NGHIEN CUU l ^ M SANG
Danh gia chiic nang that trai 6 benh nhan suy tim sau nhoi mau co tim cap dugc dieu tri bang te'bao goc tiiy xuong tu than
Pham Manh Himg; Do Thuy Can; Nguyen Thi Thu Hoai; Nguyen Ngpc Quang;
Nguyen (3uoc Anh; Do Doan Loi; Nguyen Lan Viet Vien Tim Mach Viet Nam - Benh Vien Bach Mai
•AT VAN BE
Benh tim mach la nguyen nhan gay hi vong hang dau 6 cac nuoc phat trien va dang co xu huong tang dan 6 cac nuoc dang phat trien, trong do co Viet Nam.
Moi nam, tren the'gioi co khoang 5 trieu benh nhan bi nhoi mau co tim (NMCT) va khoang gan 1 trieu nguai hi vong lien quan de'n benh ly dpng mach vanh.
M^c dil tieh bp khoa hpe ky thu^t da dua deh nhieu hucmg dieu tri moi trong NMCT cap cho phep chiia khoi trong nhieu tmong hpp hoac cai thien dang ke tien lupng b?nh nhung vin co nhieu truong hpp benh tieh trien de'n giai doan cuoi vol tinh trang suy tim nang ne. Theo uoc tinh, so b|nh nhan nay ehie'm khoang 10% - 20% tong so cac benh nhan sau NMCT va ty 1$ nay con cao hon trong cac truong hpp can thiep mupn. Trong nhiing truong hpp nay, cac bien phap thucmg quy nhu dieu tri bao ton bang thuoc, can thiep dpng mach vanh, phau thuat hay diing cac thie't bi h6 trp tim thucmg cho ke't qua rat han che'.
Ngay nay, cac tieh bp trong Y sinh hpe va dac biet la trong Hnh virc nghien ciiu
ling dung te'bao goc trong dieu tri benh da thiic day mpt hucmg tie'p can moi trong dieu tri nhung vari de nan giai tren. Cho de'n nay, da co ra't nhieu nghien ciiu ciia cac tac gia My, Ao, Diic va Trung Quoc tieh hanh thuc nghiem tren nguoi cCing cho tha'y CO su cai thien ve tinh t r ^ g tuoi mau, kich thuoc aia o nhoi mau ciing nhu kha nang co bop ca tim a nhiing benh nhin suy tim sau NMCT dupc dieu tri phoi hpp bang te'bao go'e [2-8]. Mpt so'bSng chiing thuc nghiem cho tha'y te'bao goc dua vao Cling CO the tuong tac voi cac te'bao goc tai cho de tang cuong kha nang tai sinh va bi$t hoa [9]. Dac biet, mpt nghien ciiu ngau nhien co doi chiing tie'n hanh t ^ Diic (nghien ciiu REPAIR AMI) da hoan thanh trong nam 2006 tren 200 benh nhan sau NMCT cap, cho thay ke't qua dang khich le v§" su cai thien chiic nang that trai cung nhu ve ty le hi vong a nhiing benh nhan dupc tiem te'bao goc vao dpng mach vanh thii pham [17].
Tuy nhien, van de dat ra la lam sao CO the danh gia dupc hi?u qua ciia bien phap dieu tri bSng te bao goc nay mpt each hpp ly, Ipai te'bao nao va so'lupng ra sao. Nhiing nghien ciiu gan day da cho
TAP CHi TIM MACH HOC VIET NAM - S6 54 - 2010
tha'y vai tro cijc ky quan trpng cua cac bien phap tham do hinh anh hoc va chuc nang that trai, qua do gian tie'p danh gia dupc hieu qua cua lieu phap te'bao goc.
Tai Viet Nam, trong nhirng nam gan day, cac nha khoa hpe cung da manh d ^ trien khai cac nghien cthi ca ban ve linh vuc te' bao goc ciing nhu dua vao iing dung de dieu tri cac berth mau ac tinh. Du ke't qua thu dupc ban dau con khiem ton, song do cung la nguon co vu ldn lao cho cac nha khoa hpe Vi|t Nam. Tren nhiing co so ly luan va thuc tien do, Truong Dai hpe Y Ha Npi phoi hpp cimg Vien Tim mach Quo'c gia Viet Nam tie'n hanh nghien cthi va trieh khai ung dung dieu tri cay ghep te bao goc qua duong 6'ng thong de dieu tri cho cac benh nhan suy tim sau NMCT 6 nuoc ta [2]. De danh gia hieu qua phuong phap nay, chting toi da sir dting cac bien phap tham do hinh anh, huye't dpng hi^n d^ va dang tin cay nhu: Sieu am - Doppler tim; cht^p buong tiia't trai qua duong 6'ng thong; chup MSCT that trai... de danh gia chirc nang that trai.
De tai nay ra doi voi mtic tieu nghien cthi cu the sau:
"Buac dau ddnh gid ehiic ndng that trdi a benh nhdn suy tim sau NMCT cap duac dieu tri phoi hgrp hdng cay ghep te bdo goc tu thdn tk tuy xuong henh nhdn"
TONG QUAN:
1. Tinh hinh benh tim mach hien nay tren the gio-i va 6- Viet Nam:
NMCT la mpt berth rat pho bieh tren
toan the' gioi. Mac du da co ra't nhieu ti&i bp trong chan doan va dieu tri, nhung NMCT v ^ la mpt trong nhiing nguyen nhan hang dau gay tii vong va ma't stic lao dgngtaicacnuacphattrieh riingnhungay cang tro thanh van de siic khoe dang quan tam 6 cac nuoc dang phat trieh. Tai My, theo ke't qua cua Dieu tra quo'c gia ve tirth hinh sue khoe va dinh duong (NHANES) 1999 - 2002, CO 7,1 trieu nguoi da tiing dupc chan doan NMCT voi ti-en 500.000 truang hpp mac mdi m6i nam. Trong so' do, 4,9 trieu nguoi phai chiu hau qua suy tim va khoang 1/5 cac truong hpp nay tti vong sau 12 thang. Trong bao cao ctia T6' chiic Y te the'gidi (WHO) nam 1999, ty le tii vong do benh tim thieu mau arc bp cua 6 mpt so'nuoc Chau A xa'p xi 10% (Tnmg Quo'c: 8,6%, An Dp: 12,5%, cac nude chau A khac khoang 8,3%). Ty le mac berth tang len theo tuoi va cung mot nhom tuoi thi ty le mac benh 6 nam cao hon a nu.
Tai Vi?t Nam, truoc nam 1960, mcfi chi CO 2 truang hpp NMCT dupc phat hien. De'n thap ky 90, theo Tran Do Trinh va Cpng su tong ke't tai Vien Tim mach Quoc gia Viet Nam, ty le NMCT tren tong so benh nhan nhap vien la 2,53%, trong do ty le tii vong la 27,4%. Theo thong ke oia Vien Tim m^ch qu6'c gia Viet Nam, ne'u tinh tu nam 1995 de'n nam 2006, so' chtip va can thiep dpng mach vanh da gan 4.000 trucmg hpp (1,2).
2. Sinh ly benh nhdi mau co'tim:
Sau khi xay ra tinh tiang tac dot ngpt mpt dpng mach vanh, su tuoi mau
NGHIEN CUU LAM SANG
vung co tim dupc nuoi duong btii phan mach mau phia sau bi suy giam mpt each tram trpng hoac mat hoan tpan, cac te' bao CO tim bupc phai chuyeh hoa theo con ducmg ye'm khi. Qua trinh trao doi chat npi bao bi anh huong sau sac. Cac san pham giang hoa trong qua trinh nay nhu add lactic, add pyruvic va cac goc tu do lam thay doi tinh tham ciia mang te' bao lam roi loan su tiao doi ion qua mang cimg voi tinh tiang thieu hut nang luong (ATP) gay suy giam chirc nang aia te'bao CO tim va hien tupng tai ca'u tnic co tim.
Tai cau tnic la mpt thuat ngir de chi hien tupng bie'n doi ve hinh thai va caii tnic ciia te'bao co tim ton thucmg, khong nhung tiong vimg nhoi mau ma ca 6 vimg Ian can. Qua trinh nay lien quan de'n hien tupng che't di cua cac te'bao hoai tii, bie'n doi mang luoi ngoai bao, du nhap va tan tao cac te'bao mod, ke't qua la su gian ra ciia buong tim tai vimg do, lam chiic nang that tiai xa'u dan di. Hien tupng nay CO the xay ra rat scim, chi mpt vai ngay sau NMCT, dac biet la tiong cac trucmg hpp nhoi mau co tim dien rpng.
3. Chtic nang that trai sau nhoi mau co'tim:
LlChiicnangtmnlhulhattrditodnbg:
Miic dp anh hucmg deii chiic nang tha't tiai tiong nhiing gio dau sau NMCT phu thupc vao dp rpng va dp nang aia roi loan van dpng vimg co tim nhoi mau, dp rpng ciia vimg "ria" (co roi loan van dpng vimg nhung khong do dpng mach vanh tac chi phoi), pham vi va miic dp tang van
dpng bii aia vimg co tim lanh.
3.2 Chiic nang tdm truang:
Trong NMCT, chiic nang tam trucmg oia tha't tiai bi anh hucmg chii ye'u the hien qua giam kha nang gian aia tha't tiai va roi loan do day tam trucmg. Hien tupng nay thucmg ke't hpp vcji giam dP/dt va tang ap luc cuoi tam truong, tie'p sau do the tich cuoi tam trucmg tang va ap luc cuoi tam tnrong tio ve binh thudng.
Ciing nhu chiic nang tam thu, chiic nang tam trucmg ciing tucmg quan vcii kich thuoc o nhoi mau.
4. T l bao g6c va ijng dung trong dieu tri suy tim sau nh6i mau c c tim
4.2 Khdi niem tebdo goc:
Te'bao go'e (stem cell) la nhiing te'bao dac biet, dupc dac tnmg boi 2 kha nang dp la kha nang tu doi mm va biet hoa thanh nhieu dong te'bao chuyen biet khac nhau de thay the'cho cac te'bao da che't do qua titah "gia" di mpt cadi tu nhien hay do cac yeii to'sang chan. Cac te'bao nay nam rm rac 6 khap cac mo, co quan tiong co the^ deu dan tang sinh va biet hoa, cung cap nguon te'bao mm de tai tao mo va giii ca the luon tirong tang thai can bang. Su quyet dinh hucmg phat tiim va biet hoa cua mpt dong te'bao phli thupc vao cac yeu to kich thich sinh tiudng do mo, co quan do tiei ra (cac hormon tai cho).
Hien nay, co 3 loai te'bao goc dupc nghien ciiu nhieu nha't trong cac thir nghiem lam sang tiren nguoi va dpng vat, gom:
TAP CHl TIM MACH HQC VIET NAM - SO 54 - 2010
- Te bao go'e phoi (embryonic stem cell): lay tii gan cua phoi 8 -12 tuan tuoi.
Cac te'bao nay co dac diem rai "non"
ve miic dp biet hoa nen co tiem nang bie'n doi thanh cac dong te'bao chuyen biet cao nha't, kha nang phan chia Ion nha't, nhung co hai nhupc diem chinh ctia dong te'bao nay la kha nang sinh u quai va van de d^io diic.
- Te bao gd'e 6 rau thai: lay tii mau cuohg ron (embilical cord blood stem cell) sau do dupc phan lap, tach chie't;
hoac lay tii mang day roh (embilical cord lining stem cell). Cac te'bao nay ciing co kha nang ton tai va biet hoa cao, de thu nhan ma khong gay ra cac van de ve dao dtic. Hi?n nay, nhieu nuoc tren the' gioi da xay dung cac ngan hang luu trii va bao quan te'bao go'e tii rau thai de cung cap cho vi^c dieu tri.
- Te' bao goc 6 nguai trudng thanh (adult stem cell): co mat tai nhieu mo, co quan khac nhau nhu da, co xuong, tuy xuong, mau ngoai vi... Viec thu thap te' bao thuang gap kho khan hon do so luong te'bao goc tai m6i mo khong nhieu, thuong phai dimg cac thu6'c kich thich tang sinh truac khi lay b#nh pham. Tuy nhien, sii d t ^ g nguon te'bao goc tu than nay se tranh duac cac vah de nhu thai ghep, kha nang sinh u quai va cac rao can ve dao dlic.
4.2. Ving dung te'hdo go'e trong dieu tri suy tim sau nhoi mdu ea tim:
Nam 2001, Goldman va cpng su da thong bao nhung bang chung dau
tien ve su co mat ciia cac te'bao nguon sinh mau tai mo co tim a 4 truang hap bi NMCT cap ma khong co bang chting ciia cac benh mau ac tinh hay cac benh ly toan than khac [2], Cung nam do, Orlic va cpng SIJ da sti dung te bao goc ttiy xuong de tiem vao vung ca tim chupt bi hoai tii do gay nhoi mau da cho tha'y CO su biet hoa ciia cac te'bao dupc tiem vao thanh cac te'bao co tim va tao thanh cac ca'u tnic vi mach, giam bat dien nhoi mau, giam tinh trang gian thanh tim va cai thien chtic nang tim chi sau 27 ngay.
Nhiing ke't qua ban dau nay da mo ra mpt hudng moi trong dieu tri cac b^nh tim do thie'u mau [3-10].
Hau nhu rat it nghien ciiu sti dung dong te'bao goc rieng biet, ma da so sii dung nguoh te'bao g6'c khong chpn loc tii tiiy xuong, trong do chtia s&n nhieu dong te' bao chua biet hoa nhu te bao tao mau goc, te'bao npi m?c mach non va te' bao trung m6 go'e, do kha nang lay tuy de dang, khong can nhiing thie't bi dat tien, phiic tgp de sii dung tren lam sang.
Te' bao go'e tuy xuong (bone mar- row derived stem cell) rat da dang, co the phan loai thanh hai nhom Ion (dong te'bao tao mau va dong te'bao trung mo) dua vao cac chi diem tren be mat te'bao nhu CD34 hay CD45. Nhihig chi diem khac tren be mat te bao nhu CD117, CD133, Sca-1 va Stro-1 cung dupc ap dung de phan loai nguon te' bao nay thanh cac nhom nho hon.
Te' bao g6'c tu tuy xuong rat phit
NGHIEN Ciru LAM SANG
hpp de cay vao ca tim nho kha nang phat trien theo nhieu kieu khac nhau (theo duang trung m6) de hinh thanh te'bao co tron, co tim, mach mau non (angioblast) - vo'n la ba loai te'bao chii chot ciia qua tim. Nhieu thi/c nghiem chiing to cac te bao go'e tii tuy xuong nhu te'bao tao mau go'e, te'bao npi mae mgch non, te bao dan nhan va tg' bao trung mo goc, deu co kha nang biet hoa thanh te bao eo tim va npi mac sau khi ea'y vao tim, tii do tai sinh phan mo nhoi mau da bi hoai tCr va thie'u mach mau nuoi duong. Kha nang tai sinh m6 CO the dat toi 68% vung co tim nhoi mau sau 9 ngay 6 chupt thi nghiem gay NMCT cap dupe ea'y dong te bao tao mau goc (Lin- CD117+ HSC). Te'bao go'e tu tuy xuong cOng rat phii hpp de ling dung rpng rai trong lam sang do:
kha nang tach trtrc tie'p tir dich chpc ttiy hoac thu thap tir mau ngoai vi truyen hoan hoi deu de dang, miic dp tang sinh eao trong moi truang nuoi, dac tinh sinh ly/hoa sinh co the xac dinh ehi tie't truoc khi dem ea'y...
Hien nay, 3 con duong nham dua te' bao goc de'n m6 dieh thudng dupc sii dung trong nghien cthi bao gom truyen te bao gd'e qua tiiih mach ngoai vi dong thai dimg cac ye'u to hoa ting dpng dac hieu (hieu qua khong eao), tiem true tie'p te' bao goc vao vimg s?o nhoi mau (thuang ap dung trong khi phau thuat bae cau noi chu - vanh) va truyen te'bao goc qua ohg thong vao dpng maeh vanh qua da thong qua bong bit dau.
5. Cac phLFcng phap danh gia chijc nang that trai
5.1 Chtip huong thai trdi co bom thud'e cdn quang:
Cho de'n nay, chup buong that tiai eo bom thuoc can quang van la mpt phuang phap kinh dieh de danh gia chiie nang tam thu toan bp ctia tha't trai. Thong so thudng dupc sti dung la phan so tong mau (EF). Phan so' tohg mau dupc tinh dira tren ea so so sanh the tieh that trai CUOI tam truong voi the tich that trai euoi tam thu theo eong thtic sau:
Vd-Vs EF =
Vd
Trong do, Vd: the tich that trai euoi tam truang
Vs: the tich that trai cuo'i tam thu De tinh the tich buong tha't trai, co nhieu phuang phap khac nhau, trong do CO hai phucmg phap pho big'n nhat la phuong phap Dodge va phuang phap Simpson.
* Nhupc diem etia phuang phap ehup buong tha't trai:
Tuy ehup buong that trai co tiem thudc can quang se cung cap cac thong so' CO dp ehinh xae eao nhung day la mpt phuong phap tham do gay ehay mau, co the CO eac bieh chiing nguy hiem, kho CO the thue hien lap lai nhieu lan. Mat khac, phuong phap nay doi hoi trang bi may moc hien dai dat tien eimg voi mpt dpi ngu nhan vien dupc dao tao chuyen nghiep nen khong phai co so nao cung co
TAP CHl TIM MACH HOC VIET NAM - SO 54 - 2010
the trieh khai dupe. Vi vay, ehup buong that trai co tiem thuoc can quang khong phai la phuong phap dupe chi dinh thuang quy de danh gia ehiie nang that trai trong chan doan va dieu tri benh tim mach.
5.2 Sieu dm tim:
Siiu dm tim mgt binh dien (time motion -TM):
l/u diem cua phuong phap sieu am TM la dan gian, de thirc hien va do tan so khimg cao nen dp phan giai cao. Tuy nhien, trong eac trudng hap eo r6'i logn van dpng vimg khu tni thi ke't qua do dupe se khong phan anh chinh xac kha nang CO bop etia toan bp qua tim.
Siiu dm tim hai binh dien (2D):
Do CO the eat 6 nhieu mat eat khac nhau nen sieu am 2D cho phep danh gia toan bp cac thanh tim trai va van dpng tnia timg vimg that trai. Ve phuong dien tham dd chiic nang tim va huye't dpng, sieu am 2D danh gia dupe chtic nang tam thu that trai va cae thong s6' huye't dpng.
Phuang phap dupe eoi la ehinh xac va hay sii dyng nha't la phuang phap Simp- son. Vi^c do dae thudng dupc tien hanh tren cac mat cat 4 buong, 2 buong hoac phdi hpp mat cat 2 buong vdi mat cSt trye ngan canh tic trai hay 4 buong vdi 2 buong.
Sieu am 2D edn cho phep danh gia van dpng cua cae thanh tim. De khao sat dupe toan bp cae thanh tim, can quan sat tren nhieu mat cat khac nhau, it nha't la
tren 4 mat eat chinh (trtie dpe cgnh lie trai, true ngan eanh uc trai, 4 buong va 2 buong tir mom). Ro'i loan van dpng vimg dupc danh gia dua tren dp di dpng vao trong eiia thanh tim va dd day len cnia thanh tim trong thi tam thu. De danh gia van dpng cac thanh tim khach quan va ehinh xae han, hien nay thudng ap dung caeh chia that trai thanh 16 vung va eho diem van dpng theo khuye'n eao cua Hpi sieu am Hoa Ky, tii do tinh dupc chi sd van dpng vimg. Chi sd'nay cho phep udc lupng miie dp va pham vi ciia vimg bi nhdi mau.
Ngoai ra, sieu am 2D edn giiip phat hien eae bieh chiing eiia NMCT nhu phinh thanh tim, thiing vach lien that, hd van hai la, huye't kho'i trong buong tim va tran dieh mang tim.
Siiu dm Doppler:
Tren sieu am Doppler tim, ehtie nang tam thu that trai toan bp dupc danh gia qua cae thdng sd eung lupng tim (CO) qua van dpng mach ehii, vgn td'c td'i da (Vmax) va tich phan ddng chay (VTi) qua van dpng mach chu:
- Nghien ciiu cho tha'y giam chiic nang tam truang that trai tren sieu am Doppler xua't hien ngay gid dau sau NMCT vdi da'u hieu giam van td'c sdng E va song A, tang chi so' tam thu/ tam truang eiia phd Doppler ddng chay tinh mgeh phdi, keo dai thdi gian gian ddng the tich mge dii ehua cd su thay ddi ve hinh thai. Sau 3 tuan tha'y tang ehi so E/A, giam chi so tam thu/ tam truang etia pho
NGHIEN ciru LAM SANG
Doppler ddng ehay finh mach phoi kem theo tang dien tieh nhi trai [24].
- Cae nghien cthi ve chiic nang tam truong that tiai qua ddng ehay van hai la deu eho tha'y nit ngan thdi gian dd day chgm (DT < 140ms) la dau hieu quan trpng tien lupng tir vong, tai nhap vien do suy tim do NMCT, tien lupng tinh trgng tai cau tnic co tim sau NMCT, tien lupng gian that trai mudn d benh nhan NMCT da tai tudi mau thanh eong [23].
- Chi so chtic nang co tim (Index of myocardial Performance - IMP hay Tei - index) la chi sd' ket hpp giira thdi gian tam thu va thdi gian tam truong ctia that trai eung tang len rd ret d cac benh nhan NMCT. Nghien cthi cho tha'y chi so nay
> 0,6 va nit ngin thdi gian dd day that cham (DT < 140ms) la cae ye'u td tien lupng CO y nghia trong NMCT [23]. Chi sd'nay dupe tinh b ^ g ty le giiia tdhg ciia thdi gian gian dong the tich va thdi gian CO ddng the tich so vdi thdi gian td'ng mau that trai. Chi sd'Tei dupe do dua vao ddng ehay qua van hai la va van dpng mgeh chit
5.3 Chup MSCT ddnh gid chiic ndng that trdi:
Chtip MSCT danh gia chtic nang that trai la phuong phap ehan doan hinh anh kha chinh xac de danh gia nhiing bie'n dd'i chiic nang tha't trai. l/u diem eiia phuang phap nay la tham dd khdng chay mau, khdng phu thupc vao hinh thai budng tim va trinh dp eua ngudi chup, eho phep dung lai hinh
anh budng that trai trong khong gian 3 ehi§u vdi chuyeh ddng thye. Tir do, cho phep danh gia tuang ddi khach quan su bie'n dd'i mtic dp van dpng etia cac vung co tim. Chup MSCT danh gia ehiie nang that trai eho ke't qua chinh xac cao khi so sanh vdi phuong phap ehup budng that trai qua da ciing nhu so vol xg hinh budng that trai va cd thg' lap lai nhieu Ian [17],
5.4 Phuong phdp chup hinh phong xg huong tim:
Day la mot ky thugt tham dd khdng xam nhap cho phep danh gia hinh dang, kich thudc cae budng tim. Ky thuat nay sir dting 99mTc gan vao hdng cau b^nh nhan de daitii da'u, sau dd tiem trd Igi finh mach cua ngudi benh. Hdng cau nay vao nhi phai, xudhg that phai, qua h? tuan hoan phdi sang tim trai. Cac thie't bi ghi hinh phdng xa se ve lai cac ho mau (hinh dang va kich thudc eae buong tim) trong ea ehu chuyen tim (tam thu va tam truong).
Ky thuat nay cho phep danh gia chtic nang tam thu toan bp ciia that trai va that phai, van d6ng etia eac thanh tim qua do xac dinh viing co tim bi nhdi mau (rdi logn van dpng vimg) ciing nhu cac bie'n chiing eo hpe do NMCT.
Day la mpt phuong phap ed dp ehinh xac kha cao. Tuy nhien, do su phat trieh va tinh thuan tien cua sieu am tim, ky thugt nay ngay cang it dupe ting dung de danh gia ehiie nang tim trpng thue hanh Iam sang.
TAP CHl TIM MACH HOC VIET NAM - S6 54 - 2010
BOl TI/QNG VA PHiriTNG PHAP NGHIEN CUfU
£)6i tiPO-ng nghien c i f u :
- Gdm 6 benh nhan da tinh nguyen tham gia vao nghien eihi thir nghiem ting dung te bao gd'e ttr than tir tiiy xuong trong dieu tri suy tim sau nhdi mau co tim cap trong thdi gian tii 6/2007 d a i 12/2008.
- Ca 6 benh nhan nay dupc theo doi trong thdi gian tit 20 deh 28 thang (ke tir thdi diem dupe dua te'bao gdc vao dpng mgch vanh cho de'n thdi diein ke't thiic nghien cuu vao thang 12/2009).
- Tieu chuan ehpn lua benh nhan:
+ Nhgp vien vdi ehan doan nhoi mau eo tim cap (theo tieu chuan chan doan etia Td ehtie y te the' gidi) trong khoang thdi gian < 24 gid ke tit thdi diein khdi phat b?nh.
+ Dpng maeh thii pham la dpng mach lien that trudc doan I hoae II.
+ Dupc can thiep dpng mach vanh thu phgm (nong va dat stent) vdi ke't qua tir TIMI II tiro Ien.
+ Chtic nang tim giam vira (EF do theo phuoTtg phap Simpson tren sieu am trong khoang 30 - 40%) sau khi can thiep 3 - 5 ngay.
+ Ddng y tham gia vao nghien ciiu.
- Tieu chuan logi trir:
+ Co bie'n chiing co hoc do NMCT + Da timg bi NMCT cap trudc do.
+ Nhung benh nhan khdng the thuc
hien theo doi tie'p theo.
+ Chiie nang tim EF < 30% hogc > 40%.
+ NYHA IV trude khi dupe lua chpn + Khdng tuan tiiii dieii tn ehuah sau dd.
+ Kem theo tdn thuang dang ke dpng mach vanh phai va/hogc dpng mgch mil (hep > 75% hoac tac man tinh) hogc tdh thuong doan III ddng mgch lien that trude hoae ed tdn thuang than ehung (hep > 50%).
•^ Thie'u mau nang (hemoglobin <
9mg%).
+ Co cac benh ly mgn tinh khae kem theo (berth gan, than, hd ha'p, ung thu,...) + Cd benh van tim ngng kem theo.
+ Tudi > 70.
P h i r c n g phap nghien CLPU:
- Nghien eiiu md ta ed theo doi dpe theo thdi gian.
- De danh gia hieu qua eiia phucmg phap dieu tri, ehung tdi sit dtmg nhieu phuong phap khae nhau nhu:
+ Xet nghiem sinh hoa mau.
+ Bieh ddi tren dien tam do.
+ Sieu am tim.
+ Chup MSCT danh gia ehiic nang that trai.
+ Chup budng that trai cd tiem thud'e can quang.
- Cac ket qua tham dd ve hinh anh hoc deu dupc ghi lai de tiai hanh phan tieh ddc lap bdi it nha't 2 bae sy chuyen khoa cd kinh nghiem nham dam bao su khaeh quan ctia
B & i
NGHIEN CUU IJ\M SANG ke't qua nghien ciiu. Trong tiircmg hpp cosu khach biet Ion ve ke't qua dpe giiia hai nguoi, so'lieu thu dupc se dupc danh gia lai bcri nguoi thii ba.
Cac thong s6 nghien ci>u:
a. Bdnh gid nhiing bien doi tren lam sdng:
- Danh gia thanh cong chung cua thu thuit.
- Danh gia thay doi miic dp suy tim theo NYHA qua theo doi tai cac thoi diem quy djnh
- Danh gia thay doi cac trieu chiing thuc ton khac cila suy tim nhu: phii, gan to, finh mach co noi... tai cac thoi diem quy dinh.
- Danh gia mpt so bat thucmg khac ne'u co: khoi u bat thuong, roi loan mien dich, roi loan huye't hpe...
b. Ddnh gid nhiing bieh doi ve sinh hoa mdu:
- Cac thong so xet nghiem thong thudng tai cac thcri diem: ducmg mau.
Bang 1. Thong so chung aia benh nhan
lipid mau va cholesterol mau, chiic nang th?in, mengan...
- NT- Pro BNP -CRP - Troponin
- Mpt so thong so miln dich:
c. Bdnh gid nhiing bien doi ve chic ndng that trdi (dd trinh bay chi tiei a phan tong quan):
- Cac thong so tien sieu am danh gia chiic nang that trai: EF (simpson); chi so TEI; Sieu am Doppler mo co tim truoc, va sau thu thuat tai cac thoi diein da dinh.
- Danh gia chiic nang that trai tren phim chup MSCT, chi so EF.
- Danh gia EF tren chyp buong that tiai nho phan mem QCA.
KET QUA VA BIEN lUAN 1. Tinh hinh chung
Nghien ciiu da dupc tieh hanhban dau tren 6 benh nhan vol dac diern nhu sau:
STT 1 2 3 4 5
Hp va ten Nguyen Manh C.
Le Van T.
Do Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nam sinh 1963 1946 1962 1946 1940
Gioi Nam Nam Nam Nam Nam
Chan doan lam sang NMCT cip NMCT cip NMCT cap NMCT cip/ DTD
NMCT cap
Ngay tiem TB goc 07/2007 08/2007 10/2007 11/2007 01/2008
TAP CHl TIM MACH HOC VIET NAM SO 54-2010
mm
UU
Nghiem Xuan Q. 1951 Nam N M C T cap/ D T D 02/2008 (NMCT: Nhdi mau eo tim, DTD: dai thao dudng)Vgy, nghien eihi oia chung toi cd 6 benh nhan deu la nam gidi vdi tudi tir 43 - 67 (tinh deh thdi diem lay vao nghien cthi). Cae berth nhan nay deu dupc dieu tri theo thue hanh hien nay bao gom eac bien phap dieu tri npi khoa tdi uu va dupc nong + dat stent ngay thi dau.
2. Danh gia nhu-ng thay doi phan anh chi>c nang that trai tren l i m sang va can lam sang
a. Thay doi NYHA
- Ca 6 trudng hpp deu cho tha'y co su eai thien dang ke ve trieu chiing co nang sau khi dupe dieu tri phdi hpp bang phuong phap tiem te'bao gd'e vao Idng DMV thu pham.
- Su eai thi^n dupe ghi nhan ngay tir thdi diem theo ddi sau 6 thang va dn dinh trong sud't qua trinh theo ddi keo dai 24 thang. Chi cd 1 trudng hpp benh rtiian Nghiem Xuan Q. do kiem soat dudng huye't kem da phai tai nhap vi^n sau 5 thang de dieu ehinh che dp thud'e dieu tri dai thao dudng.
Bang 2. Cae thay ddi trieu chting co nang (dp NYHA) trude va sau dieu tri
Benh nhan
Nguyen Manh C.
Le Van T Do Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nghiem Xuan Q.
Truoc
II
n
III ni II in
Sau 3 thang
I-U 11
n
II I-II
m
6 thang I I I II I II
1 nam
II
2 nam 1 I I I I II b. Nhiing kei qud ddnh gid can ldm sdng:
Co su cai thien rd ret ve trieu chting eo nang, ehi so' BNP va phan so' td'ng mau that trai (EF) eiia ngudi benh d thdi diem 1 nam sau tiem te'bao gd'e so vdi trudc dieu tri.
- Thay ddi Pro - BNP.
NGHIEN CUU U M SANG
Bang 3. Gia tii Pro BNP
B e n h n h a n
Nguyen Manh C.
L e V a n T Do Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nghiem Xuan Q.
Tnroc dieu tri
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 t h a n g 107.90 110.22 143.62 79.85 52.64 288.30
1 n a m 36.47 39.96 34.40 33.65 33.55 36.47
2 n a m 27.29 28.77 34.62
- Thay ddi chtic nang that trai thdng qua phuang phap do EF kieu Simpson bang sieu am Doppler tim. Chtic nang that trai danh gia dua tren sieu am tim (EF) eung eho tha'y cd su cai thien trung binh tir 6% deh 10% (sau 6 thang).
Bang 4. Bie'n ddi chiic nang that trai tren sieu am tim
Benh n h a n
Nguyen Manh C.
Le Van T Do Trpng T Nguyen Van L.
Nguyen Dinh S.
N'ghiem Xuan Q.
Truoc dieu tri
39,8 39 37 36 39 32
Sau 3 t h a n g
40,0 46 45 40 40 32
6 t h a n g 44,0
44 48 40 48 35
1 n a m 47 42 51 43 48 30
2 n a m 47 45
47 46 34 - Chup buong that trai bang thud'e can quang: Su bieh ddi chiic nang tam thu that trai bang phuang phap chup buong that trai qua da cho nhung ke't qua ve sir thay doi dang khieh le (Bang 5).
Bang 5. Chiie nang tam thu that trai bang phuong phap chup buong tim
B e n h n h a n
Nguyen Manh C.
L e V a n T Do Trpng T.
C h p p b u o n g that tiai q u a d a EF (%) Truoc
39 38 40
Sau 1 n a m 53 60 68
TAP CHl TIM MACH HOC VIET NAM - SO 54 - 2010
fna
Nguyin Van L.
Nguyin Dinh S.
Nghiem Xuan Q.
38 40 33
49 54 42
- Chup MSCT danh gia ehiic nang that trai (EF) eung eho tha'y su eai thien dang ke:
Bang 6. Chiie nang tam thu that trai bang phuang phap ehup MSCT budng tim
Benh nhan
Nguyen Manh C.
L e V a n T Do Trpng T.
Nguyen Van L.
Nguyen Dinh S.
Nghiem Xuan Q.
EF (%) tren chup MSCT Truoc
39.0 38.0 54.0 36.0 46.0 28.0
Sau 1 nam 41.00 39.00 60.00 39.00
44.00 32.00
Sau 2 nam
Budc dau ehiing tdi nhan tha'y vdi rihung b$nh nhan tre tud'i, su bie'n ddi ve trieu chting eo nang va cai thien chat lupng cupc sd'ng rd ret han so vdi ngudi cao tudi. Chting tdi dmg nhan tha'y nhung b^nh nhan tieu dudng, chtic nang that trai suy giam nhieu (EF <35%) thi mtic dp cai thi^n tuy cham hon nhung ciing co su thay ddi dang ke sau 1 nam.
Qua sieu am tim, chup MSCT va ehup budng that trai ed tiem thud'e can quang, chiing tdi nhan thay ngoai su cai thien dang ke ve phan so td'ng mau that
trai (EF), miie dp rd'i logn van ddng vimg ciing giam rd ret d nhiing benh nhan dupc dieu tri phdi hpp bang phuang phap tiem te'bao gd'e.
Trong so' 6 benh nhan dupc tiem te' bao gdc, cd 3 benh nhan cd huye't khdi trong budng that trai trong dd 2 benh nhan dupe phat hien sau tiem te'bao gd'e (ngay 2 va sau 1 thang sau tiem) va 1 berth nhan cd huye't khd'i nhd that trai trudc tiem. Ca 3 benh nhan tren deu ed roi logn van ddng vimg miic dp nang (khdng van ddng thanh trude va vung mom tim). Tuy
NGHIEN CCfU L A M S A N G
nhien sau 6 thang theo doi tren lam sang, chung tdi nhgn thay ca 3 benh nhan deu khdng cd bieu hien eiia bieh chiing tac mgch he thdhg eung nhu khdng edn dau hieu cua huye't khdi tha't trai qua sieu am va chtip budng that trai. Vi so lupng benh nhan cdn it chua dii de tim ra mdi lien quan giua viee dieu tri bang tiem te bao gdc. Tuy vay, chiing tdi ciing de xua't can dieu tri chohg ddng rich cue cho eac b$nh nhan trudc va sau tiem te'bao gd'e (hepa- rin phdi hpp vdi eac tiiud'c chdng ngung tap tieu cau).
Tham khao eae tai lieu nude ngoai, chiing tdi tha'y, cho ttii nay da ed nhieu cdng trinh nghien ciiu theo hudng nay tren the gidi vdi so lupng benh nhan bao cao tdhg cpng len tdi hang nghin.
Mpt nghien eihi gdp nam 2008 etia Mar- tin Redon cho tha'y viee ghep te'bao gd'e tiiy xuwowgn tu tiian aia benh nhan de dieu tri suy tim ngng sau NMCT cap nhin ehung eai thi^n dupe chtic nang tha't trai.
cd nhieu trieh vpng, mge dii ke't qua va each danh gia cd rat khac nhau.
Vah de dgt ra la ddi tupng nao ed Ipi ich nhat? tac gia phan tich cae phan nhdm eho thay: vi$e sti dung te'bao gdc dieu tri trong trudng hop nay ed ve cd Ipi ich d nhdm benh nhan sau NMCT cd suy tim vira de'n nang (EF < 50%). Ddi vdi benh nhan ed EF > 50%, hieu qua ctia phuong phap chua dupe ehiing minh so vdi nhdm ehiing. Thdi gian dieu tri ed ve tdi uu sau 5-7 ngay sau NMCT cap. Nhirng nghien cuu qiia mudn (sau 1 thang) eung khong cho thay ke't qua dang ke [2-24].
vin cdn kha nhieu eau hdi dat ra:
logi te'bao nao la tdt nhat; sd'lupng la bao nhieu? dudng truyen nao la td't nha't; theo ddi the'nao la td't nhat... Can ed mpt thdi gian va nhiing nghien ciiu vdi sd' lupng nhieu hon ciing nhu thdi gian theo doi lau hon de tra ldi cho nhiing cau hdi con bd ngd do.
Hinh 1. Hinh anh ehup budng that trai mpt benh nhan sau tiem te'bao gd'e: hinh ben trai la trude tiem vdi chirc nang co bdp ctia that trai (EF) ehi la 37,6% va sau tiem 3 thang (ben phai) vdi EF la 60,0%.
TAP CHl TIM MACH HQC VIgT NAM - S6 54 - 2010
KET LUAN VA OE NGHj 1. Ket luan
N g h i e n cihi tren 6 berth n h a n s o b p cho tha'y:
Viec g h e p te b a o gd'e tiiy x u a n g t u than b e n h n h a n vao Igi d d n g mgch v a n h - v i m g bi tdh t h u o n g - d e dieu tri suy ttm sau n h d i m a u eo tim da cho thay cai thien b u d c d a u trieu ehiing co n a n g (NYHA);
chtic n a n g that trai tren eac p h u o n g p h a p d a n h gia khae n h a u n h u Sieu a m - D o p - pler tim; MS CT; C h u p b u d n g that trai q u a d u d n g d'ng thdng.
2. Kien nghi.
- Nghien cihi n e n d u p c tie'p tue tie'n h a n h vdi sd' l u p n g n h i e u hon, thdi gian theo doi lau h o n d e cd the d u a ra d u p c n h i i n g d a n h gia ed stic thuye't p h u c h o n .
- N e n sit d u n g t h e m p h u o n g p h a p Cpng h u d n g tir (MRI) d e d a n h gia ehiie n a n g that trai.
Cd the m d rpng ddi t u p n g eho n h i i n g b ^ n h n h a n sau N M C T ed suy tim miie d p n h e h a n (EF tir 40 - 50 %) hoae n a n g hem (EF < 30%) de cd the tim hieu rd nha't ve lpi ich cua lieu p h a p nay.
TAI LIEU THAM KHAU
1. Nguyen Ngpc Quang, Wong Philipe, Pham Manh Hiing. D'ng dimg ctia te'bao gd'e trong nganh tim mach - Chuyen de Tim mach hoc can thi?p. Tcip chi Tim m^ch hoc Viet nam, 2005;40:45-63.
2. Nguyen Lan Viet, Do Doan Lgi, Pham Manh Himg, Do Thtiy Can, Nguyin Quoc Anh, Nguyen Thu Ha. Ke't qua buoc dau
nghien cihi thti nghiem te'bao goc trong dieu tri benh nhan suy tim sau nhoi mau CO tim. Tap chi Tim mach Hoc Viet Nam.
2009;51:35-42.
3. Wollert KC, Drexler H. Clinical applica- tions of stem cells for the heart. Circ Res, 2005;96:151-163.
4. Shim W, Wong P. Stem cell cardiomyo- plasty: State-of-the-Art. Ann Acad Med Singapore, 2004;33:451-60.
5. Janssens S, Dubois C, Bogaert J, Theunis- sen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Ghey- sens O, Van Cleemput ], Bormans G, Nuyts J, Belmans A, Mortebnans L, Boo- gaerts M, Van de Werf F. Autologous bone marrow-derived stem-cell transfer in pa- tients with ST-segment elevation myocar- dial infarction: double-blind, randomised controlled trial. Lancet 2006;367:113-121.
6. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary bone marrow cell transfer after myocardial infarction:
eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 2006;113:1287-1294.
7. Kang HJ, Lee HY, Na SH, Chang SA, Park KW, Kim HK, Kim SY, Chang HJ, Lee W, Kang WJ, Koo BK, Kim YJ, Lee DS, Sohn DW, Han KS, Oh BH, Park YB, Kim HS.
Differential effect of intracoronary infu- sion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myo- cardial infarction versus old myocardial
NGHI£N CLfU LAM SANG
infarction: tiie MAGIC CeU-3-DES ran- domized, controlled trial. Circulation 2006;114:1145-1151.
8. Schachinger V, Erbs S, Elsasser A, Hab- erbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Matiiey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dim- meler S, Zeiher AM. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006;355:1210-1221.
9. Lunde K, Solheim S, Aakhus S, Amesen H, Moum T, Abdelnoor M, Egeland T, En- dresen K, Ilebekk A, Mangschau A, For- fang K. Exercise capacity and quality of life after intracoronary injection of autol- ogous mononuclear bone marrow cells in acute myocardial infarction: results from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) randomized controlled trial. Am Heart J 2007,154:el-e8.
10. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myo- cardium. Nature, 2001;410:701-5.
11. AsaharaT,KawamotoA. Endothelial pro- genitor cells for postnatal vasculogenesis.
Am J Physiol Cell Physiol, 2004;287:C572- C579.
12. Rehman J, Li J, Orschell CM, et al. Periph- eral blood "endothelial progenitor cells"
are derived from monocyte/macrophages and secrete angiogenic growth factors.
Circulation, 2003;107;1164 -1169.
13. Muller M, Fleischmann BK, Selbert S, et dl. Selection of ventricular-like cardio- myocytes from ES cells in vitro. FASEB J, 2000;14:2540-8.
14. Wang JS, Shum-Tim D, Chedrawy E et dl. The coronary delivery of marrow stromal cells for myocardial regenera-
tion: pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg, 2001;122:699-705.
15. Lee SH, Wolf PL, Escudero R, et al. Ear- ly expression of angiogenesis factors in acute myocardial ischemia and infarc- tion. N Engl J Med, 2000;342:626-633.
16. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow- derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circu- lation, 2003;108:863- 868.
17. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhzmcement in acute myocardial infarction: final one-year re- sults of the TOPCARE-AMI Trial. J Am CoU CardioL 2004;44:1690 -1699.
18. Fernandez-Aviles F, San Roman JA, Gar- da-Frade J, et al. Experimental and clini- cal regenerative capability of human bone marrow cells after myocardial infarction.
Circ Res, 20a4;95:742-748.
19. Kuethe F, Richartz BM, Sayer HG, et al.
Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in hu- mans with large anterior myocardial in- farctions. Int J CardioL 2004;97;123-127 20. Wollert KC, Meyer GP, Lotz J, et al. In-
tracoronary autologous bonemarrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 2004;364:141-148.
21. Chen SL, Fang WW, Ye F, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone mar- row mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 2004;94:92-95.
TAP CHl TIM MACH HOC VIET NAM - S6 54 - 2010
22. Petzsch M, Ince H, Kleine HD, et al. No restenosis after G-CSF in acute myocar- dial infarction: insights from FIRSTLINE- AMI (Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulo- cyte Colony-Stimulating Factor). Circula- tion, 2004;110(suppl III):238.
23. Fuchs S, Baffour R, Zhou YF, et al.
Transendocardial delivery of autologous bone marrow enhances collateral perfu- sion and regional function in pigs with chronic experimental myocardial isch- emia. J Am Coll CardioL 2001;37:]726 -1732.
24. Enca Martin-Rendonl,2*, Susan J.
BrunskillS, Chris J. Hyde3, Simon J. Stan- worth3, Anthony Mathur4, and Suzanne M, Wattl,2. Autologous bone marrow stem cells to treat acute myocardial in-
farction: a systematic review. European Heart Joumal (2008) 29,1807-1818.
25. Tendera M, Wojakowski W. How to mea- sure the effects of the intracoronary stem cell therapy. Eur J Echocardiogr. 2010 Mar 22.
26. Wohrle J, Merkle N, Mailander V, Nusser T, Schauwecker P, von ScheidtP, Schwarz K, Bommer M, Wiesneth M, Schrezen- meier H, Hombach V. Results of intracor- onary stem cell therapy after acute myo- cardial infarction. Am J Cardiol. 2010 Mar 15;105(6):804-12.
