medication recommended. A majority of
the panel members recommend no b-blocker therapy
for asymptomatic animals pending further
clinical trials to examine the efficacy of therapy in
this setting. Clinical trials addressing the efficacy
of b blockers for the treatment of dogs in Stage B2
are in progress.
No other pharmacologic treatments were recommended
in Stage B2 by a majority of panelists. A
few panelists considered the use of the following
medications for patients in Stage B2 under specific
circumstances: pimobendan, digoxin, amlodipine,
and spironolactone. The panel felt in general that
these treatment strategies needed additional investigation
into their efficacy and safety in this patient
population before a consensus recommendation
could be made.
Dietary treatment was recommended by a majority
of panelists in Stage B2, a minority of the panel
recommended no dietary changes. 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.
Larger breed dogs:
Generally, panelists who recommended treatment
in smaller breed dogs strengthened their recommendations
promoting the use of both ACEI and b
blockers in larger breed dogs in Stage B2.
Dietary treatment recommendations for larger
dogs were the same as those for small breeds, emphasizing
mild sodium restriction and adequate protein
and caloric intake if changes were recommended.
Stage C—Patients have a structural abnormality and
current or previous clinical signs of heart failure caused
by CVHD. Stage C includes all patients that have had
an episode of clinical heart failure. Such patients stay
in this stage despite improvement of their clinical
signs with standard therapy (even if their clinical signs
resolve completely). Guidelines for standard pharmacotherapy
are provided for both in-hospital (acute)
management of heart failure and for home care
(chronic) management of heart failure, as well as recommendations
for chronic dietary therapy. Some
patients that present in Stage C may have life-threatening
clinical signs, and require more extensive acute
therapy than is considered standard therapy. These
acute care patients may share some medical management
strategies with dogs that have progressed to
Stage D (refractory heart failure, see below). In Stage
C, heart failure secondary to CVHD, the panel did not
make clinically relevant therapeutic distinctions between
small and larger breed dogs for either acute or
chronic medical management.
For both Stages C and D (CVHD patients with symptomatic
heart failure), the acute care of heart failure is
focused on regulating the patient’s hemodynamic status
by monitoring (as well as possible under clinical circumstances)
and pharmacologically optimizing preload,
afterload, heart rate, and contractility to improve cardiac
output, decrease the extent of mitral valve
regurgitation if possible, and relieve clinical signs associ-
Canine Chronic Valvular Heart Disease 1145
ated with either low cardiac output or excessively increased
venous pressures (preload). The broad goals of
chronic (home care) management are focused on maintaining
these hemodynamic improvements to the extent
possible, while providing additional treatments aimed at
slowing progression, prolonging survival, decreasing
clinical signs of congestive heart failure, enhancing exercise
capacity, and otherwise improving quality life.
Diagnosis for Stage C
Because of the relatively high prevalence
chronic tracheobronchial disease in the same population
at risk for CVHD, the presence of a typical
left apical regurgitant murmur in a coughing dog
does not necessarily mean that the clinical signs are
the result of CVHD.
A clinical database (including chest radiographs
and preferably an echocardiogram and basic laboratory
tests) must be obtained and examined
carefully to accurately determine the cause of clinical
signs in animals with CVHD.
Serum N-terminal pro-B-type naturetic peptide
(BNP) concentrations should become increasingly
useful in determining the cause of clinical signs in
dogs with CVHD. Although there is no doubt that,
as a group, dogs with clinical signs caused by heart
failure have higher serum BNP concentrations
than those with clinical signs caused by primary
pulmonary disease, the positive predictive value of
any single BNP concentration, obtained by a commercially
available test, has not been adequately
characterized at the time of this writing (August
2009) to make a consensus recommendation with
regard to BNP testing.
The signalment and physical examination
helpful in determining the pretest probability of
heart failure as a cause of clinical signs in patients
with CVHD. For example, obese dogs with no history
of weight loss are less likely to be in heart
failure secondary to CVHD; dogs with marked sinus
arrhythmia and relatively slow heart rates also
are less likely to have clinical signs attributable to
Most of these dogs are middle-aged or older,
is always prudent to complete the database with a
CBC, serum biochemical profile, and urinalysis,
especially if therapy for CHF is anticipated.
Acute (Hospital-Based) Therapy of Stage C
Furosemide—The specific dosing of
a dog with CHF should be related to the severity of
clinical signs and the response to initial therapy.
Lower or higher doses (eg, 1–4 mg/kg) may be appropriate
in specific cases. Repeated IV boluses or
a constant rate IV infusion may be indicated for
poorly responsive dogs.
For life-threatening pulmonary edema (expectoration
of froth associated with severe dyspnea; diffuse
pulmonary opacity on thoracic radiographs; poor
initial response to furosemide bolus with failure of
dyspnea and respiratory rate to improve over 2
hours), furosemide is administered as a constant
rate infusion (CRI) at a dose of 1mg/kg/h after the
Allow patient free access to water once
Pimobendan, 0.25–0.3 mg/kg PO q12h—Although
the clinical trial evidence supporting the chronic
use of pimobendan in the management of Stage C
heart failure from CVHD is stronger than for the
acute situation, the recommendation to use pimobendan
in acute heart failure therapy is strongly
supported by hemodynamic and experimental evidence
24–27 as well as the anecdotal experience
Oxygen supplementation, if needed, can be
via a humidity and temperature-controlled
oxygen cage or incubator or via a nasal oxygen
Mechanical treatments (eg, abdominal paracentesis
and thoracocentesis) are recommended to
remove effusions judged sufficient to impair ventilation
or cause respiratory distress.
Provide optimal nursing care, including
of an appropriate environmental temperature
and humidity, increase in the head on pillows,
and placement of sedated patients in sternal posture.
Sedation—Anxiety associated with dyspnea
be treated. Narcotics, or a narcotic combined with
an anxiolytic agent, are most often used by panelists.
Butorphanol (0.2–0.25mg/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 SQ) as well as other narcotics, including
morphine and hydrocodone, also have been utilized.
CRI of sodium nitroprusside for up to 48
often useful for life-threatening, poorly responsive
pulmonary edema (refer to Class D below for specific
No consensus was reached on the following acute care
Stage C issues:
Care must be taken to monitor the blood
and respiratory response to narcotics and tranquililzers
in the setting of acute heart failure. No
specific treatment or dosage regimen was used by
ACEI (eg, enalapril 0.5mg/kg PO q12h). Although
treatment with ACEI is a consensus recommendation
for chronic Stage C heart failure and a majority
of panelists also treat acute heart failure with ACEI,
the evidence supporting ACEI efficacy and safety in
acute therapy when combined with furosemide and
pimobendan is less clear. There is, however, clear evidence
that the acute administration of enalapril plus
1146 Atkins et al
furosemide in acute heart failure results in substantial
improvement in pulmonary capillary wedge pressure
when compared with the administration of furosemide
Nitroglycerin 2% ointment, approximately
paste per 10 kg body weight for 24–36 hours. Some
panelists recommend administering the ointment
in intervals (eg, 12 hours on, 12 hours off). Other
panelists do not use nitroglycerin in this setting.
Home-Based (Chronic) Therapy for Stage C
Continue PO furosemide administration to
commonly at a dosage of 2 mg/kg q12h. The daily
furosemide dosage for dogs with CHF is wide and
can be as low as 1–2 mg/kg PO q12h to 4–6 mg/kg
PO q8h. The dosage must be titrated to maintain
patient comfort and with attention to effects on
renal function and electrolyte status.
Chronic oral furosemide (doses 6
needed to maintain patient comfort in the face of
appropriate adjunct therapy indicates disease progression
to Stage D.
Continue or start ACEI (eg, enalapril 0.5
PO q12h) or equivalent dose of another ACEI
if approved for use. The labeled dosage range of
enalapril is 0.25–0.5 mg/kg PO q12h; most panelists
treat at the upper end of this range. Measurement
of serum creatinine and electrolyte concentrations
3–7 days after beginning an ACEI is recommended
for animals with Stage C heart failure.
Continue pimobendan (0.25–0.3 mg/kg
Panelists recommend against starting a b blocker
the face of active clinical signs of heart failure (eg,
cardiogenic pulmonary edema) caused by CVHD.
None of the panelists routinely use nitroglycerin
the chronic treatment of Stage C heart failure.
Participation in a structured, home-based
care program to facilitate body weight,
appetite, respiratory, and heart rate monitoring
while providing client support to enhance medication
compliance and dosage adjustments in
patients with heart failure is encouraged.
No consensus was reached regarding the following
home-based (chronic) treatment strategies in Stage C:
Spironolactone (0.25–2.0 mg/kg PO
recommended by a majority of panelists as an adjunct
for the chronic therapy of dogs in Stage C
heart failure. The primary purpose of spironolactone
in this situation is thought to be aldosterone
antagonism. No clinically relevant diuretic effect
should be anticipated. This treatment now is approved
in Europe at a dosage of 2 mg/kg/d.
Digoxin (0.0025–0.005 mg/kg PO q12h)
plasma concentration 8 hours postpill of 0.8–
1.5 ng/mL. For the chronic management of Stage
C heart failure, a majority of panelists recommended
the addition of digoxin in cases complicated
by persistent atrial fibrillation to slow the
ventricular response rate. Some panelists also prescribe
digoxin at this dosage for patients in Stage C
heart failure in the absence of sustained supraventricular
tachyarrhythmia, as long as no contraindication
to digoxin is evident (eg, increased
serum creatinine concentration, ventricular ectopy,
concerns over owner compliance, chronic
GI disease resulting in frequent or unpredictable
bouts of vomiting or diarrhea).
Once heart failure signs have resolved,
medication regimen has been instituted, and the
patient is eating and apparently feeling well, a minority
of panelists recommend attempting a low
dose, slow up-titration regimen of a b blocker.
There is no clinical trial evidence in dogs to support
this recommendation. If prescribed, there is
no consensus regarding which specific b blocker to
use (carvedilol, atenolol, or metoprolol is the most
frequently prescribed). The purpose of b blockade
in this setting is related to potential long-term protective
effects on myocardial function and
remodeling. These effects have been demonstrated
in some experimental animal models31 and in humans
with heart failure, but not in clinical trials.
The presence of atrial fibrillation strengthens
indication for b blockade (to slow the ventricular
response to atrial fibrillation) for those panelists
who recommended a b blocker.
In patients taking a b blocker
before the onset of
Stage C heart failure, the majority of panelists
continue b blockade; some panelists would consider
dosage reduction if needed clinically because
of clinical signs of low cardiac output, hypothermia,
Some panelists prefer administration of
(several formulations are available, some
sustained release) for chronic heart rate control in
Some panelists find cough suppressants useful
occasional patients in Stage C heart failure from
Some panelists find bronchodilators useful
patients in Stage C heart failure from
Dietary Therapy for Stage C
Cardiac cachexia is defined as the unintentional loss
of47.5% of the patient’s normal, predisease weight, not
including weight loss associated with the resolution of
edema or the removal of body cavity effusions. Cachexia
has substantial negative prognostic implications, and is
much easier to prevent that to treat.32
Maintain adequate calorie intake (maintenance
calorie intake in Stage C should provide approximately
60 kcal/kg body weight) to minimize weight
Canine Chronic Valvular Heart Disease 1147
loss (specifically muscle mass loss) that often occurs
Specifically address and inquire about the
of anorexia, and make efforts to treat any druginduced
or other identifiable causes of anorexia that
Record the accurate weight of the patient
clinic visit, and investigate the cause of weight gain or
Ensure adequate protein intake and avoid
diets designed to treat chronic kidney disease,
unless severe concurrent renal failure is present.
Modestly restrict sodium intake, taking
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.
Monitor serum potassium concentrations and
the diet with potassium from either
natural or commercial sources if hypokalemia is
identified. Hyperkalemia is relatively rare in patients
treated for heart failure with diuretics, even
in those concurrently receiving an ACEI in combination
with spironolactone.33 Diets and foods with
high potassium content should be avoided when
hyperkalemia has been identified.
No consensus was reached on the following dietary therapy
for Stage C:
Consider monitoring serum magnesium concentrations,
especially as CHF progresses and in animals
with arrhythmias. Supplement with magnesium in
cases in which hypomagnesemia is identified.
Consider supplementing with n-3 fatty acids,
in dogs with decreased appetite, muscle mass
loss, or arrhythmia.34
Stage D—Patients have clinical signs of failure refractory
to standard treatment for Stage C heart failure
from CVHD, as outlined above. Stage D heart failure
patients therefore should be receiving the maximal
recommended (or tolerated) dosage of furosemide, an
ACEI, and pimobendan, as outlined in the Stage C
guidelines above. Any indicated and tolerated antiarrhythmic
medication, needed to maintain sinus
rhythm (if possible) or regulate the ventricular response
to atrial fibrillation in a heart rate range of
80–160/min, also should be used before a patient is
considered refractory to standard therapy.
Not surprisingly, there have been very few clinical trials
addressing drug efficacy and safety in this patient
population. This leaves cardiologists treating patients
with heart failure refractory to conventional medical
therapy with a perplexing variety of treatment options.
Because of the relative lack of clinical trial evidence and
the diverse clinical presentations of patients with endstage
heart failure, development of meaningful consensus
guidelines regarding the timing and implementation of
individual pharmacologic and dietary treatment strategies
for Stage D patients proved difficult. As with Stage
C, guidelines for drug treatment are provided for both inhospital
(acute) and for home care (chronic) management
of heart failure, and recommendations for chronic
dietary therapy are also given.
Diagnosis for Stage D
Because Stage D heart failure patients are,
refractory to the treatments for Stage C
patients, defining refractory congestive heart failure
involves the same diagnostic steps outlined for
Stage C plus the finding of failure to respond to
treatments outlined in the Stage C guidelines.
Acute (Hospital-Based) Therapy for Stage D
(Refractory Heart Failure)
In the absence of severe renal insufficiency
serum creatinine concentrations 4 3 mg/dL), additional
furosemide is administered IV as a bolus
at a dosage of 2 mg/kg followed by either additional
bolus doses, or a furosemide CRI at a
dosage of 1 mg/kg/h until respiratory distress (rate
and effort) has decreased, or for a maximum of
4 hours. As indicated above, the dosage or furosemide
is a range and higher or lower doses may be
appropriate for a given case.
Continue to allow patient free access to
diuresis has begun.
Fluid removal (eg, abdominal paracentesis,
as needed to relieve respiratory
distress or discomfort.
In addition to oxygen supplementation as
C (above), mechanical ventilatory assistance may
be useful to make the patient more comfortable, to
allow time for medications35 to have an effect; and
to provide time for left atrial dilatation to accommodate
sudden increases in mitral valve
regurgitant volume in patients with acute exacerbation
of CVHD (eg, ruptured chordae tendinae
with severe cardiogenic pulmonary edema) and
impending respiratory failure.
More vigorous afterload reduction in patients
that can tolerate arterial vasodilation. Drugs potentially
beneficial include sodium nitroprusside
(starting at 0.5–1 mg/kg/min), hydralazine (0.5–
2.0 mg/kg PO), or amlodipine (0.05–0.1 mg/kg
PO). Direct vasodilators should be started at a
low dosage and up-titrated hourly until adequate
clinical improvement accompanied by a decrease
of approximately 5–10% in systolic blood pressure
is observed. These drugs are recommended in addition
to an ACEI and pimobendan. The clinician
should be mindful that any decline in blood pressure
will also depend on specific vasodilator drug.
For example, vasodilation effects are rapid onset
with nitroprusside, but slower with amlodipine.
Caution is warranted to avoid serious, prolonged
hypotension (ie, monitor blood pressure and main-
1148 Atkins et al
tain systolic arterial blood pressure485mmHg or
mean arterial blood pressure 4 60 mmHg. Serum
creatinine concentration should be measured before
and 24–72 hours after administration of these
drugs. Patients in Stage D have life-threatening
heart failure, and a trial of additional afterload reduction
is warranted. The panel emphasized that
because afterload reduction may increase cardiac
output substantially in the setting of severe MR
and heart failure, administration of an arterial dilator
in this setting does not necessarily decrease
No consensus was reached regarding the following acute
care Stage D recommendations:
Pimobendan dosage may be increased (off-label)
to include a 3rd 0.3 mg/kg daily dose. Some panelists
administer an additional dose of pimobendan
on admission of Stage D patients with acute
pulmonary edema. Because this dosage recommendation
is outside of the FDA-approved labeling
for pimobendan, this use of the drug should be
explained to and approved by the client.
In animals judged to be too sick to wait
effects of oral afterload reduction or inotropic support
(eg, pimobendan with or without hydralazine
or amlodipine), nitroprusside (for afterload reduction
in life threatening pulmonary edema) or
dobutamine (for inotropic support of the hypotensive
patient) must be administered by CRI.
Both drugs can be administered at dosages of 0.5–
1.0 mg/kg/min and up-titrated every 15–30 minutes
to a maximum of approximately 10 mg/kg/min.
These drugs, either separately or in combination,
can be used for 12–48 hours to improve hemodynamic
status and control refractory cardiogenic
pulmonary edema. Continuous electrocardiographic
and blood pressure monitoring is recommended
to minimize the potential risks of this therapy.
Sildenafil (1–2 mg/kg PO q12h) is
used by a minority
of panelists to treat acute exacerbations of
Stage D heart failure caused by CVHD, even in
the absence of diagnosed pulmonary hypertension.
Bronchodilators are recommended as an adjunct
therapy in treating cardiogenic pulmonary edema
in hospitalized patients by a minority of panelists.
Home-Based (Chronic) Stage D Therapy
Furosemide dosage should be increased as
to decrease pulmonary edema or body cavity effusions,
if use is not limited by renal dysfunction
(which generally should be monitored 12–48 hours
after dosage increases). The specific strategy and
magnitude of dosage increase (eg, same dose increased
to 3 times per day versus 2 higher doses,
substituting 1 SC dose for a PO dose q48h, or
flexible SC dose supplementation based on body
weight or girth measurements) varied widely
among the panelists.
Spironolactone, if not already started in
is indicated for chronic treatment of Stage D
b blockade generally should not be initiated at this
stage unless clinical signs of heart failure can be
controlled, as outlined in Stage C.
No consensus was reached regarding the following
chronic Stage D therapeutic recommendations:
Hydrochlorthiazide was recommended by several
panelists as adjunctive therapy with furosemide,
utilizing various dosing schedules (including only
intermittent use every 2nd–4th day). Some panelists
warned of the risk of acute renal failure and
marked electrolyte disturbances, based on personal
Pimobendan dosage is increased by some panelists
to include a 3rd 0.3 mg/kg daily dose (off-label use,
explanations and cautions apply as listed for inhospital
Digoxin, at the same (relatively low) dosages
by some panelists for Stage C heart
failure, was recommended for treatment of atrial
fibrillation for patients in Stage D, with the same
cautions listed in Stage C above.
Digoxin, at the same (relatively low) dosages
by some panelists for Stage C heart
failure, also was recommended by a minority of
panelists for all patients in Stage D in sinus rhythm,
assuming no clear contraindication was present.
Sildenafil (1–2 mg/kg PO q12h) is
used by some
panelists to treat Stage D heart failure caused by
CVHD or to treat advanced CVHD complicated
by pulmonary hypertension.
The majority of panelists felt that b blockade
at an earlier stage of heart failure in CVHD
should not be discontinued, but that dose reduction
may be needed if shortness of breath could
not be controlled by the addition of other medications
or if bradycardia, hypotension, or both were
b blockade still may be useful to decrease the ventricular
response rate in atrial fibrillation after
stabilization and digitalization.
Cough suppressants are recommended by a
of panelists to treat chronic, intractable cough
in Stage D patients receiving home care.
Bronchodilators are recommended by a minority
of panelists to treat chronic, intractable coughing
in Stage D patients receiving home careanelists.
Home-Based (Chronic) Dietary Therapy for Stage D
All of the dietary considerations for Stage
In patients with refractory fluid accumulations,
should be made to further decrease dietary
Canine Chronic Valvular Heart Disease 1149
sodium intake if it can be done without compromising
appetite or renal function.
1. Buchanan JW. Chronic valvular disease (endocardiosis) in
dogs. Adv Vet Sci Comp Med J Vet Cardiol 2004;6:6–7.
2. Borgarelli M, Zini E, D’Agnolo G, et al. Comparison of primary
mitral valve disease in German Shepherd dogs and in small
breeds. J Vet Cardiol 2004;6:27–34.
3. Beardow AW, Buchanan JW. Chronic mitral valve disease in
Cavalier King Charles Spaniels: 95 cases (1987–1991). J Am Vet
Med Assoc 1993;203:1023–1029.
4. Ha¨ ggstro¨m J, Hansson K, Kvart C, Swenson L. Chronic valvular
disease in the Cavalier King Charles Spaniel in Sweden. Vet
5. Swenson L, Haggstrom J, Kvart C, Juneja RK. Relationship
between parental cardiac status in Cavalier King Charles Spaniels
and prevalence and severity of chronic valvular disease in offspring.
J Am Vet Med Assoc 1996;208:2009–2012.
6. Olsen LH, Fredholm M, Pedersen HD. Epidemiology and inheritance
of mitral valve prolapse in Dachshunds. J Vet Intern Med
7. Black A, French AT, Dukes-McEwan J, Corcoran BM. Ultrastructural
morphologic evaluation of the phenotype of valvular
interstitial cells in dogs with myxomatous degeneration of the mitral
valve. Am J Vet Res 2005;66:1408–1414.
8. Han RI, Black A, Culshaw GJ, et al. Distribution of myofibroblasts,
smooth muscle-like cells, macrophages, and mast cells
in mitral valve leaflets of dogs with myxomatous mitral valve disease.
Am J Vet Res 2008;69:763–769.
9. Hadian M, Corcoran BM, Han RI, et al. Collagen organization
in canine myxomatous mitral valve disease: An X-ray
diffraction study. Biophys J 2007;93:2472–2476.
10. Hadian M, Corcoran B, Bradshaw J. A differential scanning
calorimetry study of collagen phase transition in myxomatous mitral
valves. Biophys J 2007;44A.
11. Corcoran BM, Black A, Anderson H, et al. Identification of
surface morphologic changes in the mitral valve leaflets and chordae
tendineae of dogs with myxomatous degeneration. Am J Vet Res
12. Pedersen HD, Lorentzen KA, Kristensen BO Echocardiographic
mitral valve prolapse in Cavalier King Charles Spaniels:
Epidemiology and prognostic significance for regurgitation. Vet
13. Mow T, Pedersen HD. Increased endothelin-receptor density
in myxomatous canine mitral valve leaflets. J Cardiovasc Pharmacol
14. Olsen LH, Mortensen K, Martinussen T, et al. Increased
NADPH-diaphorase activity in canine myxomatous mitral valve
leaflets. J Comp Pathol 2003;129:120–130.
15. Borgarelli M, Savarino P, Crosara S, et al. Survival characteristics
and prognostic variables of dogs with mitral regurgitation
attributable to myxomatous valve disease. J Vet Intern Med
16. Atkins CE, Keene BW, Brown WA, et al. Results of the veterinary
enalapril trial to prove reduction in onset of heart failure in
dogs chronically treated with enalapril alone for compensated, naturally
occurring mitral valve insufficiency. J Am Vet Med Assoc
17. Ettinger SJ, Suter PF The recognition of cardiac disease and
congestive heart failure. In: Ettinger SF, Duter PF. Canine Cardiology.
Philadelphia, PA: WB Saunders; 1970: p. 5.
18. International Small Animal Cardiac Health Council.
Recommendations for the diagnosis and treatment of heart failure
in small animals. Woodbridge, NJ: ISACHC Publication; 1994:
19. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines
for the evaluation and management of chronic heart failure in the
adult: Executive summary. A report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines (committee to revise the 1995 guidelines for the evaluation
and management of heart failure). J Am Coll Cardiol 2001;
20. Kvart C, Haggstrom J, Pedersen HD, et al. Efficacy of enalapril
for prevention of congestive heart failure in dogs with
myxomatous valve disease and asymptomatic mitral regurgitation.
J Vet Intern Med 2002;16:80–88.
21. Atkins CE, Brown WA, Coats JR, et al. Effects of long-term
administration of enalapril on clinical indicators of renal function in
dogs with compensated mitral regurgitation. J Am Vet Med Assoc
22. Pouchelon JL, Jamet N, Gouni V, et al. Effect of benazepril
on survival and cardiac events in dogs with asymptomatic mitral
valve disease: A retrospective study of 141 cases. J Vet Intern Med
23. Adin DB, Taylor AW, Hill RC, et al. Intermittent bolus injection
versus continuous infusion of furosemide in normal adult
greyhound dogs. J Vet Intern Med 2003;17:632–636.
24. Ichihara K, Abiko Y. The effect of pimobendan on myocardial
mechanical function and metabolism in dogs: Comparison with
dobutamine. J Pharm Pharmacol 1991;43:583–588.
25. Pouleur H, Gurne O, Hanet C, et al. Effects of pimobendan
(UD-CG 115) on the contractile function of the normal and ‘‘postischemic’’
canine myocardium. J Cardiovasc Pharmacol 1988;11:
26. Pouleur H, Hanet C, Schroder E, et al. Effects of pimobendan
(UD-CG 115 BS) on left ventricular inotropic state in conscious
dogs and in patients with heart failure. J Cardiovasc Pharmacol
27. Takahashi R, Endoh M. Increase in myofibrillar Ca21 sensitivity
induced by UD-CG 212 Cl, an active metabolite of
pimobendan, in canine ventricular myocardium. J Cardiovasc
28. Haggstrom J, Boswood A, O’Grady M, et al. Effect of pimobendan
or benazepril hydrochloride on survival times in dogs
with congestive heart failure caused by naturally occurring myxomatous
mitral valve disease: The QUEST study. J Vet Intern Med
29. Smith PJ, French AT, Van IN, et al. Efficacy and safety of
pimobendan in canine heart failure caused by myxomatous mitral
valve disease. J Small Anim Pract 2005;46:121–130.
30. Lombard CW, Jo¨ ns O, Bussadori CM. Clinical efficacy of
pimobendan versus benazepril for the treatment of acquired atrioventricular
valvular disease in dogs. J Am Anim Hosp Assoc
31. Tsutsui H, Spinale FG, Nagatsu M, et al. Effects of chronic
beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities
of chronic canine mitral regurgitation. J Clin Invest
32. Slupe JL, Freeman LM, Rush JE. Association of body
weight and body condition with survival in dogs with heart failure.
J Vet Intern Med 2008;22:561–565.
33. Thomason JD, Rockwell JE, Fallaw TK, Calvert CA. Influence
of combined angiotensin-converting enzyme inhibitors and
spironolactone on serum K1, Mg 21, and Na1
small dogs with degenerative mitral valve disease. J Vet Cardiol
34. Slupe JL, Freeman LM, Rush JE. Association of body
weight and body condition with survival in dogs with heart failure.
J Vet Intern Med 2008;22:561–565.
35. Adin DB, Taylor AW, Hill RC, et al. Intermittent bolus injection
versus continuous infusion of furosemide in normal adult
greyhound dogs. J Vet Intern Med 2003;17:632–636.
1150 Atkins et al
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