Evaluación-de-falla-cardiaca-congestiva-con-doppler1

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D e t e c t i o n o f Co n g e s t i v e H e a r t F a i l u r e i n D o g s b yD o p p l e r E c h o c a r d i o g ra p h y

K.E. Schober, T.M. Hart, J.A. Stern, X. Li, V.F. Samii, L.J. Zekas, B.A. Scansen, and J.D. Bonagura

Background: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated.

Hypothesis: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with

degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM).Animals: Sixty-three client-owned dogs.

Methods: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides,

and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings.

Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and step-

wise regression, and best subsets analyses.

Results: Presence of CHF secondary to MVD or DCM could best be predicted by E : isovolumic relaxation time (IVRT)

(area under the ROC curve [AUC]50.97, P o .001), respiration rate (AUC50.94, P o .001), Diastolic Functional Class

(AUC50.93, P o .001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R250.80, P o .001)

or Diastolic Functional Class (AUC51.00, P o .001), respiration rate (AUC51.00, P o .001), and E : IVRT (AUC50.99,

P o .001), and a combination of Diastolic Functional Class and E : IVRT (R250.94, P o .001), respectively, whereas other

variables including N-terminal pro-brain natriuretic peptide, E : Ea, and E : Vp were less useful.

Conclusion and Clinical Importance: Various DE variables can be used to predict CHF in dogs with MVD and DCM.

Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF

needs further study.

Key words: Canine; Degenerative mitral valve disease; Dilated cardiomyopathy; NT-proBNP; Respiration rate.

Congestive heart failure (CHF) is a common and of-

ten fatal clinical syndrome in dogs characterized bycardiac dysfunction, neurohormonal activation, sodium

and water retention, and increase in left ventricular (LV)filling pressures (LVFP).1,2 It occurs most often second-

ary to degenerative mitral valve disease (MVD)35 anddilated cardiomyopathy (DCM).4 Early recognition of

CHF is of clinical importance.5 CHF can be suspected byclinical signs although reliability of such findings may be

limited. Thoracic radiography is the most commonly ap-plied method for the diagnosis of CHF and is considered

the clinical gold standard.6 However, radiography isof unspecified sensitivity and specificity, especially in the

setting of combined heart and lung disease, and cansuffer from considerable observer variation.6,7 Plasma

concentration of N-terminal pro-brain natriureticpeptide (NT-proBNP) is increased in patients with

From the Department of Veterinary Clinical Sciences, College of

Veterinary Medicine (Schober, Hart, Stern, Samii, Zekas, Scansen,

Bonagura) and the Center for Biostatistics (Li), The Ohio State

University, Columbus, OH. Presented in part at the Annual Forum of

the American College of Veterinary Internal Medicine, Montreal,Canada, June 36, 2009. Dr Hart is presently affiliated with Univer-

sity of Minnesota Veterinary Medical Center, 1365 Gortner Avenue,

St Paul, MN 55108. Dr Stern is presently affiliated with Department

of Veterinary Clinical Sciences, Washington State University, 100

Grimes Way, Pullman, WA 99164. This work was completed at The

Ohio State University, Columbus, OH.

Corresponding author: Karsten E. Schober, DVM, PhD, Department

of Veterinary Clinical Sciences, College of Veterinary Medicine, The

Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH

43210; e-mail: [email protected].

Submitted December 21, 2009; Revised June 30, 2010;

Accepted July 20, 2010.Copyrightr 2010 by the American College of Veterinary Internal

Medicine

10.1111/j.1939-1676.2010.0592.x

Abbreviations:

Aduration duration of the late diastolic transmitral flow wave

Ao aortic annular dimension

ARduration duration of the late diastolic pulmonary vein atrial re-

versal flow wave

AUC area under the ROC curve

CHF congestive heart f ailure

CV coefficient of variation

DCM dilated cardiomyopathy

DE Doppler echocardiography

DTE deceleration time of the early diastolic transmitral flow

FAC fract ional area c hange

IVRT isovolumic relaxation time

LA left atrial

LAAmax maximum left atrial area

LAAmin minimum left atrial area

LADmax maximum left atrial dimension

LADmin minimum left atrial dimension

Lat lateral

LV left ventricular

LVDd left ventricular internal dimension in diastole

LVDs left ventricular internal dimension in systoleLVFP left ventricular filling pressure

MVD degenerative mitral valve disease

NT-proANP N-terminal pro-atrial natriuretic peptide

NT-proBNP N-terminal pro-brain natriuretic peptide

Peak A peak velocity of late diastolic transmitral flow

Peak E peak velocity of early diastolic transmitral flow

Peak Ea peak velocity of early diastolic mitral annular motion

of the mitral annulus

Peak TR peak velocity of tricuspid regurgitation

Peak Vp peak velocity of propagation of early transmitral flow

ROC receiver-operating characteristic

Sept septal

SF shortening fraction

J Vet Intern Med2010;24:13581368
mailto:[email protected]:[email protected]


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advanced MVD and DCM and may be useful in the

diagnosis of CHF.4,5,811 However, a wide overlap of cir-culating NT-proBNP concentrations in dogs with andwithout CHF has been reported and generally accepted

discrimination limits have not been determined.5,8,12 Inaddition, effects of renal function, day-to-day variability,

and considerable turn-around time make this variable

poorly suited for situations where bedside decisions areimmediately required.

The development of cardiogenic pulmonary edema is

predicted largely by the magnitude of volume overloadand resulting increase in LVFP.2,13,14 A simple but quant-

ifiable noninvasive method for estimation of volumestatus and filling pressures could not only refine the di-

agnosis, but also promote the early recognition of CHF,advance optimal medical management, and facilitate

therapeutic monitoring. The recent introduction of novelDoppler echocardiographic (DE) techniques has sparked

considerable interest in the noninvasive prediction ofCHF by DE.1519 One variable, the ratio between peak

velocity of early diastolic transmitral flow (Peak E) topeak early tissue Doppler mitral annulus velocity

(Peak Ea; E : Ea), has gained the most attention in theprediction of LVFP in dogs1517,20,21 and people.18,22

Previous validation studies15,16 in experimental dogsreported on the use of isovolumic relaxation time (IVRT)

and the ratio between Peak E to IVRT (E : IVRT) in thediagnosis of increased LVFP. These variables, however,

have not been validated in dogs with naturally acquiredheart disease.

Therefore, we undertook a study to test the hypothesisthat DE indices of LV filling would predict CHF in dogs

with spontaneous heart failure with clinically acceptableaccuracy. More specifically, we hypothesized that E : Ea,

E : IVRT, and IVRT would be most predictive of highCHF scores in dogs with MVD and DCM.

Materials and Methods

The study protocol was reviewed and approved by the

Institutional Animal Care and Use Committee (protocol

#2004A0196) and the Review Board of the Department of

Veterinary Clinical Sciences, College of Veterinary Medicine, The

Ohio State University, Columbus, OH.

Dogs, Clinical Examinations, and Group Assignment

Sixty-three client-owned dogs were prospectively studied. Dogs

were consecutively selected over a time period of 2 years (2007 and

2008) based upon the echocardiographic diagnosis of MVD3,23 and

DCM.24 All dogs underwent a thorough physical examination, a

noninvasive measurement of systolic blood pressure,a thoracic radi-

ography,b,c,d,e blood biochemical analyses, and a 2-dimensional

(2D), M-mode, and DE study.fHeart rate and respiration rate were

taken during initial physical examination without consideration

of ambient temperature and determined as the number of beats or

respirations per minute, respectively. If respiration rate could not

be obtained due to panting, dogs were reassessed within 1 hour of

arrival in order to obtain a definitive rate. Dogs with atrial flutter

and fibrillation, arrhythmogenic right ventricular cardiomyopathy,

systemic hypertension (systolic blood pressure 4170 mmHg),

and evidence of concomitant diseases or conditions such as

hypothyroidism, renal failure, primary tracheal or pulmonary dis-

ease, anemia, or cancer were excluded. Using clinical, radiographic,

and echocardiographic data, dogs were divided into 4 groups for

statistical analyses: MVD or DCM with or without evidence of

CHF (Groups 14), respectively. In preclinical (asymptomatic) dogs

with MVD (Group-1), no treatments other than an ACE inhibitor

were permitted. In dogs with asymptomatic DCM (Group-3), no

treatments other than an ACE inhibitor, spironolactone, carvedilol,

and pimobendan were permitted. In dogs with CHF (MVD, Group-

2; DCM, Group-4), no treatments other than an ACE inhibitor,

spironolactone, carvedilol, pimobendan, and furosemide (given

within 12 hours of thoracic radiographs and echocardiography)

were permitted. Dogs with signs of CHF were sedated upon arrival

at the hospital with acepromazineg (0.0250.050 mg/kg, IM; n5 2),

butorphanolh (0.150.25mg/kg, IM; n 5 21), or a combination of

both drugs (n5 7).

Thoracic Radiography

Thoracic radiographs were taken in 3 different imaging planes

(right lateral, left lateral, and ventral dorsal projections) before

echocardiography. Radiographs were assessed by the attending cli-

nician only after the echocardiographic exam was performed. Ifnoncardiac disease or cardiac disease other than MVD and DCM

were observed, dogs were disqualified from the study. For final

radiographic diagnosis and definitive group assignment (CHF

absent or CHF present), radiographic images were reassessed by 2

independent board-certified radiologists (V.F.S. and L.J.Z.) en bloc

at the end of the case recruitment period. All 63 studies were ordered

randomly and coded by the principal investigator. The radiologists

were aware of the 2 principal diagnoses (MVD and DCM); how-

ever, they were blinded to the animals identification, the date of the

examination, the initial interpretation of the images, the results of

natriuretic peptide analysis, echocardiographic findings, the clinical

diagnosis, and each others assessment. A radiographic composite

CHF score including criteria for left atrial (LA) enlargement,

pulmonary venous congestion, pulmonary infiltrates compatible

with cardiogenic edema, and pleural effusion was used (Appen-

dix 1).i,25 The final radiographic assessment revealed a numerical

radiographic CHF score and a qualitative, binary variable (CHF

absent or CHF present). For group assignment, only the latter vari-

able was used. To assure proper application of suggested diagnostic

criteria and thus consistency of data, investigators met for a 1-hour

training session before final analysis by mock radiographic images.

After interpretation of films, results of the 2 readers were compared.

If there was disagreement with regard to the principal diagnosis

(CHF absent or CHF present), the investigators collectively reas-

sessed the images in question to come up with a final definitive

diagnosis that satisfied both raters. Intraobserver reproducibility

of the radiographic diagnosis of CHF was determined by 15 studies

(7 from dogs with compensated disease and 8 from dogs with CHF)

interpreted 3 times by 1 blinded observer (V.F.S.) using a randomorder list.

Collection of Blood and Analysis ofNatriuretic Peptides

In each dog, 5 mL of blood were collected from a jugular vein

directly into serum tubes. After 20 minutes of storage at room tem-

perature (22241C) to allow for stable clot formation, samples were

centrifuged at 3,000 g for 10 minutes at 51C and further processed

within 15 minutes. The supernatant (serum) was harvested, divided

into four 0.5 mL aliquots, transferred into plastic cryotubes, and

stored at 801C for a maximum of 4 weeks until analysis. Two

aliquots of each sample were shipped on dry ice to the reference

laboratory

j

where batched analysis was done once a month. Assays

1359Congestive Heart Failure in Dogs


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were run in duplicate, and the average of the 2 values was used for

final data analysis.

Serum N-terminal pro-atrial natriuretic peptide (NT-proANP)

and serum NT-proBNP were analyzed with commercial test kits

(sandwich enzyme immunoassays) with antibodies raised against

human NT-proANP31-67k,26 and canine NT-proBNP25-41 (cap-

ture antibody) and canine NT-proBNP1-22 (detection antibody).l

The detection limits were 50pmol/L for the NT-proANP assay and

42 pmol/L for the NT-proBNP assay. The intra-assay coefficients

of variation (CV) were below 10% for the NT-proANP assay

and below 15% for the NT-proBNP assay as reported by the

manufacturer.

Echocardiography

Transthoracic 2D, M-mode, and DE examinations were per-

formed by a single operator (K.E.S.; n 5 53) or under direct

supervision of the principal investigator (n 5 10) with the dogs in

right and left lateral recumbency with a digital ultrasound systemf

with a transducer array of 3.5 MHz nominal frequency as recently

described.15 Right parasternal standard views optimized for the LA,

the LV outflow tract (long axis), or the LV (short axis) and left api-

cal parasternal standard views optimized for the LV inflow tract,longitudinal motion of the lateral and septal mitral annulus, or the

LV outflow tract were used for data acquisition. 2D cine loops and

Doppler tracings were recorded and stored on the internal hard

drive of the echocardiograph or on magneto-optical disc and ana-

lyzed off-line. A simultaneous 1-lead ECG was recorded. Heart rate

was determined from the preceding R-R interval on the ECG and

represents the mean of 512 calculations. Measurements were

obtained from digital still images as an average of 512 consecutive

cardiac cycles, irrespective of respiratory phase. Only high-quality

images were used for data analysis. All measurements were

done off-line by 1 trained investigator (T.M.H.) blinded to the dogs

identification, clinical signs, thoracic radiographs, and hemodynamic

status and verified by the principal investigator (K.E.S.).

Echocardiographic Data Analysis

Fourteen variables were measured and 10 variables were calcu-

lated as recently described in dogs.15,16,27 In brief, from right

parasternal long-axis recordings, the maximum (LADmax) and min-

imum (LADmin) septal-to-posterior dimension of the LA,27 the

maximum (LAAmax) and minimum (LAAmin) area of the LA, and

the end-diastolic dimension of the aortic valve (Ao) were measured

using imaging views optimized for the LA or the LV outflow tract

and inner edge projections. From a LV short-axis M-mode record-

ing at the level of the chordae tendineae, LV dimensions in systole

(LVDs) and diastole (LVDd) were measured. From the left apical 3-

chamber view, IVRT was measured as the time period from the

Doppler signal of aortic valve closure to the beginning of the trans-

mitral early diastolic flow wave (E wave) with a pulsed wave sample

volume of 610mm placed in an intermediate position between the

LV inflow and outflow tracts. Transmitral flow was recorded from

the left apical 2-chamber view with a pulsed wave sample volume

(2 mm in width) placed between the tips of the opened mitral valve

leaflets. Peak E and the peak velocity of the late diastolic transmitral

flow wave (Peak A) were measured. Deceleration time of the early

diastolic transmitral flow (DTE) was measured as the time from

Peak E velocity to the end of E at the baseline. Summated E and A

waves were not measured. Duration of the A wave (Aduration) was

measured from the beginning to the end of the A wave. Pulmonary

venous flow was recorded from the same left apical 2-chamber view,

with minimized baseline filter, optimized velocity scale, and with a

pulsed wave sample volume of 46 mm placed 510mm within the

pulmonary vein of the left caudal lung lobe.28 Only the duration of

the late diastolic reversal wave (ARduration) was measured. Pulsed-

wave Doppler-derived velocities of myocardial motion were

recorded from an apical 2-chamber view, with a sample volume of

56 mm placed in the septal or lateral aspects of the mitral annulus.

Frame rate during tissue Doppler studies was optimized (4160

frames per second) by narrowing the imaging sector. Peak velocity

of early diastolic septal (Peak Ea Sept) and lateral (Peak Ea Lat)

mitral annulus motion was measured. Color M-mode recordings of

early diastolic LV inflow were used to determine LV flow propaga-

tion velocity (Peak Vp). Color Doppler transmitral flow recordings

were obtained, the Nyquist limit was reduced to approximately 50%

of Peak E, and the slope of the 1st aliasing velocity line from the tip

of the mitral valve to 3 cm distally into the LV cavity was used for

determination of Peak Vp.29 From a right parasternal tilted short-

axis view or a left apical cranial view optimized for the right ven-

tricular inflow tract, peak tricuspid regurgitation (Peak TR) velocity

was recorded. A Peak TR velocity of!3.0 m/s was considered an

echocardiographic finding suggestive of mild to severe pulmonary

hypertension.30,31 Variables calculated included LA shortening frac-

tion (SF; LA-SF 5 [LADmax LADmin]/LADmax 100%), LA

fractional area change (LA-FAC 5 [LAAmax LAAmin]/LAAmax 100%), the LA-to-Ao ratio (LADmax : Ao), LV shortening frac-

tion (LV-SF 5 [LVDd LVDs]/LVDd 100%), the ratio between

Peak E (cm/s) to IVRT (ms; E : IVRT); the ratio between Peak E toPeak A (E : A); the ratio between the duration of A to the duration

of AR (Aduration : ARduration), the ratios between Peak E to Peak

Ea Sept (E: Ea Sept), Peak E to Peak Ea Lat (E : Ea Lat), and Peak

E to Peak Vp (E: Vp), and [(E : Ea Lat) 1 (E : Ea Sept)]/2. LV dia-

stolic function was classified22 based on E : A and qualified based on

E : Ea Lat Class-1: Normal pattern (1.0 E : A 2.0), Class-2:

Relaxation delay pattern (E : A o 1.0), Class-3: Pseudonormal

pattern (1.0 E : A 2.0), and Class-4: Restrictive pattern (E :

A 4 2.0). Class-1 and Class-3 were discriminated using cut-offs of

E : Ea Lat of 11.0 for dogs with MVD and 9.0 for dogs with DCM.

These discrimination values were obtained from a previous pilot

study of 25 dogs with DCM and 52 dogs with MVD.m,32 In dogs

older than 10 years, any observed E : A between 1.0 and 2.0 was

considered pseudonormal transmitral flow because of the fact that a

physiologic age-related relaxation delay pattern would be expectedin such dogs.33

Measurement reliability was determined for selected echocardio-

graphic variables. Four echocardiograms each from dogs with

MVD and DCM were randomly selected from the pool of studies

to undergo 5 repeated analyses by 1 observer (T.M.H.) to determine

intraobserver measurement variability. The same 8 echocardio-

grams underwent repeated analyses by a 2nd independent observer

(K.E.S.) to determine interobserver measurement variability. Both

investigators were blinded to the results of prior studies.

Statistical Analyses

Statistical analyses were done with commercially available soft-

ware.n,o,p All continuous outcome variables were visually inspected

and tested for normality by the Kolmogorov-Smirnov test. Descrip-

tive statistics were determined: frequencies for categorical variables

and median and 5 and 95 percentiles for continuous variables. Se-

lected data were graphically depicted as median and scatter plot of

individual data points. Groups of dogs with MVD (Group-1 versus

Group-2) and DCM (Group-3 versus Group-4) were compared us-

ing an unpaired t-test if standard assumptions were fulfilled or the

Mann-Whitney rank-sum test if not. Proportions were compared by

Fishers exact test. Receiver-operating characteristic (ROC) curve

analysis was used to determine the diagnostic ability of heart rate

(taken at physical examination), respiratory rate, NT-proANP, NT-

proBNP, and various DE variables in the diagnosis of CHF and to

define optimal discrimination limits (diagnostic cut-off values) for

such prediction. The area under the ROC curve (AUC) was used as a

summary measure for diagnostic accuracy and to quantify the ability

1360 Schober et al


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of variables to predict CHF and is reported with 95% confidence in-

tervals. Cut-off values were chosen based on the highest Youden

index (Y 5 (Se 1 Sp) 1) of various combinations of Se and Sp.34

Multivariate logistic regression was used to predict the qualitative

dichotomous variable CHF absent or CHF present (based on ra-

diographic diagnosis) from observations of 1 or more independent

variables by fitting a logistic function to the data. In addition to all

tabulated variables, variables such as prior treatment with furose-

mide and presence of azotemia were also considered in the

regression. Once variables with significant (P o .05) associations

were identified, forward selection and best subsets regression ana-

lyses were performed to identify the combination of variables that

predicted presence of CHF best and to determine the contribution of

individual variables to the final model. For model fitting, a 1 : 7 ap-

proach was used (ie, addition of no more than 1 independent

variable to the model for every 7 observations).

Conformity among observers with regard to radiographic inter-

pretation of recordings after 1st assessment were determined by the

nonparametric McNemars test,35 Bowkers test of symmetry,36 and

by calculating Cohens Kappa coefficients (k).37 Intraobserver repro-

ducibility of the radiographic diagnosis of CHF was determined by 1-

way random effects models for calculation of the intraclass

correlation coefficient (ICC).

38

Observer variability of echocardio-graphic measurements was calculated by coefficients of variation (CV

5 [standard deviation / average of measurements] 100) and ex-

pressed as CV in percent and also as absolute value of the respective

variable.39 For all analyses, P-values.05 were considered significant.

Results

Demographic data, historical findings, and results of

physical examination and blood pressure measurementare summarized in Table 1. At presentation, 11 (52%)

dogs of Group-1 and 10 (42%) dogs of Group-2 were onlong-term treatment with enalapril or benazepril. In

Group-2, 12 (50%) had received furosemide within thelast 12 hours before the study; however, they were still

diagnosed with CHF at the time of thoracic radiography

and echocardiography. At presentation, 1 (9%) dog ofGroup-3 and 2 (28%) dogs of Group-4 were on long-term treatment with enalapril or benazepril. In Group-4,

2 (28%) dogs had received furosemide within the last 12hours before the study; however, they were still diag-

nosed with CHF at the time of thoracic radiography and

echocardiography. Azotemia was detected in 1/10 dogsof Group-1, 5/24 dogs of Group-2, and no dogs inGroup-3 or Group-4. In all dogs, BUN was o50 mg/dL

(reference range, 520mg/dL) and creatinine was

o2.7 mg/dL (reference range, 0.61.6mg/dL).Results on radiographic composite score, NT-

proANP, and selected echocardiographic variables are

presented in Table 2. One dog of Group-1 and 2 dogs ofGroup-2 had a radiographic composite score of 4.0. All

other dogs were either below 4.0 (Group-1) or above 4.0(Group-2). Two dogs of Group-3 had a radiographic

composite score of 4.0. All other dogs were either below4.0 (Group-3) or above 4.0 (Group-4). The minority of

dogs with compensated heart disease (15% in Group-1and 27% in Group-3) and the majority of dogs with CHF

(71% in Group-2 and 86% in Group-4) had echocardio-graphic evidence of mild to severe pulmonary

hypertension using a diagnostic cut-off of 3.0 m/s PeakTR velocity for estimation.30,31 Summated E and A

waves seen in 2 dogs with MVD were discarded fromfurther data analysis.

Figures 1 and 2 illustrate median and scatter plots ofrespiration rate, NT-proBNP, E : A, Diastolic Func-

tional Class, IVRT, E : IVRT, E : Ea Lat, andAduration : ARduration in dogs with MVD (Fig 1) and

DCM (Fig 2) and differences between dogs with com-pensated disease (Group-1 and Group-3) and dogs with

CHF (Group-2 and Group-4).

Table 1. Demographic data and results of history, physical examination, and blood pressure measurement in 63 studydogs.

Group-1 Group-2 Group-3 Group-4

n 21 24 11 7

Number of different breeds 10 14 5 5

Most common breed (n) CKCS (9) CKCS (4) Doberman (5) Doberman (4)

Age (years) 10 (612) 10 (713) 6 (113) 7 (512)

Body weight (kg) 11 (537) 10 (436) 32 (1158) 37 (3054)

Sex (female : male) 1.10 0.85 1.20 0.75

Exercise intolerance (%) 10 100z 18 100

Cough (%) 43 84z 0 86

Tachypnea and dyspnea (%) 0 75z 9 71

Syncope and near-syncope (%) 0 29z 9 14

Respiration rate (per minute) 28 (1957) 54 (3885)z 26 (2032) 56 (3660)

Heart rate (per minute) 132 (91169) 140 (100206) 114 (70198) 160 (120210)

Systolic heart murmur (%) 100 100 91 100

Murmur grade (0/66/6) 3 (26) 4 (36)z 2 (03) 2 (13)

Systolic blood pressure (mmHg) 130 (97160) 125 (90156) 131 (112170) 113 (90128)

Group-1, degenerative mitral valve disease (MVD) without congestive heart failure (CHF); Group-2, MVD with CHF; Group-3, dilated

cardiomyopathy (DCM) without CHF; Group-4, DCM with CHF. Median (5 and 95 percentiles) for continuous data and number (n) or

percent (%) for frequency data.Within a row, values between Group-3 and Group-4 differ significantly (P .05).z

Within a row, values between Group-1 and Group-2 differ significantly (P .05).



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In dogs with MVD, DTE (P5 .59), heart rate taken atphysical exam (P 5 .39), Aduration : ARduration (P 5.79), Peak Vp (P5 .98), and SF (P5 .69) did not predictpresence of CHF (Tables 3 and 4). In dogs with DCM,

NT-proANP (P 5 .89) and Peak Vp (P 5 .87) did notpredict presence of CHF.

Regression analyses revealed that presence of CHF indogs with MVD can be predicted from a combination of

Diastolic Functional Class (step 1, R25 0.58, Po .001),IVRT (step 2, cumulative R25 0.72, Po .001), and res-

piration rate (step 3, cumulative R2 5 0.80, P o .001)leading to the general prediction model: CHF 5 X 1(0.190 Diastolic Functional Class) (0.0104 IVRT [ms])

1 (0.00935 Respiration Rate [per minute]). With the

same methods in dogs with DCM, presence of CHFcould be predicted from a combination of Diastolic

Functional Class (step 1, R2 5 0.91, P o .001) andE : IVRT (step 2, cumulative R25 0.94, P5 .021) leadingto the general prediction model: CHF 5X1 (14.273 Di-

astolic Functional Class) 1 (0.843 E : IVRT).Kappa (k) for assessment of conformity between the

2 radiographic observers was 0.78 (95% CI, 0.700.86)

for LA enlargement; 0.44 (95% CI, 0.320.55) forpulmonary infiltrates compatible with cardiogenic ede-

ma; 0.26 (95% CI, 0.05 to 0.56) for pleural effusion;0.37 (95% CI, 0.210.52) for pulmonary venous conges-

tion; and 0.65 (95% CI, 0.520.78) for the final diagnosisof CHF. Consistency of 1 radiographic observer (V.F.S.)in the diagnosis of CHF based on ICC was 0.92.

Results of studies on measurement variability of echo-

cardiographic indices are summarized in Table 5.Coefficients of variation for intra- and interobserver mea-

surement variability wereo

10 % for all but 3 variables.

Discussion

Increase in filling pressure is a unifying feature of CHF

regardless of underlying cause.2,13 Because filling pres-sure cannot be directly measured in clinical situations; aneasily applicable, reliable, noninvasive method is needed.

Results of this study support the contention that CHFsecondary to MVD and DCM can be predicted by DE.The major finding is that E : IVRT, Diastolic Functional

Class, and IVRT allow for a rapid and feasible estima-tion of whether or not CHF is present. In addition,

respiration rate taken at physical exam was equally use-ful in the prediction of CHF. Moreover, disease-specific

differences between dogs with MVD or DCM regardingthe diagnostic accuracy of individual DE variables andclinical decision thresholds were identified and thus need

to be considered clinically.

Diagnosis of CHF by Single DE Variables

Our results are in agreement with previous findingsfrom studies in anesthetized, volume loaded dogs16 and

dogs with rapid pacing-induced CHF.15 In the former16

in which mean LA pressure was measured directly,E : IVRT outperformed 8 commonly used DE variables

of filling pressure and predicted increased LA pressure

(!15 mmHg) with high accuracy. In the latter,15 a de-crease of LV end-diastolic pressure after furosemide wasbest predicted by a decrease of E : IVRT. In both stud-

ies,15,16 neither E : Ea nor E : Vp was diagnostically

useful in the prediction of increased LVFP. The ratio-nale behind the use of combined indices such as

E : IVRT, but also E : Ea and E : Vp, is to correct for

Table 2. Radiographic score, serum concentrations of NT-proANP, and selected echocardiographic variables in 63

study dogs.


n 21 24 11 7

Radiographic composite score 1 (04) 7 (49)z 1 (14) 7 (58)

NT-proANP (pmol/L) 362 (151980) 941 (3253,035)z 565 (1201,644) 542 (234990)

LADmax : Ao 2.23 (1.803.12) 3.19 (2.314.23)

z

2.18 (1.532.66) 2.81 (2.513.60)

LA-FAC (%) 37 (1749) 24 (1043)z 26 (1843) 11 (534)

LA-SF (%) 20 (728) 11 (523)z 15 (827) 6 (319)

LV-SF (%) 39 (2455) 43 (2459) 21 (1025) 16 (1023)

TR (%) 86 92 91 86

Peak TR (m/s) 2.81 (2.193.15) 3.43 (2.084.61) 2.77 (2.183.46) 3.18 (2.283.83)

TR4 3 m/s (%) 15 71z 27 86

Peak E (m/s) 0.92 (0.601.45) 1.41 (1.041.74)z 0.80 (0.541.02) 1.39 (0.701.74)

DTE (ms) 88 (65112) 86 (62120) 100 (64128) 62 (57104)

Peak Vp (cm/s) 51 (3095) 52 (3887) 33 (2348) 33 (2843)

E : Vp 1.66 (0.883.94) 2.63 (1.363.77)z 2.17 (1.413.56) 3.63 (2.474.56)

Peak Ea Lat (cm/s) 10.1 (6.316.1) 8.7 (6.217.4) 10.3 (6.717.7) 8.54 (6.717.1)

Peak Ea Sept (cm/s) 8.82 (5.1614.16) 9.80 (5.4915.10) 7.37 (5.5716.54) 7.08 (5.5512.52)

E : Ea Sept 10.6 (6.716.6) 14.7 (7.622.8)z 9.4 (5.913.2) 14.9 (8.724.6)

[(E: Ea Sept)1 (E : E a Lat)]:2 10.0 (6.515.1) 14.4 (6.122.3)z 8.4 (4.211.0) 15.2 (8.922.5)

NT-proANP, N-terminal pro-atrial natriuretic peptide; LADmax, maximum left atrial dimension; Ao, aortic annular dimension; FAC,

fractional area change; SF, shortening fraction; Peak TR, peak velocity of tricuspid regurgitation; Peak E, peak velocity of early transmitral

flow; Peak Vp, peak velocity of propagation of early transmitral flow; Peak Ea, peak velocity of early diastolic mitral annular motion; Lat,

measured at the lateral mitral annulus; septal, measured at the septal mitral annulus.

See Table 1 for key.

Median (5 and 95 percentiles) for continuous data and number (n) or percent (%) for frequency data.

1362 Schober et al


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the effect of relaxation on a variable that is largely de-pendent on filling pressure, but also influenced by

relaxation. By combining Peak E, a variable that is de-

termined mainly by filling pressure and relaxationn,18,40,41

with a variable that is most dependent on relaxation

(eg, IVRT, Peak Ea, and Peak Vp),

18,40

the effect of

Group-1 Group-20

1020

30

40

50

60

70

8090

100

Resp

irationRate(min1)

Group-1 Group-20

1

2

3

4

E:A

Group-1 Group-20

1000

2000

3000

4000

5000

6000

7000

NT-proBNP(pmol/L)

Group-1 Group-20

1

2

3

4

ClassofLVDiastolic

Function


10

20

30

40

50

60

70

80

IVRT(ms)

0

1

2

3

4

5

6

7

8

9

10

E:IVRT

Group-1 Group-20

5

10

15

20

25

E:Ealat

Group-1 Group-20.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

2.00

Aduration:ARduration

Fig 1. Medians and scatter plots of respiration rate, NT-proBNP,

and Doppler echocardiographic variables of left ventricular (LV)

filling in 21 dogs with compensated degenerative mitral valve disease

(MVD; Group-1) and 24 dogs with MVD and congestive heart fail-

ure (Group-2). Respiration rate (median, 28 versus 54 bpm, P o

.001); NT-proBNP (median, 848 versus 2,750pmol/L, P o .001);

E : A ratio (median, 1.34 versus 2.21, P o .001); Class of LV Dia-

stolic Function (median, 1 versus 4, P o .001); isovolumic

relaxation time (IVRT) (median, 57 versus 36ms, P o .001);

E : IVRT ratio (median, 1.74 versus 3.71, Po .001); E : Ea (median,

8.9 versus 15.2, Po .001); and Aduration : ARduration ratio (me-

dian, 1.30 versus 1.26, P5 .79).

Group-3 Group-410

20

30

40

50

60

70

80

90

100

RespirationRate(min1)

Group-3 Group-40

1000

2000

3000

4000

5000

6000

7000

NT-p

roBNP(pmol/L)

Group-3 Group-40

1

2

3

4

E:A

Group-3 Group-40

1

2

3

4

ClassofLVDiastolic

Function

Group-3 Group-4

0

10

20

30

40

50

60

70

80

90

IVRT(ms)

Group-3 Group-4

0

1

2

3

4

5

6

7

8

9

10

E:IVRT

Group-3 Group-40

5

10

15

20

25

E:Ealat

Group-3 Group-40.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

2.00

Aduration:ARduration

Fig 2. Medians and scatter plots of respiration rate, NT-proBNP,and Doppler echocardiographic variables of left ventricular (LV) fill-

ing in 11 dogs with compensated dilated cardiomyopathy (DCM;

Group-3) and 7 dogs with DCM and congestive heart failure (Group-

4). Respiration rate (median, 26 versus 56 bpm, Po .001); NT-pro-

BNP (median, 1,314 versus 3,830 pmol/L, P o .001); E : A ratio

(median, 1.10 versus 2.73, Po .001); Class of LV Diastolic Function

(median, 1 versus 4, P o .001); isovolumic relaxation time (IVRT)

(median, 66 versus 32 ms, P o .001); E : IVRT ratio (median, 1.11

versus 4.41, Po .001); E : Ea (median, 7.9 versus 13.3, P5 .003); and

Aduration : ARduration ratio (median, 1.47 versus 0.73, Po .001).



7/11

relaxation on Peak E can be minimized. Because increased

filling pressure, a main hemodynamic characteristic ofCHF,2,13 is associated with both increased Peak E and de-creased IVRT,13,14,19,21,41 the ratio of E : IVRT should be

high in dogs with CHF and low in dogs with compensatedheart disease.14 The latter was confirmed in this study for

both dogs with MVD or DCM.The IVRT is an index of relaxation and is linearly re-

lated to tau, the time constant of LV isovolumicrelaxation. However, it is also influenced by a multitude

of other factors including preload, afterload, heart rate,

and age.13,14 Therefore, IVRT represents the net effect ofmany determinants, only one of which is relaxation.42

Whereas a mild increase in LVFP as seen in the early

stages of heart failure shortens tau (ie, improves relax-ation) but is not associated with shortening of IVRT,

moderate and severe increase in filling pressure as seen inCHF prolongs tau (ie, makes relaxation worse) but

shortens IVRT in a linear manner.13,14,41,42 Shortened

IVRT is by definition an integral part of restrictive LVfilling, a transmitral flow pattern considered specific foradvanced diastolic dysfunction, high filling pressure, and

CHF.13,41,43 That is, high filling pressure can minimizethe effect of relaxation on IVRT, turning it into a more

specific indicator of LVFP and thus CHF.42 This wasconfirmed in our study, in particular in dogs with DCM.

Both IVRT and Peak E (and thus E : IVRT) are relativelyeasy to measure DE variables and might provide, in

concert with historical and clinical findings, immediate

information on heart failure status in dogs with DCM orMVD.

The E : Ea ratio and the E : Vp ratio have been reported

to be useful DE indices of LVFP and CHF in clinicaltrials in people19,40 with E : Ea preferred by most.18,19

Although studies on the use of such variables in experi-mental dogs are numerous,15,16,20,21,29 data on dogs with

Table 3. Areas under the receiver-operating characteristic curve (AUC) and optimal diagnostic cut-offs of clinical

and echocardiographic variables in the prediction of congestive heart failure in 45 dogs with degenerative mitral valvedisease.

AUC 95% CI Cut-off Se Sp P

E : IVRT 0.97 0.921.02 2.50 0.92 0.96 o .001

Respiration rate (per minute) 0.94 0.841.04 41 0.92 0.94 o .001

Diastolic Functional Class 0.93 0.851.01 2 0.92 1.00o

.001LA : Ao 0.90 0.810.99 2.52 0.92 0.81 o .001

E : A 0.89 0.780.99 1.58 0.87 0.86 o .001

Peak E (m/s) 0.87 0.770.98 1.08 0.96 0.71 o .001

IVRT (ms) 0.86 0.750.98 46 0.88 0.76 o .001

E : Ea Lat 0.83 0.700.95 11.5 0.75 0.91 o .001

NT-proBNP (pmol/L) 0.83 0.750.98 1,951 0.75 0.86 o .001

NT-proANP (pmol/L) 0.83 0.710.95 584 0.78 0.71 o .001

[(E: Ea Lat)1 (E : Ea Sept)]/2 0.79 0.640.93 12.4 0.74 0.86 .001

E : Vp 0.75 0.610.90 1.87 0.79 0.62 .004

E : Ea Sept 0.74 0.590.90 14.7 0.55 0.95 .006

CI, confidence interval; Se, sensitivity; Sp, specificity.


Table 4. Areas under the receiver-operating characteristic curve (AUC) and optimal diagnostic cut-offs of clinical and

echocardiographic variables in the prediction of congestive heart failure in 18 dogs with dilated cardiomyopathy.

AUC 95% CI Cut-off Se Sp P

Diastolic Functional Class 1.00 1.001.00 2 1.00 1.00 o .001

Respiration rate (per minute) 1.00 1.001.00 34 1.00 1.00 o .001

E : IVRT 0.99 0.951.03 1.88 1.00 0.91 o .001

IVRT (ms) 0.98 0.931.03 43 1.00 0.91 o .001

Aduration : ARduration 0.98 0.931.04 1.25 1.00 0.90 o .001

E : A 0.97 0.891.05 2.0 1.00 0.90 .002

E : Vp 0.95 0.851.05 3.56 0.86 0.90 .002

E : Ea Lat 0.94 0.821.05 9.0 1.00 0.73 .002

NT-proBNP (pmol/L) 0.94 0.831.05 2,492 1.00 0.82 .002

[(E: Ea Lat)1 (E : Ea Sept)]/2 0.94 0.821.06 11.0 0.86 1.00 .002

DTE (ms) 0.91 0.761.06 72 0.86 0.90 .005

Peak E (m/s) 0.89 0.691.09 1.05 0.83 1.00 .008

E : Ea Sept 0.87 0.681.07 13.9 0.71 1.00 .013

LA : Ao 0.86 0.691.03 2.46 1.00 0.73 o .001

HR (per minute) 0.83 0.601.06 135 0.71 1.00 .021

SF (%) 0.79 0.571.00 19 0.71 0.82 .046

See Tables 2 and 4 for key.

1364 Schober et al


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naturally acquired heart disease are sparse and its diag-nostic value largely unproven.m,44 Both Ea and Vp have

been shown to be relatively preload-independent indicesof LV relaxation, making them suitable for correcting

Peak E for the effects of relaxation.18,40 In healthy dogs,Vp and even more Ea are dependent on lengthening

load (load that the myocardium experiences duringrelaxation).15,16,20,21,45 Absence of diastolic abnormali-

ties primarily concerning myocardial relaxation andchamber compliance, typically seen in dogs with MVD,1

are potential reasons why Ea is sensitive to changes inpreload under such circumstances,16,21 thereby limitingthe global use of E : Ea as an index of LVFP and CHF.

In contrast, a close linear relationship between mean left

atrial pressure and E : Ea (r 5 0.83, P o .05) wasreported from studies17 using a dog model of acute LV

volume overload secondary to severe iatrogenic mitralregurgitation. In another study44 involving 39 dogs withnaturally acquired MVD, a correlation between E : Ea

and class of heart failure was documented. Using acut-off of 13.0, E : Ea identified CHF with a sensitivityof 0.80 and a specificity of 0.83, which is similarly

low compared with our findings. Conflicting resultson the use of E : Ea as a reliable index of congestion

and increased filling pressures have been reported inpeople with primary mitral valve regurgitation, with

most studies rejecting the use of E : Ea under suchcircumstances.43,46 In contrast to DCM, the preload de-pendency of Ea in hearts with preserved systolic function

and normal to only mildly affected diastolic function in

concert with disproportionate volume overload maylimit the use of E : Ea in the prediction of CHF in dogs

with MVD.

20,43,45,46

Diagnosis of CHF by Doppler Transmitral FlowPatterns and Class of Diastolic Function

The mitral inflow velocity profile is determined in a

complex manner by multiple factors, which include leftatrial pressure, relaxation, LV systolic pressure, ventric-

ular suction, preload, heart rate, and atrial function.47

The pattern of LV filling determined by Doppler trans-mitral flow is used to noninvasively evaluate LV diastolicperformance and has been described in detail in peo-

ple22,41 and validated in experimental dogs.13,14,47 Earlystages of LV dysfunction most often seen in asymptom-

atic dogs with heart disease (or healthy dogs older than10 years)33 commonly lead to a delayed relaxation trans-

mitral flow pattern.14,22,48 At this stage, LV relaxation isprolonged but filling pressure still normal or only mini-

mally increased.48 With advancement of disease, LVFPrises and overrides the relaxation abnormality dominant

influence on LV filling, leading to a renormalized (yetpseudonormal) flow pattern.14,49 The final stage in the

natural history of LV diastolic dysfunction is restrictivefilling, a flow pattern indicating markedly increased

LVFP, most commonly associated with CHF.49 From aclinical perspective it is of utmost importance to distin-

guish normal from pseudonormal flow for whichvariables such as Aduration : ARduration or E : Ea may

be instrumental.22,41 The results of the present studyproved the clinical usefulness of assessing LV diastolic

function in the DE diagnosis of CHF in dogs with MVDor DCM. Diastolic Functional Class, in particular re-strictive filling, was highly predictive of CHF status.

However, it also became obvious that because of differ-

ences in disease characteristics, LV filling patterns indogs with DCM and MVD need different clinical deci-

sion-making cut-offs and require differentialinterpretation. Whereas all dogs with preclinical DCM

had DE evidence of normal LV diastolic function or de-layed LV relaxation and all dogs with symptomatic

DCM had restrictive LV filling, the situation was less de-finitive in dogs with MVD. Owing to the fundamentalstructural and functional differences between MVD and

DCM it is unlikely that a universal approach to both

conditions can be advanced with regard to interpretationof DE variables. In DCM, there is primarily a systolic

dysfunction-dominant influence on LV filling and LVstiffness is increased.1 Early work done in experimentaldogs and people revealed that the diagnostic ability to

assess LV diastolic function using transmitral flow pat-terns is best when ejection fraction is reduced.13,22 Thiswas confirmed in our study in which 9 DE variables had

an AUC of!0.90 indicating excellent diagnostic perfor-mance in the diagnosis of CHF in dogs with DCM. Incontrast, the volume-overload dominant influence on LV

filling combined with often normal global LV systolic

function, chamber compliance, and relaxation limits thevalue of transmitral flow patterns in the diagnosis ofCHF in the setting of MVD.21,22,42 Pseudonormal and

even restrictive LV filling can both be the sole conse-quence of volume overload.21 True restrictive filling is

characterized by markedly increased E : A, a very short

DTE, and a reduced Peak Ea.

21,49

However, if E : A is

Table 5. Intra- and interobserver measurement vari-

ability of 18 echocardiographic variables assessed in 8randomly selected dogs.

Intraobserver Interobserver

CV (%) Absolute CV (%) Absolute

LADs (cm) 1.41 0.07 1.41 0.06

Ao (cm) 2.50 0.04 4.32 0.08

LADs : Ao 3.53 0.10 4.00 0.11

IVRT (ms) 4.28 2.33 7.20 4.00

Peak E (m/s) 0.48 0.01 3.44 0.03

DTE (ms) 5.21 5.19 11.04 10.75

Peak A (m/s) 1.36 0.01 1.84 0.01

E : A 1.93 0.04 3.92 0.07

E : IVRT 4.64 0.10 10.45 0.22

Aduration (ms) 3.41 3.16 5.61 5.25

ARduration (ms) 3.47 3.05 6.24 5.50

Aduration : ARduration 5.13 0.05 9.10 0.10

Vp (cm/s) 5.60 2.15 3.78 1.41

E : Vp 5.06 0.13 5.06 0.14

Ea Sept (cm/s) 2.25 0.22 4.58 0.45

E : Ea Sept 3.36 0.40 3.18 0.38Ea Lat (cm/s) 1.21 0.12 2.32 0.23

E : Ea Lat 1.59 0.18 2.26 0.26

CV, coefficient of variation.




9/11

increased but DTE is only mildly reduced and Peak Ea is

normal or even increased, the effect of volume (ventric-ular overfilling), and not pressure, is considered themain mechanism in the generation of the filling pattern

termed pseudorestrictive.21 Therefore, the diagnosis ofCHF for an individual dog with MVD requires a step-

wise approach incorporating all available data, and

caution is advised in the isolated use of transmitral flowpatterns for such purpose.21,42,43,46,49

Diagnosis of CHF Using Natriuretic Peptides

Circulating natriuretic peptides are increased in dogs

with CHF because of MVD4,5,7,10,12 and DCM4,912; and

dogs with CHF have higher blood concentrations thandogs with preclinical disease.4,5,811 Results of the present

study indicate that (a) NT-proANP concentrations indogs with decompensated MVD were significantly (Po.05) higher than in dogs with decompensated DCM de-

spite similar concentrations in dogs with preclinical

MVD or DCM; (b) NT-proBNP concentrations in dogs

with preclinical and decompensated DCM were signifi-cantly (Po .05) higher than in dogs with preclinical and

decompensated MVD; (c) both NT-proANP and NT-

proBNP can be used in the prediction of CHF in dogswith MVD although a clinically important overlap be-

tween dogs with preclinical and decompensated diseasewas found; (d) only NT-proBNP but not NT-proANPcan be used in the prediction of CHF in dogs with DCM;

and (e) both natriuretic peptides have less accuracy in the

prediction of CHF as compared with many DE variablesand respiration rate. Our findings with regard to differ-ences in natriuretic peptide concentrations between

compensated and decompensated dogs are similar to

findings from a recent studies in 156 dogs with MVD5,8

and 15 dogs with DCM11 but dissimilar, at least in part,

from findings in 20 Doberman Pinschers with DCM9 and137 dogs with MVD or DCM.4 The identification of rea-sons for such discrepancies was beyond the scope of the

present study but may indicate that more research isneeded to fully appreciate the clinical usefulness and po-

tential incremental value of natriuretic peptide analysisin the diagnosis and management of patients with MVD

and DCM.

Diagnosis of CHF Using Respiration Rate

Respiration rate and the pattern of ventilation have a

long-standing clinical basis for identification of CHF.However, effects of CHF on respiration rate have not yetbeen prospectively studied in dogs to our knowledge.

Respiration rate is controlled by involuntary and volun-tary mechanisms and, among others, correlates closely to

the amount of lung water.r,2 In the present study, respi-

ration rate taken at the hospital outperformed most DE

and laboratory variables in the diagnosis of CHF. A di-agnostic cut-off of 41 and 34 per minute in dogs withMVD and DCM, respectively, was useful in the predic-

tion of presence or absence of CHF with high accuracy

(sensitivity and specificity between 92 and 100%). Theseresults are very encouraging as respiration rate is very

simple to obtain, does not add additional costs, and can

be done repeatedly by instructed owners in the home

environment. The clinical relevance of this finding isseveral-fold: determination of respiration rate might bebeneficial in the early diagnosis of CHF in dogs with

MVD and DCM; it might allow for earlier therapeuticintervention; it could be a very cost-effective tool in the

assessment of success of treatment of CHF; and it might

allow both clinicians and owners to more accurately tai-lor home treatment to a target RR and to avoid excessiveor insufficient diuresis. Although unproven, respiration

rate might also be useful in the discrimination on respi-

ratory distress because of either CHF or primaryrespiratory disease. This study suggests that veterinari-ans should use respiration rate in the diagnosis of CHF

and instruct owners to monitor RR in dogs with MVDand DCM at risk for developing CHF.

Limitations

Certain weaknesses of this study need emphasis. One

limitation is the use of thoracic radiography in the diag-

nosis of CHF because of its limited diagnostic accuracy,owing to a multitude of factors.6,7,25 Pulmonary capillarywedge pressure, a surrogate measure of left atrial pres-

sure and thus filling pressure,50 was not measured in ourdogs. Therefore, the presence or absence of increased

LVFP could only be assumed on clinical and radio-graphic ground and a quantitative relationship between

LVFP and echocardiographic and biochemical variablescould not be determined. Furthermore, because of the

mode of selection of dogs, pretest probability of CHF insymptomatic dogs was high, limiting the more global ap-

plicability of the results of this study to all dogs withclinical signs of CHF. Dogs with CHF were sedated,

which may have influenced central hemodynamics andthus DE variables. The number of dogs studied wassmall, in particular dogs with DCM, rendering the study

underpowered to detect differences among groups.

Moreover, echocardiography and blood sampling weredone only once in each dog, neglecting day-to-day and

circadian rhythms of filling pressure and circulating nat-riuretic peptide concentrations.51,52 In addition,variables and cut-offs used for classification of LV dia-

stolic function were chosen based on recommended flow

patterns for use in people41 and data obtained from aprior pilot studym in dogs with MVD and DCM. Age,

body weight, and heart rate were not specifically consid-ered for diastolic classification and determination of

discrimination limits, although such variables may influ-ence LV diastolic function.33 Sample handlingq including

short-term (o4 weeks) storage at 801C might haveaffected analysis for natriuretic peptides. Finally, priortreatment, in particular administration of furosemide,

could have confounded interpretation of DE and radio-

graphic findings.

Conclusions

Despite these limitations, the clinical implications of

our findings are that in dogs with CHF because of de-generative MVD and DCM, E : IVRT, Diastolic

Functional Class, and IVRT are the Doppler indices best

1366 Schober et al


10/11

predicting presence of left-sided CHF but requiring

disease-specific discrimination limits for clinical use.Respiration rate has a comparably high predictivepower, is simple to obtain, but needs further study to

fully appreciate its diagnostic value. Whether goal-directed transthoracic DE focusing on evaluation of fill-

ing variables and CHF can be used to guide in the

management of patients with MVD and DCM remainsto be determined. If useful under such circumstances,E : IVRT, Diastolic Functional Class, IVRT, and respi-

ration rate may become simple to perform invaluablediagnostic studies for assessing CHF status and optimiz-

ing preload in dogs with left-sided CHF.

Footnotes

a Ultrasonic Doppler flow detector, Model 811-B, Parks Medical

Electronics Inc, Aloha, ORb Sedecal, Sedecal USA, Arlington Heights, ILc Prestige II, GE Medical Systems, Milwaukee, WI

d Digital radiography system EDR-6, Sound-Eklin, Carlsbad, CAe Viewing software E-film, Merge Healthcare, Milwaukee, WIf Vivid 7 Vantage with EchoPac software package version BT05,

GE Medical Systemsg Acepromazine maleate injection, Boehringer Ingelheim Vetmed-

ica Inc, St Joseph, MOh Butorphenol injection, IVX Animal Health Inc, St Joseph, MOi Diana A, Sanacore A, Guglielmini C, et al. Radiographic features

of pulmonary edema associated with mitral regurgitation in dogs.

Vet Radiol Ultrasound 2008;49:213 (abstract)j IDEXX Laboratories, Westbrook, MAk VetSign Canine CardioSCREEN proANP, IDEXX Laboratoriesl VetSign Canine CardioSCREEN NT-proBNP, IDEXX Laboratoriesm Schober KE, Bonagura JD. Doppler echocardiographic assess-

ment of the E : Ea ratio as an indicator of left ventricular filling

pressure in normal dogs and dogs with heart disease. J Vet Intern

Med 2005;931 (abstract)n Sigma Stat, Version 3.5, SPSS Inc, Chicago, ILo Prism 4, Graph Pad Software Inc, San Diego, CAp SPSS Statistics version 9.2, SPSS Incq Farace G, Beardow A, Carpenter C, et al. Effect of shipping tem-

perature on canine N-terminal pro-hormone atrial natriuretic

peptide and N-terminal pro-hormone brain natriuretic peptide.

J Vet Intern Med 2008;22:756 (abstract)r DaCunha DNQ, Pedraza A, Kuenzler R, et al. Trends in respira-

tion rate as an indicator of worsening heart failure. J Card Fail

2007;13 (Suppl 2): S173 (abstract)

Acknowledgments

The authors gratefully acknowledge Kathryn Meurs,

John Mattoon, Nicole Ponzio, Laura Spayd, Agnieszka

Kent, Patty Mueller, Becky Conners, and Richard Coberfor their contributions.

This study was supported by a grant from the Morris

Animal Foundation.

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Appendix 1. Radiographic composite score on conges-tive heart failure (CHF).

Variable Assessment Points

Left atrial enlargement None 0

Mild 1Moderate to severe 3

Pulmonary venous

congestion

None 0

Present 3

Pulmonary infiltrates

compatible with

cardiogenic edema

None 0

Mild interstitial 1

Diffuse interstitial 2

Alveolar 3

Pleural effusion None 0

Yes 1

Final assessment Score 02 CHF not likely

Score 34 CHF possible

Score 44 CHF likely

1368 Schober et al

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