Echocardiographic interpretations result from visual

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1 J Vet Intern Med 2005;9: Quntittive Echocrdiogrphic Evlution of Mitrl Endocrdiosis in Dogs Using Rtio Indices Donld J. Brown, John E. Rush, John McGregor, Jmes N. Ross Jr, Brbr Brewer, nd Willim M. Rnd This study compres M-mode echocrdiogrphic rtio indices (ERIs) in dogs with mitrl regurgittion due to chronic vlvulr disese (CVD/MR) for their bility to discriminte nd quntify ssocited echocrdiogrphic chnges. Weight-bsed M-mode ERIs were determined retrospectively for 2 groups of dogs, norml (n 47) nd CVD/MR (n 76). The CVD/MR group ws further subdivided into those with (CVD/MR B, n 74) nd without (CVD/MR A, n 02) left-sided congestive hert filure (LCHF). ERIs were compred descriptively (summry sttistics) nd lso by receiver-opertor chrcteristic curve res (ROCAs) for their bility to discriminte between groups. Univrite logistic regression (LR) models were used to estimte the odds rtio for ech ERI s predictor of the CVD/MR condition s well s to predict LCHF within the CVD/MR group. A novel ERI (w A), designed to express body size normlized short-xis stroke re, ws sensitive (90%) nd specific (98%) to discriminte between norml nd CVD/MR t cutoff vlue of.8 stndrd devitions (w A 2.). Prediction of LCHF within the CVD/MR group ws more problemtic, but n ERI expressing left tril size (wla) showed 76% sensitivity nd 8% specificity t cutoff vlue of 5.2 stndrd devitions (wla.55). Ours ws descriptive study of echocrdiogrphic ptterns of pthology ssocited with CVD/ MR nd determined which ERIs re sensitive nd specific for CVD/MR nd for LCHF. ERIs normlize echocrdiogrphic dt for body size in dogs nd re well-suited to quntittive descriptions nd nlysis. Key words: Dt interprettion; Hert ntomy; Reference vlues; Retrospective studies. Echocrdiogrphic interprettions result from visul comprisons within n individul (eg, reltionships between wll thicknesses nd chmber dimensions) s well s from quntittive comprisons with estblished vlues from norml nimls. Observble vrition in crdic structure nd function cn be ttributed to severl sources. Intrinsic vrition under norml circumstnces is scribed to the individul s genome nd reltes to fctors such s species, breed, ge, nd specific genetic constitution. Acute or mbient vritions my result from hemodynmic conditions (eg, prelod, fterlod, contrctility, crdic rhythm) tht cn lter the ppernce of n individul s hert from moment to moment. Finlly, persistent pthologic or physiologic crdiovsculr conditions result eventully in remodeling of the hert nd vsculture; the crdic chmbers lter their size, proportions, nd function in response to host of disese conditions. It is desirble but often problemtic to distinguish echocrdiogrphic chnges resulting from these different cuses, nd observer differences re n dditionl source of vrition. Reports of llometric scling methods pplied to M- mode echocrdiogrphic dt hve ppered recently in the veterinry crdiology literture, nd substntil sttisticl nd nlytic benefits hve been demonstrted, compred with liner regressions ginst body weight.,2 Echocrdiogrphic rtio indices (ERIs) exemplify this pproch nd define the proportions of the hert, with the norml ortic From the Deprtment of Clinicl Sciences, Cummings School of Veterinry Medicine t Tufts University (Brown, Rush, McGregor, Ross, Brewer), nd Deprtment of Fmily Medicine nd Community Helth, Tufts University School of Medicine (Rnd), North Grfton, MA. Reprint requests: Donld J. Brown, DVM, PhD, Deprtment of Clinicl Sciences, Cummings School of Veterinry Medicine t Tufts University, 200 Westboro Rod, North Grfton, MA 056; e-mil: donld.brown@tufts.edu. Submitted August 8, 2004; Revised November 9, 2004; Accepted Februry 8, Copyright 2005 by the Americn College of Veterinry Internl Medicine /05/ /$.00/0 root dimension s n internl yrdstick, effectively normlizing for body size. Ech index lso hs direct visul interprettion (ie, ech crdic dimension or re in terms of the number of ortic dimeters or res, respectively). Weight-bsed ERIs re clculted by estimting the ortic root dimension s liner function of the cube root of body weight (W / ), s opposed to the mesured ortic root dimension. The choice of the exponent (⅓) is not rbitrry nd enforces dimensionl consistency between the predictor (body weight) nd M-mode mesurements.,2 Previously, the lck of body size independent method hs imposed substntil limittions on echocrdiogrphic comprisons nd nlyses mong dogs. The purpose of this study ws to compre M-mode weight-bsed ERIs for their bility, reltive to ech other, to quntify echocrdiogrphic bnormlities ssocited with chronic mitrl regurgittion (MR) due to endocrdiosis in dogs. This report does not seek to estblish ERI criteri to dignose MR due to chronic vlvulr disese (CVD/MR), but it quntifies crdic structurl nd functionl bnormlities in wy tht hs not been possible previously (ie, independently of body size). Additionlly, predictive reltionships re sought between the ERIs nd the occurrence of left-sided congestive hert filure (LCHF) in CVD/MR. Mterils nd Methods Textul records of the electronic crdiology dtbse of Tufts University School of Veterinry Medicine were exmined retrospectively for suitble cnine echocrdiogrphic cse dt. The dtbse includes dogs exmined in the course of routine veterinry crdiology prctice, well niml screening, nd clinicl crdiovsculr reserch. Approximtely,000 records were reviewed to obtin dogs meeting the inclusion criteri. Physicl exmintions, echocrdiogrms, mesurements, nd interprettions either were performed by or directly verified by one of three ttending ACVIM Crdiology Diplomtes (DJB, JER, or JNR; subsequently designted crdiologists). The crdiologists were directly responsible for group clssifiction t the time of exmintion nd without prior knowledge of study objectives for this report (norml or CVD/MR with or without LCHF); they were not blinded to the niml s stte of helth t the time. In some nimls, echocrdiogrphic recordings nd mesurements ctully were performed by n ex-

2 Rtio Indices in Mitrl Endocrdiosis 54 Tble A. Norml dogs: popultion summry. Breeds n Weight (kg) Age (yers) All Gret Dne Golden Retriever Lbrdor Retriever Miscellneous nd mix [26.8, ] [64.55, ] [0.9, ] [.82, ] [4.77, ] [6.87, ] [4.94, ] [2.79, ] [7.50, ] [7.55, ] Age nd body weight shown s men stndrd devition [medin, rnge]. perienced crdic ultrsound technicin (BB) or one of three crdiology residents in trining. Chrcteristics of the study popultion (numbers in ech group, breed distributions, summry sttistics for ge nd weight) re presented in Tbles A D; breeds re summrized seprtely if represented by t lest individuls. M-mode recordings were performed from the right prsternl window, with 2-dimensionl echocrdiogrphy (2DE) guidnce, using the short-xis imge but with the long-xis confirmtion of crdic orienttion. Mesurements were performed in ccordnce with the Americn Society of Echocrdiogrphy stndrds nd included left ventriculr internl dimension (LVID), interventriculr septum (IVS), nd left ventriculr wll (LVW) in distole (LVIDd, IVSd, LVWd) nd systole (LVIDs, IVSs, LVWs). The stndrd ortic root (Ao, end distole) nd left tril (LA, end systole) dimensions lso were mesured (ie, M-mode cursor through the ortic root). It ws usul for M-mode dt to be verged from severl crdic cycles, but only verged dt set ws included from ech ptient for those hving multiple echocrdiogrphic exmintions. Exclusions from the study included serious complicting medicl conditions, obesity, cchexi, nd filure to record complete M-mode dt set. Additionl exclusions included studies described s difficult or cursory becuse of ptient conformtion or lck of coopertion. The dogs were not sedted, nd ech received crdiovsculr physicl exmintion long with 2DE, 2DE-guided M-mode, nd Doppler echocrdiogrphy studies. Norml dogs included in this study were presented either s norml individuls with no clinicl bnormlities or subsequently were determined to hve no cliniclly relevnt crdiovsculr bnormlities by the ttending crdiologist. hd documented history of cliniclly relevnt hert disese, systemic disese, or mediction dministrtion (eg, doxorubicin) tht my hve ffected the outcome of echocrdiogrphic interprettions. Ech individul ws in norml sinus rhythm or norml sinus rrhythmi nd ws thought to hve norml crdiovsculr physicl exmintion nd norml echocrdiogrphic studies. Dobermn Pinscher nd Boxer breeds were excluded from the norml group becuse they were overrepresented in the originl smple popultion, nd there ws concern tht these breeds might be typicl, reltive to other dogs, such tht inclusion might bis the results of norml index clcultions.,4,5 An ge restriction (.5 yers) ws pplied to this norml group. Inclusion in the CVD/MR group ws bsed on n pproprite signlment nd physicl exmintion, including systolic murmur over the left precordium, nd chrcteristic Doppler echocrdiogrphic findings confirming MR. 2DE exmintion fcilitted the confirmtion of mitrl vlve thickening or prolpse, but inclusion did not require n interprettion of left-sided crdic dilttion or volume overlod by the crdiologist. Hence, the inclusion criteri for this group were very sensitive nd specific for the disese condition nd would be expected to include individuls without discernible bnormlities of crdic size or proportion. This group ws further divided into dogs without LCHF (CVD/MR A) nd those with prior or cute LCHF (CVD/MR B) on the bsis of the crdiologist s direct ssessment of historicl, physicl, rdiogrphic, nd echocrdiogrphic evidence. Dogs with CVD/MR but without ny physicl or historicl evidence of respirtory compromise (eg, dyspne, effort, tchypne, coughing, crckles, rles) were Tble B. CVD/MR dogs: popultion summry. Breeds n Weight (kg) Age (yers) LCHF All Airedle Terrier Begle Bichon Frisé Boston Terrier Cocker Spniel Cockpoo Chihuhu Cvlier King Chrles Spniel Dchshund Lhs Apso Mltese Pekinese Pomernin Poodle Schnuzer Shetlnd Sheepdog Shih Tzu Yorkshire Terrier Miscellneous nd mix [8.8, ] [2.64, ] [9.09, ] [7.4, ] [8.7, ] [2., ] [7.27, ] [.4, ] [8.9, ] [6.6, ] [8.09, ] [.6, ] [8.8, ] [4.55, ] [5.68, ] [7.05, ] [6.55, ] [7.55, ] [.64, ] [4.9, ] [.26,.2 7.4] [.4, 8..08] [.4, ].47.5 [.4, ].2.60 [2.87, ] [.8, ] [.85, ] [0.5, ] [7.49, ] [.8,.2.7].7.28 [.24, ] [.2, ] [7.20, ] [.24, ] [2.52, ] [2.08, ] [.08, ] [2.6, ] [.54, ]. 2.7 [.8, ] CVD/MR, mitrl regurgittion due to chronic vlvulr disese. Age nd body weight shown s men stndrd devition [medin, rnge]. LCHF number with left-sided congestive hert filure.

3 544 Brown et l Tble C. CVD/MR dogs: tretment summry. Tble D. CVD/MR dogs: usculttion summry. CVD/MR A (n 02) CVD/MR B (n 74) CVD/MR A (n 02) CVD/MR B (n 74) ACEI Furosemide Hydrochlorothizide Spironolctone Digoxin Nitroglycerin ointment Nitroprusside infusion Hydrlzine -Blocker Diltizem Oxygen 2/5 (2/50) 2/4 (2/4) 0/ (0/) /5 (/5) 42/72 (57/97) 57/74 (77/00) /6 (/22) 9/27 (2/6) 0/20 (4/27) 5/6 (7/8) 5/ (7/4) /2 (4/) 6/0 (8/4) / (4/4) 8/ (24/5) I/VI murmur II/VI murmur III/VI murmur IV/VI murmur V/VI murmur VI/VI murmur S gllop () 2 (2) (0) 25 (25) 4 (4) 2 (2) () 8 () 22 (0) 9 (5) 2 () 0 (4) CVD/MR, mitrl regurgittion due to chronic vlvulr disese. Number (%). ACEI, ngiotensin converting enzyme inhibitor; CVD/MR, mitrl regurgittion due to chronic vlvulr disese. Preexmintion/postexmintion (% preexmintion/% postexmintion). ssigned to the CVD/MR A group (without LCHF). Assignment to the LCHF group (CVD/MR B) required rdiogrphic determintion by the crdiologist nd estblishment of LCHF due to CVD/MR s the cuse of respirtory signs. Dogs for which no determintion could be mde relibly were excluded from the study, s were dogs with history of LCHF but unccompnied by thorcic rdiogrph confirming the condition. Medicl tretments nd usculttory findings re summrized in Tbles C nd D. Numbers nd percentges of dogs receiving ech mediction t the time of the echocrdiogrphic exmintion re tbulted, s re the number nd percentge of dogs for which ech mediction ws recommended s result of the crdiovsculr ssessment. The drugs present t the time of exmintion my ffect the outcome of echocrdiogrphic mesurements, wheres the therpeutic recommendtions reflect the crdiologist s ssessment of CVD/MR disese severity. ERI clcultions detiled in previous report re reiterted in Tble 2. Weight-bsed ERIs of this report (prefixed with w throughout) derive from n estimte of the M-mode ortic root dimeter, Ao w kw /, where W is the body weight in kilogrms, nd k is speciesdependent constnt, in the dog. The multiplictive constnt cts solely to enhnce the visul interprettion of the ERIs nd hs no effect on the sttisticl evlutions presented. Weight-bsed ERIs re obtined by dividing the corresponding rw M-mode mesurement by Ao w nd hve direct visul interprettion (ie, ech crdic dimension expressed s number of weight-bsed ortic dimeters). ERIs not referenced to the individul s body weight re referred to s reltive indices. Exmples include the well-known frctionl shortening (FS) nd ejection frction; the nomenclture used in this study includes the word frctionl or frction nd the letter F in the designtion of ech. Results of hypothesis testing re reported in some situtions, nd significnce ws scribed t P.05. ERI vlues for ech group re tbulted s the men stndrd devition, with the medin nd rnge lso shown. These sttistics were used descriptively (ie, to summrize group ERI chrcteristics); no sttisticl tests were used inppropritely tht depended on specific probbility distribution type. Similrly, ERI vlues for bnorml groups re reported in stndrdized formt (seris), computed s follows, where X is the ERI of interest, is the stndrd devition, the subscript n refers to vlues from the norml group, nd the overbr indictes the men vlue: X X n n This ws done s generl mens of rescling ERI dt, so tht seri units re ll in terms of stndrd devitions of the norml group, but this does not necessitte Gussin (norml) distributions. Distributions were tested for normlcy by the Kolmogorov-Smirnov test with Lilliefors correction or by the Shpiro-Wilks test if n 50. Differences in index distributions between 2 groups were evluted by the Mnn-Whitney U-test nd were cross-checked by independent t- tests when norml distributions could be ssumed. ERIs were compred for their bility to discriminte between group pirs, by mens of receiver-opertor chrcteristic curves, nd were summrized s the re under the curve (ROCA); the vlue of ROCA cn rnge from 0.5 (no discrimintion) to.0 (complete discrimintion). Univrite logistic regression (LR) models were used to estimte the odds rtios of individul ERIs for distinguishing the norml nd CVD/MR groups s well s for predicting LCHF within the CVD/MR group. LR model constnts were corrected for differences in group size (Appendix). Consequently, the LR models estimte conditionl probbility (ie, given tht the test subject is member of one of the 2 groups under considertion nd hs equl prior probbility of group membership). seris were used in LR model clcultions, s this pproch llows direct comprisons of the model prmeters nd odds rtios. Within ech group, body weight nd ge were tested for correltion with ech ERI (Spermn rnk correltion, ), nd selected correltions re reported. Where pproprite (ie, norml distributions), correltions were cross-checked by the Person product moment correltion coefficient. Sttisticl clcultions were ccomplished by mens of SPSS softwre. b Results Tble A depicts group-dependent summry sttistics for the ERIs nd indictes there were significnt differences between the norml nd CVD/MR groups for every weightbsed ERI, except for wao nd wivsd; reltive ERIs were different, except for systolic frctionl wll thickness nd re (FWTs, FWAs) nd frctionl chnge in wll re (F WA). The Stndrdized CVD/MR column represents these sme ERI bnormlities for the bnorml group in terms of stndrd devitions from the norml group nd is summrized grphiclly in Figure. Box plots of Figure hve been sorted ccording to bsolute men vlue, most bnorml ERI t the bottom, nd with 2 stndrd devition boundries indicted by dotted lines to ssist interprettions. Stndrdized FS, for exmple, verged only.6 stndrd devitions from norml in the CVD/MR group, rnging from. to 6. nd showing substntil overlp with the norml group. Stndrdized stroke re (w A), on the other hnd, verged 5.85 stndrd devitions from norml nd rnged from 0.8 to 7.95, spnning 8.78

4 Rtio Indices in Mitrl Endocrdiosis 545 Tble 2. Description nd clcultion of M-mode echocrdiogrphic rtio indices. ERI Clcultion wivsd IVSd/Ao w wlvidd LVIDd/Ao w wlvwd LVWd/Ao w wivss IVSs/Ao w wlvids LVIDs/Ao w wlvws LVWs/Ao w wao Ao m /Ao w wla LA/Ao w wlvodd (IVSd LVIDd LVWd)/Ao w wlvods (IVSs LVIDs LVWs)/Ao w wwtd (IVSd LVWd)/(kW ⅓ ) wwts (IVSs LVWs)/Ao w w A (LVIDd 2 LVIDs 2 2 )/ Ao w wwad (LVODd 2 LVIDd 2 2 )/ Ao w wwas (LVODs 2 LVIDs 2 2 )/ Ao w FS (LVIDd LVIDs)/LVIDd FWTd WTd/LVODd FWTs WTs/LVODs F A (LVIDd 2 LVIDs 2 )/LVIDd 2 FWAd (LVODd 2 LVIDd 2 )/(LVODd 2 ) FWAs (LVODs 2 LVIDs 2 )/(LVODs 2 ) F WA (wwas wwad)/wwas EF (LVIDd LVIDs )/LVIDd Description Index of interventriculr septl thickness, distole Index of left ventriculr internl dimension, distole Index of left ventriculr wll thickness, distole Index of interventriculr septl thickness, systole Index of left ventriculr internl dimension, systole Index of left ventriculr wll thickness, systole Index of ortic root dimension Index of left tril dimension Index of left ventriculr outer dimension, distole Index of left ventriculr outer dimension, systole Index of combined septl nd left ventriculr wll thickness, distole Index of combined septl nd left ventriculr wll thickness, systole Index of chnge in left ventriculr internl re, i.e., short-xis stroke re Index of left ventriculr short-xis myocrdil wll re, distole Index of left ventriculr short-xis myocrdil wll re, systole Frctionl shortening. Reltive index of LV internl wll motion Frctionl LV myocrdil wll thickness, distole. Reltive index of LV wll thickness in distole Frctionl LV myocrdil wll thickness, systole. Reltive index of LV wll thickness in systole Frctionl chnge in LV internl re. Reltive index of LV wll motion Frctionl LV myocrdil wll re (short xis), distole. Reltive index of LV wll thickness in distole Frctionl LV myocrdil wll re (short xis), systole. Reltive index of LV wll thickness in systole Frctionl chnge in LV myocrdil wll re (short xis). Reltive index of LV shortening in the longitudinl (long xis) direction Ejection frction. Reltive index of LV volume chnge LV, left ventricle; IVS, interventriculr septum; LVID, left ventriculr internl dimension; LVW, left ventriculr wll; LVOD, left ventriculr outer dimension; LA, left tril dimension; Ao w, weight-bsed ortic root dimension clculted s kw ⅓, where W is body mss (kg) nd k is species-dependent constnt equl to for dogs. Letters s nd d refer to systolic nd distolic determintions, respectively. stndrd devitions with nerly 2.5 times s much observble vrition s FS. For 5% of the CVD/MR dogs (9 of 76), w A ws the most bnorml ERI in units of stndrd devitions from the norml group. Stndrdized summry sttistics for the CVD/MR group re compred for those with (CVD/MR B) nd without LCHF (CVD/MR A) in Tble B, where ll vlues re expressed in terms of stndrd devitions from the norml group. LCHF ws ssocited with significnt differences from the CVD/MR A group for mny of the ERIs, including greter vlues for ventriculr distolic internl (wlvidd) nd outer (wlvodd) dimensions, LA dimension (wla), nd short-xis stroke re (w A) in prticulr. Somewht unexpectedly, the systolic internl dimension (wlvids) ws not different between these 2 groups. The ROCA quntifies globlly the cpcity of the individul ERIs to discriminte between groups; the ROCA vlue cn rnge from 0.5 (no discrimintion) to.0 (complete discrimintion). Severl likely ERIs confer substntil discrimintion between the CVD/MR nd norml groups by this criterion (Tble 4A), including left ventriculr distolic internl (wlvidd, ROCA.956) nd externl (wlvodd, ROCA.950) dimensions, long with wla (ROCA.954). Body size normlized short-xis stroke re (w A, ROCA.976) ws the most discriminting ERI quntittively, but it ws not significntly better thn the other listed. Two other novel indices lso were highly discriminting, wwad (ROCA.889) nd wwas (ROCA.924), which were formulted to represent short-xis left ventriculr myocrdil wll re, normlized for body size, in distole nd systole, respectively (ie, hypertrophy). The ERIs were less efficcious for distinguishing between dogs with (CVD/MR B) nd without (CVD/MR A) hert filure within the CVD/MR group. The most discriminting ERI ws wla (ROCA.876), with w A 2nd best by substntil mrgin (ROCA.806). End-systolic ventriculr dimension (wlvids) ws not predictive of LCHF. Univrite LR models lso were clculted using stndrdized vlues of individul ERIs s predictors, using model prmeters B nd C reported in Tbles 4A (norml versus CVD/MR) nd 4B (CVD/MR group A versus B). P e (B seri C) This LR eqution estimtes the probbility (P) of group membership, where seri represents the vlue of the individul s ERI, stndrdized with respect to the norml group. For exmple, the gretest odds rtio mgnitude ws tbulted for w A (5.6), reltive to other ERIs, nd indictes the gretest increse in CVD/MR probbility for ech stndrd devition of increse. Optiml discrimintion ctully occurs when there is equl probbility of group membership

5 546 Brown et l An optiml cutoff vlue of stndrd devitions for w A indictes substntil degree of volume overlod before LCHF becomes likely nd is very ner the verge vlue of the CVD/MR group by chnce (Fig 2B D). Spermn rnk correltions within the norml group identified minor but sttisticlly significnt ssocitions between body size nd 2 of the ERIs (wlvodd, 0.0; w A, 0.99). Three ERIs were mrginlly ssocited with ge in the norml group (wwts, 0.0; FWTs, 0.26; FWAs, 0.25). The issue ws further ddressed by subdividing the norml dogs into lrge (n 26) nd smll (n 2) breed subgroups nd subsequently evluting the ERI distributions for sttisticl differences. Men body weight of the lrge breed subgroup ws kg ( ), wheres the smll breed subgroup consisted only of breeds tht were plusible cndidtes for CVD/MR nd with body weight of.6.89 kg ( ) (ie, no overlp of body size with the lrge breed subgroup). Only w A showed sttisticlly detectble difference between the subgroups, with men of for the smll breed subgroup nd men of for the lrge breeds (6.5% different or 0.52 stndrd devitions). Fig. Stndrdized echordiogrphic rtio index (ERI) distributions of the mitrl regurgittion due to chronic vlvulr disese (CVD/MR) group. Box plots depict ERI distributions of the CVD/MR group, stndrdized with respect to the norml group (men 0.0; SD.0). Dotted verticl lines represent 2.0 stndrd devitions with respect to the norml group, nd CVD/MR ERI distributions re shown sorted by bsolute men displcement. The ltitude of ech stndrdized ERI quntifies its sensitivity to echocrdiogrphic chnge in terms of the mount of vrition expected within the norml group. (P.5), corresponding to w A cutoff vlue of.796 stndrd devitions (w A 2.066), tbulted in the Test Vlue column. At this vlue of w A, the ERI discrimintes between the norml nd CVD/MR groups with the sensitivity (0.90) nd specificity (0.979) s tbulted, determined from the ctul group dt. Probbility distribution functions (PDFs) (Fig 2A), plots of sensitivity nd specificity s function of cutoff vlue (Fig 2A), receiveropertor chrcteristic curves (ROCA; Fig 2C), nd LR model predictions (Fig 2D) re shown for w A, exemplifying its discrimintory vlue for differentiting between the norml nd CVD/MR groups. Other ERIs demonstrting efficcy for differentiting between the CVD/MR groups were wlvidd, wla, wlvodd, nd wwas, s previously indicted by the ROCA vlue. By comprison, ERIs did not discriminte s well between CVD/MR B nd A (ie, CVD/MR with nd without LCHF). Nevertheless, n odds rtio of.70 for wla indictes the substntil predictive vlue of wla size for LCHF. The optiml cutoff vlue of 5.7 stndrd devitions for this ERI (wla.545) ws 75.7% sensitive nd 8.4% specific for LCHF within the CVD/MR group. The next best ERI (w A) ws only 66.2% sensitive nd 75.5% specific for LCHF. Other ERIs showed more discriminting odds rtios thn w A (wlvidd, wlvodd, wlvods, wwad, FS, FWTd, F A, FWAd), but distributions were not s well seprted, leding to lower vlue for ROCA. Discussion The principl dvntge of weight-bsed ERIs is tht they cn be used prcticlly for body size normlized echocrdiogrphic comprisons by mens of llometric scling.,2 The procedure circumvents severl sttisticl fults of previous methods (ie, liner regressions ginst body weight) nd lso lends itself to quntittive methods for echocrdiogrphic clssifiction nd discrimintion mong ptient groups. ERIs quntify echocrdiogrphic proportions in comprison with body size (ie, weight-bsed indices) or with other crdic structures (ie, reltive indices). The full benefit of the pproch is most pprent in conjunction with computer-ssisted index clcultions nd grphic disply (eg, by n Excel c spredsheet). The objective of this study ws to compre M-mode ERIs for their reltive bility to quntify echocrdiogrphic chnges ssocited with CVD/MR in dogs; this ws ccomplished descriptively by compring ERI summry sttistics nd distributions, odds rtios, nd ROCAs. Although the bility of ERIs to distinguish mong ptient groups my be expected to depend on study inclusion/exclusion criteri, comprisons mde mong the ERIs re reltively independent of these considertions. Mny of the echocrdiogrphiclly detectble remodeling chnges ssocited with chronic MR re well known nd hve been described qulittively nd semiquntittively. 6,7 The current study recpitultes essentil bnormlities known to occur with CVD/ MR, such s LA nd ventriculr dilttion (ie, incresed wla, wlvidd) nd recsts them into the body size independent formt of ERIs. ERI dt of this report lso were presented rescled (ie, s stndrdized vlues with respect to the norml group, Tbles A, B). This pproch conveys directly the reltive sensitivity of ech ERI to the echocrdiogrphic chnges typicl of CVD/MR nd, consequently, the bility of ech to quntify these chnges (Fig ). FS, for exmple, is rel-

6 Rtio Indices in Mitrl Endocrdiosis 547 Tble A. ERI summry sttistics for norml nd CVD/MR groups. Norml CVD/MR Stndrdized CVD/MR wivsd wlvid b wlvwd b wivss b wlvids b wlvws b wao wla b wlvodd b wlvods b wwtd b wwts b w A wwad b wwas b FS b FWTd b FWTs F A b FWAd b FWAs F WA EF b [0.4, ] [.65,..86] [0.4, ] [0.60, ] [.08, ] [0.62, ] [0.99, 0.8.4] [.0, ] [2.46, ] [2.27, ] [0.86, 0.68.] [.22, ] [.44, ] [.44, ] [4.06, ] [0.4, ]* [0.4, ] [0.5, ] [0.56, ]* [0.57, ] [0.78, ] [0., ] [0.7, ]* [0.45, ] [2.,.44.6]* [0.44, ]* [0.70, 0.8.6]* [.6, ]* [0.7, ]* [.0, ] [.44, ]* [.04, ]* [2.6, ]* [0.89, 0.59.] [.4, ].9.2 [.0,.2 7.]* [4.7, ] [5.45, ]* [0.45, ] [0.0, ] [0.55, ] [0.70, ] [0.5, ] [0.80, ] [0.5, ] [0.84, ]* [0.2, ] [.6,.8.5] [0.6, ] [.5, ] [0.6, ] [.46, ] [0.9, 2..70] [4.5, ] [.22,.0 9.7] [2.7,.6 9.9] [0., ] [.7, ] [4.97, ] [2.22, ] [2.60, ].6.27 [.64,. 6.].5. [.49, ] [0.7, ] [.59, ] [.54, ] [0.4, ] [0.25, ] [.5,.47.4] ERI, echocrdiogrphic rtio index; CVD/MR, mitrl regurgittion due to chronic vlvulr disese; IVS, interventriculr septum; LVID, left ventriculr internl dimension; LVW, left ventriculr wll; Ao, stndrd ortic root; LA, left tril; LVOD, left ventriculr outer dimension; WT, wll thickness; WA, wll re; FS, frctionl shortening; FWT, frctionl wll thickness; FWA, frctionl wll re; EF, ejection frction. Dt shown s men stndrd devition [medin, rnge]. Stndrdized column represents dt in terms of stndrd devitions of the norml group. b Significnt differences between norml nd CVD/MR groups. * Significntly nonnorml distribution. tively insensitive to CVD/MR chnges compred with distolic internl dimension (wlvidd) or stroke re (w A). The ltter (w A) is novel index of volume overlod (w A) tht ws mong the most sensitive nd specific of M-mode ERIs for quntifiction of the CVD/MR condition. The purpose of this index ws not erly detection of CVD/ MR, which is redily ccomplished by usculttion in conjunction with Doppler echocrdiogrphy. Seril echocrdiogrphic evlution of dogs with CVD/ MR is common prctice in veterinry crdiology, but it is without proven benefit for the timing of medicl or surgicl interventions. Our study reltes ERI bnormlities of CVD/MR to the probbility of LCHF in terms of LR models. Most predictive of LCHF ws wla, n ERI very similr to the better-known rtio of LA dimension to the mesured ortic root (LA of our previous report). A wla test vlue of 5.2 stndrd devitions (wla.55) ws the optimlly discriminting cutoff vlue nd ws 76% sensitive nd 8% specific for LCHF within the CVD/MR group; other ERIs were substntilly less predictive. The LR models tbulted lso cn be used to estimte the risk of LCHF. A dog with CVD/MR nd wla.7 ( 6.7 stndrd devitions), for exmple, hs n estimted probbility of /( e 0.8 ) 0.69 of LCHF, where the vlue of the logistic discriminnt function is (Tble 4B, B seri C). Hence, the model estimtes tht 69 dogs of 00 with CVD/MR nd left trium this lrge will hve LCHF. However, this clcultion is not intended s mens of LCHF determintion, which is normlly ccomplished by rdiogrphic nd clinicl evlution. Fctors determining the discrimintory vlue of the LR model re the bsolute mgnitude of prmeter B, which directly estblishes the odds rtio, nd C/B, which reltes to the degree of seprtion of the distributions. Use of the stndrdized vlues for ech ERI llows meningful direct comprisons of the odds rtios nd tbulted prmeters. The clcultion from the previous prgrph indictes tht dog with CVD/MR nd wla 6.7 stndrd devitions is t considerble risk for LCHF, but clinicl signs my not be present. The clinicin might be inclined to initite ngiotensin-converging enzyme inhibition (ACEI) therpy empiriclly with the intent of forestlling the onset of clinicl signs or improving longevity. This ppliction, however, is not justified by our results or by those of existing clinicl trils demonstrting the benefits of ACEIs for CVD/MR fter the onset of LCHF. However, our study suggests tht met-nlyses of erlier clinicl trils might prove useful in determining echocrdiogrphic criteri for the initition of therpy in terms of ERIs. 8 There re importnt limittions of our study inherent to its design, but these re not expected to ffect gretly on the chosen objectives. Perhps the most importnt of these is tht the bility of ech ERI to discriminte mong groups depends on the prticulr probbility distributions tested (eg, norml versus CVD/MR, CVD/MR A versus B) (ie,

7 548 Brown et l Tble B. B). Stndrdized ERI summry sttistics for CVD/MR group: no LCHF (CVD/MR A) versus LCHF (CVD/MR wivsd wlvidd b wlvwd wivss b wlvids wlvws wao b wla b wlvodd b wlvods b wwtd wwts b w A b wwad b wwas b FS b FWTd b FWTs F A b FWAd b FWAs F WA EF b Stndrdized CVD/MR A [0.4, ] [2.68, ]* [0.2, ]* [0.87, ] [0.59, ].5.2 [.9, ]* [0.50,.8.70] [2.85, ]* [2.49,.0 7.0]* [.92, ]* [0.27, ].66.5 [.56, ] [.5, ]* [.67, ] [2.20, ]*.2.08 [.45,..89] [.2, ] [0.7,.68.78] [.4,.40.24]*.26.7 [.24, ] [0.4, ] [0.4, ]* [.9, ]* Stndrdized CVD/MR B [0.05, ] [4.74, ]* [0.7,.92.6] [.56, ].2 2. [.06, ] [.7, ] [0.05, ] [7.6, ] [4.7, ].2.87 [2.97, ] [0.4,.86.68] [2.2, ] [7.2, ]* [2.9, ] [.25, ]* [2.06,. 6.] [.9, ] [0.40,. 5.27]*.78.5 [.94,.7 4.4] [.99, ] [0.45,.95.80]* 0..7 [0.0, ] [.82,.2.4]* Abbrevitions re explined in the st footnote to Tble A. Dt shown s men stndrd devition [medin, rnge]. Stndrdized columns represent dt in terms of stndrd devitions of the norml group. b Significnt differences between CVD/MR A nd CVD/MR B groups. * Significntly nonnorml distribution. the severity of dogs included in ech group). Hence, the bsolute vlues for sensitivity, specificity, ROCA, LR prmeters, nd computed probbilities re specific to the inclusion/exclusion methods s well s the bises introduced by including only the dogs presented to our specilty prctice t Tufts. Comprisons mong the ERIs (specificity, sensitivity), however, re meningful becuse they re mde t the sme severity (ie, in the sme dogs). CVD/MR dogs were selected retrospectively for our study using sensitive nd specific criteri (eg, signlment, physicl exmintion, Doppler confirmtion) independent of M-mode or 2DE criteri, which could not be used. Among quntittive M-mode nd 2DE evlutions in veterinry crdiology, only the llometric methods typified in this report hve been evluted for body size independence nd scrutinized for sttisticl vlidity, to our knowledge. Consequently, no quntittive M-mode or 2DE criteri could be used s vlid inclusion/exclusion criteri of the CVD/MR group other thn the ERIs themselves; the ltter would result in circulr rgument, nd the ERIs used in the selection criteri would be expected to show fllciously exggerted specificity nd sensitivity in reltion to the others. Consequently, the CVD/MR group included not only dogs with crdic size nd proportions considered norml by the crdiologists, but lso the echocrdiogrphic extremes of crdiology referrl prctice. This prctice hs no impct on the study objectives s defined, nd prospective design would not be expected to enhnce interprettions pprecibly. Tble A indictes tht the norml group ws substntilly different from the CVD/MR group with respect to body size, ge, nd breed distribution. This limittion ws thoroughly evluted nd determined to be minor one tht did not ffect our study objectives. The ERIs showed miniml body size dependency, nd restriction of the norml group to CVD/MR breeds nd the sme weight rnge s the CVD/MR group hd lmost no detectble effect on the norml ERI distributions or the interprettions given. Norml smll breed dogs showed slight but detectbly greter men stroke re (w A) thn lrge breeds, which exggertes the pprent sensitivity of this ERI for the CVD/MR condition. Similrly, the ERIs showed miniml ge dependency within the norml group; this group ws limited to dogs older thn.5 yers to void potentil ERI ge dependencies in young nimls. In contrdistinction, severl ERIs showed both ge nd body size dependency within the CVD/MR group (dt not shown). These correltions re scribed principlly to expected dependencies of the disese process (ie, ge-relted progression nd the wellknown ssocition of CVD/MR severity with smller dogs). 6 Miniml breed dependency of llometriclly normlized echocrdiogrphic mesurements hs been demonstrted previously when certin typicl breeds re excluded from nlyses. 2 The potentil for ERI differences in specific breeds prompted us to exclude Dobermn Pinschers, Boxers, nd sight hounds from our norml group. 4,5 Complete evlution of this issue would require sttisticl compri-

8 Rtio Indices in Mitrl Endocrdiosis 549 Tble 4A. Discrimintion between norml nd CVD/MR groups. ROCA B b C c Sensitivity Specificity Test Vlue d Rtio e Odds wlvidd wlvwd wivss wlvids wlvws wla wlvodd wlvods wwtd wwts w A wwad wwas FS FWTd F A FWAd F WA EF [.8] [0.429] [0.65] [.2] 0.74 [0.670].477 [.72].420 [2.727].088 [2.446] [0.88] 0.85 [.8].796 [2.066] [4.054].84 [4.694] [0.92] [0.2] 0.70 [0.625] 0.72 [0.54] 0.0 [0.40] 0.74 [0.766] Abbrevitions re explined in st footnote to Tble A. ROCA, re under receiver-opertor chrcteristic curve. b B is the coefficient of the stndrdized ERI (stndrdized with respect to norml group). c C is the logistic regression constnt, corrected to equl group size (prior probbility.5). d Test vlue is the equl probbility cutoff vlue of the logistic regression model: presented s stndrdized ERI vlue [ctul ERI vlue]. Model specificity nd sensitivity re computed t the test vlue shown. e Odds rtio e B, where e is the nturl logrithm bse, The conditionl probbility of CVD/MR (4A) or LCHF (4B) is estimted by the logistic regression eqution /( e (B seri C) ), where seri is the stndrdized vlue for n individul dose. Only significnt models re shown. sons of distributions for ech ERI nd mong breed groups. This pproch ws beyond the scope of our study, but the remrkble similrities of the norml lrge nd smll breed subgroups strongly support the clinicl ppliction of ERIs for wide rnge of body size nd breed. Other echocrdiogrphic methods for CVD/MR quntifiction hve been evluted previously. One of the simplest methods is by determintion of mitrl regurgitnt jet size nd extent by color flow Doppler (CFD), either subjectively (ie, to 4) or quntittively by plnimetry. 9,0 Such methods my be highly dependent on technique nd dt cquisition settings s well s hemodynmic fctors pertining to flow geometry nd fluid entrinment by the regurgitnt jet.,2 Wheres detection of MR by CFD is very sensitive nd specific, jet size determintion is semiquntittive method t best. Tble 4B. Discrimintion between CVD/MR A (no LCHF) nd CVD/MR B groups (LCHF). ROCA B b C c Sensitivity Specificity Test Vlue d Odds Rtio e wlvidd wlvwd wivss wao wla wlvodd wlvods wwts w A wwad wwas FS FWTd F A FWAd EF [2.97] 0.57 [0.448].7 [0.74] 0.27 [.08] 5.7 [.545].595 [.0] [2.675] 2.0 [.467] [.92] 2.40 [4.89].0 [5.682].65 [0.452].580 [0.294].522 [0.694].67 [0.499].4 [0.825] Abbrevitions re explined in st footnote to Tble A. Footnotes e re explined in Tble 4A.

9 550 Brown et l Fig 2. Probbility distribution functions (PDFs), sensitivity, specificity, receiver-opertor chrcteristic curves (ROCAs), nd logistic regression (LR) models for selected echordiogrphic rtio indices (ERIs). (A) Distributions for novel ERI of short-stroke re (w A). Stylized (Gussin) PDFs for the norml nd mitrl regurgittion due to chronic vlvulr disese (CVD/MR) groups re bsed on the estimted men nd stndrd devition of ech. Specificity nd sensitivity, determined from ctul group dt, lso re plotted s functions of the cutoff vlue of the ERI in units of stndrd devitions from the norml group. (B) Similr plots re shown for the CVD/MR group to depict the cpcity of left tril size (ERI wla) to discriminte between those with (CVD/MR B) nd without (CVD/MR A) left-sided congestive hert filure (LCHF). (C) ROCAs re derived by plotting the true-positive rte (sensitivity) ginst the flse-positive rte ( specificity) for the tests described in (A) nd (B). (D) LR model output is shown, indicting the probbility of CVD/MR, determined from ERI w A, s well s the probbility of LCHF on the bsis of ERI wla. Recently, the proximl isovelocity surfce re (PISA) method ws evluted in dogs with CVD/MR.,4 This pproch is bsed on sound fluid dynmic principles but is difficult techniclly, time-consuming, nd dependent on ssumptions, the vlidity of which my be difficult to evlute for individul dogs. Wheres the PISA method hs been rigorously evluted in well-controlled bench top experiments, its reltionship to hemodynmic severity in dogs hs been compred with subjective ssessments of MR only, not quntittive determintions or clinicl outcomes ; the ERI methods of our study hve these limittions s well. The regurgitnt volume derived by the PISA method is cliniclly uninterpretble in CVD/MR without further correction for body size, which typiclly is ccomplished by clcultion of reltive Doppler ERI, the regurgitnt frction; determintion of the ltter echocrdiogrphiclly entils further, nontrivil ssumptions to obtin the forwrd crdic stroke volume. A somewht unexpected result of this study ws the finding tht incresing end-systolic dimension ws unrelted to LCHF in the CVD/MR group. Clinicl studies in both humns nd dogs from the pre-acei er proposed tht incresing end-systolic volume index (ESVI) is ssocited with myocrdil filure in chronic MR. 5,6 It is not cler tht our report contrdicts ny of these erlier conclusions becuse of differences in therpy, study design, nd gols. The study by Kittleson et l 5 included only CVD/MR dogs with severe LCHF in which the degree of myocrdil dysfunction ws determined presumptively on the bsis of the clculted ESVI, with grouping criteri extrpolted from the literture on humns. It is not cler whether some of the dogs of the erlier study suffered from dilted crdiomyopthy secondry to turine deficiency, n entity unknown t tht time, but ESVI still is considered mrker for stging CVD/MR. 7 Like the previous study, ours shows tht LCHF my occur with or without incresed end-systolic dimension (wlvids) but lso tht the sme distribution of wlvids exists for CVD/MR dogs without LCHF. Wheres correltion is certin, reltionships between physicl quntities (eg, ctul stroke re, myocrdil wll

10 Rtio Indices in Mitrl Endocrdiosis 55 re, ejection frction) nd the ERIs designed to reflect them (eg, w A, wwad, EF) hve not been evluted fully in dogs. Ech derivtion crries ssumptions bout crdic geometry tht re known to be pproximtions, the vlidity of which is vrible. 8 These shortcomings often re of minor importnce for clinicl evlutions, s evidenced, for exmple, by the widespred utility of the (circumferentil) FS, the physicl interprettion of which, like the other ERIs described, depends on circulr cross-section ssumption for the left ventricle. For clinicl purposes, it is of greter importnce to estblish reltionships mong the indices of interest nd prognosis or tretment groups; extensive informtion of this nture is lcking. However ERI clcultions re suitble to define ctegoric criteri (ie, to chrcterize clinicl study groups) nd s predictive vribles s explored in this study in LR models. Severl dditionl sources of ERI vrition re not ccounted for in our study, including inter- nd intr-observer vrition nd the effects of medictions. Some of these effects could be controlled for by well-designed prospective study; therefore, these re limittions of the current study. 9,20 Reltive to prospective study, our design might be expected to increse the observed vrition within the ERI probbility distributions nd possibly bis some of the interprettions. More severely ffected dogs, for exmple, would be expected to receive greter number or higher dosge of crdioctive medictions or both tht could led to systemtic ltertions of the ERI distributions. On the other hnd, the results presented re more representtive of circumstnces present in clinicl prctice nd likely give more conservtive estimtes of ERI predictive vlue thn might be obtined under more stringently controlled conditions. Our principl objective (ie, comprisons mong the ERIs) is not ffected by observer vrition, becuse ech ERI ws determined by the sme observer for ech dog. Another limittion of our study ws due to the M-mode modlity itself. Although llowing ccurte dimensionl mesurements, subject to the diligence nd expertise of the opertor, M-mode studies do not represent sptil reltionships mong structures in 2 or dimensions. Abnormlities of structures with complex shpe, such s the left trium or right ventricle, my require 2- or even -dimensionl constructs for dequte representtion. 2 2 The rtio of the left ventriculr longitudinl to cross-sectionl dimensions, for exmple, is n ERI (sphericity) tht reltes to crdic dilttion (ie, dilted crdiomyopthy) nd is not represented in our study. 24 However, the ERI pproch is redily extensible to 2 or dimensions, with the use of pproprite echocrdiogrphic dt, by dhering to the similrity principle nd the use of nondimensionl rtios. The weight-bsed pproch to ERIs entils nother limittion tht hs been noted previously. Although body weight is conveniently mesured globl index of body size, it is subject to bnormlities from mny cuses tht do not represent chnge in ctul intrinsic body size, most notbly obesity nd cchexi. Anecdotlly, our clinicl experience suggests tht this is likely the gretest limittion of weight-bsed ERIs, not breed-dependency. Future studies might tke into ccount body condition score to correct for this ltter problem or use length reference not bsed on body weight (eg, femur length). This study describes novel pproch to echocrdiogrphic interprettions tht demonstrtes potentil for future quntittive evlutions. ERIs provide frmework for echocrdiogrphic evlution tht is pplicble for breedspecific mesurements, 2DE, nd Doppler echo for pprecible rnges of body size. The study ws not intended to quntify breed- or CVD/MR-specific ERI distributions, nor did it resolve specific therpeutic or dignostic dilemm in veterinry crdiology. Clinicl crdiovsculr evlutions re bsed on multiple lines of evidence not limited to the echocrdiogrm, nd the indices described encompss only limited informtion (ie, stndrd M-mode mesurements nd body weight). The methods described, however, my be uniquely pplicble for quntittive dignostic nd prognostic evlutions. Footnotes O Grdy MR. Echocrdiogrphic evlution of the norml Dobermn Pinscher. J Vet Intern Med 990;4:6 (bstrct). b Softwre, SPSS Inc, Chicgo, IL c Excel, Microsoft Corportion, Redmond, WA Acknowledgments We cknowledge nd thnk Sybil Crwford, PhD, nd Jennifer L. Kelsey, PhD, of the University of Msschusetts Medicl School, Deprtment of Preventtive & Behviorl Medicine, for expert sttisticl ssistnce. References. Brown DJ, Rush JE, McGregor J, et l. M-mode echocrdiogrphic rtio indices in norml dogs, cts, nd horses: A novel quntittive method. J Vet Intern Med 200;7: Cornell CC, Kittleson MD, Dell Torre P, et l. Allometric scling of M-mode vribles in norml dult dogs. J Vet Intern Med 2004; 8: 2.. Shn D, DeMri A, Kisslo J, Weymn A. Recommendtions regrding quntittion in M-mode echocrdiogrphy: Results of survey of echocrdiogrphic mesurements. Circultion 978;58: Minors SL, O Grdy MR. Resting nd dobutmine stress echocrdiogrphic fctors ssocited with the development of occult dilted crdiomyopthy in helthy Dobermn Pinscher dogs. J Vet Intern Med 998;2: Bongur JD, Fuentes VL. Echocrdiogrphy. In: Ettinger SJ, Feldmn EC, eds. Textbook of Veterinry Internl Medicine: Diseses of the Dog nd Ct, 5th ed. Phildelphi, PA: WB Sunders; 2000: Kvrt C, Hggstrom J. Acquired vlvulr hert disese. In: Ettinger SJ, Feldmn EC, eds. Textbook of Veterinry Internl Medicine: Diseses of the Dog nd Ct, 5th ed. Phildelphi, PA: WB Sunders; 2000: Lombrd CW, Spencer CP. Correltion of rdiogrphic, echocrdiogrphic, nd electrocrdiogrphic signs of left hert enlrgement in dogs with mitrl regurgittion. Vet Rdiol 985;26: Kvrt C, Hggstrom J, Pedersen HD, et l. Efficcy of enlpril for prevention of congestive hert filure in dogs with myxomtous vlve disese nd symptomtic mitrl regurgittion. J Vet Int Med 2002;6: Uehr Y, Tkhshi M. Quntittive evlution of the severity

11 552 Brown et l of mitrl insufficiency in dogs by the color doppler method. J Vet Med Sci 996;58: Olsen LH, Mrtinussen T, Pedersen HD. Erly echocrdiogrphic predictors of myxomtous mitrl vlve disese in dchshunds. Vet Rec 200;52: Thoms JD. Doppler echocrdiogrphic ssessment of vlvr regurgittion. Hert 2002;88: Deserrnno D, Greenberg NL, Thoms JD, Grci MJ. A new utomted method for the quntifiction of mitrl regurgitnt volume nd dynmic regurgitnt orifice re bsed on normlized centerline velocity distribution using color M-mode nd continuous wve Doppler imging. J Biomech Eng 200;25: Kittleson MD, Brown WA. Regurgitnt frction mesured by using the proximl isovelocity surfce re method in dogs with chronic myxomtous mitrl vlve disese. J Vet Intern Med 200;7: Doiguchi O, Tkhshi T. Exmintion of quntittive nlysis nd mesurement of the regurgittion rte in mitrl vlve regurgittion by the proximl isovelocity surfce re method. J Vet Med Sci 2000;62: Kittleson MD, Eyster GE, Knowlen GG, et l. Myocrdil function in smll dogs with chronic mitrl regurgittion nd severe congestive hert filure. J Am Vet Med Assoc 984;84: Borow KM, Green LH, Mnn T, et l. End-systolic volume s predictor of postopertive left ventriculr performnce in volume overlod from vlvulr regurgittion. Am J Med 980;68: Griffiths LG, Orton EC, Boon J. Evlution of techniques nd outcomes of mitrl vlve repir in dogs. J Am Vet Med Assoc 2004; 224: Atkins CE, Curtis MB, McGuirk SM, et l. The use of M-mode echocrdiogrphy in determining crdic output in dogs with norml, low, nd high output sttes: Comprison to thermodilution method. Vet Rdiol Ultrsound 992;: Chetboul V, Athnssidis N, Concordet D, et l. Observerdependent vribility of quntittive clinicl endpoints: The exmple of cnine echocrdiogrphy. J Vet Phrm Ther 2004;27: Chetboul V, Concordet D, Pouchelon JL, et l. Effects of internd intr-observer vribility on echocrdiogrphic mesurements in wke cts. J Vet Med Ser A 200;50: O Grdy MR, Bongur JD, Powers JD, Herring DS. Quntittive cross-sectionl echocrdiogrphy in the norml dog. Vet Rdiol 986;27: Rishniw M, Erb HN. Evlution of four 2-dimensionl echocrdiogrphic methods of ssessing left tril size in dogs. J Vet Intern Med 2000;4: Hnsson K, Hggstrom J, Kvrt C, Lord P. Left tril to ortic root indices using two-dimensionl nd M-mode echocrdiogrphy in cvlier King Chrles spniels with nd without left tril enlrgement. Vet Rdiol Ultrsound 2002;4: Dukes-McEwn J, Borgrelli M, Tidholm A, et l. Proposed guidelines for the dignosis of cnine idiopthic dilted crdiomyopthy. J Vet Crdiol 200;5:7 9. Appendix The constnt term of n LR model my be djusted to represent specific prior probbility; model constnts ( C in Tbles 4A, 4B) were ltered to reflect equl prior probbility, thereby correcting for unequl group size (norml versus CVD/MR nd CVD/MR A versus B). Let B 0 nd C 0 be the prmeters computed for univrite LR model with predictor X nd known prior probbility, P 0. The vlue of the predictor ssocited with P 0 is X 0 nd is determined from the LR eqution nd known model prmeters. P 0 C 0 ln P 0 P0 X0 (C0 B0X 0) e B 0 Prior probbility my depend on the prevlence of the condition in the test popultion (eg, reltive group size). P 0 ws determined from group size in our study (ie, the frction of ll dogs hving CVD/MR or the frction of CVD/MR dogs with LCHF). An lternte model constnt, C, cn be computed to represent n lternte prior probbility, P : P (C B0X 0) e P B 0 X 0 C ln P PP 0 P C C0 ln PP P 0 0 C is derived by substituting the bove solution for X 0 bck into the LR eqution nd rerrnging to solve for C. P ws chosen to be.5 for our study, reflecting equl prior probbility nd corresponding to n ssumption of equl test group size. The finl LR model is identicl to the originl with C 0 replced by C, clculted s shown.