Real-Time Three-Dimensional Transesophageal Echocardiography: Improvements in Intraoperative Mitral Valve Imaging

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1 Rel-Time Three-Dimensionl Trnsesophgel Echocrdiogrphy: Improvements in Intropertive Mitrl Vlve Imging Mximilin Dominik Hien, MD,* Helmut Ruch, MD, Artur Lichtenberg, MD, Rffele De Simone, MD, Mrc Weimer, DSc, Orin Amnd Pont, MSc, nd Christin Rosendl, MD, DESA BACKGROUND: Successful surgicl repir of regurgitnt mitrl vlve (MV) is dependent on comprehensive ssessment of its complex ntomy. Although there is limited evidence of the fesibility nd ccurcy of intropertive rel- time 3-dimensionl trnsesophgel echocrdiogrphy (RT3DTEE) in MV surgery, its use is incresing worldwide. We designed this prospective observtionl study of ptients with mitrl regurgittion to test initil findings on the ccurcy of RT3DTEE imges in the dignosis of MV prolpse nd chordl rupture reltive to 2D imging nd to ssess the potentil of RT3DTEE for visulizing leflet clefts. METHODS: TEE- certified nesthesiologists exmined 62 consecutive ptients undergoing MV surgery by cquiring full stndrd set of 2D TEE sections nd 3D zoom recordings. Offline, 2D nd 3D imges were presented independently nd in rndomized order to 2 expert interpreters. Accurcy ws determined using the surgicl findings s the gold stndrd. RESULTS: Surgicl inspection identified 52 cses of MV prolpse (MVP). RT3DTEE correlted stronger with the surgicl findings thn 2D TEE for detection nd locliztion of MVP (difference in proportions = 33.9%, P < 0.001) nd chordl rupture (difference in proportions = 25.8%, P < 0.001). The superiority of RT3DTEE ws significnt for scllops A2, P1, P2 in MVP nd A2, P2 in chordl rupture (ll P < 0.05). In 22 ptients, leflet clefts were lso surgiclly repired, nd RT3DTEE ws fesible in ccessing them (κ = 0.65, confidence intervl [0.44, 0.81]). CONCLUSION: Although 2D TEE is currently the stndrd tool for intropertive imging in MV surgery, RT3DTEE improves the visuliztion of MV pthology nd increses the ccurcy of interprettion by fcilitting sptil orienttion. Further investigtions, prticulrly those imed t estblishing its cost effectiveness, re indicted. (Anesth Anlg 2013;116:287 95) A comprehensive ssessment of the mitrl vlve (MV) pprtus with 2-dimensionl (2D) intropertive trnsesophgel echocrdiogrphy (TEE) is necessry for successful surgicl repir of regurgitnt MV. 1 3 The demnd for comprehensive imging hs further incresed with dvncements in MV repir 4 nd minimlly invsive pproches. 5 Recent studies hve ssessed MV prolpse (MVP) locliztion using rel- time (RT) 3D trnsthorcic echocrdiogrphy reltive to either 2D trnsthorcic echocrdiogrphy or 2D TEE. 6 8 The trnsition from offline 3D reconstruction to intropertive RT imging hs been fcilitted by RT3DTEE, which llows for 3D imging without interruption of the surgicl procedure. Severl pilot studies From the *Deprtment of Peditrics, Reserch Trining Group 1126, Heidelberg University, nd Deprtments of Anesthesiology nd Crdiovsculr Surgery, nd Division of Crdiovsculr Surgery, Heidelberg University, Heidelberg, Germny; nd Germn Cncer Reserch Center (DKFZ), Deprtment of Biosttistics, Heidelberg, Germny. Accepted for publiction My 30, Supplementl digitl content is vilble for this rticle. Direct URL cittions pper in the printed text nd re provided in the HTML nd PDF versions of this rticle on the journl s Web site (www. nesthesi- nlgesi.org). The uthors declre no conflicts of interest. Artur Lichtenberg, MD, is currently ffilited with the Division of Crdiovsculr Surgery, Duesseldorf University, Duesseldorf, Germny. Reprints will not be vilble from the uthors. Address correspondence to Mximilin Dominik Hien, MD, Deprtment of Peditrics, Reserch Trining Group 1126, Heidelberg University, Neckrstden 18, Heidelberg, Germny. Address e- mil to mximilin. hien@med.uni-heidelberg.de. Copyright 2013 Interntionl Anesthesi Reserch Society DOI: /ANE.0b013e318262e154 hve explored the dvntges of RT3DTEE for dignosing MV pthology Sugeng et l. 14 used considerble study popultion (47 ptients) to explore new methods of prosthetic vlve visuliztion using RT3DTEE, but 2D TEE ws not used for comprison. Grewl et l. 13 provided the first sttisticl comprison of MVP locliztion with RT3DTEE nd 2D TEE in 42 individuls undergoing MV repir. They reported superiority of RT3DTEE over 2D TEE for severl leflet scllops nd for the detection of chordl rupture. Leflet clefts re frequently encountered lesions in MV repir, lthough their detection by TEE hs not been systemticlly investigted Confident identifiction of leflet clefts using 2D TEE hs proven problemtic nd my dversely ffect the outcome of MV repir. This prospective observtionl tril ws designed to test whether RT3DTEE is superior to 2D TEE in the detection nd locliztion of MVP nd ruptured chorde tendinee. In ddition, lthough cleft ssessment ws not prt of our stndrd 2D TEE routine, we hypothesized tht RT3DTEE would be fesible nd ccurte for the ssessment of MV leflet clefts. METHODS Study Popultion Sixty- two consecutive ptients with mitrl regurgittion (MR) who were scheduled for MV repir becuse of suspected MVP were enrolled in this study fter permission from the Institutionl Ethics Committee ws obtined. The only exclusion criterion ws contrindiction to TEE. All studied ptients provided informed written consent to prticipte in the investigtion. Februry 2013 Volume 116 Number

2 Rel- Time 3D TEE in Mitrl Vlve Imging Intropertive TEE Two- dimensionl nd RT3DTEE were performed using n ie33 system equipped with n X7-2t mtrix rry trnsducer (Philips Medicl Systems, Bothell, WA) fter the induction of nesthesi. Five echocrdiogrphers certified by the Europen Assocition of Echocrdiogrphy, with dditionl trining in RT3DTEE (TS, MH, CS, TM, nd JM), b cquired the imges. All opertors performed TEE on similr number of cses, nd no priority ws given to ny specific opertor. The TEE exmintion ws conducted following our stndrd clinicl intropertive TEE protocol (described below), which is bsed on the Americn Society of Echocrdiogrphy/Society of Crdiovsculr Anesthesiologists guidelines 1 nd newer literture. 18,19 A single echocrdiogrpher cquired both 2D nd RT3DTEE imges during the sme exmintion to minimize the potentil effects of ltertion in hemodynmic sttus nd to minimize bis cused by vribility mong echocrdiogrphers. Imge qulity ws grded s excellent, stisfctory, or poor by the interpreters depending on the disply of the entire profile of the MV. The 2D TEE Exmintion The MV ws exmined in multiple cross- sectionl views. They were optimized to disply the entire MV tking cre to optimize detil nd imge qulity by djusting the sector depth, width, lterl gin, nd trnsducer frequency settings. The MV ws imged in the midesophgel (ME) 5-chmber views t 0, which trnsected the nterior segments (A1/P1), followed by grdul dvncement of the probe to cquire the ME 4-chmber view t 0, in which the djcent middle nd cudl segments were visulized vrying with ptient ntomy nd the probe position (A2/P1 or A2/P2, further cudl A3/P2 or A3/P3). Next, the 60 ME commissurl view (with clockwise nd counterclockwise rottion nd withdrwl or dvncement of the probe nterior [A1-A2-A3], middle [P1-A2-P3], nd posterior [P1-P2-P3]), the 90 ME 2-chmber view (P3, free mrgin A3-A1), nd n nterior, middle, nd posterior section of the 120 to 150 ME long- xis view (A1-P1, A2-P2, A3-P3) were obtined. The 2D exmintion ws supplemented by color Doppler recordings of the MV imging plnes nd whenever fesible by trnsgstric bsl short- xis view. The RT3DTEE Exmintion Strting in the ME 4-chmber view, 2D imges were optimized in the x-plne mode (feturing 2 orthogonl 2D sections) before RT3DTEE recordings were cquired in the 3D zoom mode. This mode displys selectble pyrmidl volume tht cn be focused to cpture the MV with mximum resolution. TEE Interprettion The 2D nd RT3DTEE imges were interpreted offline by 2 seprte investigtors certified by the Europen Assocition of Echocrdiogrphy nd the Germn Assocition of Anesthesiology nd Intensive Cre with dditionl trining Two- dy intensive trining course on 3D TEE nd clinicl prctice. b Tnj Scconi, Mximilin Hien, Christoph Schrmm, Thoms Müller, nd Johnn Motsch. in RT3DTEE (HR, CR), blinded to ptient dt, imges of the other modlity, preopertive dignosis, nd intropertive findings. TEE dt were stored on n externl worksttion with 2D nd 3D files mintined in seprte loctions. Ech interpreter exmined the 2D nd 3D recordings of 31 rndomly selected ptients in rndomized order. MVP ws defined s the displcement of leflet tissue bove the mitrl nnulr plne into the left trium by t lest 2 mm during systole, considering the nnulr sddle shpe. 18 Three- dimensionl interprettion ws performed on 3D zoom recordings using Qlb 7.1 softwre (Philips Medicl Systems). An initil en- fce view of the left tril perspective of the MV ws used for the primry orienttion nd djustment of gin nd color schemes. The imge ws rotted to resemble the surgicl orienttion, with the ort t 12 o clock (Fig. 1). The imge ws tilted to the left nd right to compenste for the sddle shpe of the MV 19 nd detect prolpsing scllops, chordl ruptures (systole), nd leflet clefts (erly distole). A more detiled inspection of the lesions ws performed in the multiplnr reconstruction (MPR) mode of the sme RT imge, which fetures 3 cross- sectionl views in ny desired plne or ngle (Fig. 2). The defult settings of the MPR mode provide 2 orthogonl plnes intersecting pproximtely the short nd long xis of the MV nnulus when recorded from n initil 2D ME 4-chmber view. Using the 3D imge for orienttion, these plnes cn be djusted by the opertor to intersect ny leflet or scllop. Additionlly, the third, horizontl, plne cn be djusted to detect displcement inside the left trium during systolic frmes. Drgging the short- xis plne from one commissure to the other in systolic frme (with djustments to compenste for the curved commissurl line) llows both MV leflets to be inspected for the displcement of leflet tissue into the left trium pst the mitrl nnulr plne in systolic frmes. Clefts through the nterior or posterior leflet tht lck connective tissue were ssessed in frmes before nd fter end systole nd evluted t different gin levels for consistency. Surgicl Evlution The MV ws ssessed from the opened left trium during crdiopulmonry bypss (Fig. 1c). Six crdic surgeons performed the opertions in this study. The operting surgeon inspected the MV in the rrested hert for ruptured chorde nd clefts tht required surgicl repir. The left ventricle ws filled with sline to test for regurgittion nd MVP, which ws clssified ccording to the Crpentier nomenclture. 1 Mesured Vribles Vribles ssessed with both 2D nd RT3DTEE were the bsence or presence of MVP, the locliztion of the predominnt prolpse, the locliztion of ll prolpsing scllops of ech ptient, the scllop of origin of ruptured chorde tendinee, nd the imge qulity of 2D nd 3D imges of ech ptient. Detection nd locliztion of leflet clefts were ssessed with RT3DTEE, but not with 2D TEE nesthesi & nlgesi

3 Figure 1. Rel- time 3-dimensionl trnsesophgel echocrdiogrphy (RT3DTEE) versus 2D TEE nd surgicl inspection. Ptient with n isolted P2 prolpse., End- systolic RT3DTEE left tril en-fce mitrl vlve (MV) view with Crpentier stndrd model projected onto the 3D imge, which illustrtes the pproximte commissure behind the prolpsing P2 scllop s dotted blck line nd the interscllop indenttions (short nd dotted blck lines). The ortic vlve (Ao) nd left tril ppendge (LAA) serve s orienttion. b, Two- dimensionl TEE midesophgel long- xis view (through centrl MV scllops) of the sme ptient. c, Surgicl findings of the sme ptient. Intct chorde tendinee re visible through the vlve (*). ALC = nterolterl commissure; PMC = posteromedil commissure. Figure 2. Multiplnr reconstruction (MPR) mode of 3-dimensionl (3D) trnsesophgel echocrdiogrphy (TEE). Ptient with P1 P2 prolpse., Rel- time 3D TEE (RT3DTEE) left tril en- fce mitrl vlve (MV) view. A Crpentier model is projected onto the vlve, outlining the 6 scllops; the commissurl line is dotted where it is hidden by the prolpse rising bove the plne. RT3DTEE provides full view of the entire MV (), which cn be further dissected so tht ny component cn be interrogted in 3 freely chosen 2D sections simultneously (b d). The sections re mrked s colored lines in ech imge. MPR sections in this figure re rrnged perpendiculrly to ech other nd to the MV. Red: section through the MV short xis, corresponding to the 2D midesophgel (ME) long- xis view t 120. In this cse, lthough the lterl prt of scllop P2 is prolpsing, the red section cutting through A2 nd P2 misses the MV prolpse (MVP). Green: Section through the MV long xis, corresponding to the 2D ME commissurl view t 60. Both red nd green sections need to be put in context with () nd (c) to infer whether certin vlve prt is intersected or not. This is not possible with 2D TEE sections. Blue: Horizontl plne t nnulr level with commissurl line nd segment lines from the Crpentier model bove. The MVP circumference cn be seen inside the 2D MV nnulr re. Ao = ortic vlve. Sttisticl Anlysis The sensitivity nd specificity were clculted for 2D nd RT3DTEE for MVP presence, predominnt scllop, prolpsing scllops, ruptured chorde tendinee (per scllop), nd leflet clefts. The ccurcy for ech scllop ws determined s the sum of the true positive nd true negtive divided by the number of cses investigted. Differences in ccurcy of 2D nd RT3DTEE for the respective lesions of ech scllop were ssessed using 2-sided sttisticl testing nd by the clcultion of 2-sided 95% confidence intervls (CIs) for differences in pired- smple proportions ccording to methods described by Tngo 20 with the difference in proportions (delt sttistic) = 0. Any P vlues <0.05 were considered significnt findings. Imge qulity ws nlyzed with the Wilcoxon signed rnk test. Agreement of RT3DTEE nd 2D TEE imges with surgicl findings ws ssessed using Cohen kpp (κ) coefficient. 21 κ [ ] ws considered lmost perfect, κ [ ] substntil, κ [ ] moderte, κ [ ] fir, nd κ [ ] slight greement. 21 The 95% CIs for κ bis- corrected nd ccelerted bootstrp intervls were determined; ech intervl ws clculted from 1000 bootstrp smples. After 6 months, the studies of 20 ptients were rndomly selected, reviewed, nd tested for inter- nd introbserver vribility using the κ sttistic. Sttisticl testing nd the clcultion of CIs were performed using the sttisticl softwre R (Bell Lbortories, Murry Hill, NJ) nd SPSS Sttistics 19 (IBM, Armonk, NY). Bootstrpping ws performed using the R pckge version RESULTS Study Popultion As determined by the crdic surgeon, the underlying cuse of MR ws myxomtous degenertion in 52 cses (21 with leflet clefts), functionl or ischemic in 9, nd n isolted leflet cleft in 1 cse. The detils of the surgicl inspection re summrized in Tble 1 nd the findings for ech of the 6 scllops re presented in Tbles 2 nd 3. The mjority of lesions involved the posterior leflet. Thirty- six ptients were treted with minimlly invsive surgery vi lterl thorcotomy, nd 17 ptients received vlvulr replcement insted of repir. Thirty- five ptients hd Februry 2013 Volume 116 Number

4 Rel- Time 3D TEE in Mitrl Vlve Imging Tble 1. Surgicl Inspection Prolpse complexity Ptients (n = 62) Single scllop prolpse % Multiple scllop prolpse % Bileflet prolpse b % No prolpse % Chordl rupture % No chordl rupture % Rupture of ppillry muscle 2 3.2% Leflet cleft % No leflet cleft % Single leflet. b Includes multiscllop disese involving both leflets nd/or diffuse bileflet involvement. Tble 2. Surgicl Findings per Scllop Scllop Prolpse Percentge Chordl rupture Percentge A % 1 1.6% A % 2 3.2% A % 1 1.6% P % % P % % P % 5 8.1% Proportions pertining to ll 62 ptients. Proportions exceed 100% becuse of cses with multiscllop disese nd cses without mitrl vlve prolpse or chordl rupture. Tble 3. Surgicl Findings: Clefts Scllop Cleft Percentge Through A % Between A1-A2 0 Through A % Between A2-A % Through A % Through P1 0 Between P1-P % Through P % Between P2-P % Through P % Double cleft P2 nd P2-P % Proportions pertining to ll 62 ptients. Tble 4. Mitrl Vlve Surgery (n = 62) Surgicl mitrl vlve procedures Ptients (Minimlly invsive surgery) Annuloplsty 45 (28) Vlvulr replcement 17 (8) Additionl reconstructive procedures Prolpse resection 7 (7) Neochorde 22 (16) Cleft repir 17 b (8) Annulorrhphy (nulr ruffle) 1 (0) Segmentl ruffle 1 (1) One to 5 neochorde per ptient. b Five cses with clefts received mitrl vlve replcement. concurrent surgery (tricuspid vlve reconstruction, closure of persisting formen ovle, myxom, coronry rtery bypss grfts, ortic vlve replcement, grfting of the ort, myocrdil resection). Surgicl MV procedures re listed in Tble 4. There ws frequent incidence of complex MV disese (MVP involving >1 scllop [19 ptients]). Figure 2 nd Tble 5. Ptient Chrcteristics Vrible Men ± SD Age 62 ± 13 y BMI 26 ± 4 kg/m 2 MAP t time of TEE exmintion 85 ± 9 mm Hg Hert rte t time of TEE exmintion 69 ± 17 bpm CVP t time of TEE exmintion 10 ± 5 mm Hg Ptients n 62 Gender: men/women 46/16 (74%/26%) Atril fibrilltion 23 (37%) Left-ventriculr function Good 33 (53%) Modertely impired 18 (29%) Severely impired 11 (18%) Coronry rtery disese b 25 (39%) Minimlly invsive surgery 36 (58%) BMI = body mss index; CVP = centrl venous pressure; LVF = left- ventriculr function; MAP = men rteril blood pressure; TEE = trnsesophgel echocrdiogrphy. The left- ventriculr ejection frction ws visully estimted from the 2-dimensionl TEE imges. b Presence of coronry rtery disese (mt50% lesions) or history of coronry rtery bypss grfting or percutneous trnsluminl coronry ngioplsty. online Figures 1 nd 2 (see Supplementl Digitl Content 1, nd 2, com/aa/a433; see Appendix for online figure legends) show different cses of complex MV disese. Further ptient chrcteristics re shown in Tble 5. TEE cquisition did not prolong or interrupt surgicl procedures nd no ptient ws subsequently excluded from our study. Mitrl Vlve Prolpse The presence or bsence of MVP ws dignosed correctly in ll 62 cses (100%) using RT3DTEE nd in 57 cses (91.9%) using 2D TEE (difference in proportions = 8.1%, CI [1.8%, 17.5%], P = 0.025). In the 52 ptients with MVP, the predominnt prolpse ws correctly dignosed with RT3DTEE in 51 cses (98.1%), nd ws misdignosed s occurring in A3 insted of P3 in 1 cse. The predominnt prolpse ws ccurtely dignosed in 46 cses (88.5%) with 2D TEE (difference in proportions = 9.6%, CI[ 0.5%, 21.5%], P = 0.059). In evluting the predominnt prolpse s well s ll prolpsing scllops, RT3DTEE ws identicl to the surgicl inspection in 48 of the 62 study cses (77.4%) compred with 27 cses (43.5%) using 2D TEE (difference in proportions = 33.9%, CI [17.5%, 48.6%], P < 0.001). Agreement nlysis with κ reveled substntil greement of surgicl findings nd RT3DTEE (κ = 0.69, CI [0.54, 0.81]) compred with the fir greement of surgicl findings nd 2D TEE (κ = 0.28, CI [0.17, 0.42]). When considering the potentil impct of surgicl pproch (e.g., lterl thorcotomy versus sternotomy), greement of both 2D nd 3D TEE ws lower in ptients operted with the lterl thorcotomy pproch. This decline ffected both methods to the sme extent. Accurcy ws clculted seprtely for ech of the 6 MV scllops for further differentition (Tble 6). RT3DTEE ccurcy ws significntly higher in scllops A2 (difference in proportions = 11.3%, CI [2.3%, 22.2%], P = 0.020), P1 (difference in proportions = 19.4%, CI [6.6%, 32.5%], P = 0.005), nd P2 (difference in proportions = 16.2%, CI [9.0%, 27.2%], P = 0.002). The most frequent error in 2D TEE ws nesthesi & nlgesi

5 Tble 6. Anlysis of Locliztion per Scllop: Three- Dimensionl Trnsesophgel Echocrdiogrphy Versus Two- Dimensionl Trnsesophgel Echocrdiogrphy nd Surgicl Inspection True count 3D 2D 3D 2D 3D 2D P (2-tiled) Prolpse (per scllop) A A * A P * P * P Chorde (per scllop) A A * A P P <0.001* P Cleft P = P vlue of significnce for difference in ccurcy. *P < 0.05: sttisticlly significnt. Sensitivity % Specificity % Accurcy % Figure 3. Posterior prolpse with chordl ruptures in 2-dimensionl trnsesophgel echocrdiogrphy. b, Two imges of the midesophgel (ME) 5-chmber section without chnges of probe position. Identified scllops: A1/P1 nd lterl portion of A2/P2., No chorde re visible. Two scllops in superposition (red rrows), one prolpsing. b, Chord is visible fliling into the left trium. Prolpse of the posterior leflet, probbly P1/(P2). c, Posterior ME 4-chmber view, expected scllops: A3/P3 nd medil portion of A2/P2. Red line indictes the nnulr level. No significnt mitrl vlve prolpse in this section. d nd e, Two ME long- xis sections in the centrl position cutting through the ortic vlve (Ao). d, Prolpse with one dherent ruptured chord (white rrow), in fvor of P2. e, In n lmost identicl section to (d), ruptured chord cn be seen (white rrow), but prolpse is not visible (red line is nnulr level). f, ME 2-chmber view: no prolpse. Three ruptured chorde (white rrows), insertion t the leflet uncler, presumbly locted on the posterior scllops, which cnnot be seen. differentiting P1 nd P2 in posterior prolpse (10 cses), s shown in Figure 3. Chorde Tendinee Surgicl inspection identified 37 nd 25 ptients with nd without chordl rupture, respectively. RT3DTEE correctly dignosed the presence or bsence of chordl rupture in 59 of these ptients (95.2%) s opposed to 43 ptients (69.4%) using 2D TEE (difference in proportions = 25.8%, CI [16.6%, 37.9%], P < 0.001). Agreement of TEE nd surgicl reference regrding the scllops of origin of ruptured chorde ws lmost perfect using RT3DTEE (κ = 0.82, CI [0.68, 0.93]) nd fir using 2D TEE (κ = 0.27, CI [0.14, 0.44]). Chordl rupture of the posterior leflet is compred in Figures 3 nd 4. Online Figure 2 (see Supplementl Digitl Content 2, see Appendix for online figure legends) shows chordl rupture of the nterior leflet. The nlysis by scllop is listed in Tble 6. The ccurcy of RT3DTEE ws significntly higher for the most frequent lesions, scllop P2 (difference in proportions = 24.2%, CI [13.1%, 36.7%], P < 0.001), nd for A2 (difference in proportions = 6.5%, CI [0.2%, 15.4%], P = 0.046). There were 2 cses of ppillry muscle rupture nd both were correctly identified by either method. Leflet Clefts The surgeon described 22 nd 40 ptients with nd without leflet clefts, respectively. RT3DTEE ws fesible for the detection of surgiclly relevnt MV leflet clefts (Fig. 5) with substntil greement of RT3DTEE nd intropertive findings (κ = 0.65, CI [0.44, 0.81]). Five clefts reported Februry 2013 Volume 116 Number

6 Rel- Time 3D TEE in Mitrl Vlve Imging stisfctory in 21.0%, nd poor in 14.5% of the 3D exmintions compred with 74.2% excellent, 24.2% stisfctory, nd 1.2% poor in 2D. The men imge qulity rting in 2D TEE ws better thn in RT3DTEE (P = 0.03). Poor 3D imge qulity ws ttributble to () n incomplete cpture of the MV structures in single 3D clip (n = 3), (b) interruption of cquisition by the surgicl procedures (n = 2), nd (c) poor echocrdiogrphic signl qulity (n = 4). None of these ptients ws excluded from the sttisticl evlution. Inter- nd Introbserver Agreement Inter- nd introbserver greement ws substntil for both methods with medin κ vlue of 0.75 (rnge [0.35; 0.83]) nd 0.80 (rnge [0.44; 0.89]) for inter- nd introbserver interprettions, respectively. Figure 4. Posterior prolpse with chordl ruptures in rel- time (RT) 3-dimensionl (3D) trnsesophgel echocrdiogrphy. RT 3D en- fce view of the sme ptient s Figure 3, surgicl orienttion. A1 nd A2 scllops re hidden behind the prolpsing P2 scllop with t lest 3 ruptured chorde (white rrows). The origin of ll chorde is P2. P1 prolpse or involvement in chordl rupture cn sfely be excluded. Ao = ortic vlve; LAA = left tril ppendge. Figure 5. Mitrl vlve leflet clefts. A deep intrscllop cleft (*) through the middle of the P2 scllop in n erly distolic frme; () left tril view, (b) left- ventriculr view; when tilting the imge 180 (b), the cleft cn be seen from the left- ventriculr view (*). c, Different ptient. Interscllop cleft between the P2 nd P3 scllops (*) in erly distole. Both clefts required surgicl correction. AL = nterior leflet; Ao = ortic vlve. by surgicl inspection were not detected by RT3DTEE. Conversely, 7 clefts reported by RT3DTEE were not reported by surgicl inspection (Tble 6), which equls flse- positive rte of 17.5%. All true- positive clefts detected with RT3DTEE were loclized ccurtely. Imge Qulity Three- dimensionl zoom recordings hd n verge of 10.3 ± 2.1 frmes per second compred with 42.8 ± 8.4 in 2D recordings. Imge qulity ws rted excellent in 64.5%, DISCUSSION Mitrl Vlve Prolpse RT3DTEE ws more ccurte thn 2D TEE for the dignosis of MVP in ptients with MR. However, the predominnt prolpse ws correctly identified in the mjority of cses using both RT3DTEE nd 2D TEE. Although 2D TEE ws relible for the locliztion of mjor prolpse of the MV, RT3DTEE ws more ccurte in detecting ll prolpsing scllops in complex cses or excluding the involvement of djcent scllops. The close visul resemblnce of the 3D imges to the surgicl inspection is n dvntge of RT3DTEE nd ws confirmed by the κ nlysis, which illustrted lrge difference of 2D versus 3D greement with the surgeon when evluting the entire vlve for prolpsing scllops (difference in proportions = 33.9%) nd for chordl ruptures (difference in proportions = 25.8%) (Figs. 3 nd 4). However, superiority of RT3DTEE ws not proven for ll scllops. This effect is relted to the smll number of lesions in less frequently involved scllops (Tble 6). Differences were significnt in scllops P1 nd P2, which ccounted for two- thirds of ll prolpsing scllops. Similr results were obtined for chordl rupture with significnce for scllop P2 nd trend for P1. The frequent incidence of P2 lesions is consistent with the published literture 22 nd my reflect surgicl ptient selection. 23,24 The differentition of P1 versus P2 or combined involvement is chllenging in 2D TEE imges (Figs. 3 nd 4). Slight differences in ptient ntomy or probe position my cuse ltertions in 2D sections, leding to intersection with the scllop tht is djcent to the expected one. The chllenge increses when 2 scllops pper simultneously in one 2D section (Fig. 3). Dignosis in these cses ws better using RT3DTEE, in which the physiologicl interscllop indenttions were observed in 3D en- fce views, which fcilitted the locliztion of MVP. Three- dimensionl imges obvite these difficulties by including the entire informtion of the vlve tht is necessry for sptil orienttion in 1 imge (Fig. 2). MPR plnes, which re very similr to 2D sections, cn be obtined from the sme hertbet nd cn be rrnged freely, to intersect the MV nnulus nywhere. Chordl Ruptures Although 2D TEE cn detect chordl ruptures sensitively, 25 locliztion remins chllenging (Fig. 3) (online Fig. 2, nesthesi & nlgesi

7 Figure 6. Pseudodefects in rel- time 3-dimensionl trnsesophgel echocrdiogrphy imges. Ptient without mitrl vlve prolpse. Red rrows indicte defects in both leflets, which were intct (but very thin) leflet tissue on surgicl inspection. The trnsprent line mrks the commissure for orienttion. AL = nterior leflet; ALC = nterolterl commissure; Ao = ortic vlve; PL = posterior leflet; PMC = posteromedil commissure. see Appendix for online figure legends) becuse these fine structures only prtilly pper in the imge, often without visuliztion of their leflet insertion. Updting the results on RT3DTEE in previous studies, 7,26 we found tht the insertion t the leflet of the mjority of ruptured chorde cn be detected ccurtely (Fig. 4) (online Fig. 2, A433). The visuliztion of multiple ruptured chorde in one bird s eye view provides n dvntge for the precise description of complex MV pthology. Leflet Clefts Even though 22 ptients in our study were reported to hve MV leflet clefts, the ntomicl definition of leflet clefts is not well defined nd their clinicl significnce is uncertin. In ddition to visuliztion, it is chllenging to distinguish physiologicl interscllop indenttions 27 from clefts in the mitrl leflets tht cuse regurgittion nd require surgicl intervention. These clefts cn rise from interscllop indenttions tht exceed wht Victor nd Nyk 27 refer to s ntomiclly regulr slits (online Fig. 1, see Supplementl Digitl Content 1, see Appendix for online figure legends), nd intrscllop clefts in bnorml plces 20 (Fig. 5). We found substntil greement of RT3DTEE with the surgicl inspection. Seventeen clefts were correctly visulized using RT3DTEE, providing new informtion tht my be used for surgicl plnning. Two resons likely ccount for the number of flse- positive clefts in RT3DTEE: the overestimtion of interscllop indenttions t low gin settings, nd the exceptionlly fril leflet tissue tht sometimes presents s tissue defect in RT3DTEE (Fig. 6) nd leds to flse- positive dignosis. When imging with low number of frmes per second, cleft my be visible in one single frme only, mking it difficult to determine true ntomicl clefts from imging rtifcts. Limittions of 2D TEE Intropertive 2D TEE is the stndrd method for the evlution of MV pthology nd provides ccurte dt with proven fesibility in the operting room. 2,25,28 However, sptil orienttion is often difficult with 2D TEE, nd interprettion of 2D imges remins chllenging nd requires high level of expertise. Clinicins limited to 2D imging re often confronted with mbiguous 2D recordings, in which the ffection of djcent scllops cnnot be distinguished with certinty. Informtion regrding the position of the probe t the moment of cquisition nd the impct of mnul djustments on imges is essentil for correct interprettion, thus mking it highly opertor- dependent. Ahmed et l. suggested tht the limittions of conventionl 2D TEE lie in its inbility to disply the entire surfce of the mitrl leflets in the short xis, nd true locliztions my differ from the estblished stndrd 2D sections. 29,30 Further fctors leding to these berrtions re ntomicl differences of ptients, the left lterl positioning in minimlly invsive surgery, nd cses with complex MV disese. 6 Sensitivity hs been reported between 50% nd 96% for the dignosis of MVP with 2D TEE. 2,6,9,28 The ccurcy of 2D TEE in our study is consistent with these numbers nd reflects the forementioned chllenges. Color Doppler helps with orienttion in ddition to 2D imging of the MV pprtus. Limittions of RT3DTEE Although the sptil resolution of RT3DTEE technology hs dvnced notbly, temporl resolution remins limited. Three- dimensionl zoom recordings offer pproximtely 25% of the frme rte of 2D imging, which my led to n inbility to dignose scllop pthologies ssocited with motion, such s ruptured chorde nd leflet clefts. RT3DTEE lso hs greter tendency to misidentify norml structures s pthology (Fig. 6), especilly when the imge gin is reduced to suppress imge noise. 27,29 In our study, this led to flse- positive rte of 17.5% for leflet clefts with respect to the surgicl findings. RT3DTEE cquisition of one 3D zoom- mode recording tkes pproximtely 1 to 2 minutes. Considering tht one recording hs to be mde compred with full set of 2D recordings, cquisition of RT3DTEE is considerbly fster. However, thorough interprettion of 3D zoom- mode recording requires gin chnges, rottion, nd MPR nlysis fter cquisition, which is not necessry with 2D TEE interprettion. In this study, the verge imge qulity ws rted higher with 2D TEE thn RT3DTEE. This difference my hve been ttributble to longer experience with 2D cquisition. RT modes such s the 3D zoom mode cn obvite the problem of rtifcts cused by the stitching of subvolumes with fulty lignment cused by rrhythmi or movements. 31 Unfortuntely, it is restricted by its mximum imge window width, nd ntomiclly significnt structures my be cut off in lrge vlves. At present, there is only one vendor who offers RT3DTEE for intropertive use, nd the nlysis of RT3DTEE dt requires specific softwre, which limits widespred clinicl vilbility. Februry 2013 Volume 116 Number

8 Rel- Time 3D TEE in Mitrl Vlve Imging Limittions of This Study The comprison of 2D versus RT3DTEE ws performed fter surgery to ensure proper blinding of the interpreters. The reltive dignostic inferiority of 2D TEE, s shown in our study, might hve been influenced by the offline nlysis of 2D imges. In everydy clinicl prctice, the intropertive physicin is using color flow Doppler long with 2D imging. Two- dimensionl interprettion lso depends on the experience of the echocrdiogrphers nd the knowledge of the probe depth or right- left turn. This informtion ws not recorded nd could hve impired 2D interprettions, wheres it is not necessry for RT3DTEE interprettion becuse the imges contin ll of the informtion. In severl cses, more leflets were reported s prolpsing in RT3DTEE imges thn during surgicl inspection. Using TEE before institution of crdiopulmonry bypss, MV function cn be evluted in reltively physiologicl stte (ssuming norml ventriculr loding conditions). However, the surgeon is evluting the ntomicl fetures in resting hert devoid of blood during the surgicl inspection period. Consequently, smller lesions my be missed by the surgeon despite correct dignosis with TEE. CONCLUSION In this prospective study of intropertively cquired TEE imging, RT3DTEE proved fesible nd more ccurte thn 2D for the detection, locliztion, nd description of MVP nd ruptured chorde tendinee. The new genertion of RT3DTEE imging fcilittes the detection of leflet clefts. RT3DTEE provides full view of the MV nnulus, which cn be further dissected offline so tht ny component cn be interrogted. Two- dimensionl TEE is n indispensble tool in MV surgery, but RT3DTEE offers distinct improvements in sptil orienttion nd visuliztion of vlvulr pthology. The incresing sophistiction of MV surgery requires tht the surgeon be supplied with the best vilble imgery. We recommend RT3DTEE s routine supplement to intropertive MV imging. E Appendix: Online Figure Legends Online Figure 1: Complex mitrl vlve prolpse (MVP) involving ll scllops. Severe mitrl vlve (MV) bi-leflet prolpse disese tht involved ll scllops. All imges re from the sme ptient. Red lines mrk the nnulr level in both 2-dimensionl (D) nd rel-time 3-dimensionl trnsesophgel echocrdiogrphy (RT3DTEE) imges. (-d) Stndrd 2D ME sections. It seems s if there is no A1 prolpse in () nd no A2 prolpse in (d). In (b), A2 prolpse is visible, in (c), A1 nd A2 prolpse is visible, which would contrdict () nd (d). (c): in this complex cse involving bileflet prolpse of different extents, it is difficult to specify which scllops re intersected. An MPR would be helpful. (e-f): RT3DTEE imges. (e) The nnulr level nd the commissurl line re mrked in white. (*) mrks PL interscllop indenttions. In (e), ll scllops, with the exception of A2, re clerly prolpsing. (f) The sme imge turned clockwise nd cropped from the PMC shows tht A3 nd A2 re lso prolpsing bove the nnulr level (red line). [AL: nterior leflet; ALC: nterolterl commissure; Ao: ortic vlve; LV: left ventricle; ME: midesophgel; MPR: multiplnr reconstruction; PL: posterior leflet; PMC: posteromedil commissure] Online Figure 2: Anterior prolpse with chordl ruptures. (-d) Four stndrd midesophgel (ME) views of the mitrl vlve (MV) in 2-dimensionl (D) trnsesophgel echocrdiogrphy (TEE) revel prolpse nd chordl rupture of the nterior leflet. (e) Four Chorde (blck rrows) cn be distinguished in the rel-time (RT) 3D en-fce view t end systole, including their exct origin, corresponding to the surgeon s view. (f) Surgeon s view (minimlly invsive ccess) with prolpse nd brod ter-off of chorde in A2 (blck rrows). DISCLOSURES Nme: Mximilin Dominik Hien, MD. Contribution: This uthor ssisted in the study design, conducted the study, nlyzed the dt, nd wrote the mnuscript. Attesttion: Mximilin Dominik Hien hs seen the originl study dt, reviewed the nlysis of the dt, pproved the finl mnuscript, nd is responsible for rchiving the study files. Nme: Helmut Ruch, MD. Contribution: This uthor ssisted in the study design, conducted the study, nd supervised the performnce of the study. Attesttion: Helmut Ruch hs seen the originl study dt, reviewed the nlysis of the dt, nd hs pproved the finl mnuscript. Nme: Artur Lichtenberg, MD. Contribution: This uthor ssisted in the conduct of the study nd the revision of the mnuscript. Attesttion: Artur Lichtenberg hs seen the originl study dt, reviewed the nlysis of the dt, nd hs pproved the finl mnuscript. Nme: Rffele De Simone, MD. Contribution: This uthor conducted the study, ssisted in the writing nd revising of the mnuscript, nd provided vluble dvice. Attesttion: Rffele De Simone hs seen the originl study dt, reviewed the nlysis of the dt, nd hs pproved the finl mnuscript. Nme: Mrc Weimer, DSc. Contribution: This uthor ssisted in dt nlysis, clculted the sttistics, nd cted s consultnt. Attesttion: Mrc Weimer hs seen the originl study dt, reviewed the nlysis of the dt, nd hs pproved the finl mnuscript. Nme: Orin Amnd Pont, MSc. Contribution: This uthor ssisted in dt nlysis, clculted the sttistics, nd cted s consultnt. Attesttion: Orin Amnd Pont hs seen the originl study dt, reviewed the nlysis of the dt, pproved the finl mnuscript, nd is responsible for rchiving the study files. Nme: Christin Rosendl, MD, DESA. Contribution: This uthor ssisted in the study design, conducted the study, nlyzed the dt, nd wrote the mnuscript. Attesttion: Christin Rosendl hs seen the originl study dt, reviewed the nlysis of the dt, nd hs pproved the finl mnuscript. This mnuscript ws hndled by: Mrtin J. London, MD nesthesi & nlgesi

9 ACKNOWLEDGMENTS The uthors thnk Thoms Müller, Tnj Scconi, Christoph Schrmm, nd Johnn Motsch for their ssistnce in dt cquisition. They lso thnk the Reserch Trining Group 1126 nd the Germn Reserch Foundtion (DFG) for supporting the reserch project. REFERENCES 1. Shnewise JS, Cheung AT, Aronson S, Stewrt WJ, Weiss RL, Mrk JB, Svge RM, Sers- Rogn P, Mthew JP, Quinones MA, Chln MK, Svino JS. ASE/SCA guidelines for performing comprehensive intropertive multiplne trnsesophgel echocrdiogrphy exmintion: recommendtions of the Americn Society of Echocrdiogrphy Council for Intropertive Echocrdiogrphy nd the Society of Crdiovsculr Anesthesiologists Tsk Force for Certifiction in Periopertive Trnsesophgel Echocrdiogrphy. Anesth Anlg 1999;89: Foster GP, Isselbcher EM, Rose GA, Torchin DF, Akins CW, Picrd MH. Accurte locliztion of mitrl regurgitnt defects using multiplne trnsesophgel echocrdiogrphy. Ann Thorc Surg 1998;65: Johnson ML, Holmes JH, Spngler RD, Pton BC. 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