- Email: [email protected]
Results of intracoronary recombinant human vascular endothelial growth factor (rhVEGF) administration trial
JACC
l:ebm~n.' I~,~)~
R(~I~: ~
ABSTRACT~ ~ Oral
clinical results elm as foltows:
AV~
Ci,n~ ~ u ~ Ac~e proc~lu,a h ~ - e ~ AcutePamon~ucc~ Aoute~ ~ 6,,T,~-,~'~TLR ~t!o~'1MA~
94.i% 99,I% 97:1~,, 84% 161%
P~s ~t.P.~. 9~8% 05.2% 81% 14,6%
6~A
~a~¢y a ~ I o ~ Of ~ r ~ y mVEGF tn¢lumo~ ct,~ta mqu~md stal~e e~edio~l a ~ n a , a ~ig,~f~-.anl remm~g~ ~ t~/nu¢lea, ~i~ve~= t ~ ! ~tuo~yand sul~ottmal canrk4~le~ for PTCA o~ C&BG, ~ mrew~d lwo tO.m~r~e trma¢oror,ary infu~mn~ ~! cor,,¢en~a,,~or~of 0.00S, 0,017, 0.050, or 0.167 . ~ n ~ ~ ~ i~r ~ I¢~,I, P h l l ~
p NS 0053 NS NS N~
~ RVO
2.~1 ~:~.4
283 ~ 0.,!'t
N~
P~ma,l-O
2 ~ , 0:~
2T/~ 046
-~005
( ~ % ~
31x 19
34 i ~
N,~
~tt h e l o ~ do=e ~
a 4 ~
m~
emPmm~e~ m fturk~r p ~ u e k ~ if1111~ m Coe¢tt,~: ~hVI~OFalq~am ~
emo= I ~
m¢.mt~e
L~ L~tfi~t~ ~
M
~ l e m ~ ~ ¢ommw infumm~at nl~m
ana=~enem,
T~e ~ MLO,
~,m~e
~
~ ~ , e ~
~
~ po=t~p,~,~
~
10:45 Kinetleu o f 1 1 ~ , in Plmmw a m l t ~ ~ Et~ml O f ~ l Ant~ t o l r l ~ o , tn M y e l i n i C 1
11:45
N- N i ~ , A,- I ~ , S. EIAZi.H Wafter, H. i ~ l ~ l e ~ / L SCll~,~. H e , z z ~ ' n ~ ~. Medmtr~:;-~ K~t~ ~ u m n~d~ts der ~a,. Tec~n~cf~eUm,ws~r. Mun¢~ Ths study was camed o~ to a~ess me nmuraJ c o u ~ Of asymptoma~ msteno~ att~ c o n ~ ry implantatmn ot Pa~az Schatz s t m = . evaluams me feaaw-~p m 122~ eea~z~lpabentsw~'m~ of 50-75% si~ mo,nths a~te~rste~ implan~Jon. 6~ of me 122 pa~m~ had a second a n g ~ ~0~ow--upat 12 moths after ste~ i m ~ Quantities o~ona~ ar,g ~ g r a ~ vras W ~ d ~medmt~V ~e~ ~ ~ at 6and 12 momhs afte~stem implantalion. Ntet.s~em CommW~,nos~l%l
45z121
Mmm~d (ut'~na~ diameter tMlO|
3.0 • 0 6
After 591=7.7 124z 04
N'~,t" 5441:15-r t 3N6t 0 5
~*~th~
O(mq~~
m~.-n~),a~ndm hsanhy ~
by ~
~
P ~ s m a TNF~ teve~ were ele~mm m ~ ~ m w,e e a g y ~ Of AMI (mea~ :~ SE 1.47 + 0.10 n 10-82 ~: 0 . 1 6 ~ 1 m control, p < 0.01) w~d~ peak vakm at 4 heu~m a~er e~m~t ot cheml pare. TNF~ leve~ w m conse~eney h~,=- m pamm~ ~ h AMI (V~p cla= in-N~ man in pamm~ with AMI (l~lEp class I--Ii) m 4. B. 12 hes after onm~t Of d1~1 pro1 (p < 0-01l- TNF= l e ~ b fall Itlm~ftm, a~l were ~'~ilar 10 the control value at ~ m'~ a ~ r r m m o~ AMI. To c,tra~y ema~ee me role Of TNF. rekm~ m ~ in~a~ s~,e. Sprague O a ~ S rms ~mremmmd wlrn a m o m c k ~ an~1~dy (MAb) I0 TNF,, (n = 12) or l~r~r (n = 12). =-~ sul~ected to global
myoca~rml ischemia-re~r~m. T,ea~1~t v~thTNF=,-M.Abaecrea=mOthe p-=OOt3 p = 00047
re~ssto~ el resterms~s(3MLD >+03 mm)~was noted in 24 ot the 62 pabent=, t0 paUentsd~ayeO a process=on (AMID > -0.3 ram). Comr~ry angi¢olasty of the scented lesmn was ~ m 5% of ltm 122 paliems included m the study, ~ later then 1 year after stenl iml~ardalic~. One myocarclial mlatcUon eccuned 286 days. one cardiac clea~ occuned 230 days after stent ~ l i o n . The 1-year-event kee suneivalrate was 98.4%. Condeeuon~" The data show tttat the maionty ot ~ t i c patk~ts troth mstenosis Itave a favoreble ang~aphic a.,'KIclinical outo0me. Regression of the a n g i o ~ mesures of res~ermsis occurs ~ 6 and 12 months after stent Implantation in these patients. New Approaches to Myocardial Preservation in Acute Myocardial Infarction M o n d a y , M a r c h 30, 1998, 1 0 : 3 0 a . m . - N o o n Georgia World Congress Center, Room 255W
•
~ plays a ~ sole in l~e ~ 0f acute ~ ;~,;,=,c;k,,,(Aim). Tumor n e o o m ~-~o~.,, ( T N ~ ) a ~ cytolm~ is an mnammatmVt~ger th = ~ m l cea ~ To deUm~me if mWopa e ~ clm~ m auecmu~ w ~ TNF. n~ease m ,~wo,we ~ me al~ra#on=
10:30 Results of Intracomnary Recombinant H u m a n Vascular Endothelial Growth Factor (rhVEGF) Administration Trial
am.a of ~ (23.B = 4.5 v~ 47.4 ± 5.3 m buffer-tmaled ra1~,p < 0.01), the numb~ of circulating en~othelmi ceils, an index of e n d o t h ~ m/my (11 7 ~ 0.6 ~ 21.3 +- 1.3~,t, p .: 0.01) and Iq~d T.,e~io~tto~ (mez.sured as ~ . 22 9 t 2.1 vs 32.6 ~- 4 3 nmotmd p < 0 01). This study SHOWSthat a. TNFu release occurs eady in the course of AMI, b. higher orcu~Ung levem of TNF~ correfme w ~ exlenswe cardiac dysfunclmn, and c. m l ~ ; o ~ ol "rNRz decreases i~a¢t ~ m by t~lue~cmg o,-..~o;r~va~-ular
11:00 1 8 1 0 3 1 Morphine Mimk:= l a c h e m ~ Pmconclitionln0 in Human M y o c a m i . m Oudng F t C A N.P. Xermpoufos,M Lesser, R. BoI1L~ Scho~. Loumwne,K~. USA
of Lou~v~WeMeo'Ca/
Recent stua~s ~ that ~ receptorsrne~te ~ preeon~d~n. mg in experimental ammals and that morphine m~mcs this c a r ¢ ~ o ~ olfect. However, it is unknown w t ~ e r mOrphine p ~ human my. ocardhml. A~o~rd~ngly.16 i~lJents (pts) were ~ z ~ B ¢ l to recewe a 10.,rain ~n(r"acococtary0C) infusion of serme (controls [C|, n = 8) or moq~hine sulfate (MS) (n = 8, 15 p/kg). No hecqodyr~!c cringes w~'re noted dum~g Ihe IC infusion of MS. Ten mm after the completionof the IC ~ . 10isunderwent ,'~rcA (three 2~-nin ~ each separatod by 5 min). The S T - ~ shirts horn baseline in the IC-ECG and in the sudace ECG (S-ECG) were measured at the end o! each inflation: X ~. SEM; "P ~ 0 05 vs ¢ontrcls. tC-ECG (ram) C MS
S-ECG (ram) C MS
T.D. Henry, K. Rocha-Singh, J.M, Isner, D.J. Kemiakes, FJ. Giordano, M. Simons, D.W. Losordo, R.C. Hendel, R.O. Bonow, J.M. Rothman, E.R. Bodoas, E.R. McCluskey. Hennepin County Medical Center. Minneapofis, MN. Genentech, Inc., So. San Francisco, CA, USA
Inffatmn I Innaf~n 2 Inflation 3
Background: Few therapeutic option~"currently exiStfor 10tSwith severe coronary artory disease who have areas of viable but underperfused myocardium and who are not optimat candidates for PTCA or CA~G. Atlima! models using rhVEGF have demonstrated angiogenesis leading to improvement in ischemic myocardium. This is the first human study designed to determine
Dunng the figst inflation, the ST-segment shift in both the IC-ECG and S-ECG was significantty attenuated in the MS group compared with controls (-51% and -60%). In contrel~, the ST shift was tess dunng the second and third inflation than dunng the first, indicating ischemic preconditioning.
29~:4 18~3 16~3
14÷3" 15±3 14+-.3
23±4 15~3 12"-3
g±2" 11 ± 2 11 ~ 2
l:ebm~n.' I~,~)~
R(~I~: ~
ABSTRACT~ ~ Oral
clinical results elm as foltows:
AV~
Ci,n~ ~ u ~ Ac~e proc~lu,a h ~ - e ~ AcutePamon~ucc~ Aoute~ ~ 6,,T,~-,~'~TLR ~t!o~'1MA~
94.i% 99,I% 97:1~,, 84% 161%
P~s ~t.P.~. 9~8% 05.2% 81% 14,6%
6~A
~a~¢y a ~ I o ~ Of ~ r ~ y mVEGF tn¢lumo~ ct,~ta mqu~md stal~e e~edio~l a ~ n a , a ~ig,~f~-.anl remm~g~ ~ t~/nu¢lea, ~i~ve~= t ~ ! ~tuo~yand sul~ottmal canrk4~le~ for PTCA o~ C&BG, ~ mrew~d lwo tO.m~r~e trma¢oror,ary infu~mn~ ~! cor,,¢en~a,,~or~of 0.00S, 0,017, 0.050, or 0.167 . ~ n ~ ~ ~ i~r ~ I¢~,I, P h l l ~
p NS 0053 NS NS N~
~ RVO
2.~1 ~:~.4
283 ~ 0.,!'t
N~
P~ma,l-O
2 ~ , 0:~
2T/~ 046
-~005
( ~ % ~
31x 19
34 i ~
N,~
~tt h e l o ~ do=e ~
a 4 ~
m~
emPmm~e~ m fturk~r p ~ u e k ~ if1111~ m Coe¢tt,~: ~hVI~OFalq~am ~
emo= I ~
m¢.mt~e
L~ L~tfi~t~ ~
M
~ l e m ~ ~ ¢ommw infumm~at nl~m
ana=~enem,
T~e ~ MLO,
~,m~e
~
~ ~ , e ~
~
~ po=t~p,~,~
~
10:45 Kinetleu o f 1 1 ~ , in Plmmw a m l t ~ ~ Et~ml O f ~ l Ant~ t o l r l ~ o , tn M y e l i n i C 1
11:45
N- N i ~ , A,- I ~ , S. EIAZi.H Wafter, H. i ~ l ~ l e ~ / L SCll~,~. H e , z z ~ ' n ~ ~. Medmtr~:;-~ K~t~ ~ u m n~d~ts der ~a,. Tec~n~cf~eUm,ws~r. Mun¢~ Ths study was camed o~ to a~ess me nmuraJ c o u ~ Of asymptoma~ msteno~ att~ c o n ~ ry implantatmn ot Pa~az Schatz s t m = . evaluams me feaaw-~p m 122~ eea~z~lpabentsw~'m~ of 50-75% si~ mo,nths a~te~rste~ implan~Jon. 6~ of me 122 pa~m~ had a second a n g ~ ~0~ow--upat 12 moths after ste~ i m ~ Quantities o~ona~ ar,g ~ g r a ~ vras W ~ d ~medmt~V ~e~ ~ ~ at 6and 12 momhs afte~stem implantalion. Ntet.s~em CommW~,nos~l%l
45z121
Mmm~d (ut'~na~ diameter tMlO|
3.0 • 0 6
After 591=7.7 124z 04
N'~,t" 5441:15-r t 3N6t 0 5
~*~th~
O(mq~~
m~.-n~),a~ndm hsanhy ~
by ~
~
P ~ s m a TNF~ teve~ were ele~mm m ~ ~ m w,e e a g y ~ Of AMI (mea~ :~ SE 1.47 + 0.10 n 10-82 ~: 0 . 1 6 ~ 1 m control, p < 0.01) w~d~ peak vakm at 4 heu~m a~er e~m~t ot cheml pare. TNF~ leve~ w m conse~eney h~,=- m pamm~ ~ h AMI (V~p cla= in-N~ man in pamm~ with AMI (l~lEp class I--Ii) m 4. B. 12 hes after onm~t Of d1~1 pro1 (p < 0-01l- TNF= l e ~ b fall Itlm~ftm, a~l were ~'~ilar 10 the control value at ~ m'~ a ~ r r m m o~ AMI. To c,tra~y ema~ee me role Of TNF. rekm~ m ~ in~a~ s~,e. Sprague O a ~ S rms ~mremmmd wlrn a m o m c k ~ an~1~dy (MAb) I0 TNF,, (n = 12) or l~r~r (n = 12). =-~ sul~ected to global
myoca~rml ischemia-re~r~m. T,ea~1~t v~thTNF=,-M.Abaecrea=mOthe p-=OOt3 p = 00047
re~ssto~ el resterms~s(3MLD >+03 mm)~was noted in 24 ot the 62 pabent=, t0 paUentsd~ayeO a process=on (AMID > -0.3 ram). Comr~ry angi¢olasty of the scented lesmn was ~ m 5% of ltm 122 paliems included m the study, ~ later then 1 year after stenl iml~ardalic~. One myocarclial mlatcUon eccuned 286 days. one cardiac clea~ occuned 230 days after stent ~ l i o n . The 1-year-event kee suneivalrate was 98.4%. Condeeuon~" The data show tttat the maionty ot ~ t i c patk~ts troth mstenosis Itave a favoreble ang~aphic a.,'KIclinical outo0me. Regression of the a n g i o ~ mesures of res~ermsis occurs ~ 6 and 12 months after stent Implantation in these patients. New Approaches to Myocardial Preservation in Acute Myocardial Infarction M o n d a y , M a r c h 30, 1998, 1 0 : 3 0 a . m . - N o o n Georgia World Congress Center, Room 255W
•
~ plays a ~ sole in l~e ~ 0f acute ~ ;~,;,=,c;k,,,(Aim). Tumor n e o o m ~-~o~.,, ( T N ~ ) a ~ cytolm~ is an mnammatmVt~ger th = ~ m l cea ~ To deUm~me if mWopa e ~ clm~ m auecmu~ w ~ TNF. n~ease m ,~wo,we ~ me al~ra#on=
10:30 Results of Intracomnary Recombinant H u m a n Vascular Endothelial Growth Factor (rhVEGF) Administration Trial
am.a of ~ (23.B = 4.5 v~ 47.4 ± 5.3 m buffer-tmaled ra1~,p < 0.01), the numb~ of circulating en~othelmi ceils, an index of e n d o t h ~ m/my (11 7 ~ 0.6 ~ 21.3 +- 1.3~,t, p .: 0.01) and Iq~d T.,e~io~tto~ (mez.sured as ~ . 22 9 t 2.1 vs 32.6 ~- 4 3 nmotmd p < 0 01). This study SHOWSthat a. TNFu release occurs eady in the course of AMI, b. higher orcu~Ung levem of TNF~ correfme w ~ exlenswe cardiac dysfunclmn, and c. m l ~ ; o ~ ol "rNRz decreases i~a¢t ~ m by t~lue~cmg o,-..~o;r~va~-ular
11:00 1 8 1 0 3 1 Morphine Mimk:= l a c h e m ~ Pmconclitionln0 in Human M y o c a m i . m Oudng F t C A N.P. Xermpoufos,M Lesser, R. BoI1L~ Scho~. Loumwne,K~. USA
of Lou~v~WeMeo'Ca/
Recent stua~s ~ that ~ receptorsrne~te ~ preeon~d~n. mg in experimental ammals and that morphine m~mcs this c a r ¢ ~ o ~ olfect. However, it is unknown w t ~ e r mOrphine p ~ human my. ocardhml. A~o~rd~ngly.16 i~lJents (pts) were ~ z ~ B ¢ l to recewe a 10.,rain ~n(r"acococtary0C) infusion of serme (controls [C|, n = 8) or moq~hine sulfate (MS) (n = 8, 15 p/kg). No hecqodyr~!c cringes w~'re noted dum~g Ihe IC infusion of MS. Ten mm after the completionof the IC ~ . 10isunderwent ,'~rcA (three 2~-nin ~ each separatod by 5 min). The S T - ~ shirts horn baseline in the IC-ECG and in the sudace ECG (S-ECG) were measured at the end o! each inflation: X ~. SEM; "P ~ 0 05 vs ¢ontrcls. tC-ECG (ram) C MS
S-ECG (ram) C MS
T.D. Henry, K. Rocha-Singh, J.M, Isner, D.J. Kemiakes, FJ. Giordano, M. Simons, D.W. Losordo, R.C. Hendel, R.O. Bonow, J.M. Rothman, E.R. Bodoas, E.R. McCluskey. Hennepin County Medical Center. Minneapofis, MN. Genentech, Inc., So. San Francisco, CA, USA
Inffatmn I Innaf~n 2 Inflation 3
Background: Few therapeutic option~"currently exiStfor 10tSwith severe coronary artory disease who have areas of viable but underperfused myocardium and who are not optimat candidates for PTCA or CA~G. Atlima! models using rhVEGF have demonstrated angiogenesis leading to improvement in ischemic myocardium. This is the first human study designed to determine
Dunng the figst inflation, the ST-segment shift in both the IC-ECG and S-ECG was significantty attenuated in the MS group compared with controls (-51% and -60%). In contrel~, the ST shift was tess dunng the second and third inflation than dunng the first, indicating ischemic preconditioning.
29~:4 18~3 16~3
14÷3" 15±3 14+-.3
23±4 15~3 12"-3
g±2" 11 ± 2 11 ~ 2