~^ TAPCHlYDl/qCLAMSANGIOS T^p 12-S67/2017
A Danh gia chuc nang that trai triro^c va sau di§u tri phoi
;' hap bang t§ bao g6c tuy xuong tu than 6* benh nhan suy
^! tim do nhoi mau ca tim
'' Evaluation of left ventricular function before and after self-grafting
^ bone marrow stem cell transplant in heart failure patient due to myocardial infarction
-J Nguygn Dinh Hien Benh vien Xanh Pan
Tom tSt
Muc tiiu: Nghien cUu n h I m muc dich danh gia chUc nang t h i t t r l i d nhQng benh nhan suy tim do nhoi mau ca tim trude va sau dieu trj phdi hpp b i n g te bao goe. Ddi tugng vd phuang phdp: Nghien cQu tien hanh tren 6 b§nh n h i n dupe dieu trj tai Vien Tim mach Qudc gia vdi chan doan suy tim do nhdi mau CO tim cap trong khoing thdi gian tQ t h i n g 7/2007 den t h i n g 7/2008. Day la mdt nghien cQu can thiep, hdi cQu, ngau nhien. Benh nhan duac lUa chpn theo trinh t u thdi gian. Kit qud: Ket qua nghien cQu cho thIy, benh nhan dupe dieu trj ghep te bao gdc theo doi trong thdi gian 1 nam cd 1 trudng hpp phai nhap vien vi suy tim. Khdng cd trudng hpp nao tU vong vi cac nguyen nhan tim mach, tai nhdi m l u hay tai bien mach nao. Thu thuat dUOc tien hanh thanh cong tren c l 6 benh nhan (100%). Khong gap trUQng ' hpp nao x l y ra bien chQng nang lien quan den thd thuat thu gom t^ bao gdc hay tiem te bao gdc vao dpng mach vanh (0%). Danh gia ve d i thien ehUc nang that trai qua phan sd tdng m l u EF, chung tdi thay rang cd s u d i thien EF t U 2 - 1 1 % sau 6 t h i n g theo ddi va tang t Q 4 - 1 4 % d e l 6 benh nhan duac ghep te b l o gdc tuy xUPng. Kit ludn: TQ cac ket q u i tren chung toi thay ghep te bao gdc tuy xUPng t u t h i n eho benh nhan sau nhdi mau co tim cap da dupc can thiep maeh vanh thi deu eo tang EF mac du cd khiem tdn nhung c6 y nghTa sau 6 v l 12 t h i n g dieu trj ghep.
Tdkhda: Ghep te bao gdc tCiy xuang, suy tim, nhdi m l u co tim.
•i Summary
Objective: To assess left ventricular function in patients w/ith heart failure due to myocardial infarction (Ml) before and after combination therapy with stem cells. Subject and method: The study was condurted at the National Heart Institute from July 2007 to July 2008 on 6 patients of heart failure due to Ml. This was a retrospective, randomized, and interventional study. Patients were selected in chronological order. Result: Results showed that patients who received stem cell transplant treatment for one year had 1 case of hospitalization for heart failure. There were no death from cardiovascular causes, re-infarctions or cerebrovascular accidents. The procedure was performed successfully in all six patients (100%). No serious complications related to stem cell or root cell embolization (0%) occurred. In
Ngdy nhdn bdi: 11/4/2017, ngdy chdp nhdn ddng. 04/5/2017
Ngucriphdn hoi: Nguyen Dinh Hien, Email- [email protected] - Benh viin Xanh Pdn
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.12-N''7/2017 evaluating left ventricular funrtion improvement by ejection fraction EF, we found that there was an improvement in EF by 2 - 1 1 % after 6 months of follow-up and a 4 - 1 4 % increase in all 6 patients who received transplant bone marrow stem cells. Conclusion: Bone marrow stem cell self-grafting for patients after acute myocardial infarction who had PCI, had increased EF modestly but significantly after 6 and 12 months of transplant treatment.
Keywords: Bone marrow stem cell transplantation, heart failure, myocardial infarction.
1 . Dat v a n de
Nhdi m l u ea tim (NMCT) la mdt benh thudng gap v l la mdt trong eac nguyen nhan gay t d vong hang d i u trong d c benh ly tim maeh. Cung vdi su gia t i n g cda cae yeu t d nguy eo nhU hut thude 11, tang huyet ap, dai thao dUdng, beo phi, Idi sdng it van ddng..., sd ngUdi m I c benh dang ngay c l n g tang len v l tudi m I c benh cung ngay cang tre hda.
Theo thdng kd tai Hoa Ky cho thay, hang nam ed tdi g i n 1 trieu ngudl p h l i nhap vien vi nhdi m l u ca tim d p [1]. Theo dieu tra eda Nguyen Lan Viet va cpng sU, sd benh n h i n cd hdi chQng vanh d p tai Vien Tim maeh Qudc gia tQ n l m 2003 - 2007 la 3362 [2]. Mac du da cd nhieu tidn bd t r o n g chan d o l n v l dieu trj nhdi mau co tim nhQng d e bien chQng ve lau dai eua benh van cdn la mdt thaeh thQe Idn. NhQng sau dd, d ngudi benh va t h I y thude se p h l i ddi mat vdi tinh trang suy tim nang ne, t h u d n g dan den p h l i t l i nhap vien nhidu l l n keo t h e o nhQng ganh nang ve kinh te, tam ly va xa hdi. Trudc t i n h hinh n l y , nhu d u t i m ra phUPng phap mdi dieu tri eho d c benh nhan suy t i m sau nhdi mau cP tim khdng chi b i n g c l e loai thude nham " g i l m b d t "
hau q u i eua viJng nhdi mau ma cdn Ung d u n g khoa hpc hien dai de "sQa chQa" nhQng vung t d n t h u a n g khdng hdi phue dang ngay d n g t r d nen d p thiet.
2. Ooi t i f m i g va phUorng p h a p 2.J.0oitu'c»tg
Nghidn cQu tien hanh tren 6 benh n h i n dugc dieu tri tai Vien Tim maeh Qude gia vdi chan d o l n suy tim do nhdi mau co tim cap trong k h o i n g thdi gian tU t h i n g 7/2007 den t h i n g 7/2008.
2.2. PhiAmgphdp
D l y la m p t nghien cUu can thiep, hdi cijij, ngau nhidn. Benh nhan dupe lUa ehpn theo trinh t u t h d i gian.
Tat e l d e ddi tupng nghien cQu deu dupc nh^n dieu trj theo quy trinh ehuan theo phac do khuyen d o ve dieu trj NMCT eua Hdi Tim maeh Viet Nam ban hanh thang 11/2006 [1]. Trong q u i trinh nam vien, d c ddi tUpng dUpc lam d e xet nghiem thildng quy nhu xet nghiem mau, dien t i m dd va sieu im tim qua thanh ngUc.
Mot sd thdng sd dukien trong ddnh gid chdc nang thdt trdi
Ty le thanh edng, that bai, bien chQng lien quan den thd thuat.
Ty le tQ vong va d c bien cd tim mach ehinh (tiJ vong, suy t i m , nhap vien) qua theo ddi.
Cae thdng sd lam sang cP ban: MUe dd suy tim theo danh gia NYHA.
CIc thdng sd ehinh d i n h g i l chQe nang that trai tren sieu I m t i m : D i n h g i l EF va rdi loan van ddng vQng tren sieu am tim theo phuang phap Simpson, ehi sd chQe nang ca t i m , chQe nang tam trUPng t h i t t r l i ; danh gia ehUe nang that trai tr^n MSCT; d i n h gia chQc nang that t r l i thdng qua EF va rdi loan van dpng vung tren ehup mach.
Mdt sd thdng so xet nghiem khae: Xet nghiem danh g i l mQe suy tim (pro-BNP)...
3. Ket q u d
3.7. Mpt so dac ^em ciia doi ti/ong nghien cda Trong thdi gian nghien cQu tren da ed 6 benh nhan dUpe ghep te b l o gdc (TBG) dieu trj. Die diem chung dupc m d t l trong Bang 1,2.
'i TAP CHlY DUOC LAM SANG 108 Tap 12-So 7/2017
Bdng 1 . Dac diem chung ciia nhom benhnhSn ducrc ghep TBG STT
1 2 3 4 5 6
Ho va ten Nguyen Manh C LeVanT.
Do Trpng T.
Nguyen Van L Nguyen Dinh S.
Nghiem Xuan Q.
Nam sinh 1963 1946 1962 1946 1940 1951
Gi6i Nam Nam Nam Nam Nam Nam
Chan doan lam sang NMCT cap NMCT cap NMCTcgp NMCT cSp/BTB
NMCT cap NMCT cap/BTB
Ngay tiem TBG 07/2007 08/2007 10/2007 11/2007 01/2008 02/2008 (NMCT: Nhoi mdu ca tim, DTD:Ddi thdo di/dng)
Bdng 2. Dac d'litn 13m sang chung cilia nhom STT
1 2 3 4 5
Dac diem Tuoi trung binh (nam)
Gidi nam/nCf Ty le dai thao dudng (%)
Gid tir luc bj nhoi mau cdtim den Ichi dUdc can thiep (gid) EF tren sieu am sau can thiep BMV (%)
5 6 ± 1 2 6/0 2/6 7 ± 5 34 ± 7 (DMV: Ddng mgch vdnh)
3.2. Vecac thong so theo ddi sau thu thuSt Cae t h d n g sd lam sang, can lam sang co b i n , sieu I m t i m , chup budng t i m dugc d i n h gia theo dung quy trinh d e r a .
Thdi gian n l m vidn: Tat e l d c benh n h i n deu
dung nap tdt, khdng cd nhQng bien ed nang nao ^\^^ trj vi suy tim va dudng huydt khd khdng che
•_^ Hen quan den thQ thuat. sau 5 t h i n g va sau dd thi dn djnh.
T i t c l bdnh nhan dupe ra vien vdi thdi gian nam vien trung binh: 9 ± 5 ngay (7 -15).
Tat d benh n h i n deu sdng sdt sau 1 nam theo doi, trong do: 5 benh n h i n de chju t r d v e eude sdng gan nhu binh thudng ma khdng ed nhQng bidn cd tim maeh nang nao. Cd 1 bdnh nhan p h l i nhap vien
3.3. Ket qui ddnh gia chdc nang thai trai di/a trdn nhOhg thay doi lam sang va can lam sang 3.S. 1. Biin doi trin Idm sdng
Bhnq 3. Cac thay doi trieu chi^Tng ctf nang (do NYHA) trUdc va sau ^ e u tri
B§nh nhan
Nguyen Manh C LeVanT.
B6 Trpng T.
Nguyen Van L Nguyen Dinh S.
Nghiem Xuan Q.
TrUdc
III III III III III III
Sau 3 thang
i - l l II II II l - l l
Hi
6 thdng 1 1 1 II 1 II
1 nam
II
2 nam
li
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY VOI.12-N7/2017
Nhdn xet Ket q u i cho thay e l 6 benh nhan deu ed g i l m NYHA sau khi dieu trj phdi hpp b i n g tiem te bao gdc vao Idng DMV thu pham.
S.3.2. Nhdng kit qud ddnh gid can Idm sdng
Ket q u i so bd: Cd sU d i thien rd ret ve trieu chdng eP nang, chi sd pro-BNP va p h l n sd tdng mau that t r l i (EF) eua ngUdl benh d thdi diem 1 nam sau tiem te bao gdc so vdi trUdc dieu trj (BIng 5,6).
A. Xet nghiim Pro-BNP.
BSng 4. Gia trj Pro-BNP cua nhufng benh nhan dUOc ghep TBG
Benh nhan
Nguyen Manh C.
Le Van T.
Do Trpng T.
Nguyen Van L Nguyen Dinh S.
Nghiem XuIn Q.
TrUdc dieu
"1
273,75 312,95 324,95 334,99 366,70 471,34
Sau 3 thang
107,49 189,50 120,86 157,52 134,40 407,21
6 thang 107,90 110,22 143,62 79,85 52,64 288,30
1 nam 36,47 39,96 34,40 33,65 33,55 36,47
2 nam 27,29 28,77 34,62
Don vi do: Don vj qudc te/litte (U/l) 6. Ddnh gid chdc ndng thdt trdi trin sieu dm tim.
Bing 5. Bien doi chuTc nang that trai tren sieu am tim (cac thong so trong bSng la phdn s5 tong mau EF%
cua that trai do tren sieu am tim bang phUOng phap Simpson)
Benh nhdn Nguyen Manh C.
Le Van T.
Do Trpng T.
Nguyen Van L.
Nguyen Blnh S.
Nghiem Xuan Q.
TrUdc dieu trj 39,8
39 37 36 39 32
Sau 3thang
40,0 46 45 40 40 32
6 thang 44,0
44 48 40 48 35
1 nam 47 42 51 43 48 34
2 nam 47 45
47 46 35
Bieu do 1 . SU thay ddi ve thdng sd EF do tren sieu I m tim trUdc tiem va sau ttem 1 nam (bing phuong phapSimson)
TAP CHl Y DUOC LAM SANG 108 Tap 12-So 7/2017
ChQe nang that trai dQpc danh gia tren chi sd chQe nang co tim (Tel-index) eho t h I y cd giam so vdi trUdc khi dieu trj sau 6 t h i n g tiem te bao gdc (4/6) va t i t c l 6 benh n h i n deu cd giam ehi sd Tel sau 1 nam.
Being 6. Bien d o i chi so chuTc n a n g cO t i m (chi sd Tei) d o t r ^ n sieu a m t i m Benh nhan
Nguyen Manh C.
LeVanT.
Bo Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nghiem Xuan Q.
Trudc di4u t r i 0,53 0,58 0,58 0,53 0,47 0,79
Sau 3 thang
0,51 0,46 0,46 0,47 0,47 0,46
6 thang 0,59 0,30 0,50 0,42 0,40 0,74
1 nam 0,52 0,30 0,44 0,41 0,41 0,60
2 nam 0,52 0,23 0,40 0,21
Nhdnxet. Cd the thay rang 6 benh nhan dUpe ghep te bao gde deu ed giam chi sd Tei. D l y la ehi so p h l n anh chQc nang t i m that (el tam t h u va tam trQong) cua benh nhan dupe c l i thien dang ke.
C. Suthay doi chdc nang thdt trdi (EF) trin chup budng tim vd ciiup MSCT Bdng 7. ChuTc n a n g t a m t h u t h a t t r a i (EF %) b a n g phiTCng p h d p chup b u o n g t h ^ t t r a i qua dUdng d n g t h d n g Benh nhan
Nguyen Manh C.
Le Van T.
Do Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nghiem Xuan Q.
Trung binh
TrUdc 39 38 40 38 40 33 3S,0±3,6
Sau 1 nam 53 60 68 49 54 42 S4,3±6,S Nhdn xet Ket q u i chQc nang that trai d d e benh n h i n trQde ghep te bao gde cd EF trung blnh la 38 ± 3,6 (%). Sau 1 nam ghep te b l o goe EF trung binh la 54,3 ± 6,5 (%).
Bdng 8. Chu'c n a n g t a m t h u t h a t t r a i (EF %) b a n g phUcfng p h a p c h u p MSCT b u d n g t i m co t i e m cdn q u a n g Benh nhan
Nguyen Manh C.
Le Van T.
Bo Trong T.
Nguyen Van L Nguyen Dinh S.
Nghiem Xuan Q.
Trung brnh
Trudc 39,0 38,0 44,0 36,0 46,0 28,0 3S,S±4,3
Sau 1 nam 41,00 39,00 60,00 39,00 44,00 32,00 42,S±6,I
Nhdn xit Ket q u i ehQc nang that trai d d e benh nhan trQde ghep te bao goe cd EF trung binh la 38,5 ; 4,3 (%). Sau 1 nam ghep te b l o gde EF trung binh la 42,5 ± 6,1 (%).
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.l2-N''7/aon
Ve ket q u i dieu trj phdi hop te b l o gdc d benh nhan suy tim sau nhdi mau eP tim.
4.1. Ve su an toan va khi thi cua ky thuat tiem te bao goe
T i t c l cac benh nhan deu tuan thu dung theo ele bQdc nghien cQu da dupe de cap d tren (100%).
Thu thuat dupc tien hanh thanh cdng tren c l 6 benh nhan (100%).
Khdng gap trudng hpp nao xay ra bien ehUng n l n g lien quan den thu thuat thu gam te bao gde hay tidm te bao gdc vao dpng mach vanh (0%).
Viec danh gia chQc nang that trai bang ehup budng tim v l sieu I m tim dUpe thue hien thanh edng tren t i t e l ele benh n h i n ngay trude va sau ele thdi gian theo ddi.
So s i n h vdi ele nghien eUu Boost [9], REPAIR- AMI [7] da dupc thuc hidn d nhidu nUde tren the gidi thi deu cho thay rang ghep te bao gdc tuy xUOng t u t h i n b i n g can thiep mach vanh qua da cd tinh an toan va k h i t h i cao.
4.2. Vecacbi&i cotim mach chinh sau can thiep Ket qua nghien cUu eho t h I y , benh nhan dUOc dieu trj ghep te bao gdc theo ddi trong thdi gian 1 nam ed 1 trudng hpp p h l i nhap vien vl suy t i m . Khdng ed trudng hpp nao tQ vong vi d e nguyen n h i n tim maeh, t l i nhdi mau hay tai bien maeh nao.
Ddi vdi trudng hop p h l i nhap vien vi suy t i m , qua dieu tra va khai thac benh n h i n cd tien sQ d l i thao dudng hon 10 n l m va cd kidm s o l t dUdng huydt khd khdng che, sau khi dupc kiem s o l t t d t thi benh nhan tien trien t d t hon, do dd chung tdi ghi nhan trudng hpp bien cd nay.
Trong nghien cUu REPAIR-AMI [7], d e tac g i l nhan t h I y t i n s u i t eua bien cd tim mach gdm tQ vong 2%, nhap vien vl suy tim 0%, t i n suat bien cd chung ket hpp glQa tQ vong, nhap vien vi suy t i m , t l i nhdi mau la 2%.
Trong nghien cUu TOPCARE-AMI [6] t J le bien cd tim mach d nhdm dQpc dieu t n te bao gde sau 1 nam theo ddi lan lupt la tQ vong 3%, nhdi m l u eo tim lai 3%, nhap vien vl suy tim 0%.
So vdi d c nghien edu tren, t i n s u i t bien cd tin mach trong nghien edu eua chung tdi cd ket qu;
g i n tQOng tU. Tuy the, c l n ed nghien cQu dai hon v6 sd lupng nhieu hon de danh gia dupe hieu qui cQ;
phuong phap nay ddi vdi tinh trang suy tim va ta c l u true that t r l i .
4.3. Ve sd thay doi khi nang ging sdc sat ghdp te bao gdc
Ve tidu chi danh g i l c l l thien trieu chUng co nanc sau can thiep, trong nghien eUu cda chung tdi, tat d d c trudng hop deu cd c l i thien trieu chUng co nang SQ d i thien nay xuat hien d thdi diem sau can thiep i t h i n g va ben vUng trong 1 n l m theo ddi sau dd.
Trong nghien cQu A5TAMI [5], 50 benh nhar NMCT trude vach d p dupe can thiep dpng mach vanh qua da sau 2 tdi 12 gid tU thdi diem cd triei chQng. Trong dd cd 4 benh n h i n ed NYHA III, 18 benli n h i n ed NYHA II, dQpc theo ddi trong thdi gian 6 t h i n g sau do. Ket q u i cho thl'y nhdm NYHA 111 gilir xudng cdn 1 ngQdi, nhdm NYHA II cdn 12 ngudi. Kei q u i nghien cQu eho thay ed su d i thien dau hiei chQc nang d benh nhan dQpc ghep te b l o goe.
4.4. V4 kei qui thay doi pro-BNP De danh g i l ve mQc dp thay doi cda pro-BNF sau can thiep, chung tdi da tien h l n h so sanh kel q u i xet nghiep pro-BNP trQde va sau can thiep d cat thdi diem 3, 6 t h i n g va 1 nam sau dd. Ket q u i che thay, sau ghep te bao gdc c l 6 benh nhan deu cc g i l m pro-BNP bat d i u tQ thdi diem t h i n g thU 3 vi tiep tue g i l m sau 1 nam theo ddi.
G i l tri pro-BNP trung binh cCia 6 b&nh nhin triTdi can thiep la 347,45pmol/mL Qua theo ddi 1 nam gi;
trj pro-BNP l l n iQpt la 186,2; 130,4; 35,7 tQOng Ung vd cac thdi diem sau can thiep 3,6,12 t h i n g .
Ket q u i nay cung phu hpp vdi nghien ciJi TOPCARE-CHD [3] theo ddi pro-BNP d 121 b|nl nhan bj suy t i m sau nhdi mau cP t i m . Trong nghier cQu nay pro-BNP g i l m cd y nghla ngay sau 3 thant dQpc truyen te bao gdc.
TAP CHfY Dl/pc LAM SANG 108 Tap 12-56 7/2017
4.5. Ve ket qui thay d6i chdc nang that trai sau can thiip
Danh g i l ve c l i thien chQe nang t h i t trai qua phan sd t o n g m l u EF, ehung tdi thay rang ed sQ c l i thien EF tQ 2 - 1 1 % sau 6 thang theo doi va tang tQ 4 - 1 4 % d c l 6 benh n h i n dupe ghep te bao gde tdy xuang.
Ket q u i nghien cdu eua chung tdi cung tUPng t u nhu trong nghien cQu BALANCE [8] va nghien eUu BOOST [9] va mdt sd nghien cQu khIc.
5. Ket l u a n
Ket q u i nghien eUu tren 6 benh n h i n da bUdc dau cho thay.
Danh g i l sU thay ddi chUe n l n g that t r l i d benh nhan suy t i m do nhdi m l u ca t i m dugc dieu trj phdi hpp b i n g te bao gde tuy xuong tQthan.
Ty le t h l n h edng cua ky t h u l t la 100%.
Can thiep te baa gdc lam d i thien trieu chQng ea nang d benh nhan suy t i m do nhdi m l u eP t i m .
Ghep te bao gdc lam c l i thien chQc n l n g that trai.
Tren sieu am tim sau 6 t h i n g t h I y trung binh ed t i n g EF 6%.
Tren chup budng that t r l i va MS-CT cd tang k h o i n g 4 % sau 1 nam theo ddi.
Tai lieu t h a m khdo
1 Thach Nguyen, Pham Gia KhIi, Nguyin Lan Viet (2007) Diiu tri nhoi mdu ca tim cdp cd STchinh lin.
Mpt sd van de cap n h l t trong ehan d o l n va dieu tri benh tim maeh, NXB Y hoc, tr. 25-57.
2 Nguyen Lan Viet, Pham Viet Tuin, Pham Manh Hung, Van DQc Hanh (2010) Nghiin cdu mo hlnh binh tdt d binh nhdn diiu tri ndi trd tgi Viin tim
mgch Viet Nam trong thdi gian 2003-2007. Tap chf Tim Mach Hoc Viet Nam 52:11-18.
Assmus B et al (2007) Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: Results of the TOPCARE-CHD registry. Circulation: 1234.
Ge J et al (2006) Efficacy of emergent transcatheter transplantation of stem ceils for treatment of acute myocardial infaraion (TCT-AMI). Heart (92): 1764-1767.
Lunde K et al (2007) Exercise capacity and quality of life after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infaction: Results from the autologous stem cell translantation in acute myocardial infarction (ASTAMI) randomized controlled triai Am Heart J, (154): 1-8.
Sehachinger V, Assmus B et al (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one-year results of the TOPCARE-AMI trial. JACC (44): 1690-1699.
Sehachinger V et al (2006) Improved clinical outcome after intracoronary administration of bone- marrow-derived progenitor cells in acute myocardial infarction: Final 1-year results of the REPAIR-AMI trial. Eur HeartJ (27): 2775-2783.
Yousef M et al (2009) The BALANCE Study: Clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. J Am Coll Cardiol (53): 2262-2269.
Wolert KC et al (2004) Intracoronary autologous bonemarrow cell transfer after myocardial infarction:
TheeOOSTfr/o/. Lancet (364): 141-148.
