Does normal pump function belie muscle dysfunction in patients with chronic

Transcription

1 PATHOPHYSIOLOGY AND NATURAL HISTORY VALVULAR HEART DISEASE Does norml pump function belie muscle dysfunction in ptients with chronic severe mitrl regurgittion? THOMAS WISENBAUGH, M.D. Downloded from by on October 29, 2018 ABSTRACT Left ventriculr cinengiogrphy nd micromnometry were performed simultneously in 27 ptients with chronic severe mitrl regurgittion (MR group) nd in 23 norml subjects (NL group). Stress (c) nd volume (V) were computed frme by frme. Mesurements were repeted fter phrmcologic lod mnipultion in subsets of MR (n = 10) nd NL (n = 11) groups. An inverse reltionship (r = -.90) between EFc (ejection frction determined from common prelod) nd 1es (fterlod) ws observed for the NL group. For the MR group, 10 of 14 with EFs less thn 0.60 nd four of 13 with EFs greter thn 0.60 hd muscle dysfunction, flling below the 95% prediction bnd of the norml EFC-Ges reltionship. Mximum myocrdil stiffness (mxen) determined from the end-systolic stress-strin reltionship of Mirsky, (ces = mxenwy 1og0(Ves/V0), ws in the MR (n = 10) vs in the NL group (n = 11, NS). EF ws in the MR nd in the NL group. Mitrl vlve surgery ws performed on 19 of the ptients with MR. All survived nd ll but one were symptomticlly improved; tht ptient required reopertion in the erly postopertive period becuse of trnsverse midventriculr disruption. Thus, contrctile function s ssessed by stress-strin nd EFc-fterlod reltionships is frequently norml in individuls with MR when EF is norml. When EF is depressed, contrctile function s ssessed by EFc-fterlod reltionships is frequently depressed, but this does not preclude stisfctory surgicl result. Circultion 77, No. 3, , EJECTION FRACTION is often depressed fter chronic mitrl regurgittion (MR) is corrected with prosthetic vlve. This occurs even when preopertive ejection frction is norml.1 Since reduced fterlod tends to ugment ejection performnce in cute MRII1,2 3it seems logicl tht correction of chronic MR might cuse the ejection frction to be depressed by fterloding the ventricle, thereby "unmsking" preopertive contrctile dysfunction. This hypothesis, which hs long been ccepted s n explntion for the disppointing surgicl results in ptients with chronic MR,4-9 hs not been confirmed with studies of preopertive contrctile function, since no lod-independlent methods hve been vilble for clinicl use. Accordingly, the purpose of the present study ws to ssess preopertive contrctile stte in ptients with chronic, severe MR by use of recently developed meth- From the Veterns Administrtion nd University of Kentucky Medicl Centers, Lexington, KY. Supported in prt by grnt from the Americn Hert Assocition, Kentucky Affilite. Address for correspondence: Thoms Wisenbugh, M.D., MN 670 Crdiovsculr Division, University of Kentucky Medicl Center, 800 Rose St., Lexington, KY Received July 15, 1987; revision ccepted Nov. 20, Vol. 77, No. 3, Mrch 1988 ods tht re reltively independent of lod. The possible prognostic significnce of these mesures of contrctile stte were then exmined in ptients undergoing mitrl vlve surgery. Methods Subjects. Ptients with mitrl regurgittion in whom simultneous cinengiogrphy nd micromnometry were performed in our lbortories between Mrch 1983 nd September 1987 were included in the present nlysis if: (1) MR ws judged to be the predominnt mitrl lesion, i.e., there ws 3 + to 4 + regurgittion of contrst into the left trium on ngiogrphy, nd mitrl vlve re of 1.3 cm2 or greter ccording to ngiogrphic flow nd the Gorlin eqution, (2) there ws no significnt ortic vlve disese, i.e., no more thn 1 + ortic insufficiency nd no more thn 5 mm Hg ortic vlve grdient, nd (3) there ws no history of myocrdil infrction or segmentl wll motion bnormlities on ngiogrphy. Twenty-seven ptients who hd predominnt or isolted severe mitrl regurgittion by these criteri nd who hd left ventriculogrms dequte for edge detection were included in this study, nd comprise the MR group. The men estimted regurgitnt frction for the MR group ws (n = 23; tble 1). MR ws judged to be chronic in ll but one of these ptients on the bsis of symptoms or physicl findings tht were present for t lest 3 months; the remining ptient hd symptoms for only 3 weeks but hd incresed end-distolic dimeter (6.1 cm) s ssessed by echocrdiogrphy. All but six ptients were in norml sinus 515

2 WISENBAUGH TABLE 1 Clinicl nd ngiogrphic dt Ptient FC Age BSA EDVI ESVI LVMI No. CuseA NYHA (yr) (m2) RF (m/rm2) (m/rm2) EF (g/m) Downloded from by on October 29, 2018 MR group 1 Myx Myx III Myx III Myx IT RHD II RHDB IV RHD III Afib RHDB III SBE I RHD III Afib Myx IV RHDB III RHD III Myx RHD1B IV Afib RHDB IV Abib Myx IV Myx II Myx II RHD III Myx IV Myx III RHD I Myx IV RHDB II CCM IV Myx III Men SD c 2lc 0.lIC 33C NL group Men SD FC NYHA preopertive New York Hert Assocition functionl clss; BSA = body surfce re; RF regurgitnt frction; EDVI = end-distolic volume index; ESVI = end-systolic volume index; EF = ejection frction; LVMI = left ventriculr mss index. Atril fibrilltion (Afib) precluded computtion of n ccurte RE in two ptients. ACuse of mitrl disese ws myxomtous (m'yx), rheumtic (RHD), myopthic (CCM), or heled endocrditis (SBE). BPorcine heterogrft degenertion fter surgery for RHD. csignificnt difference from norml in MR group. rhythm: four of these were in tril fibrilltion but hd well- (3) left ventriculr ngiogrphic wll thickness less thn 1. 1 cm, opcified bets preceded by cycle length tht differed by no nd (4) no evidence of vlvulr hert disese. more thn 15% from the verge cycle length; two others, one Long-term crdic medictions tken by the ptients were - ofwhom ws lso in tril fibrilltion, hd VVI pcemkers, nd blockers (three in MR group, nine in NL group), digoxin (20 in thus hd regulr rhythm t the time of study. Coronry rte- MR group, one in NL group), diuretics (15 in MR group, three riogrms were norml in ll but three ptients who hd signif- in NL group), long-cting nitrtes (seven in MR group, 11 in NL icnt single-vessel disese but no history of myocrdil infrc- group), clcium-chnnel ntgonists (five in MR group, seven in tion, unstble ngin, or wll motion bnormlities on NL group), either hydrlzine or cptopril (nine in MR group, one cinengiogrphy. in NL group), nd miodrone (one in MR group). Medictions An NL group ws comprised of 23 "norml" subjects who were not discontinued for ctheteriztion, with the exception of underwent ctheteriztion for evlution of chest pin syn- nitrtes nd clcium ntgonists tht were omitted for ergonovine dromes tht were not typicl of ngin, nd who were found to chllenges in four members of the NL group (see below). hve: (1) norml coronry rteries, (2) norml left ventriculr Ech ptient gve informed consent to protocol pproved function s defined by n ngiogrphic ejection frction of 0.60 by the joint University of Kentucky/VA Institutionl Review or more or, in four ptients who did not undergo bseline Bord. cinengiogrphy until fter 515IRUAT6 intervention (see below), minor- Procedure. Ptients were premedicted with orl dizepm, xis shortening frction of 0.30 or more by echocrdiogrphy, 5 to 10 mg. Right hert ctheteriztion ws performed in ll 516 CIRCULATION

3 PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE Downloded from by on October 29, 2018 ptients in the MR group. Left hert ctheteriztion ws performed retrogrde vi femorl or brchil rtery with the use of n 8F micromnometer ctheter with pigtil configurtion. Left ventriculr pressure ws recorded simultneously with injection of 39 to 54 ml meglumine ditrizote into the left ventricle during biplne cine ngiogrphy (30 degree right nterior oblique nd 60 degree left nterior oblique). In subsets of the MR group (n = 10) nd norml group (n - 11), ngiogrphy ws performed twice: once with, nd once without phrmcologic fterlod mnipultion. In ll ptients in the MR group, lod ws reduced by n infusion of sodium nitroprusside beginning t 0.25,ug/kg/min, nd incresing by 0.25 ig/kg/min every 3 min to decrese ortic systolic pressure by 20% to 40% but to no less thn 80 mm Hg. In the NL group, lod ws ltered by one of three methods: 0.35 mg ergonovine in three divided intrvenous doses in four subjects, 0.8 mg nitroglycerin in two eqully divided sublingul doses in three subjects, or intrvenous nitroprusside by the method described bove in the remining subjects. A 15 to 20 min intervl seprted the first nd second ventriculogrms to llow the hemodynmic effects of the contrst gent to dissipte. During this time neither the ptient nor the imging equipment ws moved. Ptients were instructed not to perform Vlslv mneuver during inspirtion held for the ventriculogrphic exmintion. Immeditely fter the second contrst cinengiogrm, rdiogrphic grid positioned t midchest ws imged biplne to provide corrections for mgnifiction. During the erly period of study, bseline cinengiogrm ws obtined before the infusion of nitroprusside nd second cinengiogrm. However, we soon lerned tht it ws esier to reduce lod with nitroprusside before rther thn fter the first injection of contrst. Subsequently, therefore, the nitroprusside cinengiogrm ws obtined first; the drug ws then discontinued nd the second cinengiogrm ws obtined 15 to 20 min lter. This llowed for greter difference in lod between the two cinengiogrms since the volume-loding effect of contrst further elevted pressures bove bseline. Precise synchroniztion between pressure nd cinengiogrphy ws chievble with cine frme mrker, which records mrk for ech film exposure (60/sec) simultneously with the pressure recording, nd exposes every hundredth frme with diode simultneously with n ccentuted mrk on the pressure recording. No ptient experienced ny symptom other thn mild fcil flushing during the infusion of nitroprusside, nd there were no complictions. Anlysis of ctheteriztion dt. Methods were similr to those used previously in this lbortory. `0 Briefly, left ventriculr silhouettes for ech frme of the first well-opcified bet of ech left ventriculr cinengiogrm not preceded by n ectopic bet were digitized with hnd-held cursor. Left ventriculr wll thickness ws mesured t the mid third of the nterior wll in the right nterior oblique view for the end-distolic frme. Correction fctors for ventriculr mesurements were derived from the grids positioned t the center of the ventricle. Left ventriculr volume ws computed by the re-length method nd regression eqution.1' Since the silhouette borders in the left nterior oblique view were sometimes uncler over the spine nd diphrgm, nd since segmentl dyssynergy ws bsent, volumes were computed from the single-plne right oblique view. Left ventriculr mss ws computed with wll thickness mesured t end-distole.12 Dynmic wll thickness ws computed for ll frmes subsequent to end-distole ssuming constnt mss for ech frme ccording to the method of Hugenholtz et l.'3 Left ventriculr pressure for the corresponding crdic cycle ws digitized with use of the midportion of the QRS complex s reference point for end-distole. Men circumferentil wll stress ws computed with Mirsky's`4 eqution: 06 = (PDm/2h)-[1 - h/din - Dm2/2Lm2I where P is pressure, h is wll thickness, nd D. nd L. re dimeter nd length, respectively, t the midwll. Lgrngin strin ws defined s: EL= (D. nd nturl strin ws defined s: - Dom)JDom EN = loge(dmid0m) where Dom is the theoreticl DM t zero stress. In terms of cvity volume, nturl strin cn be defined lterntively s: -N = ylog(vivn) where VO is the zero stress volume, nd y is the geometric fctor relting systolic D.. to V in the eqution: DM = A.V' where A is regression constnt.15 End-systolic reltionships re obtined by fitting the dt, which ws not smoothed, to the equtions: Cyes for Lgrngin strin nd Ges = mxel*(dm - Dom)IDom = mxen-y10oge(ves/vo) for nturl strin, where mxe is the mximum myocrdil stiffness nd V is the volume t mximum stiffness. For this nlysis, n initil vlue of Do. or V0 ws pproximted by the pproprite extrpoltion; the mximum slope of the c--e reltionship ws obtined by modifiction of the method of Kono et l.`6 Briefly, this is n itertion tht first finds the mximum quotient of o(t)/c(t) for ech loop (t = time), then performs three-point liner regression with use of these two vlues nd with the first pproximtion of DO, (or V.) s the third point. A second intercept is obtined from this regression eqution, nd the process is repeted until convergence occurs on mximum vlue for the slope with finl vlue for D., (or VJ. To determine distolic volume t common prelod for ll ptients, three-constnt exponentil eqution ws fit to ech ptient's distolic stress-volume dt: Od = + b.ek.vd nd solved for Vd t d = 50 (figure 1). For the ptients receiving nitroprusside, the best fit to the vilble dt from both loops ws obtined. Vd nd ESV (end-ejection volume) were then used to compute ejection frction from common prelod: EFc = (Vd -ESV)/Vd Men normlized systolic ejection rte ws computed s: MNSER = EF/ET where EF is ejection frction nd ET is ejection time. Dt re reported s men ± SD. Group comprisons were Vol. 77, No. 3, Mrch

4 Downloded from by on October 29, 2018 WISENBAUGH y _ (Gd = + b.ek.vd 80_ 60_ 40K 20K o Volume (ml) FIGURE 1. The distolic stress-volume reltionship for two differently loded bets (open squres re dt points during bseline cinengiogrm, solid squres re dt points fter lod ugmenttion with ergonovine) in norml subject. These dt were used to determine distolic volume t common prelod of 50 kdynes/cm'. This volume ws then used to compute EF, s described in Methods. performed with nlysis of vrince, with.05 s the criticl level. Results Clinicl nd ngiogrphic dt for ech individul ptient with MR re listed in tble 1. Left ventriculr end-distolic volume ws incresed nd ejection frction ws decresed in the MR compred with the NL group, but there ws wide vrition for both of these vribles. Ejection frction ws less thn 0.60 in 14 of the 27 ptients with MR. There ws modest depression in ejection frction for those with rheumtic disese ( ) compred with those with mitrl disese of nother cuse (0.63 ± 0.10, p =.06). Afterlod estimted s end-systolic stress ws not reduced in the group with chronic MR ( kdynes/cm2) vs the NL group (192 ± 54 kdynes/cm2, NS), nd in only one of the ptients in the MR group did end-systolic stress fll below the lowest vlue in the NL group (82 kdynes/cm2). Prelod estimted s enddistolic stress ws incresed in the MR (71 ± 29 kdynes/cm2) vs the NL group (49 ± 19 kdynes/cm2, p <.01). There ws strong inverse correltion (r -.90, = SEE = 0.046) between ejection frction corrected for prelod (EFc) nd end-systolic stress mong the 23 norml subjects (figure 2, top). Lod mnipultion in 11 of these norml subjects resulted in shifts in individul EFC-end-systolic stress reltionships tht were nerly prllel to those for the entire group (figure 2, bottom), suggesting tht significnt chnges in con- 518 trctile stte did not occur during lod mnipultion. Figure 3 shows EF,-end-systolic stress coordintes for the 27 ptients in the MR group vs the norml 95% prediction bnd (top pnel); lod mnipultion ws performed in 10 (bottom pnel). Of the 13 ptients in the MR group in whom bseline ejection frction ws greter thn 0.60 (men ejection frction NS vs norml group), nine hd vlues tht fell within or bove the 95% prediction bnd for the norml EFC-end-systolic stress reltionship; thus, norml pump function did not belie muscle dysfunction in these ptients. However, contrctile stte estimted s EFC-end-systolic stress ws depressed in four of 13, despite preservtion of ejection frction by ugmented prelod (end-distolic stress kdynes/cm2). Of the 14 ptients in the MR group in whom bseline ejection frction ws depressed below 0.60 (men ejection frction , p <.001 vs norml), three hd norml EFC-end-systolic stress reltionships, suggesting preservtion of contrctile stte nd depression in ejection frction due to incresed fterlod (end-systolic stress 272, 223, nd 253 kdynes/cm2). An dditionl ptient who hd depressed ejection frction (0.45) nd fell long the lower limit of the 95% prediction bnd lso hd incresed fterlod (end-systolic stress 343 kdynes/cm2). In the remining 10 the EFC-end-systolic stress reltionship fell below norml due to muscle dysfunction. Thus, pump function s ssessed by ejection frction ccurtely reflected muscle function (EFc-end-systolic stress) in 19 of 27 ptients with MR, but overestimted it in four, nd underestimted it in four. Since distolic wll stress is ffected by fctors extrinsic to the left ventricle, such s pericrdil restrint nd left ventriculr-right ventriculr interction, prelod my hve been overestimted in some of the ptients in the MR group due to subcute crdic dilttion. This possibility is supported by the downwrd shifts tht were pprent in the distolic stressvolume curves of three of 10 of these ptients fter infusion of nitroprusside. The velocity-stress reltionship hs been suggested s prelod-insensitive lterntive to the shortening-stress reltionship, 17 nd nlysis with its use (figure 4) reveled fewer contrctile bnormlities thn did the nlysis using the EFc-endsystolic stress reltionship (figure 3). Stress-strin nlysis ws ssessed from two differently loded bets in subsets from the NL (n = 11) nd MR (n - 10) groups for whom the men ejection frction ws nd , respectively. The influence of phrmcologic lod mnipultion on hemodynmic vribles, nd the resulting CIRCULATION

5 PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE 0.9 EFC l1-v H 0.6 Downloded from by on October 29, 2018 EFC _ 0.3 _ 0.2 h 0.1 _ n _._ n Ges(kdyn/cm ) FIGURE 2. Liner regression line (r = -.90, SEE = 0.046, p <.0001) nd 95% prediction bnd for EF, vs end-systolic stress (Ges) in 23 norml subjects (top), 11 of whom hd second cinengiogrm performed during lod mnipultion (see Methods). Pired EFc-1es coordintes from differently loded bets re connected by solid lines (bottom). stress-strin dt, re presented in tble 2. Figure 5 shows the derivtion of Dom from o-dimeter loops (left pnel); Dom ws then used to compute the O-EL reltionship (middle pnel). The o-- reltionship is nonliner when expressed in terms of cvity volume (right pnel). Mximum myocrdil elstnce (mxen) ws preserved in the MR group (tble 2), despite significnt ventriculr dilttion, s illustrted in figure 6. Use of the Lgrngin definition of strin did not lter this result (mxel vs Vol. 77, No. 3, Mrch 1988 kdynes/cm2 in NL, NS). In only one ptient did mxen fll below the lowest norml vlue (778 kdynes/cm2); this ptient ws believed to hve primry crdiomyopthy bsed on ctheteriztion done 3 yers erlier, which showed depressed ejection frction t time when the severity of MR ws only mild to moderte. Relxtion mesured s the mximum rte of erly distolic pressure decy (-dp/dtm.x) ws depressed in the MR group ( vs mm Hg/sec in the NL group, p <.002). However, in 10 of 519

6 WISENBAUGH EFC o o 0.31 _~~~~~~~ C ) 1., IlII [ Downloded from by on October 29, 2018 EFC t 1~ ~~ ~~~~~~~~~~~~~~~~~~~ J I Ges(kdyn/cm 2) FIGURE 3. EFc-end-systolic stress (des) dt point in the 27 ptients with MR vs the norml 95% prediction bnd generted for figure 2 (top). Lod intervention ws performed in 10 of the ptients in the MR group, nd the pired dt points re connected by solid lines in the bottom pnel. the 11 ptients in the MR group with bnorml relxtion (i.e., tht 2SDs below the norml men vlue of - dp/dtmx), there ws concomitnt depression in contrctile performnce s ssessed by the EF,-endsystolic stress reltionship, suggesting tht relxtion bnormlities often ccompny - but do not precede - contrctile bnormlities. Although there hs been specultion tht the ventricle might continue to empty into the left trium fter the end of mechnicl systole in the presence of mitrl 520 regurgittion, figures 5 nd 6 illustrte the proximity of end-ejection to the frme t which elstnce ws mximum. End-ejection volume ( ml/m2) ws only 7% less thn the mximl elstnce volume (68 31) in the 10 ptients in the MR group in whom mxen ws mesured. Nineteen ptients underwent mitrl vlve surgery nd received Bjork-Shiley prosthesis (n = 9), Omniscience prosthesis (n = 1), St. Jude prosthesis (n - 5), tissue vlve (n = 2), or mitrl vlve reconstruction CIRCULATION

7 PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE n z Downloded from by on October 29, I I ' (es FIGURE 4. Men normlized systolic ejection rte (MNSER) ws inversely relted to end-systolic stress (oes) in norml subjects (n = -.72, SEE = 0.33, p <.0001), s represented by open squres. The correltion ws not improved fter correcting MNSER for hert rte (r = -.64). MR group ptients re represented by solid squres. The solid nd broken lines re the regression line nd 95% prediction bnd, respectively, for the NL group. (n = 2). There were no periopertive deths nd no lte deths fter men postopertive follow-up intervl of months. All but one ptient ws in New York Hert Assocition functionl clss I or II fter surgery; the remining ptient required emergency reopertion in the erly postopertive period for trnsverse midventriculr disruption (figure 7). Clinicl improvement occurred (kdyn/cm2) mxac/adm = 1851 Dom = 5.38 cm m (yes = mxel.el Dom = 5.38 cm 2 mxe, = 994 kdyn/cm r E) /C* ': s 11 E despite EF,-end-systolic stress reltionships tht were depressed in nine of the 19. Stress-strin dt were vilble on eight operted ptients, ll of whom improved; mxen ws within the norml rnge in ll eight. The end-systolic stress-volume index rtio ws 3.7 ± 1.7 in the MR group (vs 6.3 ± 1.3 in the NL group, p <.001), nd in five of the 19 operted ptients, this rtio ws 2.7 or less, level ssocited c]* OP * O1 % , _ es mxew'y.loge(ves/vo) Vo = = 41 ml - mxen = 835 kdyn/cm 2 / c - ~~~ 00 - ~ - / O *0.. 0 U * I /1;, 1 1 I Midwll Dimeter (cm),= (Dm-Dom)/Dom Volume (ml) FIGURE 5. The method for determining the unstressed midwll dimeter (D.m) from the end-systolic stress (o)-midwll dimeter dt during control cinengiogrm (open squres) nd during lod reduction with nitroprusside (solid squres) in ptient with MR (left). Derivtion of slope (mxel) of the end-systolic stress (j)-lgrngin strin (EL) reltionship is illustrted in the middle. The dt cn, lterntively, be expressed in terms of cvity volume (right) by use of the nturl definition of strin (EN) nd the regression constnt (y) relting volume to dimeter during systole. Vol. 77, No. 3, Mrch Cl O: D 1 E) 13 qp [3 % U (1 cl p'cb % cl -f

8 WISENBAUGH TABLE 2 Hemodynmic nd stress-strin dt resulting from lod mnipultion LVP LVP VI ce Ptient (mm Hg) (mm Hg) (ml/m') (kdynes cm') mxe No (ml) (kdyneslcm2) MR group Men SD A 29A 21 A A 716 NL group Men SD Influence of lod mnipultion on pek left ventriculr pressure (LVPp,k), pressure t mximl elstnce (LVPeS), nd the corresponding volume index (VIes) nd stress (c,s) t mximl elstnce (mxen). V0 is the zero stress volume (not indexed for BSA). 1 = before nitroprusside; 2 = fter nitroprusside. ASignificnt difference from norml in MR group. Downloded from by on October 29, 2018 with poor outcome fter mitrl vlve replcement in the studies of Crbello et l,4. The influence of ventriculr dilttion on end-systolic stress/volume index rtio independent of contrctile function'8 is illustrted in figure 6. (y m o m El NL MR *m (yes/vies mxen Discussion Intuitively we would expect tht correction of chronic MR, by removing the so-clled low-impednce lek into the left trium, would increse the fterlod on the ventricle, nd thereby reduce the ejection frcl U MR : 0 / cl n. O11oo D u D Volume (ml) Volume (ml) FIGURE 6. Stress (o)-volume dt in norml subject (left) nd ptient with MR (right). Although the reltionship between end-systolic stress nd end-systolic volume (solid curve) is depressed compred with norml (due to ventriculr dilttion), the V,-normlized mxe. vlue indictes preservtion of contrctile force t ny degree of stretch in the ptient with MR. The simple end-systolic stress-end-systolic volume index (o3,-v105) rtio is lso much lower thn norml (t common fterlod, ocs, 200 kdynes/cm2) in the MR ptient due to ventriculr dilttion. 522 CIRCULATION

9 PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE Downloded from by on October 29, z I < PRE-OP POST-OP FIGURE 7. Preopertive nd postopertive New York Hert Assocition functionl clss in 19 ptients with MR who underwent mitrl vlve surgery. tion. This concept derives support from studies in dogs tht demonstrted tht brupt MR results in decresed ventriculr wll stress nd ugmented ejection performnce.2 Reversl of this condition hs the opposite effect on ventriculr lod nd performnce.3 Studies by Wong nd Spotnitz'9 demonstrting incresed wll stress immeditely fter discontinution of crdiopulmonry bypss in ptients undergoing mitrl vlve replcement lso supports the concept tht correction of MR fterlods the ventricle. It hs therefore been ssumed tht preopertive contrctile dysfunction, msked by fvorble loding conditions, is the bsis for depressed postopertive ejection frction in ptients who hve norml ejection frctions before surgery. Tht chronic volume overlod depresses myocrdil contrctile stte hs been inferred from clinicl observtions but never directly proven. Cooper et l.,20 in fct, found norml muscle function with experimentl volume-induced hypertrophy tht ws of severity comprble to tht ssocited with muscle dysfunction when produced by pressure overlod. However, it is possible tht muscle function might deteriorte with more severe overlod pplied for longer durtion. Depressed performnce hs long been recognized in ptients with volume overlod due to MR, but whether this cn be ttributed to the volume overlod per se or Vol. 77, No. 3, Mrch 1988 n ssocited condition, such s rheumtic myocrditis or other crdiomyopthy, is uncertin. The present study confirms the presence of contrctile dysfunction by lod-independent methods in substntil portion of ptients with chronic, severe MR. However, contrctile function estimted s mxen or EFc-end-systolic stress ws frequently norml when the ejection frction ws preserved, which csts doubt on the concept tht reduced fterlod msks contrctile dysfunction in chronic MR. Indeed, previous studies hve lso shown tht fterlod is norml or slightly incresed in chronic MR,21 22 nd recent experimentl study demonstrted tht reduced fterlod returns to norml short while fter MR is bruptly produced.23 Thus, some degree of pump dysfunction in ptients with MR my ctully be due to pressure overlod, s hs previously been recognized in the presence of ortic stenosis.24 If correction of MR were to reduce ejection performnce by incresing fterlod, n increse in endsystolic volume would be expected. To the contrry, Boucher,1 Schuler7 nd their collegues found endsystolic volume nd dimeter, respectively, to be essentilly unchnged fter mitrl vlve replcement. Prticulrly interesting re the findings fter repir of mitrl incompetence without the use of prosthetic vlves. Lessn24 nd Bonchek25 nd their collegues found tht end-systolic volume decresed fter repir of mitrl incompetence, nd ejection frction fell only slightly. These dt suggest tht fterlod my ctully decline fter repir of the incompetent mitrl vlve. Removl of excessive prelod probbly ccounts for the slight fll in ejection frction fter repir of MR, since the men end-distolic volumes returned to norml (40% reduction) in both of these studies An lterntive to this time-honored hypothesis, tht correction of chronic MR decreses ejection frction by fterloding the ventricle, is the hypothesis tht severing the chorde tendinee during mitrl vlve replcement redistributes stresses within the myocrdil wll in such wy s to "untether" the ventricle. This my explin why globl25-28 nd regionl28 ventriculr function seem to be better when chordl ttchments re preserved. An extreme form of "untethering" my ccount for the ctstrophic phenomenon of trnsverse midventriculr disruption described by Cobbs et l.29 fter mitrl vlve replcement. Wht fctors predispose to this type III rupture,29 which occurred in one of our ptients, is unknown. The lck of suitble index of contrctility hs impeded our understnding of the effects vlvulr lesions on the myocrdium. Both the slope of the pres- 523

10 Downloded from by on October 29, 2018 WISENBAUGH sure-volume reltionship (Emx) nd the simple rtio of stress/volume index t end-systole hve recently been used to estimte contrctile stte,4' 5but both re dependent on the size of the ventricle30 (figure 6). To normlize for the lod nd/or size-dependence of these indexes, lterntives hve recently been proposed. The reltionship between ejection frction nd fterlod in ptients compred with tht in norml subjects is one method tht hs been used by other investigtors.31 Although this method tkes fterlod into ccount, prelod remins vrible. In the present study, therefore, ejection frction ws computed from distolic volume t common prelod derived from the pssive stress-volume curves for ech ptient. A method of correcting Emx for size dependence, recently proposed by Mirsky,'5 is the nlysis of stress nd strin to derive systolic myocrdil stiffness (mxen nd mxel in the present study). The stress-strin reltionship for the ventricle should be directly relted to the reltionship between force nd normlized length for isolted muscle, nd this reltionship describes the totl systolic force tht cn be ttined t ny given degree of stretch.32 As previously discussed,'0 the mjor methodologic limittions imposed by considertions of ptient sfety in this study re the use of only two differently loded bets to determine mxen, nd the fct tht utonomic blockde ws not routinely used. Thus, sctter in the stress-strin dt produced by chnges in contrctile stte during lod mnipultion (figure 3, bottom) might obscure deficits in mxen for ptients with MR vs norml subjects. The fct tht EFc-end-systolic stress reltionships were depressed in three ptients in whom mxen ws norml rises questions gin10 bout the sensitivity of this index s we hve mesured it. The usefulness of the EFC-end-systolic stress reltionship is limited by the extent to which corrections for prelod (end-distolic stress) re ffected by fctors extrinsic to the left ventricle. Ludbrook et l.33 demonstrted downwrd displcement of the distolic pressure-volume reltionship with nitroglycerin, nd suggested reduction of right ventriculr filling pressure s the mechnism. Studies of Tyberg et l.34 demonstrting close correltion between right tril pressure nd left ventriculr pericrdil surfce pressure lso suggested tht externl constrint on the left ventricle is in prt determined by right ventriculr filling pressure. However, Herrmnn et l.35 were not ble to completely negte nitroprusside-induced displcements in the distolic pressure-volume curves by correcting for right tril pressure. Likewise, mong the ptients with MR in the present study, n obvious shift 524 occurred in ptient with right tril pressure of only 4 mm Hg, wheres little or no shift ws observed in ptients with right tril pressures of 12 to 17 mm Hg. Thus, estimtion of prelod (i.e., trnsmurl distolic stress) is beset by problems tht re not immeditely solvble. Coln et l.'7 suggested velocity of shortening corrected for hert rte s less preloddependent index thn extent of shortening. As shown in figure 4, there ws greter stndrd error of the estimte for the ejection rte-end-systolic stress reltionship thn for the EF,-end-systolic stress reltionship, nd this sctter ws not improved by correcting for hert rte. However, this nlysis does support the conclusion lso derived from EFC-end-systolic stress nlysis tht contrctile impirment is uncommon in ptients with mitrl regurgittion when ejection frction is norml. The filure of depressed contrctile stte s mesured by EFc-end-systolic stress to predict poor surgicl outcome my not be pplicble to ll ptients undergoing surgery for MR. The number of ptients with MR undergoing surgery ws smll (n = 19). The surgicl mortlity ws nil. Few ptients were in tril fibrilltion. Ptients without two consecutive wellopcified nonectopic bets during ngiogrphy were excluded. Thus, the predictive vlue of EF,-end-systolic stress nd mxen needs further study. The finding of Crbello et l.5 tht the end-systolic stress/volume index rtio, when corrected for ventriculr size, hd no predictive vlue independent of end-systolic volume index suggests tht ventriculr size my influence surgicl outcome more thn contrctility per se. The present findings likewise indicte tht impired contrctility s mesured by EFc-end-systolic stress does not preclude symptomtic improvement fter surgicl correction of chronic, severe MR. The findings lso cst doubt on some long-held beliefs bout the mechnics of this lesion nd its influence on myocrdil function nd lod. The ssistnce of Dr. Dvid Booth in collecting the ctheteriztion dt on ptients 15 nd 26 is pprecited. References 1. Boucher CA, Binghm JB, Osbkken MD, Okd RD, Struss WH, Block PC, Levine FH, Phillips HR, Pohost GM: Erly chnges in left ventriculr size nd function fter correction of left ventriculr volume overlod. Am J Crdiol 47: 991, Urschel CW, Covell JW, Sonnenblick EH, Ross J Jr, Brunwld E: Myocrdil mechnics in ortic nd mitrl vlvulr regurgittion: the concept of instntneous impednce s determinnt of the performnce of the intct hert. i Clin Invest 47: 867, Sprtt JA, Olsen CO, Tyson GS Jr, Glower DD Jr, Dvis JW, Rnkin JS: Experimentl mitrl regurgittion: physiologic effects of correction on left ventriculr dynmics. J Thorc Crdiovsc Surg 86: 479, Crbello BA, Noln SP, McGuire LB: Assessment of preopertive CIRCULATION

11 PATHOPHYSIOLOGY AND NATURAL HISTORY-VALVULAR HEART DISEASE Downloded from by on October 29, 2018 left ventriculr function in ptients with mitrl regurgittion: vlue of the end-systolic wll stress-end-systolic volume rtio. Circultion 64: 1212, Crbello BA, Willims H, Gsh AK, Kent R, Belber D, Murer A, Siegel J, Blsius K, Spnn JF: Hemodynmic predictors of outcome in ptients undergoing vlve replcement. Circultion 74: 1309, Kennedy JW, Doces JG, Stewrt DK: Left ventriculr function before nd following surgicl tretment of mitrl vlve disese. Am Hert J 97: 592, Schuler G, Peterson KL, Johnson A, Frncis G, Dennish G, Utley J, Dily PO, Ashburn W, Ross J: Temporl response of left ventriculr performnce to mitrl vlve surgery. Circultion 59: 1218, Borow KM, Green LH, Mnn T, Sloss LJ, Brunwld E, Collins JJ Jr, Cohn L, Grossmn W: End-systolic volume s predictor of postopertive left ventriculr performnce in volume overlod from vlvulr regurgittion. Am J Med 68: 655, Zile MR, Gsch WH, Crroll JD, Levine HJ: Chronic mitrl regurgittion: predictive vlue of preopertive echocrdiogrphic indexes of left ventriculr function nd wll stress. J Am Coll Crdiol 3: 235, Wisenbugh T, Elion JL, Nissen SE: Influence of ortic vlve disese on systolic stiffness of the humn ventriculr myocrdium. Circultion 75: 964, Wynne J, Green LH, Grossmn W, Mnn T, Levin D: Estimtion of left ventriculr volumes in mn from biplne cinengiogrms filmed in oblique projections. Am J Crdiol 41: 728, Rckley CE, Dodge HT, Coble YT, Hy RE: A method for determining left ventriculr mss in mn. Circultion 29: 666, Hugenholtz PG, Kpln E, Hull E: Determintion of left ventriculr wll thickness by ngiocrdiogrphy. Am Hert J 78: 513, Mirsky I: Left ventriculr stress in the intct humn hert. Biophys J 9: 189, Mirsky I, Murkmi T, Hess OM, Kryenbuehl HP: Systolic myocrdil stiffness in ortic vlve disese. Circultion 72(suppl III): III-1464, 1985 (bst) 16. Kono A, Mughn WL, Sungw K, Hmilton K, Sgw K, Weisfeldt ML: The use of left ventriculr end-ejection pressure nd pek pressure in the estimtion of the end-systolic pressure-volume reltionship. Circultion 70: 1057, Coln SD, Borow KM, Neumnn A: Left ventriculr end-systolic wll stress-volocity of fiber shortening reltion: lod-independent index of myocrdil contrctility. J Am Coll Crdiol 4: 715, Tjimi T, Widmnn T, Mtsuzki M, Lee JD, Peterson KL: Left ventriculr end-systolic pressure volume nd stress volume reltions in experimentl mitrl regurgittion. Circultion 70(suppl II): IL- 354, 1985 (bst) 19. Wong CYH, Spotnitz HM: Systolic nd distolic properties of the humn left ventricle during vlve replcement for chronic mitrl regurgittion. Am J Crdiol 47: 40, Cooper G, Pug FJ, Zujko KJ, Hrrison CE, Colemn HN: Norml myocrdil function nd energetics in volume-overlod hypertrophy in the ct. Circ Res 32: 140, Eckberg DL, Gult JH, Bouchrd RL, Krliner JS, Ross J: Mechnics of left ventriculr contrction in chronic severe mitrl regurgittion. Circultion 47: 1252, Wisenbugh T, Spnn JF Jr, Crbello BA: Differences in myocrdil performnce nd lod between ptients with similr mounts of chronic ortic versus chronic mitrl regurgittion. J Am Coll Crdiol 3: 916, Berko B, Gsch WH, Tnigw N, Smith D, Crige E: Disprity between ejection nd end-systolic indexes of left ventriculr contrctility in mitrl regurgittion. Circultion 75: 1310, Gunther S, Grossmn W: Determinnts of ventriculr function in pressure-overlod hypertrophy in mn. Circultion 59: 679, Lessn A, Herremn F, Boffety C, Cosm H, Gurein F, Kr M, DeGeorges M: Hemodynmic nd cinengiogrphic study before nd fter mitrl vlvuloplsty (Crpentier's technique). Circultion 64(suppl II): , Bonchek LI, Olinger GN, Siegel R, Tresch DD, Keeln MH Jr: Left ventriculr performnce fter mitrl reconstruction for mitrl regurgittion. J Thorc Crdiovsc Surg 88: 122, Spence PA, Peniston CM, Tirone DE, Mihic N, Jbr AK, Nrini P, Slerno TA: Towrd better understnding of the etiology of left ventriculr dysfunction fter mitrl vlve replcement: n experimentl study with possible clinicl implictions. Ann Thorc Surg 41: 363, Hnsen DE, Chill PD, DeCmpli WM, Hrrison DC, Derby GC, Mitchell RS, Miller DC: Vlvulr-ventriculr interction: importnce of the mitrl pprtus in cnine left ventriculr systolic performnce. Circultion 73: 1310, Cobbs BW Jr, Htcher CR, Crver JM, Jones EL, Sewell CW: Trnsverse midventriculr disruption fter mitrl vlve replcement. Am Hert J 99: 33, Sug H, Hisno R, Goto Y, Ymd 0: Normliztion of endsystolic pressure-volume reltion nd Emx of different sized herts. Jpn Circ J 48: 136, Borow KM, Green LH, Grossmn W, Brunwld E: Left ventriculr end-systolic stress-shortening nd stress-length reltions in humns. Am J Crdiol 50: 1301, Brunwld E, Sonnenblick E, Ross J Jr: Mechnisms of contrction of the norml nd filing hert. Boston, Little, Brown nd Co., p Ludbrook PA, Byrne JD, McKnight RC: Influence of right ventriculr hemodynmics on left ventriculr distolic pressure-volume reltions in mn. Circultion 59: 21, Tyberg JV, Tichmn GC, Smith ER, Dougls NES, Smiseth OA, Keon WJ: The reltionship between pericrdil pressure nd right tril pressure: n intropertive study. Circultion 73: 428, Herrmnn HC, Ruddy TD, Dec GW, Struss HW, Boucher CA, Fifer MA: Distolic function in ptients with severe hert filure: comprison of the effects of enoximone nd nitroprusside. Circultion 75: 1214, 1987 Vol. 77, No. 3, Mrch