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Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Disease
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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 failure; Therapy.

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 (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 to

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: bwkeene@ncsu.edu.

Submitted June 12, 2009; Revised August 7, 2009; Accepted

August 17, 2009.

Copyright r 2009 by the American College of Veterinary Internal

Medicine

10.1111/j.1939-1676.2009.0392.x

Abbreviations:

ACEI angiotensin converting enzyme inhibitors

ACVIM American College of Veterinary Internal Medicine

CRI constant rate infusion

CVHD chronic valvular heart disease

ECG electrocardiography

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 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 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 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.

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

‘‘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.

Guidelines for Diagnosis and Treatment of CVHD

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.

Diagnosis for Stage A

Consensus recommendations:

Small breed dogs, including breeds with known

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

Consensus recommendations:

No drug therapy is recommended for any patient.

No dietary therapy is recommended for any patient.

Potential breeding stock should no longer be bred

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 are generally

recognized during a screening or routine health

examination with a heart murmur typical of mitral

valve insufficiency.

Diagnosis for Stage B

Consensus recommendations:

Thoracic radiography is recommended in all patients

to assess the hemodynamic significance of the

murmur and also to obtain baseline thoracic radiographs

at a time when the patient is asymptomatic

for CVHD.

Blood pressure measurement is recommended for

all patients.

In small breed dogs with typical murmurs, echocardiography

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 in larger

breed dogs because the murmur of MR is more

likely to be related to other causes (eg, dilated

cardiomyopathy).

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 and dietary)

is identical for both small and large breed dogs.

Consensus recommendations:

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 LA, LV,

or both); normotensive.

Therapy for Stage B2 (both pharmacologic and dietary)

is controversial, and no consensus could be

reached with currently available evidence.

No consensus:

Small breed dogs:

Angiogensin converting enzyme inhibitor (ACEI):

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 breed

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

Consensus recommendations:

Because of the relatively high prevalence of

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 can be

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

CVHD.

Most of these dogs are middle-aged or older, and it

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

Consensus recommendations:

Furosemide—The specific dosing of furosemide in

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

initial bolus.23

Allow patient free access to water once diuresis has

begun.

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 of

the panelists.

Oxygen supplementation, if needed, can be administered

via a humidity and temperature-controlled

oxygen cage or incubator or via a nasal oxygen

canula.

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 maintenance

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 should

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 hours is

often useful for life-threatening, poorly responsive

pulmonary edema (refer to Class D below for specific

dosing recommendations).

No consensus was reached on the following acute care

Stage C issues:

Care must be taken to monitor the blood pressure

and respiratory response to narcotics and tranquililzers

in the setting of acute heart failure. No

specific treatment or dosage regimen was used by

all panelists.

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

alone.

Nitroglycerin 2% ointment, approximately 1/2’’

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

Consensus recommendations:

Continue PO furosemide administration to effect,

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 mg/kg q12h)

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 mg/kg,

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 PO

q12h).28–30

Panelists recommend against starting a b blocker in

the face of active clinical signs of heart failure (eg,

cardiogenic pulmonary edema) caused by CVHD.

None of the panelists routinely use nitroglycerin in

the chronic treatment of Stage C heart failure.

Participation in a structured, home-based extended

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 q12–24h) was

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) with target

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, a stable

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 the

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,

or bradycardia.

Some panelists prefer administration of oral diltiazem

(several formulations are available, some

sustained release) for chronic heart rate control in

atrial fibrillation.

Some panelists find cough suppressants useful in

occasional patients in Stage C heart failure from

CVHD.

Some panelists find bronchodilators useful in occasional

patients in Stage C heart failure from

CVHD.

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

Consensus recommendations:

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

in CHF.

Specifically address and inquire about the occurrence

of anorexia, and make efforts to treat any druginduced

or other identifiable causes of anorexia that

occur.

Record the accurate weight of the patient at every

clinic visit, and investigate the cause of weight gain or

loss.

Ensure adequate protein intake and avoid low-protein

diets designed to treat chronic kidney disease,

unless severe concurrent renal failure is present.

Modestly restrict sodium intake, taking into consideration

sodium from all dietary sources

(including dog food, treats, table food, and foods

used to administer medications) and avoid any

processed or other salted foods.

Monitor serum potassium concentrations and supplement

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, especially

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, by definition,

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)

Consensus recommendations:

In the absence of severe renal insufficiency (ie,

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 water once

diuresis has begun.

Fluid removal (eg, abdominal paracentesis, thoracocentesis)

as needed to relieve respiratory

distress or discomfort.

In addition to oxygen supplementation as in Stage

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

blood pressure.

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 for the

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

Consensus recommendations:

Furosemide dosage should be increased as needed

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 Stage C,

is indicated for chronic treatment of Stage D

patients.

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

experience.

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

care, above).

Digoxin, at the same (relatively low) dosages recommended

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 recommended

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 initiated

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

present.

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 minority

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

Consensus recommendations:

All of the dietary considerations for Stage C

(above) apply.

In patients with refractory fluid accumulations, attempts

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.

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1150 Atkins et al

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