- Email: [email protected]
The frequency of familial disease in a consecutive series of 51 patients with idiopathic dilated cardiomyopathy
66A
JACC FChnlar~' 1~)9~
AII$1'RA(."I'S -Oi':d
In contrast, in trio MS group them was no additional decrease in ST shill during the second and third Inflation compared with the first. The reduction in ST shift altor,~od by MS during the first Inltetlon (--51% on IC-ECG vs first inflation in C) wets equivalent to that afforded by ischemlc preconditioning in controls (-~44% during the third vs first Inllallon), In conclusion, protroatment with MS mimics Iscbomle. preconditioning during PTCA, To our knowlodgo, these result9 provide the first evidence that morphine preeondltione humnn myoc~rdlum egemst I~chemia In viva end suggest that oplold recapture may play I1 r01e In the signaling pathways responsible for Ischemle precondition. Ing In rc~n, Bec¢t(mo of It~ efficacy and anlety, morphine could be used prophylactically to 11ttonuato i~chem111In high risk PTCA,
11:15 BriefAntecedent"preconditioning"lachem/n A¢celttretee CoronaryThrombolyeleIn the ~nnlne
~
Modal K, Przykl(~nl~, Ho,lrP In~ttflffe, Good S,Imwlrfffl~ Ho,qptf~f ,~ use, Los Angeles CA, USA
0
0
B~lckgrol~nd; It Is w(dl-ost~bllsl~ed that brlsl episodes of antoctedont iachomia "pmenndltton" (PC) the heart ~nd rodll~11 infarct Sl~e Caused by stlbs0, quont ~ut~t~ined coronary occlusion, In {lddllion, recent shldlne from o=Jr labor~tory rove~led that bdnl antecedent PC Ischemia al~o 11ffonuate8 sub. ~equont plrffelet aug'aeolian in damaged nnd 8tenotic coronary arteries by an adonoslno,medlated mechnnlsm, Our cgrmnt nlm wns to detelmlna whether the 11nltpl~tolotp~operties of PC Ischemie result iu morn rapid mpe~dugion rind better tnnlnl(~nnnco at '3t,b~equont vessel p~ton~,y in the t~otting el coronary thrombosls/lhrombol~sls, Mef/~,~: AneMhltttted doge undon~enl 10 mtn PC iscl~omla + 10 rain rollow (n ,. ?) or no intervention ( n . 7) prior to Initiation of thrombotic eomn~iry aftory occlusion. At 1 I~ allot the onset of thmmbo.qL% el! dogs received 1,.3mg/kg rt.PA, Primary study endpotnts included lifo timo required to achieve rollew', tht) duration of spontanoo(ls reoecluslon during the 2 h 11liar initial lysts: and the total duration of thrombotic ocQlugmn (all with nonperercotrlc dlstrlbt, tlons and ff~uS reported as the median [2.5th', 7.51h] percentiles), Ae socondnry ondpolntn, collateral blood flow was moesured during thrombotic occlusion bv inlcctton 0l mdtolnbolod mtcmsphor08, and infarct si~e delineated oy toh(t,:olitml Bt(tinieg altd expressed a~ ~ % at Ulo myocardlum at risk. Results'. Control
Procondlhonod
Time to lyt~i~, (fnin) "rime ~pont mocchldOd (rain)
47 113: 50] 20 [21 521
1117; 14)" (.~re: 101
T0t,'ltbraeoccludedthl
1 9 [1 ~,:261
13 i1 1. I 41"
11:30 ln Viva Suppressionof Myocardial Apoptotic Cell Death by Insulin-like GrowthFactor IGF I and II
M, Schoinowitz 1. G. Sangiorgi 2, L.G SpagnolP, A. Or;d.dP, A. Kotlyar ~, D, Hasdai ~. ~The Neufeld Cardiac Research Institute, TeI-Aviv, Israel: ~'Mayo Clinic, Rochesfer, USA: 3University of Rome Tar Vergata, Rome, Italy
Background: Apoptosis (Ape) is a form of programmed cell death occurring in physiological and patophysiological slates including myocardial infarction (MI), Insulin-like growth factors (IGF) t and II have been shown to suppress Ape in vitro, but their in viva effects are unknown. The purpose of this study ;i 100
R Control In • 4) ,. IGF-I (n - 4) tGF.U (n m4) • p < , 0 S v t , tGF-I
Oo •"~
and
N o r m l? zone
Border zone
Inflrct tone
tt:45 ~ U e a of a Novel AntI-ApoptotlcAgent (LXR017) Reduces Infemt Sire Following la©hemle,Reperfuslonin the Canine Myoeardlum M,,I, Silver, S,P, Chetcutl, DB~ Mukheqeo, J L Matycky, D,L Tomei ! , S, Um~tnsky t , FA. Nicolini, The C/eve/and Clinic Fo~lr~tatlon, Clevel~Tr~, OH, USA; t l, J~R BtoteCflne/egy tim, Rchmond, CA, USA We h~ve previously shown that ~ phospholipld agent (LXRO17) spc'cific11!ty prevents apeptotio cell death induced by semmtglucoso depnvation, a Imlralia! to in-viva ischomia mpodusion iniury, in rat neonate! catdiomyocytes ~inco apoptosis pl~ys a major rote in myocardial cell death following ischemia mpodusion, we sought to lest the efficacy of LXR017 in an in.viva model et ischomla mpodusion, Twenty open-chested dog~ um:lorwent temporan/ LAD occlusion (90 min) followed by rcpeduston (3 hrs). AI! dogs had continuous monitoring el ECG, loll ventricual pressure, and alP/dr. Fifteen rain prior ropodusion, dogs wore randomly administered either an intracoronary infusion of placebo (n = 6), SOD.Catalnso (5 mg/kg; n = 5) a positive control group, or LXR0t? (250 .g; n = 9) for a total of 75 rain. Endpoints included infarct stt.o measured by TI'C staining (% el area at ask), regional shodenin9 traction (SF) via sonomicmmotor crystals, regional myocardial blood llow via radioactive micresphems, and myelopemxidase (MPO) aetivdy. Baseline homodynamics as well aa regional myocardial blood flow were similar among groups and did not differ dunng the course el the study. Infarct size, MPO and SF findings at 3 hrs el repeduslon indicate that LXR0t7 prelects the tschom¢-mpertused cameo myocardium, and may provide a valuable new adjunct to repeduston therapy for acute myocardial infarction.
Placebo SOD-Cat~Iso LXR017
The time roqu,od to achieve initial lysis was signilicanlly shortened, and mlbsequont vessel potency tended to be bettor maintained, in dogs that received ~ntocodent PC ischemia va controls ("p . 0.05). This was, not St.lrprlsingiy, accompanied by a signifiennt reduction in infarct size (11% v~ 32% of the rlsk region; p • 0.0.5), despite comparable collateral pedusion, in the PC group. Conclusions: Briol preconditioning ischomia - in addition to its well-dec. umonted eardioprotectivo propedies - markedly shortens the time required for rt-PA-lndueod thmmbolysis in this canine model.
~
was to examine the effects ot tntmcomnary IGF-I end II administration on myocardial Ape in acute MI, Motltods: Coronary mlcmembollzation was porlormed using 100. affigol beads in pigs randomly .assigned to 0,5 I~g IGF.I, IGF.II, or bovine albumin, incorporated within the beads and gradually released. Altar sacrifice at 4 weoks, myocardial samples from tho Infarct (I), border (B), end normal zones iN) were asseeeod for Ape by TUNEL end Ilgatton.modlatod PeR, Results: TUNEL.posltlve celia wore obsontod particularly In 111nd B 11nd worn reduced In the treated antm1110~,Using PCR, IGF.I and II were also found to reduo0 the DNA ladderlng signal in I, with a eimllllr treed in I~ (~ee figure), Conchlsion~: Both IGF-I and II suppressed Ape in thi~ porcine, mod~l o! acute myocardial infarction, supporting ~ role for IGF.I 11nd .ll in regulating myocardial Apo in viva,
IO F-tl
InfarctSize (%) 22 ~ 2 11 ~ 6" 10 4'
D¢~ta,1[OWesor~todin me;.u~ ~ SD "P
MPO IU/rnm'g) 0198 ~ 009 0096 t OO1" 0094 ~ 003"
SF ~%) 332 : 308 28~ : 285" 312 ~ 259"
0 04 '~s Pl~ct.!boby ANOVA
Dilated Cardiomyopathies: New Observations and Approaches Monday, March 30, 1998, 2:00 p.m.-3:30 p.m Georgia World Congress Center, Room 367W 2:00 ]811-1) The Frequency of Familial Disease in a Consecutive Series o~ 51 Patients With Idiopathic Dilated Cardiornyopathy A. Gavazzi, M. Ponzetta, C. Campana, M. Giralch, C. Inserra, A. Raisaro. M.L. Laudisa, E. Colombi, B. Del Belle t , E. Arbustini ~. Div~sione d~ Cardiotogia. Italy: wIstituto dl Anatomia Patotogica dell'Universita, IRCCS Policlinico S. Matteo, Pavia, Italy
Background: Familial disease may account for a significant proportion of patients with dilated cardiomyopathy (DCM) and coutd be more frequent than is often recognised. Most previous repeals are of anedoctal or retrospective nature and only a few prospective studies have been published, Consequently, the real fr, queney of fan,trial disease in DCM remains to be established. Methods: Our aim was to assess the frequency and mode of inheritance of lamilial disease by prospectively screening relatives from a series of 51 consecutively diagnosed patients with DCM, The diagnosis of DCM was confirmed invasively in every patient, All patients had a 2-3 generation pedigree constructed. Familial disease was diagnosed when at least one relative was affected by DCM. Screening consisted of history, clinica~ examination with blood pressure measurement, 12 lead ECG, two dimensional Doppler echocardiography, signal averaged ECG (SAECG) and blood sample (serum CK).
JACC
Fehnta~, lqtlX
ABSTRA(q'~,
Left ventncutar enlargement (LVE) was defined as a LVEDDI . 32 mnVm2 ~nd a depressed left vonfhcuidr systolic function was defined affher as LVFS • 25% or LVEF -riO% R~sutts: Between 12/1994 and 3/1997, 208 ml~ttve~ were screened, moan ag~ 32 + ~ 17 yrs (range 4-73): 122 (58%) were 1st dogro0 rotor=yes, 59 (~8%) ~r',d, 27 (14%) 3r.J dot]me, DCM w ~ documented *n 1'~ relatives (9%) corlling from 12 famdws end repms~ted 23.5% of tt~L~ ~ r e e n ~ , The mode of inh~nfance in most famdms was autosomeI dominant, Ot the SAIECG, 11 (5,~;%)d~m~sed LVF$, ! 0 ( ¢ ~ ) L V E F -G0% SemmCK :. !90 mU/ml w~s p m ~ n t in 16-/!~3 mt~tive~s I 1 ~ ) and olher minor ~bnorn~fitief, w~re doo~mer~ed in 5 (~,4%) C O - - K I n ; Th~ f~mili~! p f ~ v ~ ! e ~ of DCM ¢PPeam 1o be higher than pmvo~s~t t~gSl~¢~ =fed (23,5% in th~ prospective sends): Fgrlhermore a t~ignifi, cant p r o g o ~ of i~arent!y health retalWes ~how~ minor ~'¢hoIa~_ ographlc or efe¢1~rdingraphi¢ abnormalities, s~ling a proitin~al disease, Early dtagnostK; emen~ for ~ M are ~ , 2;15 ~
CMdlm: Abno~litk~
!n O l a ! ~ t l c P N t e n t s
ASSO¢IMeRIWith a Milochondt!a13243bpI R N A Mutation
Y. Mom~yama, Y. Suzuki, F. Obsuzu ~, Y A~sum~, K MatSooka. M- K,mura
Satsezk~i Central H O s ~ . Tokyo, Japan; 'National Defense ~ t College. Saeam,a. Japan Background: t% el d~abetes melhtus (DM) msasseoatod wtth a m~tochondnal 3~43t~ IRNAt~uun~ m u t a t ~ wh~:h ~ ongmafly found m mitocho~foal encephalomyopathy (MELAS). Since carckac hypertrophy and failure are often reported in MELAS. the heart may be one of the large( organs of t.K~ mutatron also in thLStype of DM. Methods: We mves~gated cardiac structure and function using echocard~ocjr"~3~ in 11 ~ l ~ t i C I~t~ents (pts) wrth the IRNAL~=~'~i mutation (group A) compared wzth 70 control DM pts (group B). All pts were negatwe tar an exerets~ testing Or dip~ndamote ~ t T I ima~eg. ReSUlt'S: Between groups A and B, there was no d~fference m age. sex, body mass index. DM dural(on, blood gtycer~c ~evelsand blood pressures (p = NS) On the echocart~ograms, none showed any wall me,on abnormalmes LV hypertrophy of wall thickness • 12 mm was found in 3 of 11 pts t27%) m group A vs 3 of 70 pts (4%) in group B (p - 0.05). LV wall th~ckrtess and mass were greater in group A than in group B (9.8 : I 6 ram. 174 = 66 g ,~s 8.6 1.1 mm. 134 ~ 37g, p - 0005). In the pulsed Doppler analys~s of LV inflow velocmes, the A:E robe of peak velooty and the deCeleratzonbrae (DT) of E wave were greater ~ngroup A than in group B it .20 : 0 19, 212 _- 34 ms vs 099 : 021, 178 ~ 22 ms, p - 0005). All pts =n group A showed maternal inheritance ol OM and~or heanng ~mpa~rment, but 16 of 70 pts (23%) =ngroup B also had d~ab~tic mothers In group B. pts ~ t h diabetic mothers had slightly thicker LV walt (8 7 vs 8 6 ram), a greater A/E rst~o (1 03 vs 0.98) and longer DT (187 vs 175 ms) than pts without them. However, even compare~t wrth pts with diabetic mothers in group B, group A had sigoifrcantly thicker LV wall. a greater ~ ratio and longer DT. Conctusron:1 Diabetic pts with the tRNA L~¢uum mutation are likely to have impaired LV d~asto!ic function assocqated wdh hypertrophied LV, compared with ordinary DM pts.
2:30 ~~~
Infiltrative Cardiomyopathy Non-amyloid in Plasma Cell D y s c r a s t a s
J. Buxbaum, E. Genega. I. Kronzon. P A Tunick, G Gaffe VA Meal;col
Center & NYU Medical Center. NY. NY. USA Background: In moneclonal plasma ceil disorders, organ ,~mpmmise is produced by tissue deposition of monoclonal lmmunoglobulins fig). Deposits may be Congo red positive (AL amyloid) or negative (light chain deposition disease (LCDD)). Purpose: To determine the nature of cardiac dysfunction in pts wlth nonamyloid LCDD cardiomyopathy. Methods: Cardiac tissue (biopsy or necropsy) from 5 pts with ptasma cell dyscrasia and cardiac dysfunction was examioed by immunoh=stochemistry and electron microscopy. Charts were reviewed as were EKGs and eehocardiograros. Results: All 5 pts had non-amyloid menoclonal Ig myocardial deposits. The average ege was 47 (3 men). Heart size was normal on x-ray. EKG showed low voltage in 4 of 5 pts and arrhythmias in all 5. Echo shewed pericardial ~ftusion in 3. The average septal thickness was 1.4 cm and postenor wall thickness was 1.45 cm. The ejection fractions were normal (mean 65%). Left ventncular mass was increased and mitral valve deceleration times were shorter, than normal. The voltage/mass ratio was decreased.
()~,l
~?A
CO~CIUSIOnSr~l Although non-amytmd monnctonal Ig light CheladePO~ff~on in the myocardium ha~ a different localization and ~ltrastructur3| qrg~e,z~tton than dO~s the tibnltaf Congophil~ dop~sil~on of AL ~:myfo~d, ff ~ul~s ~n a patlom el dlaSlotlC dyslunchon an0 afflrtylhmla~ IcI~ntlcalto 1hOe6 ~ tn Ivp,caIcard),~: ~mylo~ddopo~,t)on 2 The d~algnos!~ of LCDD car~omyopathy shoutd be coesKk~md *n ptS w=th i ~ e ~ i ~ n 6 y (~as.lol¢ 0 y s l u r ¢ l ~ ~ = t~h Congo led staint~z for amylo~l is f~gatwe, 3, The ~ , s of L C ~ can be made by ~pp~oprl~te qmm~tnohist~hemcat ~p~j uftrSstm~l~rsI tissue
2:45
~
Succeutul~
of IdlOi;~hi¢Otm~d
Oa~llomyo!~tl~ by IgG Immuno~l~P,~io~, Relzg!t#
o f a ContfOlle¢l S t u d y J M~l!er, G W~llukaL K Brandes, S~ Sp~egelsL~r~,.er,H B ~ . W, Krqpe~ M Hummel, R. Hetzer German Heart Ir~tute Be~tm, Berlin, Gem~ny ~ g r o u n d : A causative therapy et idiopath~ ~!aN~l ~rd]omyop~thy (IDC) is not known. In 70% of patients w~th IDC a p a l p a l revel Of a~to~an1~bodies dtrecfoa against ca.'dtac t h - a d r e ~ p f o r s (MB) can be found We wanted to evaluate whether immmunoad~orpt~se has a posdive effect on cardiac functron and d~mens~no, Le left ventnoular el~'t~on f m c t ~ (EF) and left venmcular internal diameter m dta~ote (LVIDdL Meflx~s: Th=rty4our pasents wtlh IDC were randomly ~ rote two groups (I.C) 0f 17 patients each. Bolh groups were not statistmally d~fterent regar~ng the follov~ng paramcters: age, sex, NYHA ctase, El::, LVIDd, level of AAB and drug therapy regarding cardiac insufficiency After ~tudy recruitment all pahents who were not on r~-btockerread,cartoonrecewed these add~ona!ly After synchronisat~ of both groups, group ! reee~ecl ~mmunoadserpt~on wl~ereas group C was not treate~. Results: The ruble shows the resuPs mrm months after i m m u e o a ~ 1 1 o n as compared to the data at the beginning of the sludy at the time at recrudmep3 EF LVIDD AAB NYHA EF [%] lmml [LU] class [%1 0~oupl 2 3 ~ 3 7 4 . ~ S 5 2 , r 0 6 3 4 ± 0 2 39z8 .]mupC24:3T3:754~0732±03 30-.,5 ns n5 n$ ne p. 001 n a - not ~rectaDte
after nine monff~ LVIDD AAB NYHA irrmll [LUI class 67~:7 nd 21+'03 71...6 5 2 ~ 0 6 3 0 z 0 4 p O0t p. O000t p 001
Co,'~clus~on:Immunoadsorptron led to a s~ged~camimprovement of cant=ac funcbon and dtmensron AAB directed against cardiac Pt -receptors seem to be a su=tsblo parameter to assess the success at ~mmunoadsorpt~on The mas-~n why fire cardiac funchon el the control group also improved may 13e due to the pc~mv= effect et the ,~- blocker therapy
•
3:00 I m p r o v e m e n t o f Left V e n t r i c u i a r E j e c t i o n P e r f o r m a n c e A f t e r Partial L e f t V e n t r i c u l e c t o m y : A Consequenceof C h a n g e d L e f t V e n l r i c u l a r Geometry?
Z, Popowc, M Mine, S. Gradinac. A N Ne~kovid. Lj, Jovovic, Li, Vuk, M. BoFc. Dedmje Car.Jiova.~cularfnstttute, B~qrade. YU Partial left ventnculoCtOmy procedure (PLV) is a novel approach for venthcular unloading in pts w t h end-stage '.~arl failure it may be hypothesized that its benefioal effects are due to imp.~vemen! el LV geometry dunng eiechon Methods: Single plane LV ve.mculography wilh simultaneous measurement of femoral artery pressure was pertormed in 1~,10ts~ t h one-stage heart failure due to biopsy-proven idiopathic dilated cardiomyopathy (ago 20-63, mean 50 years. 14 males) before and 2 weeks after PLV, as wail as in 12 control subjOCts. ResultS: PLV significantly d~.',cressedLV volumes with no effect on stroke volume (Table). The increase In EF was paralleled by a decrease in endsystolic stress. There was a correlation between the increase in EF and the increase ~f meier-to-minor LV ax~ ratio at end-systole (r = 056, p = 004) Hoar,ever, postoperative indices were still aDrtorrnal when comparc~l to control EOvi Control 73 -. 20 Pro-op 168 ± 315 Post~op 103 ~ 24t
SV, EF 53 -. 19 72 ~ 8 42 : 25 25 ± 7*" 44 ~_17 43 .- 14?t
Ax~srat,o 24 ~ 02 14 = 02 = 20 r 0.4r5
LMM= 84 ± 19 184 ± 27t 144 : 20rr
ESSc 125 ~ 44 268 ~ 69r 163 ± 441"
EDVf. end-diastoltcvolume index(mt:m2):SV=.strokevoTumoindox lint/re'?"l: EF. o~,ctmn fraction (%); LMML LV muscle mass index(gm/rn2): ES,Sc, clrcumferem~alend.syslotK: strolls (gm/cm2). t. p . 0 01 post-opvs pre-op:~:.p - 001 Dre-opvs control: . p . a05 post*opvs control. Conclusion: These data indicate that improvement in LV ejec~on may be mediated by correction of LV geometry
JACC FChnlar~' 1~)9~
AII$1'RA(."I'S -Oi':d
In contrast, in trio MS group them was no additional decrease in ST shill during the second and third Inflation compared with the first. The reduction in ST shift altor,~od by MS during the first Inltetlon (--51% on IC-ECG vs first inflation in C) wets equivalent to that afforded by ischemlc preconditioning in controls (-~44% during the third vs first Inllallon), In conclusion, protroatment with MS mimics Iscbomle. preconditioning during PTCA, To our knowlodgo, these result9 provide the first evidence that morphine preeondltione humnn myoc~rdlum egemst I~chemia In viva end suggest that oplold recapture may play I1 r01e In the signaling pathways responsible for Ischemle precondition. Ing In rc~n, Bec¢t(mo of It~ efficacy and anlety, morphine could be used prophylactically to 11ttonuato i~chem111In high risk PTCA,
11:15 BriefAntecedent"preconditioning"lachem/n A¢celttretee CoronaryThrombolyeleIn the ~nnlne
~
Modal K, Przykl(~nl~, Ho,lrP In~ttflffe, Good S,Imwlrfffl~ Ho,qptf~f ,~ use, Los Angeles CA, USA
0
0
B~lckgrol~nd; It Is w(dl-ost~bllsl~ed that brlsl episodes of antoctedont iachomia "pmenndltton" (PC) the heart ~nd rodll~11 infarct Sl~e Caused by stlbs0, quont ~ut~t~ined coronary occlusion, In {lddllion, recent shldlne from o=Jr labor~tory rove~led that bdnl antecedent PC Ischemia al~o 11ffonuate8 sub. ~equont plrffelet aug'aeolian in damaged nnd 8tenotic coronary arteries by an adonoslno,medlated mechnnlsm, Our cgrmnt nlm wns to detelmlna whether the 11nltpl~tolotp~operties of PC Ischemie result iu morn rapid mpe~dugion rind better tnnlnl(~nnnco at '3t,b~equont vessel p~ton~,y in the t~otting el coronary thrombosls/lhrombol~sls, Mef/~,~: AneMhltttted doge undon~enl 10 mtn PC iscl~omla + 10 rain rollow (n ,. ?) or no intervention ( n . 7) prior to Initiation of thrombotic eomn~iry aftory occlusion. At 1 I~ allot the onset of thmmbo.qL% el! dogs received 1,.3mg/kg rt.PA, Primary study endpotnts included lifo timo required to achieve rollew', tht) duration of spontanoo(ls reoecluslon during the 2 h 11liar initial lysts: and the total duration of thrombotic ocQlugmn (all with nonperercotrlc dlstrlbt, tlons and ff~uS reported as the median [2.5th', 7.51h] percentiles), Ae socondnry ondpolntn, collateral blood flow was moesured during thrombotic occlusion bv inlcctton 0l mdtolnbolod mtcmsphor08, and infarct si~e delineated oy toh(t,:olitml Bt(tinieg altd expressed a~ ~ % at Ulo myocardlum at risk. Results'. Control
Procondlhonod
Time to lyt~i~, (fnin) "rime ~pont mocchldOd (rain)
47 113: 50] 20 [21 521
1117; 14)" (.~re: 101
T0t,'ltbraeoccludedthl
1 9 [1 ~,:261
13 i1 1. I 41"
11:30 ln Viva Suppressionof Myocardial Apoptotic Cell Death by Insulin-like GrowthFactor IGF I and II
M, Schoinowitz 1. G. Sangiorgi 2, L.G SpagnolP, A. Or;d.dP, A. Kotlyar ~, D, Hasdai ~. ~The Neufeld Cardiac Research Institute, TeI-Aviv, Israel: ~'Mayo Clinic, Rochesfer, USA: 3University of Rome Tar Vergata, Rome, Italy
Background: Apoptosis (Ape) is a form of programmed cell death occurring in physiological and patophysiological slates including myocardial infarction (MI), Insulin-like growth factors (IGF) t and II have been shown to suppress Ape in vitro, but their in viva effects are unknown. The purpose of this study ;i 100
R Control In • 4) ,. IGF-I (n - 4) tGF.U (n m4) • p < , 0 S v t , tGF-I
Oo •"~
and
N o r m l? zone
Border zone
Inflrct tone
tt:45 ~ U e a of a Novel AntI-ApoptotlcAgent (LXR017) Reduces Infemt Sire Following la©hemle,Reperfuslonin the Canine Myoeardlum M,,I, Silver, S,P, Chetcutl, DB~ Mukheqeo, J L Matycky, D,L Tomei ! , S, Um~tnsky t , FA. Nicolini, The C/eve/and Clinic Fo~lr~tatlon, Clevel~Tr~, OH, USA; t l, J~R BtoteCflne/egy tim, Rchmond, CA, USA We h~ve previously shown that ~ phospholipld agent (LXRO17) spc'cific11!ty prevents apeptotio cell death induced by semmtglucoso depnvation, a Imlralia! to in-viva ischomia mpodusion iniury, in rat neonate! catdiomyocytes ~inco apoptosis pl~ys a major rote in myocardial cell death following ischemia mpodusion, we sought to lest the efficacy of LXR017 in an in.viva model et ischomla mpodusion, Twenty open-chested dog~ um:lorwent temporan/ LAD occlusion (90 min) followed by rcpeduston (3 hrs). AI! dogs had continuous monitoring el ECG, loll ventricual pressure, and alP/dr. Fifteen rain prior ropodusion, dogs wore randomly administered either an intracoronary infusion of placebo (n = 6), SOD.Catalnso (5 mg/kg; n = 5) a positive control group, or LXR0t? (250 .g; n = 9) for a total of 75 rain. Endpoints included infarct stt.o measured by TI'C staining (% el area at ask), regional shodenin9 traction (SF) via sonomicmmotor crystals, regional myocardial blood llow via radioactive micresphems, and myelopemxidase (MPO) aetivdy. Baseline homodynamics as well aa regional myocardial blood flow were similar among groups and did not differ dunng the course el the study. Infarct size, MPO and SF findings at 3 hrs el repeduslon indicate that LXR0t7 prelects the tschom¢-mpertused cameo myocardium, and may provide a valuable new adjunct to repeduston therapy for acute myocardial infarction.
Placebo SOD-Cat~Iso LXR017
The time roqu,od to achieve initial lysis was signilicanlly shortened, and mlbsequont vessel potency tended to be bettor maintained, in dogs that received ~ntocodent PC ischemia va controls ("p . 0.05). This was, not St.lrprlsingiy, accompanied by a signifiennt reduction in infarct size (11% v~ 32% of the rlsk region; p • 0.0.5), despite comparable collateral pedusion, in the PC group. Conclusions: Briol preconditioning ischomia - in addition to its well-dec. umonted eardioprotectivo propedies - markedly shortens the time required for rt-PA-lndueod thmmbolysis in this canine model.
~
was to examine the effects ot tntmcomnary IGF-I end II administration on myocardial Ape in acute MI, Motltods: Coronary mlcmembollzation was porlormed using 100. affigol beads in pigs randomly .assigned to 0,5 I~g IGF.I, IGF.II, or bovine albumin, incorporated within the beads and gradually released. Altar sacrifice at 4 weoks, myocardial samples from tho Infarct (I), border (B), end normal zones iN) were asseeeod for Ape by TUNEL end Ilgatton.modlatod PeR, Results: TUNEL.posltlve celia wore obsontod particularly In 111nd B 11nd worn reduced In the treated antm1110~,Using PCR, IGF.I and II were also found to reduo0 the DNA ladderlng signal in I, with a eimllllr treed in I~ (~ee figure), Conchlsion~: Both IGF-I and II suppressed Ape in thi~ porcine, mod~l o! acute myocardial infarction, supporting ~ role for IGF.I 11nd .ll in regulating myocardial Apo in viva,
IO F-tl
InfarctSize (%) 22 ~ 2 11 ~ 6" 10 4'
D¢~ta,1[OWesor~todin me;.u~ ~ SD "P
MPO IU/rnm'g) 0198 ~ 009 0096 t OO1" 0094 ~ 003"
SF ~%) 332 : 308 28~ : 285" 312 ~ 259"
0 04 '~s Pl~ct.!boby ANOVA
Dilated Cardiomyopathies: New Observations and Approaches Monday, March 30, 1998, 2:00 p.m.-3:30 p.m Georgia World Congress Center, Room 367W 2:00 ]811-1) The Frequency of Familial Disease in a Consecutive Series o~ 51 Patients With Idiopathic Dilated Cardiornyopathy A. Gavazzi, M. Ponzetta, C. Campana, M. Giralch, C. Inserra, A. Raisaro. M.L. Laudisa, E. Colombi, B. Del Belle t , E. Arbustini ~. Div~sione d~ Cardiotogia. Italy: wIstituto dl Anatomia Patotogica dell'Universita, IRCCS Policlinico S. Matteo, Pavia, Italy
Background: Familial disease may account for a significant proportion of patients with dilated cardiomyopathy (DCM) and coutd be more frequent than is often recognised. Most previous repeals are of anedoctal or retrospective nature and only a few prospective studies have been published, Consequently, the real fr, queney of fan,trial disease in DCM remains to be established. Methods: Our aim was to assess the frequency and mode of inheritance of lamilial disease by prospectively screening relatives from a series of 51 consecutively diagnosed patients with DCM, The diagnosis of DCM was confirmed invasively in every patient, All patients had a 2-3 generation pedigree constructed. Familial disease was diagnosed when at least one relative was affected by DCM. Screening consisted of history, clinica~ examination with blood pressure measurement, 12 lead ECG, two dimensional Doppler echocardiography, signal averaged ECG (SAECG) and blood sample (serum CK).
JACC
Fehnta~, lqtlX
ABSTRA(q'~,
Left ventncutar enlargement (LVE) was defined as a LVEDDI . 32 mnVm2 ~nd a depressed left vonfhcuidr systolic function was defined affher as LVFS • 25% or LVEF -riO% R~sutts: Between 12/1994 and 3/1997, 208 ml~ttve~ were screened, moan ag~ 32 + ~ 17 yrs (range 4-73): 122 (58%) were 1st dogro0 rotor=yes, 59 (~8%) ~r',d, 27 (14%) 3r.J dot]me, DCM w ~ documented *n 1'~ relatives (9%) corlling from 12 famdws end repms~ted 23.5% of tt~L~ ~ r e e n ~ , The mode of inh~nfance in most famdms was autosomeI dominant, Ot the SAIECG, 11 (5,~;%)d~m~sed LVF$, ! 0 ( ¢ ~ ) L V E F -G0% SemmCK :. !90 mU/ml w~s p m ~ n t in 16-/!~3 mt~tive~s I 1 ~ ) and olher minor ~bnorn~fitief, w~re doo~mer~ed in 5 (~,4%) C O - - K I n ; Th~ f~mili~! p f ~ v ~ ! e ~ of DCM ¢PPeam 1o be higher than pmvo~s~t t~gSl~¢~ =fed (23,5% in th~ prospective sends): Fgrlhermore a t~ignifi, cant p r o g o ~ of i~arent!y health retalWes ~how~ minor ~'¢hoIa~_ ographlc or efe¢1~rdingraphi¢ abnormalities, s~ling a proitin~al disease, Early dtagnostK; emen~ for ~ M are ~ , 2;15 ~
CMdlm: Abno~litk~
!n O l a ! ~ t l c P N t e n t s
ASSO¢IMeRIWith a Milochondt!a13243bpI R N A Mutation
Y. Mom~yama, Y. Suzuki, F. Obsuzu ~, Y A~sum~, K MatSooka. M- K,mura
Satsezk~i Central H O s ~ . Tokyo, Japan; 'National Defense ~ t College. Saeam,a. Japan Background: t% el d~abetes melhtus (DM) msasseoatod wtth a m~tochondnal 3~43t~ IRNAt~uun~ m u t a t ~ wh~:h ~ ongmafly found m mitocho~foal encephalomyopathy (MELAS). Since carckac hypertrophy and failure are often reported in MELAS. the heart may be one of the large( organs of t.K~ mutatron also in thLStype of DM. Methods: We mves~gated cardiac structure and function using echocard~ocjr"~3~ in 11 ~ l ~ t i C I~t~ents (pts) wrth the IRNAL~=~'~i mutation (group A) compared wzth 70 control DM pts (group B). All pts were negatwe tar an exerets~ testing Or dip~ndamote ~ t T I ima~eg. ReSUlt'S: Between groups A and B, there was no d~fference m age. sex, body mass index. DM dural(on, blood gtycer~c ~evelsand blood pressures (p = NS) On the echocart~ograms, none showed any wall me,on abnormalmes LV hypertrophy of wall thickness • 12 mm was found in 3 of 11 pts t27%) m group A vs 3 of 70 pts (4%) in group B (p - 0.05). LV wall th~ckrtess and mass were greater in group A than in group B (9.8 : I 6 ram. 174 = 66 g ,~s 8.6 1.1 mm. 134 ~ 37g, p - 0005). In the pulsed Doppler analys~s of LV inflow velocmes, the A:E robe of peak velooty and the deCeleratzonbrae (DT) of E wave were greater ~ngroup A than in group B it .20 : 0 19, 212 _- 34 ms vs 099 : 021, 178 ~ 22 ms, p - 0005). All pts =n group A showed maternal inheritance ol OM and~or heanng ~mpa~rment, but 16 of 70 pts (23%) =ngroup B also had d~ab~tic mothers In group B. pts ~ t h diabetic mothers had slightly thicker LV walt (8 7 vs 8 6 ram), a greater A/E rst~o (1 03 vs 0.98) and longer DT (187 vs 175 ms) than pts without them. However, even compare~t wrth pts with diabetic mothers in group B, group A had sigoifrcantly thicker LV wall. a greater ~ ratio and longer DT. Conctusron:1 Diabetic pts with the tRNA L~¢uum mutation are likely to have impaired LV d~asto!ic function assocqated wdh hypertrophied LV, compared with ordinary DM pts.
2:30 ~~~
Infiltrative Cardiomyopathy Non-amyloid in Plasma Cell D y s c r a s t a s
J. Buxbaum, E. Genega. I. Kronzon. P A Tunick, G Gaffe VA Meal;col
Center & NYU Medical Center. NY. NY. USA Background: In moneclonal plasma ceil disorders, organ ,~mpmmise is produced by tissue deposition of monoclonal lmmunoglobulins fig). Deposits may be Congo red positive (AL amyloid) or negative (light chain deposition disease (LCDD)). Purpose: To determine the nature of cardiac dysfunction in pts wlth nonamyloid LCDD cardiomyopathy. Methods: Cardiac tissue (biopsy or necropsy) from 5 pts with ptasma cell dyscrasia and cardiac dysfunction was examioed by immunoh=stochemistry and electron microscopy. Charts were reviewed as were EKGs and eehocardiograros. Results: All 5 pts had non-amyloid menoclonal Ig myocardial deposits. The average ege was 47 (3 men). Heart size was normal on x-ray. EKG showed low voltage in 4 of 5 pts and arrhythmias in all 5. Echo shewed pericardial ~ftusion in 3. The average septal thickness was 1.4 cm and postenor wall thickness was 1.45 cm. The ejection fractions were normal (mean 65%). Left ventncular mass was increased and mitral valve deceleration times were shorter, than normal. The voltage/mass ratio was decreased.
()~,l
~?A
CO~CIUSIOnSr~l Although non-amytmd monnctonal Ig light CheladePO~ff~on in the myocardium ha~ a different localization and ~ltrastructur3| qrg~e,z~tton than dO~s the tibnltaf Congophil~ dop~sil~on of AL ~:myfo~d, ff ~ul~s ~n a patlom el dlaSlotlC dyslunchon an0 afflrtylhmla~ IcI~ntlcalto 1hOe6 ~ tn Ivp,caIcard),~: ~mylo~ddopo~,t)on 2 The d~algnos!~ of LCDD car~omyopathy shoutd be coesKk~md *n ptS w=th i ~ e ~ i ~ n 6 y (~as.lol¢ 0 y s l u r ¢ l ~ ~ = t~h Congo led staint~z for amylo~l is f~gatwe, 3, The ~ , s of L C ~ can be made by ~pp~oprl~te qmm~tnohist~hemcat ~p~j uftrSstm~l~rsI tissue
2:45
~
Succeutul~
of IdlOi;~hi¢Otm~d
Oa~llomyo!~tl~ by IgG Immuno~l~P,~io~, Relzg!t#
o f a ContfOlle¢l S t u d y J M~l!er, G W~llukaL K Brandes, S~ Sp~egelsL~r~,.er,H B ~ . W, Krqpe~ M Hummel, R. Hetzer German Heart Ir~tute Be~tm, Berlin, Gem~ny ~ g r o u n d : A causative therapy et idiopath~ ~!aN~l ~rd]omyop~thy (IDC) is not known. In 70% of patients w~th IDC a p a l p a l revel Of a~to~an1~bodies dtrecfoa against ca.'dtac t h - a d r e ~ p f o r s (MB) can be found We wanted to evaluate whether immmunoad~orpt~se has a posdive effect on cardiac functron and d~mens~no, Le left ventnoular el~'t~on f m c t ~ (EF) and left venmcular internal diameter m dta~ote (LVIDdL Meflx~s: Th=rty4our pasents wtlh IDC were randomly ~ rote two groups (I.C) 0f 17 patients each. Bolh groups were not statistmally d~fterent regar~ng the follov~ng paramcters: age, sex, NYHA ctase, El::, LVIDd, level of AAB and drug therapy regarding cardiac insufficiency After ~tudy recruitment all pahents who were not on r~-btockerread,cartoonrecewed these add~ona!ly After synchronisat~ of both groups, group ! reee~ecl ~mmunoadserpt~on wl~ereas group C was not treate~. Results: The ruble shows the resuPs mrm months after i m m u e o a ~ 1 1 o n as compared to the data at the beginning of the sludy at the time at recrudmep3 EF LVIDD AAB NYHA EF [%] lmml [LU] class [%1 0~oupl 2 3 ~ 3 7 4 . ~ S 5 2 , r 0 6 3 4 ± 0 2 39z8 .]mupC24:3T3:754~0732±03 30-.,5 ns n5 n$ ne p. 001 n a - not ~rectaDte
after nine monff~ LVIDD AAB NYHA irrmll [LUI class 67~:7 nd 21+'03 71...6 5 2 ~ 0 6 3 0 z 0 4 p O0t p. O000t p 001
Co,'~clus~on:Immunoadsorptron led to a s~ged~camimprovement of cant=ac funcbon and dtmensron AAB directed against cardiac Pt -receptors seem to be a su=tsblo parameter to assess the success at ~mmunoadsorpt~on The mas-~n why fire cardiac funchon el the control group also improved may 13e due to the pc~mv= effect et the ,~- blocker therapy
•
3:00 I m p r o v e m e n t o f Left V e n t r i c u i a r E j e c t i o n P e r f o r m a n c e A f t e r Partial L e f t V e n t r i c u l e c t o m y : A Consequenceof C h a n g e d L e f t V e n l r i c u l a r Geometry?
Z, Popowc, M Mine, S. Gradinac. A N Ne~kovid. Lj, Jovovic, Li, Vuk, M. BoFc. Dedmje Car.Jiova.~cularfnstttute, B~qrade. YU Partial left ventnculoCtOmy procedure (PLV) is a novel approach for venthcular unloading in pts w t h end-stage '.~arl failure it may be hypothesized that its benefioal effects are due to imp.~vemen! el LV geometry dunng eiechon Methods: Single plane LV ve.mculography wilh simultaneous measurement of femoral artery pressure was pertormed in 1~,10ts~ t h one-stage heart failure due to biopsy-proven idiopathic dilated cardiomyopathy (ago 20-63, mean 50 years. 14 males) before and 2 weeks after PLV, as wail as in 12 control subjOCts. ResultS: PLV significantly d~.',cressedLV volumes with no effect on stroke volume (Table). The increase In EF was paralleled by a decrease in endsystolic stress. There was a correlation between the increase in EF and the increase ~f meier-to-minor LV ax~ ratio at end-systole (r = 056, p = 004) Hoar,ever, postoperative indices were still aDrtorrnal when comparc~l to control EOvi Control 73 -. 20 Pro-op 168 ± 315 Post~op 103 ~ 24t
SV, EF 53 -. 19 72 ~ 8 42 : 25 25 ± 7*" 44 ~_17 43 .- 14?t
Ax~srat,o 24 ~ 02 14 = 02 = 20 r 0.4r5
LMM= 84 ± 19 184 ± 27t 144 : 20rr
ESSc 125 ~ 44 268 ~ 69r 163 ± 441"
EDVf. end-diastoltcvolume index(mt:m2):SV=.strokevoTumoindox lint/re'?"l: EF. o~,ctmn fraction (%); LMML LV muscle mass index(gm/rn2): ES,Sc, clrcumferem~alend.syslotK: strolls (gm/cm2). t. p . 0 01 post-opvs pre-op:~:.p - 001 Dre-opvs control: . p . a05 post*opvs control. Conclusion: These data indicate that improvement in LV ejec~on may be mediated by correction of LV geometry