consenso endoc

ACVIM Consensus Statement

Guidel ines for the Diagnosis and Treatment of Canine ChronicValvular 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 Veteri-nary Internal Medicine (ACVIM) Specialty ofCardiology consensus panel convened to formulateguidelines for the diagnosis and treatment of chronic val-vular heart disease (CVHD, also known as endocardiosisand myxomatous valve degeneration) in dogs. It is esti-mated that approximately 10% of dogs presented toprimary care veterinary practices have heart disease, andCVHD is the most common heart disease of dogs inmany parts of the world, accounting for approximately75% of canine cases of heart disease cases seen by veter-inary practices in North America.CVHD most commonly affects the left atrioventricu-

lar or mitral valve, although in approximately 30% ofcases the right atrioventricular (tricuspid) valve also isinvolved. The disease is approximately 1.5 times morecommon in males than in females. Its prevalence is alsohigher in smaller (o20 kg) dogs, although large breedsoccasionally are affected.1 In small breed dogs, the dis-ease generally is slowly but somewhat unpredictablyprogressive, with most dogs experiencing the onset of arecognizable murmur of mitral valve regurgitation years

before the clinical onset of heart failure. When largebreed dogs are affected by CVHD, the progression of thedisease appears to be more rapid than that observed insmall breed dogs.2 Cavalier King Charles Spaniels arepredisposed to developing CVHD at a relatively youngage, but the time course of their disease progression toheart failure does not appear to be markedly differentfrom that of other small breed dogs except for the earlyage of onset.3,4

The cause of CVHD is unknown, but the disease ap-pears to have an inherited component in some breedsstudied.5,6 CVHD is characterized by changes in the cel-lular constituents as well as the intercellular matrix of thevalve apparatus (including the valve leaets and chordaetendineae).7,8 These changes involve both the collagencontent and the alignment of collagen brils within thevalve.9,10 Endothelial cell changes and subendothelialthickening also occur,11 although affected dogs do notappear to be at increased risk for arterial thromboembo-lism or infective endocarditis. Mitral valve prolapse is acommon complication of myxomatous valve degenera-tion and represents a prominent feature of CVHD insome breeds.6,12 Progressive deformation of the valvestructure eventually prevents effective coaptation andcauses regurgitation (valve leakage). Progressive valvu-lar regurgitation increases cardiac work, leading toventricular remodeling (eccentric hypertrophy and inter-cellular matrix changes) and ventricular dysfunction.

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide theveterinary community with up-to-date information on the pathophysiology, diagnosis, and treatment ofclinically important animal diseases. The ACVIM Board of Regents oversees selection of relevant topics,identication of panel members with the expertise to draft the statements, and other aspects of assuring theintegrity of the process. The statements are derived from evidence-based medicine whenever possible and thepanel offers interpretive comments when such evidence is inadequate or contradictory. A draft is preparedby the panel, followed by solicitation of input by the ACVIM membership, which may be incorporated intothe statement. It is then submitted to the Journal of Veterinary Internal Medicine, where it is edited prior topublication. The authors are solely responsible for the content of the statements.

From the Department of Clinical Sciences, North Carolina StateUniversity, Raleigh, NC (Atkins, Keene); Department of VeterinaryClinical Sciences (Bonagura), Department of Veterinary Biosciences(Hamlin), The Ohio State University, Columbus, OH; CaliforniaAnimal Hospital, Los Angeles, CA (Ettinger); Department ofMedicine, Animal Medical Center, New York, NY (Fox); Depart-ment 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 ofLondon, London, UK (Luis-Fuentes); and Department of MedicalSciences, University of Wisconsin-Madison, Madison, WI (Stepien).

Corresponding author: Bruce Keene, Department of Clinical Sci-ence, 4700 Hillsborough Street, North Carolina State University,Raleigh, NC 27606; e-mail: [email protected].

Submitted June 12, 2009; Revised August 7, 2009; AcceptedAugust 17, 2009.

Copyright r 2009 by the American College of Veterinary InternalMedicine

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;23:11421150

Abnormal numbers or types of mitogen receptors (eg,any of the subtypes of serotonin, endothelin, or angio-tensin receptors) on broblast cell membranes in thevalves of affected dogs may play a role in the pathophys-iology of the valvular lesions.13 Systemic or localmetabolic, neurohormonal or inammatory mediators(eg, endogenous catecholamines and inammatory cyto-kines) also may inuence progression of the valve lesionor the subsequent myocardial remodeling and ventriculardysfunction that accompany long-standing, hemody-namically signicant valvular regurgitation. However,these factors are poorly understood at this time.14

The prevalence of CVHD increases markedly with agein small breed dogs (with up to 85% showing some evi-dence of the lesion at necropsy by 13 years of age), butthe presence of the pathologic lesion does not necessarilyindicate that a dog will develop clinical signs of heartfailure. Like the underlying cause of the disease, the fac-tors that determine the progression of the lesion remainunknown, although age, left atrial size, and heart ratehave been shown to predict outcomes.15,16

Classication of Heart Disease and Heart Failure

Heart failure is a general term that describes a clinicalsyndrome that can be caused by a variety of specic heartdiseases, including CVHD. Heart failure from any cause ischaracterized by cardiac, hemodynamic, renal, neurohor-monal, and cytokine abnormalities. The classicationsystems for heart failure most familiar to veterinarians arethe modied New York Heart Association (NYHA)17 andInternational Small Animal Cardiac Health Council18

functional classication systems, both of which were de-signed to provide a framework for discussing andcomparing the clinical signs of patients in heart failure.These functional classication systems vary in their

details, but both serve as semiquantitative schemes forjudging the severity of a patients clinical signs. Such cat-egorization aids in teaching therapeutic protocols andconstitutes a basis for stratication of subjects in clinicaltrials. The modied NYHA functional classication ofheart failure can be summarized as follows:

Class I describes patients with asymptomatic heartdisease (eg, CVHD is present, but no clinical signs areevident even with exercise).

Class II describes patients with heart disease thatcauses clinical signs only during strenuous exercise.

Class III describes patients with heart disease thatcauses clinical signs with routine daily activities ormild exercise.

Class IV describes patients with heart disease thatcauses severe clinical signs even at rest.

Functional classication systems share a commonproblem in that they are based on relatively subjectiveassessments of clinical signs that can change frequentlyand dramatically over short periods of time. Further-more, treatments may not differ substantially across thefunctional classes.

A newer classication system that might more objec-tively categorize patients in the course of their heartdisease has been developed, and this scheme was used bythe panel for consensus recommendations. The goal wasto link severity of signs to appropriate treatments at eachstage of illness. In formulating these guidelines, the con-sensus panel adapted the 2001 American College ofCardiology/American Heart Association classicationsystem for the treatment of heart disease and failure inhuman patients to the management of canine CVHD.19

In this approach, patients are expected to advance from 1stage to the next unless progression of the disease is al-tered by treatment.The classication system presented below and used in

these guidelines is meant to complement, not replace,functional classication systems. The new system de-scribes 4 basic stages of heart disease and failure:

Stage A identies patients at high risk for developingheart disease but that currently have no identiablestructural disorder of the heart (eg, every CavalierKing Charles Spaniel without a heart murmur).

Stage B identies patients with structural heart disease(eg, the typical murmur of mitral valve regurgitation ispresent), but that have never developed clinical signscaused by heart failure. Because of important clinicalimplications for prognosis and treatment, the panelfurther subdivided Stage B into Stage B1 and B2.

Stage B1 refers to asymptomatic patients that haveno radiographic or echocardiographic evidence ofcardiac remodeling in response to CVHD.

Stage B2 refers to asymptomatic patients that havehemodynamically signicant valve regurgitation,as evidenced by radiographic or echocardiograph-ic ndings of left-sided heart enlargement.

Stage C denotes patients with past or current clinicalsigns of heart failure associated with structural heartdisease. Because of important treatment differences be-tween dogs with acute heart failure requiring hospitalcare and those with heart failure that can be treated onan outpatient basis, these issues have been addressedseparately by the panel. Some animals presenting withheart failure for the 1st time may have severe clinicalsigns requiring aggressive therapy (eg, with additionalafterload reducers or temporary ventilatory assistance)that more typically would be reserved for those with re-fractory disease (see Stage D).

Stage D refers to patients with end-stage disease withclinical signs of heart failure caused by CVHD that arerefractory to standard therapy (dened later in thisdocument). Such patients require advanced or special-ized treatment strategies in order to remain clinicallycomfortable with their disease. As with Stage C, thepanel has distinguished between animals in Stage Dthat require acute, hospital-based therapy and thosethat can be managed as outpatients.

This classication system emphasizes that there arerisk factors and structural prerequisites for the develop-ment of heart failure in CVHD. The use of thisclassication system is meant to encourage veterinary cli-

1143Canine Chronic Valvular Heart Disease

nicians to think about heart disease in a way analogousto the current clinical approach to cancer. This classi-cation system is designed to aid in:

Developing screening programs for the presence ofCVHD in dogs known to be at risk.

Identifying interventions that may (now or in the fu-ture) decrease the risk of disease development.

Identifying asymptomatic dogs with CVHD early in thecourse of their disease, comparable to in situ cancer,so that they can perhaps be treated more effectively.

Identifying symptomatic dogs with CVHD so thatthese patients can be treated medically and either po-tentially cured (interventionally or surgically) ormanaged with their chronic disease.

Identify symptomatic dogs with advanced heart failurefrom CVHD and refractory to conventional therapythese patients require aggressive or new treatment strat-egies or potentially hospice-type end-of-life care.

Evaluating the Evidence for Efcacy and Safety

In classifying dogs with CVHD according to their dis-ease stage and clinical status and matching them withdiagnostic, pharmacologic, and dietary treatment recom-mendations, the consensus panel considered both thequantity and quality of evidence available to inform thediagnostic and therapeutic decisions made in these pa-tients. The heading Consensus recommendationpreceding a diagnostic, therapeutic, or dietary recom-mendation indicates that the panelists were unanimous intheir opinion that the combination of available clinicaltrial evidence, other published experimental or anecdotalevidence, clinical experience, and expert opinion indicatethat the potential benet of the approach under discus-sion clearly outweighs the potential risks to the patientand minimizes nancial impact on the client.In situations in which the available evidence regarding

the efcacy of a diagnostic or therapeutic maneuver wasconicting, weak, or absent and no consensus on a rec-ommended course of action could be reached by thepanelists based on the available evidence and their col-lective clinical experience, the panels opinions andreasoning on clinically important issues are briey sum-marized. These bulleted summary statements aregrouped together and summarized under the headingNo consensus.The panel recognized that there is considerable varia-

tion in the scientic quality of the evidence available tosupport clinical decision making, and sought to includetopically relevant references. Whereas the status of a par-ticular recommendation (consensus versus no consensus)reects the collective judgment of the panel on each ques-tion addressed, no attempt was made to assign a specicscientic grade or value to each included citation.

Guidelines for Diagnosis and Treatment of CVHD

Stage ADogs at high risk for development of heartfailure, 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 knownpredisposition to develop CVHD (eg, CavalierKing Charles Spaniels, Dachshunds, Miniatureand Toy Poodles) should undergo regular evalua-tions (yearly auscultation by the family veter-inarian) as part of routine health care.

Owners of breeding dogs or those at especiallyhigh risk, such as Cavalier King Charles Spaniels,may choose to participate in yearly screeningevents at dog shows or other events sponsored bytheir breed association or kennel club and con-ducted by board-certied cardiologists partici-pating 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 pa-

tient. Potential breeding stock should no longer be bred

if mitral regurgitation (MR) is identied early,during their normal breeding age ofo68 years.

Stage BThese patients have a structural abnormalityindicating the presence of CVHD, but have never hadclinical signs of heart failure. These patients are gener-ally recognized during a screening or routine healthexamination with a heart murmur typical of mitralvalve insufciency.

Diagnosis for Stage B


Thoracic radiography is recommended in all pa-tients to assess the hemodynamic signicance of themurmur and also to obtain baseline thoracic radio-graphs at a time when the patient is asymptomaticfor CVHD.

Blood pressure measurement is recommended forall patients.

In small breed dogs with typical murmurs, echo-cardiography is recommended to answer specicquestions regarding either cardiac chamber en-largement or the cause of the murmur if thosequestions are not answered adequately byauscultation and thoracic radiography.

Echocardiography generally is indicated in largerbreed dogs because the murmur of MR is morelikely to be related to other causes (eg, dilatedcardiomyopathy).

Basic laboratory work (a minimum of hematocrit,total protein concentration, serum creatinine concen-tration, and urinalysis) is indicated in all patients.

Because their prognosis and therapy may differ sub-stantially, asymptomatic patients with murmurs of

1144 Atkins et al

mitral valve insufciency are further subcategorized into2 groups based on the results of the above evaluation:

Stage B1: Hemodynamically insignicant MR (denedas radiographically or echocardiographically normal orequivocally enlarged LA, LV, or both, with normal LVsystolic function; normal vertebral heart score on radi-ography; normotensive, normal laboratory results).

Therapy for Stage B1 (both pharmacologic and di-etary) 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 ap-proximately 12 months (some panelists rec-ommend more frequent follow-up in large dogs).

Stage B2: Hemodynamically signicant MR with car-diac remodeling (dened as clearly enlarged LA, LV,or both); normotensive.

Therapy for Stage B2 (both pharmacologic and di-etary) is controversial, and no consensus could bereached with currently available evidence.

No consensus:

Small breed dogs:

Angiogensin converting enzyme inhibitor (ACEI):For patients with clinically relevant left atrial en-largement on either initial examination, or thosein which the left atrium has increased in size dra-matically on successive monitoring examinations, amajority of the panel members recommend initia-tion of therapy with an ACEI. Clinical trialsaddressing the efcacy of ACEI for the treatmentof dogs in Stage B2 have had mixed resultseitherno effect or a small positive effect delaying the on-set of congestive heart failure.2022 A minority ofthe panel members recommend no therapy forasymptomatic animals pending further clinical tri-als to examine the efcacy of therapy in this setting.

b blockers: For patients with clinically relevant leftatrial enlargement on either initial examination, orwhen the left atrium has increased in size dramat-ically on successive monitoring examinations, aminority of the panel members recommend initia-tion of therapy with a low dosage of a b blocker,titrating to the highest tolerated dose over a periodof approximately 12 months depending on thespecic medication recommended. A majority ofthe panel members recommend no b-blocker ther-apy for asymptomatic animals pending furtherclinical trials to examine the efcacy of therapy inthis setting. Clinical trials addressing the efcacy

of b blockers for the treatment of dogs in Stage B2are in progress.

No other pharmacologic treatments were recom-mended in Stage B2 by a majority of panelists. Afew panelists considered the use of the followingmedications for patients in Stage B2 under speciccircumstances: pimobendan, digoxin, amlodipine,and spironolactone. The panel felt in general thatthese treatment strategies needed additional inves-tigation into their efcacy and safety in this patientpopulation before a consensus recommendationcould be made.

Dietary treatment was recommended by a major-ity of panelists in Stage B2, a minority of the panelrecommended no dietary changes. Principles guid-ing dietary treatment at this stage include milddietary sodium restriction and provision of ahighly palatable diet with adequate protein andcalories for maintaining optimal body condition.

Larger breed dogs:

Generally, panelists who recommended treatmentin smaller breed dogs strengthened their recom-mendations promoting the use of both ACEI and bblockers in larger breed dogs in Stage B2.

Dietary treatment recommendations for larger breeddogs were the same as those for small breeds, empha-sizing mild sodium restriction and adequate proteinand caloric intake if changes were recommended.

Stage CPatients have a structural abnormality andcurrent or previous clinical signs of heart failure causedby CVHD. Stage C includes all patients that have hadan episode of clinical heart failure. Such patients stayin this stage despite improvement of their clinicalsigns with standard therapy (even if their clinical signsresolve completely). Guidelines for standard pharma-cotherapy are provided for both in-hospital (acute)management of heart failure and for home care(chronic) management of heart failure, as well as rec-ommendations for chronic dietary therapy. Somepatients that present in Stage C may have life-threat-ening clinical signs, and require more extensive acutetherapy than is considered standard therapy. Theseacute care patients may share some medical manage-ment strategies with dogs that have progressed toStage D (refractory heart failure, see below). In StageC, heart failure secondary to CVHD, the panel did notmake clinically relevant therapeutic distinctions be-tween small and larger breed dogs for either acute orchronic medical management.

For both Stages C and D (CVHD patients with symp-tomatic heart failure), the acute care of heart failure isfocused on regulating the patients hemodynamic statusby monitoring (as well as possible under clinical circum-stances) and pharmacologically optimizing preload,afterload, heart rate, and contractility to improve car-diac output, decrease the extent of mitral valveregurgitation if possible, and relieve clinical signs associ-


ated with either low cardiac output or excessively in-creased venous pressures (preload). The broad goals ofchronic (home care) management are focused on main-taining these hemodynamic improvements to the extentpossible, while providing additional treatments aimed atslowing progression, prolonging survival, decreasingclinical signs of congestive heart failure, enhancing exer-cise capacity, and otherwise improving quality life.

Diagnosis for Stage C


Because of the relatively high prevalence ofchronic tracheobronchial disease in the same pop-ulation at risk for CVHD, the presence of a typicalleft apical regurgitant murmur in a coughing dogdoes not necessarily mean that the clinical signs arethe result of CVHD.

A clinical database (including chest radiographsand preferably an echocardiogram and basic labo-ratory tests) must be obtained and examinedcarefully to accurately determine the cause of clin-ical signs in animals with CVHD.

Serum N-terminal pro-B-type naturetic peptide(BNP) concentrations should become increasinglyuseful in determining the cause of clinical signs indogs with CVHD. Although there is no doubt that,as a group, dogs with clinical signs caused by heartfailure have higher serum BNP concentrationsthan those with clinical signs caused by primarypulmonary disease, the positive predictive value ofany single BNP concentration, obtained by a com-mercially available test, has not been adequatelycharacterized at the time of this writing (August2009) to make a consensus recommendation withregard to BNP testing.

The signalment and physical examination can behelpful in determining the pretest probability ofheart failure as a cause of clinical signs in patientswith CVHD. For example, obese dogs with no his-tory of weight loss are less likely to be in heartfailure secondary to CVHD; dogs with marked si-nus arrhythmia and relatively slow heart rates alsoare less likely to have clinical signs attributable toCVHD.

Most of these dogs are middle-aged or older, and itis always prudent to complete the database with aCBC, serum biochemical prole, and urinalysis,especially if therapy for CHF is anticipated.

Acute (Hospital-Based) Therapy of Stage C


FurosemideThe specic dosing of furosemide ina dog with CHF should be related to the severity ofclinical signs and the response to initial therapy.Lower or higher doses (eg, 14mg/kg) may be ap-propriate in specic cases. Repeated IV boluses ora constant rate IV infusion may be indicated forpoorly responsive dogs.

For life-threatening pulmonary edema (expectora-tion of froth associated with severe dyspnea; diffusepulmonary opacity on thoracic radiographs; poorinitial response to furosemide bolus with failure ofdyspnea and respiratory rate to improve over 2hours), furosemide is administered as a constantrate infusion (CRI) at a dose of 1mg/kg/h after theinitial bolus.23

Allow patient free access to water once diuresis hasbegun.

Pimobendan, 0.250.3mg/kg PO q12hAlthoughthe clinical trial evidence supporting the chronicuse of pimobendan in the management of Stage Cheart failure from CVHD is stronger than for theacute situation, the recommendation to use pimo-bendan in acute heart failure therapy is stronglysupported by hemodynamic and experimental ev-idence2427 as well as the anecdotal experience ofthe panelists.

Oxygen supplementation, if needed, can be admin-istered via a humidity and temperature-controlledoxygen cage or incubator or via a nasal oxygencanula.

Mechanical treatments (eg, abdominal paracente-sis and thoracocentesis) are recommended toremove effusions judged sufcient to impair venti-lation or cause respiratory distress.

Provide optimal nursing care, including mainte-nance of an appropriate environmental tempera-ture and humidity, increase in the head on pillows,and placement of sedated patients in sternal posture.

SedationAnxiety associated with dyspnea shouldbe treated. Narcotics, or a narcotic combined withan anxiolytic agent, aremost often used by panelists.Butorphanol (0.20.25mg/kg) administered IM orIV was the narcotic most often utilized for this pur-pose; combinations of buprenorphine (0.00750.01mg/kg) and acepromazine (0.010.03mg/kgIV, IM, or SQ) as well as other narcotics, includingmorphine and hydrocodone, also have been utilized.

CRI of sodium nitroprusside for up to 48 hours isoften useful for life-threatening, poorly responsivepulmonary edema (refer to Class D below for spe-cic dosing recommendations).

No consensus was reached on the following acute careStage C issues:

Care must be taken to monitor the blood pressureand respiratory response to narcotics and tranquil-ilzers in the setting of acute heart failure. Nospecic treatment or dosage regimen was used byall panelists.

ACEI (eg, enalapril 0.5mg/kg PO q12h). Althoughtreatment with ACEI is a consensus recommenda-tion for chronic Stage C heart failure and a majorityof panelists also treat acute heart failure with ACEI,the evidence supporting ACEI efcacy and safety inacute therapy when combined with furosemide andpimobendan is less clear. There is, however, clear ev-idence that the acute administration of enalapril plus

1146 Atkins et al

furosemide in acute heart failure results in substantialimprovement in pulmonary capillary wedge pressurewhen compared with the administration of furose-mide alone.

Nitroglycerin 2% ointment, approximately 1/2paste per 10 kg body weight for 2436 hours. Somepanelists recommend administering the ointmentin intervals (eg, 12 hours on, 12 hours off). Otherpanelists do not use nitroglycerin in this setting.

Home-Based (Chronic) Therapy for Stage C


Continue PO furosemide administration to effect,commonly at a dosage of 2mg/kg q12h. The dailyfurosemide dosage for dogs with CHF is wide andcan be as low as 12mg/kg PO q12h to 46mg/kgPO q8h. The dosage must be titrated to maintainpatient comfort and with attention to effects onrenal function and electrolyte status.

Chronic oral furosemide (doses 6mg/kg q12h)needed to maintain patient comfort in the face ofappropriate adjunct therapy indicates disease pro-gression to Stage D.

Continue or start ACEI (eg, enalapril 0.5mg/kg,PO q12h) or equivalent dose of another ACEIif approved for use. The labeled dosage range ofenalapril is 0.250.5mg/kg PO q12h; most panel-ists treat at the upper end of this range. Measure-ment of serum creatinine and electrolyte concen-trations 37 days after beginning an ACEI is rec-ommended for animals with Stage C heart failure.

Continue pimobendan (0.250.3mg/kg POq12h).2830

Panelists recommend against starting a b blocker inthe face of active clinical signs of heart failure (eg,cardiogenic pulmonary edema) caused by CVHD.

None of the panelists routinely use nitroglycerin inthe chronic treatment of Stage C heart failure.

Participation in a structured, home-based ex-tended care program to facilitate body weight,appetite, respiratory, and heart rate monitoringwhile providing client support to enhance medica-tion compliance and dosage adjustments inpatients with heart failure is encouraged.

No consensus was reached regarding the followinghome-based (chronic) treatment strategies in Stage C:

Spironolactone (0.252.0mg/kg PO q1224h) wasrecommended by a majority of panelists as an ad-junct for the chronic therapy of dogs in Stage Cheart failure. The primary purpose of spironolac-tone in this situation is thought to be aldosteroneantagonism. No clinically relevant diuretic effectshould be anticipated. This treatment now is ap-proved in Europe at a dosage of 2mg/kg/d.

Digoxin (0.00250.005mg/kg PO q12h) with tar-get plasma concentration 8 hours postpill of 0.81.5 ng/mL. For the chronic management of StageC heart failure, a majority of panelists recom-

mended the addition of digoxin in cases compli-cated by persistent atrial brillation to slow theventricular response rate. Some panelists also pre-scribe digoxin at this dosage for patients in Stage Cheart failure in the absence of sustained supraven-tricular tachyarrhythmia, as long as no contra-indication to digoxin is evident (eg, increasedserum creatinine concentration, ventricular ec-topy, concerns over owner compliance, chronicGI disease resulting in frequent or unpredictablebouts of vomiting or diarrhea).

Once heart failure signs have resolved, a stablemedication regimen has been instituted, and thepatient is eating and apparently feeling well, a mi-nority of panelists recommend attempting a lowdose, slow up-titration regimen of a b blocker.There is no clinical trial evidence in dogs to sup-port this recommendation. If prescribed, there isno consensus regarding which specic b blocker touse (carvedilol, atenolol, or metoprolol is the mostfrequently prescribed). The purpose of b blockadein this setting is related to potential long-term pro-tective effects on myocardial function andremodeling. These effects have been demonstratedin some experimental animal models31 and in hu-mans with heart failure, but not in clinical trials.

The presence of atrial brillation strengthens theindication for b blockade (to slow the ventricularresponse to atrial brillation) for those panelistswho recommended a b blocker.

In patients taking a b blocker before the onset ofStage C heart failure, the majority of panelistscontinue b blockade; some panelists would con-sider dosage reduction if needed clinically becauseof clinical signs of low cardiac output, hypo-thermia, or bradycardia.

Some panelists prefer administration of oral diltia-zem (several formulations are available, somesustained release) for chronic heart rate control inatrial brillation.

Some panelists nd cough suppressants useful inoccasional patients in Stage C heart failure fromCVHD.

Some panelists nd bronchodilators useful in oc-casional patients in Stage C heart failure fromCVHD.

Dietary Therapy for Stage C

Cardiac cachexia is dened as the unintentional lossof47.5% of the patients normal, predisease weight, notincluding weight loss associated with the resolution ofedema or the removal of body cavity effusions. Cachexiahas substantial negative prognostic implications, and ismuch easier to prevent that to treat.32


Maintain adequate calorie intake (maintenancecalorie intake in Stage C should provide approxi-mately 60 kcal/kg body weight) to minimize weight


loss (specically muscle mass loss) that often oc-curs in CHF.

Specically address and inquire about the occurrenceof anorexia, and make efforts to treat any drug-induced or other identiable causes of anorexia thatoccur.

Record the accurate weight of the patient at everyclinic visit, and investigate the cause of weight gain orloss.

Ensure adequate protein intake and avoid low-pro-tein diets designed to treat chronic kidney disease,unless severe concurrent renal failure is present.

Modestly restrict sodium intake, taking into con-sideration sodium from all dietary sources(including dog food, treats, table food, and foodsused to administer medications) and avoid anyprocessed or other salted foods.

Monitor serum potassium concentrations and sup-plement the diet with potassium from eithernatural or commercial sources if hypokalemia isidentied. Hyperkalemia is relatively rare in pa-tients treated for heart failure with diuretics, evenin those concurrently receiving an ACEI in combi-nation with spironolactone.33 Diets and foods withhigh potassium content should be avoided whenhyperkalemia has been identied.

No consensus was reached on the following dietary ther-apy for Stage C:

Consider monitoring serummagnesium concentra-tions, especially as CHF progresses and in animalswith arrhythmias. Supplement with magnesium incases in which hypomagnesemia is identied.

Consider supplementing with n-3 fatty acids, espe-cially in dogs with decreased appetite, muscle massloss, or arrhythmia.34

Stage DPatients have clinical signs of failure refrac-tory to standard treatment for Stage C heart failurefrom CVHD, as outlined above. Stage D heart failurepatients therefore should be receiving the maximalrecommended (or tolerated) dosage of furosemide, anACEI, and pimobendan, as outlined in the Stage Cguidelines above. Any indicated and tolerated antiar-rhythmic medication, needed to maintain sinusrhythm (if possible) or regulate the ventricular re-sponse to atrial brillation in a heart rate range of80160/min, also should be used before a patient isconsidered refractory to standard therapy.

Not surprisingly, there have been very few clinical tri-als addressing drug efcacy and safety in this patientpopulation. This leaves cardiologists treating patientswith heart failure refractory to conventional medicaltherapy with a perplexing variety of treatment options.Because of the relative lack of clinical trial evidence andthe diverse clinical presentations of patients with end-stage heart failure, development of meaningful consensusguidelines regarding the timing and implementation ofindividual pharmacologic and dietary treatment strate-

gies for Stage D patients proved difcult. As with StageC, guidelines for drug treatment are provided for both in-hospital (acute) and for home care (chronic) manage-ment of heart failure, and recommendations for chronicdietary therapy are also given.

Diagnosis for Stage D

Because Stage D heart failure patients are, by de-nition, refractory to the treatments for Stage Cpatients, dening refractory congestive heart fail-ure involves the same diagnostic steps outlined forStage C plus the nding of failure to respond totreatments outlined in the Stage C guidelines.

Acute (Hospital-Based) Therapy for Stage D(Refractory Heart Failure)


In the absence of severe renal insufciency (ie,serum creatinine concentrations 4 3mg/dL), ad-ditional furosemide is administered IV as a bolusat a dosage of 2mg/kg followed by either addi-tional bolus doses, or a furosemide CRI at adosage of 1mg/kg/h until respiratory distress (rateand effort) has decreased, or for a maximum of4 hours. As indicated above, the dosage or furose-mide is a range and higher or lower doses may beappropriate for a given case.

Continue to allow patient free access to water oncediuresis has begun.

Fluid removal (eg, abdominal paracentesis, thor-acocentesis) as needed to relieve respiratorydistress or discomfort.

In addition to oxygen supplementation as in StageC (above), mechanical ventilatory assistance maybe useful to make the patient more comfortable, toallow time for medications35 to have an effect; andto provide time for left atrial dilatation to accom-modate sudden increases in mitral valveregurgitant volume in patients with acute exacer-bation of CVHD (eg, ruptured chordae tendinaewith severe cardiogenic pulmonary edema) andimpending respiratory failure.

More vigorous afterload reduction in patientsthat can tolerate arterial vasodilation. Drugs po-tentially benecial include sodium nitroprusside(starting at 0.51 mg/kg/min), hydralazine (0.52.0mg/kg PO), or amlodipine (0.050.1mg/kgPO). Direct vasodilators should be started at alow dosage and up-titrated hourly until adequateclinical improvement accompanied by a decreaseof approximately 510% in systolic blood pressureis observed. These drugs are recommended in ad-dition to an ACEI and pimobendan. The clinicianshould be mindful that any decline in blood pres-sure will also depend on specic vasodilator drug.For example, vasodilation effects are rapid onsetwith nitroprusside, but slower with amlodipine.Caution is warranted to avoid serious, prolongedhypotension (ie, monitor blood pressure and main-

1148 Atkins et al

tain systolic arterial blood pressure4 85mmHg ormean arterial blood pressure 4 60mmHg. Serumcreatinine concentration should be measured be-fore and 2472 hours after administration of thesedrugs. Patients in Stage D have life-threateningheart failure, and a trial of additional afterload re-duction is warranted. The panel emphasized thatbecause afterload reduction may increase cardiacoutput substantially in the setting of severe MRand heart failure, administration of an arterial di-lator in this setting does not necessarily decreaseblood pressure.

No consensus was reached regarding the following acutecare Stage D recommendations:

Pimobendan dosage may be increased (off-label)to include a 3rd 0.3mg/kg daily dose. Some panel-ists administer an additional dose of pimobendanon admission of Stage D patients with acutepulmonary edema. Because this dosage recom-mendation is outside of the FDA-approved label-ing for pimobendan, this use of the drug should beexplained to and approved by the client.

In animals judged to be too sick to wait for theeffects of oral afterload reduction or inotropic sup-port (eg, pimobendan with or without hydralazineor amlodipine), nitroprusside (for afterload reduc-tion in life threatening pulmonary edema) ordobutamine (for inotropic support of the hypo-tensive patient) must be administered by CRI.Both drugs can be administered at dosages of 0.51.0mg/kg/min and up-titrated every 1530 minutesto a maximum of approximately 10mg/kg/min.These drugs, either separately or in combination,can be used for 1248 hours to improve hemody-namic status and control refractory cardiogenicpulmonary edema. Continuous electrocardiograph-ic and blood pressure monitoring is recommendedto minimize the potential risks of this therapy.

Sildenal (12mg/kg PO q12h) is used by a minor-ity of panelists to treat acute exacerbations ofStage D heart failure caused by CVHD, even inthe absence of diagnosed pulmonary hypertension.

Bronchodilators are recommended as an adjuncttherapy in treating cardiogenic pulmonary edemain hospitalized patients by a minority of panelists.

Home-Based (Chronic) Stage D Therapy


Furosemide dosage should be increased as neededto decrease pulmonary edema or body cavity effu-sions, if use is not limited by renal dysfunction(which generally should be monitored 1248 hoursafter dosage increases). The specic strategy andmagnitude of dosage increase (eg, same dose in-creased to 3 times per day versus 2 higher doses,substituting 1 SC dose for a PO dose q48h, orexible SC dose supplementation based on body

weight or girth measurements) varied widelyamong the panelists.

Spironolactone, if not already started in Stage C,is indicated for chronic treatment of Stage Dpatients.

b blockade generally should not be initiated at thisstage unless clinical signs of heart failure can becontrolled, as outlined in Stage C.

No consensus was reached regarding the followingchronic Stage D therapeutic recommendations:

Hydrochlorthiazide was recommended by severalpanelists as adjunctive therapy with furosemide,utilizing various dosing schedules (including onlyintermittent use every 2nd4th day). Some panel-ists warned of the risk of acute renal failure andmarked electrolyte disturbances, based on per-sonal experience.

Pimobendan dosage is increased by some paneliststo include a 3rd 0.3mg/kg daily dose (off-label use,explanations and cautions apply as listed for in-hospital care, above).

Digoxin, at the same (relatively low) dosages rec-ommended by some panelists for Stage C heartfailure, was recommended for treatment of atrialbrillation for patients in Stage D, with the samecautions listed in Stage C above.

Digoxin, at the same (relatively low) dosages rec-ommended by some panelists for Stage C heartfailure, also was recommended by a minority ofpanelists for all patients in Stage D in sinus rhythm,assuming no clear contraindication was present.

Sildenal (12mg/kg PO q12h) is used by somepanelists to treat Stage D heart failure caused byCVHD or to treat advanced CVHD complicatedby pulmonary hypertension.

The majority of panelists felt that b blockade ini-tiated at an earlier stage of heart failure in CVHDshould not be discontinued, but that dose reduc-tion may be needed if shortness of breath couldnot be controlled by the addition of other medica-tions or if bradycardia, hypotension, or both werepresent.

b blockade still may be useful to decrease the ven-tricular response rate in atrial brillation afterstabilization and digitalization.

Cough suppressants are recommended by a minor-ity of panelists to treat chronic, intractable coughin Stage D patients receiving home care.

Bronchodilators are recommended by a minorityof panelists to treat chronic, intractable coughingin Stage D patients receiving home careanelists.

Home-Based (Chronic) Dietary Therapy for Stage D


All of the dietary considerations for Stage C(above) apply.

In patients with refractory uid accumulations, at-tempts should be made to further decrease dietary


sodium intake if it can be done without compro-mising appetite or renal function.

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