159

Vertebral-heart size on thoracic radiographswas increased. Mean interventricular septumthickness in diastole, mean left ventricularposterior wall thickness in diastole, andmean left atrial dimension at end-systolewere above the reference range. Five catsdied or were euthanized because of CHF.Seven cats recovered and were long-termsurvivors. Repeat echocardiograms dis-closed partial or complete resolution of theM-mode abnormalities in these cases. Allcardiac medications were eventually discon-tinued, and there was no recurrence of CHF.It was concluded that the 12 cats in thisstudy suffered from a unique form of CHFassociated with corticosteroid administra-tion. Consequently, CHF should be listed asa potential adverse effect of corticosteroidadministration in cats.

INTRODUCTIONCats are reported to be remarkably resistantto the adverse effects of exogenous cortico-steroids.1,2 Although there are reports of cor-ticosteroid administration in cats leading toglucose intolerance (or “transient diabetes

Corticosteroid-AssociatedCongestive Heart Failure in 12 CatsStephanie A. Smith, DVM, MS, DACVIM (Internal Medicine)a

Anthony H. Tobias, BVSc, PhD, DACVIM (Cardiology)Deborah M. Fine, DVM, MS, DACVIM (Cardiology)b

Kristin A. Jacob, DVM, DACVIM (Cardiology)Trasida Ployngam, DVM

Intern J Appl Res Vet Med • Vol. 2, No. 3, 2004

KEY WORDS: Methylprednisoloneacetate, triamcinolone acetonide, pred-nisolone, betamethasone diproprionate, dex-amethasone sodium phosphate,corticosteroid, congestive heart failure

ABSTRACTCats are reported to be remarkably resistantto the adverse effects of exogenous cortico-steroids. However, antecedent corticosteroidadministration has been noted in cats withcongestive heart failure (CHF) due to hyper-trophic cardiomyopathy. Consequently, astudy was conducted to describe the clinicaland laboratory findings and outcomes in 12cats diagnosed with CHF following corti-costeroid administration. Methylprednisoloneacetate was the most common corticosteroidadministered. Time from initial cortico-steroid administration to diagnosis of CHFranged from 1 to 19 days. Mean respiratoryrate was elevated, mean heart rate was rela-tively low for cats with CHF, and meanbody temperature was subnormal. Systolicblood pressure and total serum thyroxineconcentration were normal or below normal.

Department of Veterinary Clinical SciencesCollege of Veterinary MedicineUniversity of MinnesotaSt. Paul, MN 55108

aCurrent address:Department of BiochemistryCollege of Medicine at Urbana-ChampaignUniversity of IllinoisUrbana, IL 61801

bCurrent address:Department of Veterinary Medicine and SurgeryCollege of Veterinary MedicineUniversity of MissouriColumbia, MO 65211

Vol. 2, No. 3, 2004 • Intern J Appl Res Vet Med160

mellitus”), skin fragility, iatrogenic hypera-drenocorticism, and recrudescence ofmycotic lesions caused by Sporothrixschenckii, these are rare in the veterinary lit-erature.3–8 Additionally, adverse cardiovascu-lar effects attributable to corticosteroidadministration in cats have not been report-ed. However, a recent retrospective study ofcats with hypertrophic cardiomyopathynoted a history of antecedent corticosteroidadministration in 13 of 160 cases (8%) withcongestive heart failure (CHF).9 At theUniversity of Minnesota Veterinary MedicalCenter (UMVMC), a conspicuous history ofcorticosteroid administration has beenobserved among many cats diagnosed withCHF.10 Consequently, a retrospective studywas conducted to describe clinical and labo-ratory findings as well as short-term andlong-term outcomes in cats diagnosed withCHF soon after corticosteroid administra-tion. In just over half of the qualifyingcases, CHF resolved, morphologic cardiacchanges partially or completely normalized,and all cardiac medications were eventuallydiscontinued. The temporal associationbetween corticosteroid administration andthe initial diagnosis of CHF, together withthe clinical course of the disease, suggestthat this is a unique form of CHF, which hasbeen given the designation corticosteroid-associated CHF.

MATERIALS AND METHODS

Selection of SubjectsMedical records of cats diagnosed withCHF at the UMVMC from January 1992 toOctober 2001 were reviewed. The diagnosisof CHF was based on acute onset respirato-ry distress; radiographs that showed pul-monary infiltrates consistent withcardiogenic edema (with or without pleuraleffusion); and confirmed cardiac diseasebased on physical examination, thoracicradiography, electrocardiography, andechocardiography. Data were further ana-lyzed if a history of corticosteroid adminis-tration preceded the diagnosis of CHF, andthere was a reasonable temporal association

between corticosteroid administration andCHF. For the purposes of this study, a “rea-sonable temporal association” was definedas corticosteroid administration (oral, par-enteral, or both) at any time during the 7days preceding the initial diagnosis of CHF.Cases also were required to meet additionalrelatively conservative entry criteria to beincluded in the study population. Caseswere excluded if corticosteroids had beenchronically administered (i.e., for severalmonths to years) prior to the initial diagno-sis of CHF; if there was a history of pre-existing cardiac disease before corticosteroidadministration; if clinical signs potentiallyascribable to CHF were present prior to cor-ticosteroid administration; if the historyincluded confounding events or disordersthat may have precipitated CHF; or if thecase was lost to follow-up.

EvaluationsData collected from the medical records

of the study population cases included pre-senting complaint; signalment; type, dose,and reason for corticosteroid administration;and length of time from corticosteroidadministration to initial diagnosis of CHF.Physical examination findings, systolic bloodpressure measured by Doppler, and results oflaboratory tests were recorded. Thoracic radi-ographs, electrocardiograms, and echocardio-grams were reviewed by at least two (usuallythree) board-certified cardiologists(American College of Veterinary InternalMedicine). Additional data obtained from themedical record included treatment during theinitial episode of CHF, survival to discharge,long-term medical management of cases thatsurvived to discharge, and follow-up infor-mation, including the results of all rechecks.Finally, owners of all surviving cats werecontacted by telephone during April 2004 todetermine long-term outcomes.

Statistical Analysis

Normally distributed data are reported asmean ± standard deviation. Data that werenot normally distributed are reported asmedian (range). Variables that were meas-

161

ured at two time points in individual catswere compared by a paired Student’s t-test,with P < .05 designated as the threshold forstatistical significance. All statistical analy-ses were performed using NCSS 2004Statistical Software (Number CruncherStatistical System).

RESULTS

Study Population

From January 1992 to October 2001, 271cats were diagnosed with CHF at theUMVMC. Among these 271 cases, 41 (15%)received corticosteroids at some time duringthe 7 days that preceded diagnosis of CHF.Of the 41 cases identified, 29 did not meetthe entry criteria and were excluded. Amongthe excluded cases was one cat that hadreceived daily oral corticosteroids forinflammatory bowel disease for more than 2years prior to the initial diagnosis of CHF,suggesting that the development of CHF wasunrelated to corticosteroid administration.One cat had a history of heart disease beforecorticosteroid administration. Corticosteroidshad been administered to 21 cats because ofrespiratory abnormalities (coughing, wheez-ing, and labored breathing), which had beenattributed to feline bronchial asthma. Thediagnosis of feline bronchial asthma in thesecases was based on history, physical exami-nation, and occasionally on thoracic radiog-raphy, but thorough cardiac evaluations hadnot been performed before corticosteroidadministration. Consequently, CHF could notbe excluded as a cause for the respiratorysigns that preceded corticosteroid adminis-tration. Corticosteroids were administered totwo cats for vague clinical signs (anorexiaand lethargy) that could potentially beascribed to CHF.

The history for three cats included con-founding events or disorders. One of thesethree cats had received corticosteroids short-ly after being hit by a car. A murmur detect-ed on physical examination prompted anechocardiogram, which disclosed severehypertrophic obstructive cardiomyopathy.

Heart failure developed approximately 12hours after an excessively high dose ofatenolol was inadvertently administered.The second of these cats received a largevolume of IV fluids and a methylpred-nisolone acetate injection for a 4-month his-tory of weight loss and vomiting.Endoscopy under general anesthesia wasperformed 4 days after corticosteroidadministration, and CHF developed 2 daysthereafter. The third of these cats developedCHF following corticosteroid administrationfor a head tilt, and was subsequently foundto be hyperthyroid. Finally, one cat was lostto follow-up immediately following dis-charge from the UMVMC. The remaining12 cases formed the study population of catswith corticosteroid-associated CHF.

Presenting Complaint and History

Presenting complaints in the 12 study popu-lation cats were similar, i.e., acute onsetlethargy, anorexia, respiratory distress, andtachypnea. Signalment, the type and dose ofcorticosteroid administered, reason for corti-costeroid administration, and time from cor-ticosteroid administration to initial diagnosisof CHF are presented in Table 1. Affectedcats were 9.0 ± 3.4 years of age and weightwas 5.5 ± 1.1 kg. Ten of the 12 cats weremixed breeds; seven were males and fivewere females. Parenteral methylpred-nisolone acetate was the most common formof corticosteroid used (n = 8); however, avariety of parenteral and oral corticosteroidsand corticosteroid combinations wereadministered. Time from corticosteroidadministration to initial diagnosis of CHFwas as short as 1 day following an injectionof methylprednisolone acetate to as long as19 days in a cat that received a course oforal prednisolone followed by an injectionof triamcinolone acetonide.

Four cats had previously received cor-ticosteroids at times ranging from 72 daysto approximately 1 year before theirepisode of CHF. Two of these cats hadreceived corticosteroids on multiple occa-sions. None of the cats had shown prior

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Vol. 2, No. 3, 2004 • Intern J Appl Res Vet Med162

adverse effects for whichveterinary attention hadbeen sought. However,one owner reported thattheir cat “behaved asthough tranquilized for2 days” following eachcorticosteroid injection.

Physical Examinationand Blood Pressure

Rectal temperature was98.7˚ ± 2.2˚F; respiratoryrate was 70 ± 27 breathsper minute and heart ratewas 145 ± 31 beats perminute. Heart rate was150 beats per minute orslower in eight of the 12cats. Heart rhythm wasregular in 11 of the 12 catsand irregular in one.Auscultation revealedmurmurs in two cats, dia-stolic gallop sounds intwo, and both abnormalitieswere detected in one cat.Pulmonary auscultationdisclosed increased inten-sity of breath sounds bila-terally in nine cats, finecrackles bilaterally in one,crackles and wheezes bila-terally in one, and ventrallymuffled breath sounds in one.

Systolic blood pres-sure measured in six catsat the initial presentationwas low (<100 mm Hg)in all cases, with a meanof 82 ± 12 mm Hg. Atsubsequent examinations(2, 7, or 124 days afterthe initial presentation),systolic blood pressurefor three other cats was90, 134, and 126 mmHg, respectively.

Tab

le 1

.Sig

na

lme

nt,

Hist

ory

,an

d T

ime

to

On

set

of

Co

ng

est

ive

He

art

Fa

ilure

(C

HF)

in 1

2 C

ats

with

Co

rtic

ost

ero

id-A

sso

cia

ted

CH

F

Wei

gh

tC

ort

ico

ster

oid

(s)

Do

seR

easo

n f

or

Day

s to

Cat

No

.A

ge

(yr)

Sex

Bre

ed(k

g)

Ad

min

iste

red

Ro

ute

(mg

)C

ort

ico

ster

oid

CH

F

18.

2M

cD

MH

4.7

Pre

dnis

olon

e O

ral

5aP

rurit

us,

susp

ect

alle

rgy

19Tr

iam

cino

lone

ace

toni

deP

aren

tera

l2.

53

210

.5F

sD

SH

6.7

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

20S

neez

ing,

sus

pect

alle

rgy

6

314

.7M

cD

LH5.

6P

redn

isol

one

Ora

l7.

5bC

hron

ic d

iarr

hea,

sus

pect

13in

flam

mat

ory

bow

el d

isea

se

412

.4M

cD

SH

8.2

Tria

mci

nolo

ne a

ceto

nide

Par

ente

ral

2H

indq

uart

er p

ain

and

stiff

ness

5

55.

6M

cD

LH6.

1M

ethy

lpre

dnis

olon

e ac

etat

e P

aren

tera

l15

Der

mat

itis,

sus

pect

alle

rgy

4B

etam

etha

sone

dip

ropr

iona

teP

aren

tera

l1

4

65.

7M

cR

agdo

ll4.

3D

exam

etha

sone

sod

ium

pho

spha

teP

aren

tera

l2

Bac

k pa

in5

Dex

amet

haso

ne s

odiu

m p

hosp

hate

Par

ente

ral

123

Dex

amet

haso

ne s

odiu

m p

hosp

hate

Par

ente

ral

82

Pre

dnis

olon

eO

ral

5b1

78.

2M

cD

SH

5.2

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

24A

topy

1

810

.3M

cD

SH

5.9

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

20C

hron

ic v

omiti

ng,

susp

ect

1in

flam

mat

ory

bow

el d

isea

se

911

.7F

sR

ussi

an B

lue

4.2

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

20R

ecur

rent

pod

oder

mat

itis

4

108.

8F

sD

SH

5.3

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

20A

lope

cia,

sus

pect

alle

rgy

5

112.

0F

sD

MH

4.8

Met

hylp

redn

isol

one

acet

ate

Par

ente

ral

20C

hin

acne

5

129.

7F

sD

LH5.

3M

ethy

lpre

dnis

olon

e ac

etat

eP

aren

tera

l12

Der

mat

itis,

sus

pect

alle

rgy

7a E

very

24

hour

s fo

r 4

days

, th

en e

very

48

hour

s un

til 5

day

s be

fore

ons

et o

f co

nges

tive

hear

t fa

ilure

.b E

very

12

hour

s un

til o

nset

of

cong

estiv

e he

art

failu

re.

DLH

= d

omes

tic lo

ng h

air;

DM

H =

dom

estic

med

ium

hai

r; D

SH

= d

omes

tic s

hort

hai

r; F

s =

fem

ale

spay

ed;

Mc

= m

ale

cast

rate

d.

163

Additional Diagnostic Tests

Thoracic radiographs revealed mild to mod-erate pleural effusion in nine cats (identifiedas modified transudates in three of the cats),moderate to severe diffuse interstitial pul-monary infiltrates in 11, and a severe diffusealveolar infiltrate in one. The cardiac silhou-ette was subjectively assessed to be large rel-ative to the thorax in all 12 cats, although itwas partially obscured by pleural effusionand pulmonary infiltrates in two. Vertebral-heart size calculated from lateral view radi-ographs was 8.5 ± 0.4 (reference range = 7.5± 0.3) in the 10 cats for which the cardiacsilhouette could be adequately delineated.11

Diagnostic electrocardiograms recordedin four cats disclosed sinus bradycardia (120bpm) with a left anterior fascicular block-likeconduction pattern and occasional ventricularpremature complexes conducted with rightbundle-branch block morphology; sinusbradycardia (80 bpm); atrial standstill withregular ventricular depolarizations (160 bpm)conducted with left bundle-branch blockmorphology; and atrial fibrillation (ventricu-lar depolarization rate = 120 bpm), withoccasional ventricular escape complexes con-ducted with left bundle-branch block mor-phology following any periods greater than orequal to 0.74 seconds of ventricular asystole.

Blood samples were collected from eachof 10 cats for hematology and serum bio-chemistry analyses within the first 12 hoursof presentation. Blood samples were collect-ed prior to initiating treatment for CHF(other than providing supplemental oxygen)for seven cats, and three cats had bloodsamples collected at 1, 11, or 12 hours aftertherapy had been initiated. Hemograms wereunremarkable. The mean white cell count(16.3 ± 7.1 × 10–3/µl; reference range =3.4–15.7 × 10–3/µl) and segmented neu-trophil count (14.2 ± 6.7 × 10-3/µl; referencerange = 1.2–13.2 × 10-3/µl) were increased,and a stress leukogram was present in six ofthe 10 cats. Serum biochemistry analysisrevealed increased mean concentrations ofalanine aminotransferase, aspartate amino-transferase, blood urea nitrogen, cholesterol,

creatinine, glucose, and magnesium, anddecreased mean concentrations of calciumand chloride. Additional details regardingserum biochemistry results are presented inTable 2.

Total thyroxine concentrations weremeasured in serum collected during the first12 hours of presentation in seven cats and inserum collected at 1, 10, or 124 days afterthe initial presentation in three cats. Meantotal serum thyroxine concentration was 1.1± 0.6 µg/dl (reference range = 0.8–4.0µg/dl). None of the cats had an elevatedtotal serum thyroxine concentration, andlevels were below the reference range infive cats.

After a period of in-hospital stabilization,cardiac disease was confirmed by echocardio-graphy in 11 cats. Median time from initialvisit to echocardiography was 1 day (range =0–5 days). On M-mode echocardiography,mean interventricular septum thickness indiastole, mean left ventricular posterior wallthickness in diastole, and mean left atrialdimension at end-systole were all above refer-ence range (Table 3). Additional echocardio-graphic abnormalities were mild or moderatemitral regurgitation in six cats, mild tricuspidregurgitation in one, and systolic anteriormotion of the mitral valve in three.

One of the cats in the study population(cat 9) died before an echocardiogram couldbe performed. A necropsy was not permittedby the owner, and no heart murmur, dias-tolic gallop sound, or arrhythmia was detect-ed on physical examination. Despite theabsence of echocardiographic confirmationof the presence of cardiac disease, data fromthis cat were included based on thoracicradiographs that disclosed a moderate pleu-ral effusion, diffuse pulmonary interstitialinfiltrates, and an enlarged cardiac silhou-ette relative to the thorax with a vertebral-heart size of 8.8.

Survival to Discharge, Treatment,and Outcome

Immediate therapy for CHF in all casesincluded supplemental oxygen, cage rest,

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Vol. 2, No. 3, 2004 • Intern J Appl Res Vet Med164

and parenteral furosemide. Topical nitro-glycerine was applied in one case. Five ofthe cats (cats 8–12) died or were euthanizedbecause of CHF. One cat died in hospitalwithin 1 day, and 3 were euthanized becauseof poor response to therapy 1 to 3 days afteradmission. One cat was discharged from theUMVMC after 6 days, and survived on car-

diac medications (furosemide, enalapril, anddiltiazem) for 186 days before being eutha-nized because of uncontrolled CHF.Necropsies were not permitted in any ofthese five cases.

Seven cats (cats 1–7) were long-termsurvivors that recovered from CHF and hadno recurrences. These cats were discharged

Table 2. Serum Biochemistry Values from 10 Cats with Corticosteroid-Associated CongestiveHeart Failure

No. of Reference % Cases % CasesBiochemistry Variable Cats Mean � SD Range Increased Decreased

Albumin (g/dL) 10 2.8 ± 0.3 2.2–3.4 0 0

Alkaline phosphatase (IU/L) 10 37 ± 19 1–80 0 0

Alanine aminotransferase (IU/L) 10 123 ± 79 19–91 40 0

Amylase (IU/L) 9 934 ± 244 362–1410 11 0

Aspartate aminotransferase (IU/L) 6 100 ± 38 9–53 100 0

Bilirubin (mg/dL) 9 0.5 ± 0.4 0.0–0.5 33 0

Blood urea nitrogen (mg/dL) 10 34 ± 17 14–33 50 0

Cholesterol (mg/dL) 10 171 ± 61 15–150 60 0

Total carbon dioxide (mEq/L) 6 20 ± 3 12–21 50 0

Calcium (mg/dL) 10 8.8 ± 0.7 8.9–11.3 0 60

Chloride (mEq/dl) 9 114 ± 6 117–128 0 67

Creatinine (mg/dL) 10 1.5 ± 0.4 0.6–1.4 60 0

Glucose (mg/dL) 10 256 ± 114 50–150 80 0

Magnesium (mg/dL) 6 3.2 ± 0.6 1.8–2.6 100 0

Phosphorus (mg/dL) 10 5.6 ± 1.8 3.8–8.2 20 20

Potassium (mEq/L) 9 4.2 ± 0.5 3.9–6.3 0 22

Sodium (mEq/L) 9 150 ± 6 149–158 22 44

Protein (g/dL) 10 6.9 ± 0.7 5.5–7.6 20 0

Table 3. M-mode Echocardiography Measurements from 11 Cats with Corticosteroid-AssociatedCongestive Heart Failure

Reference % Cases % CasesVariable Mean � SD Range Increased Decreased

Interventricular septum in diastole (mm) 6.5 ± 1.2 <6.0 64 0

Left ventricular diameter in diastole (mm) 13.5 ± 2.1 13.0–17.0 0 46

Left ventricular posterior wall in diastole (mm) 6.9 ± 1.1 <6.0 82 0

Interventricular septum in systole (mm) 8.5 ± 1.1 NA NA NA

Left ventricular diameter in systole (mm) 5.5 ± 1.7 5.0–9.0 0 36

Left ventricular posterior wall in systole (mm) 9.8 ± 1.3 NA NA NA

Left atrial dimension at end-systole (mm) 17.7 (15.4–22.6)a 10.0–14.0 100 0

Aortic root diameter (mm) 8.3 ± 1.9 8.0–11.0 0 55aMedian (range) reported for data that are not normally distributed.NA = not applicable.

165

from the UMVMC with prescribed oralmedications after a median of 3 days (range= 1–8). Details of their medications at dis-charge and outcomes are provided in Table4. These seven cats were regularly recheckedby clinical examination, thoracic radiogra-phy, and echocardiography at the discretionof the consulting cardiologist and owner.Echocardiography performed a median of218 days (range = 10–1,550) after dischargedisclosed partial or complete resolution ofthe M-mode abnormalities that had beenpresent during the initial episode of CHF.Physical examinations performed at therecheck examinations disclosed softparasternal systolic murmurs in four of theseven cats. One cat showed mild and equiv-ocal systolic anterior motion of the mitralvalve on echocardiography. The cause(s) ofthe soft murmurs eluded detection in theremaining three cases. In one of the long-term survivors, an electrocardiogram per-formed during the initial episode of CHFhad shown a left anterior fascicular block-like conduction pattern. A follow-up electro-cardiogram was performed in that case afterthe echocardiogram had normalized, and itwas unremarkable. Based on resolution ofclinical and radiographic signs of CHF, par-tial to complete resolution of echocardio-graphic abnormalities, and normalization ofthe electrocardiogram in one case, all car-diac medications in these seven cats werecautiously discontinued by tapering themedications over a median of 18 days

(range = 13–161). Median duration of treat-ment with cardiac medications followingdischarge in these seven cases was 356 days(range = 36–1,563 days).

In four of the seven cats, the echocardio-grams that prompted discontinuation ofcardiac medications were the final echocar-diograms performed. In the other three cats,the final echocardiograms were performed at383, 529, or 571 days after their cardiac med-ications had been discontinued. The finalechocardiograms showed significant decreas-es in interventricular septum thickness indiastole (from 6.6 ± 1.0 to 5.0 ± 0.9 mm; P =.01; reference range <6.0 mm), left ventricularposterior wall thickness in diastole (from 7.1± 0.5 to 4.7 ± 0.6 mm; P = .01; referencerange <6.0 mm), and left atrial dimension atend-systole (from 17.7 ± 1.3 to 14.1 ± 0.7mm; P < .01; reference range = 10–14 mm).There was also a significant increase in leftventricular diameter in diastole (from 13.9 ±1.7 to 15.9 ± 1.0 mm; P = .01; referencerange = 13–17 mm). The M-mode measure-ments that changed significantly between firstand final echocardiograms in these seven catsare shown graphically in Figure 1.

At the time of last contact (April 2004),four of the seven cats were alive, and noneof these cats had received any cardiac med-ications for at least 846 days. Additionally,CHF had not recurred, and the total survivaltime from date of discharge was 1,432 daysor more.

Intern J Appl Res Vet Med • Vol. 2, No. 3, 2004

Table 4. Treatments at Discharge and Outcomes in Seven Cats with Corticosteroid-AssociatedCongestive Heart Failure That Were Long-Term Survivors

Cat Cardiac Medications Days to Examination That Tapering Total SurvivalNo. at Discharge Prompted Drug Tapering Period (Days) Time (Days)

1 Furosemide, diltiazem, aspirin 1216 16 >2078a

2 Furosemide 338 18 >1608a

3 Furosemide, diltiazem 203 19 457b

4 Furosemide, atenolol 1550 13 2406c

5 Furosemide, enalapril, aspirin 218 161 >1708a

6 Furosemide, aspirin 10 26 >1432a

7 Furosemide, enalapril 124 18 366d

aAlive at last contact in April 2004.bEuthanized due to gastrointestinal lymphoma.cEuthanized due to chronic renal failure.dEuthanized due to severe interstitial pancreatitis.

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Three of the seven cats were euthanizedfor reasons unrelated to cardiac disease (gas-trointestinal lymphoma, chronic renal failure,and severe interstitial pancreatitis). At thetime of euthanasia, these three cats hadreceived no cardiac medications for 235, 843,or 224 days, there had been no recurrence oftheir CHF, and their individual total survivaltimes were 457, 2,406, and 366 days.

A necropsy was performed in one of thelong-term survivors (cat 7). The cat hadreceived no cardiac medications during thepreceding 224 days and had shown no recur-rence of CHF when it was presented forvomiting. An abdominal mass was detectedon palpation, and a soft parasternal systolicmurmur was noted. The cat was euthanizedafter inflammation of the pancreas, withsaponification of omental fat and extensiveintestinal adhesions, were found during anexploratory laparotomy. A necropsy con-

firmed severe chronic active suppurativeinterstitial pancreatitis. With respect to thecardiovascular system, the heart:body weightratio was normal (3.7 g/kg; reference range =3–5 g/kg).12 However, on histopathology, theleft ventricle and interventricular septum con-tained hypereosin-ophilic myocytes withplump vesicular nuclei and perinuclear lipo-fuscin. There were also many areas ofmyofibrillar disarray and a mild increase ininterstitial fibrosis. These histopathologicabnormalities led to a necropsy diagnosis ofhypertrophic cardiomyopathy. Histopathologyof the lungs showed multifocal acute pyo-granulomatous bronchopneumonia. Therewas no evidence of CHF.

DISCUSSIONThe cats described in this report presentedwith similar chief complaints, and manysimilar clinical, radiographic, and echocar-

Figure 1. M-mode variables that changed significantly (P � .01) from first to final echocardio-gram in seven cats that were long-term survivors. Interventricular septal thickness in diastole(IVSd) (A), left ventricular posterior wall thickness in diastole (LVPWd) (B), and left atrial dimensionat end-systole (LADs) (C) all decreased; left ventricular diameter in diastole (LVDd) (D)increased. Shaded areas represent reference range for each variable.

A B

C D

167

diographic abnormalities associated withCHF due to various forms of feline idiopath-ic cardiomyopathy. When compared withresults from a recent retrospective study of106 cases of feline idiopathic cardiomyopa-thy, signalment was similar with respect tobreed and gender.13 However, the cats in thestudy population described here were slightlyolder than those with feline idiopathiccardiomyopathy (9.0 ± 3.4 versus 6.8 ± 4.3years). Serum biochemistry abnormalities incats with CHF due to hypertrophic cardio-myopathy frequently include hypochloremia,hyponatremia, hypokalemia, a high total car-bon dioxide, and elevated liver enzymes, andthese abnormalities were detected in many ofthe cases of the present report.9 Indeed, basedon the chief complaints, physical examinations,thoracic radiographs, electrocardiograms,echocardiograms, and serum biochemistryresults, together with exclusion of hyperthy-roidism and hypertension in most cases, theinitial diagnoses in the 12 cases that com-prised the study population were hypertro-phic cardiomyopathy (n = 6), hypertrophicobstructive cardiomyopathy (n = 3), andfeline unclassified cardiomyopathy (n = 3).

However, several features of the diseasein these cases led to the eventual conclusionthat this was a unique form of CHF associ-ated with corticosteroid administration. Thetemporal association between corticosteroidadministration and initial diagnosis of CHFwas compelling. Selection of the study pop-ulation was intentionally conservative.Consequently, some cases of corticosteroid-associated CHF may have been excluded.However, while readily acknowledging thelimitations inherent in any retrospectivestudy, there is a reasonable level of confi-dence that none of the population of catssuffered from CHF prior to corticosteroidadministration.

Another feature that contributed to theconclusion was the strikingly slow meanheart rate (145 ± 31 beats per minute)among the study population. One cat was inatrial fibrillation, yet even in that case, heartrate was only 150 beats per minute on phys-

ical examination, and ventricular depolariza-tion rate was 120 beats per minute on elec-trocardiogram. A previous study of cats withhypertrophic cardiomyopathy reported amean heart rate of 173 ± 33 beats per min-utes in 24 cases with CHF, and slow heartrates are unusual in cats with CHF due toother forms of cardiac disease.14 Low rectaltemperature was common among the casespresented here, and hypothermia can lead tobradycardia. Although low rectal tempera-tures are frequently found among cats withCHF due to other cardiac diseases, heartrates are seldom as low as in the cases thatcomprised this present study population.Furthermore, it is unlikely that a mean rectaltemperature of 98.7 ± 2.2˚F alone would below enough to result in a mean heart rate of145 ± 31 beats per minutes in cats in CHF.In a study that included 120 cats with CHFdue to hypertrophic cardiomyopathy, meanrectal temperature was just 1˚F higher thanin cases presented here, but the mean heartrate was greater than 30 beats per minutehigher.9 In the same study, average rectaltemperature in cats with arterial throm-boembolism (n = 43) was virtually identicalto average rectal temperature in the presentstudy population, and heart rate was 200 ±36 beats per minute. Thus, slow heart rate inthe present study population is not ascrib-able to hypothermia alone, but ratherappears to be a feature of corticosteroid-associated CHF.

Several aspects of the progression of thedisease in the seven long-term survivors inthe present study population are unique. Thefirst M-mode echocardiograms performed inall seven cats showed increased left atrialdimension at end-systole and increasedthickness of the left ventricular posteriorwall in diastole as well as increased thick-ness of the interventricular septum in dias-tole in five of the seven cases. Over time,these morphologic abnormalities normalizedor approached normal, even when echocar-diograms were performed for three of theseven cats several months after all cardiacmedications had been discontinued. One cat

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showed normalization of its electrocardio-gram after initially having a left anterior fas-cicular block-like conduction pattern.Cardiac medications were eventually discon-tinued in all seven cases without recurrenceof CHF, and survival times were consider-ably longer than would be anticipated withCHF from other forms of cardiac disease,including feline idiopathic cardiomyopathy.The authors are not aware of any previouslydescribed form of cardiac disease in catsthat follows this clinical course.

Naturally-occurring hyperadrenocorti-cism in humans is associated with echocar-diographic abnormalities. Left ventriculardiameter in diastole is significantly reduced,left ventricular mass index and wall thick-ness are significantly increased, and diastolicfunction measured by transmitral Doppler isimpaired.15 Morphologic changes occur inde-pendently of the hypertension that frequentlyaccompanies hyperadrenocorticism inhumans.16 In the majority of affected humanpatients, there is complete regression of theleft ventricular hypertrophy following suc-cessful therapy.17,18 The type of structuralchanges and the reversible nature of the leftventricular changes observed in the presentfeline population are similar to thoseobserved in humans with hyperadrenocorti-cism. However, the ventricular remodelingdescribed in humans is associated withchronically elevated corticosteroid concen-trations (months to years), and the frequencyof these changes is related to the duration ofdisease. Whether similar left ventricularchanges occur much more rapidly in cats fol-lowing exogenous corticosteroid administra-tion remains to be established.

It is unclear whether the cats in this pop-ulation had underlying heart disease thatpredisposed them to corticosteroid-associat-ed CHF. Cats with known pre-existing heartdisease were excluded from the study, butthis does not preclude the possibility thatoccult or undetected heart disease existedprior to corticosteroid administration. Thequestion about pre-existing heart disease isan extremely difficult one to answer defini-

tively in a retrospective study such as this,but it is an important issue and some specu-lation is necessary. In the opinion of theauthors, several aspects of the data tend tosupport the existence of underlying heartdisease in this study population. One pieceof evidence is that it seems unlikely thatcorticosteroid administration alone couldhave resulted in heart disease of sufficientseverity to result in atrial fibrillation andatrial standstill as was found in two cases.Also, although left atrial dimension at end-systole in 11 of the cases was moderatelyincreased (15.4–19.8 mm), it was extremelylarge (22.6 mm) in one cat that did notrecover from CHF. In all probability, thelarge left atrial dimension in that cat repre-sented pre-existing heart disease. Further,soft systolic heart murmurs persisted in fourof the seven cats that recovered from CHFand no longer required cardiac medications.Cardiac morphology among these seven catsnormalized on echocardiography, but slightdimension abnormalities persisted in severalcases. The final echocardiograms in five ofthe seven cats showed left atrial dimensionat end-systole to be either at the upper endof the reference range or slightly above it(Figure 1C). In two of the seven cats, thick-ness of the interventricular septum in dias-tole was slightly above the reference range(Figure 1A). Systolic anterior motion of themitral valve persisted in one of the cases,although it was mild and equivocal. Finally,histopathology in one case showed myocar-dial changes consistent with hypertrophiccardiomyopathy. Although the above find-ings suggest that underlying heart diseaseexisted in the cats with corticosteroid-asso-ciated CHF, the possibility that they reflectadverse effects entirely attributable to corti-costeroid administration cannot be excluded.Further studies are necessary to address thisimportant issue.

Irrespective of the uncertainty regardingunderlying heart disease, the data indicatethat all cardiac medications can eventuallybe discontinued in many cats with corticos-teroid-associated CHF, and that prolongedsurvival without recurrence of CHF can be

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anticipated. This is crucial prognosticallyand has clear quality-of-life implications forboth the cat and the owner. The study popu-lation evaluated here is too small to allowmeaningful statistical analyses to distinguishbetween cats that will and those that will notrecover from CHF. Rather, this distinctionshould be made based on response to timeand therapy and findings on follow-upexaminations that include echocardio-graphy.

A study by the authors to investigate thepathophysiology of corticosteroid-associatedCHF in cats is nearing completion; however, atthe present time, it is not known. Severalmechanisms could be involved, including leftventricular concentric hypertrophy with dias-tolic dysfunction, similar to what occurs inhumans with hyperadrenocorticism; volumeoverload secondary to a mineralocorticoideffect of some corticosteroids; increased leftventricular preload and afterload secondary tothe effects of corticosteroids to increase vascu-lar reactivity; and plasma volume expansion,similar to what occurs in humans with hyper-glycemia from diabetes mellitus, as a result ofthe diabetogenic effect of corticos-teroids.3,15,19–26 In addition to the pathophysiol-ogy of corticosteroid-associated CHF,important questions remain, including the fre-quency of corticosteroid-associated CHF fol-lowing corticosteroid administration and howbest to predict and avoid this adverse effect.Until these questions are answered, it is rec-ommended that any cat requiring cortico-steroid therapy should be thoroughly evaluatedfor presence of pre-existing heart disease andthat CHF should be listed as a potentialadverse effect of corticosteroid administrationin this species.

ACKNOWLEDGMENTSThe authors thank Pamela L. Grumbles forher outstanding assistance with recordreview and data acquisition. The authorsalso appreciate the tremendous cooperationof the numerous referring veterinarians whoprovided case records, laboratory data, andthoracic radiographs.

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