Nghien cuu Y hpc Y Hpc TP. Ho Chi Minh * T^p 21 * S6 2 * 2017
GIA TRI CUA XET NGHIEM MR-proANP
TRONG TIEN L U O N G DAI HANTREN BENH NHAN KHO T H 6 CAP
Li Xudn Trudng', Nguyin Chi Thanh"
TOMTAT
Mb ddu: Khb thd cap Id triiu chimg chinh gap ciui suy tim sung huyii vd mot sobenh hd hiq), trang 36 co viim phoi. Nhung dm tugng ndy thubng co tien lugng xau. Do do ran phdi xdy dung mo Kinh tien lugng sao dw CO thedu bdo mot cdch dan gidn, hiiu qua trin nhom dm tugng ndy. Nhieu nghien deu dii ra rang vung giUa cua tiin hormon ANP (MR-proANP) cb gid tri trong Hen lugng tie vong ddi hqn tqi khoa c^ dm.
MlfC tieu: Xdc dinh vai trb cim xet nghiem MR-proANP trong tien lugng tie vong sau tgi thbi dian 12 thdng trin binh nhan khd thb cap tm khoa caip cieu binh viin Chg Ray.
Doi tugng- phiamg phdp n^ien dht: Nghien cuu tien deu, khdng can thiip, hang loqt ca. Co 230 binh nhdn nhdp khoa cap ciru do kho thb cap.
Kei qud: Nbng tip bAR-proANP b miec 316 pmol/l co gid tri toi trong tiin lugng tie vong vbi ^ nhay, do dqc hieu Ian lugt theo thii tu Id 82°/o vd 61°/o. MR-proANP Id ym td'nguy ca tien dodn tie vong ddc l&p trong nghien cieu ndy.
K^ ludn: O rwng do 316 -pmol/l, MR-proANP gidp tiin lugng tie vong tren binh nhdn kho tha ccq).
ABSTRACT
THE VALUE OF MR-proANP IN LONC^TERM PROGNOSIS IN PATIENTS WTTH ACUTE DYSPNEA Le Xuan Truong Nguyen Chi Thanh
* Y Hoc TP. Ho Chi Minh * Vol. 21 - No 2 - 2017:16 - 20 Backgrotmd: Acute dyspnea is a common symptom in heart frilure and pneumonia. These patients have poor outcomes. So, it is very essential to establish prognostic model which is convenient, effective. Many researches indicated that MR-proANP had a usefril marker in long term prognosis in patients with acute dyspnea.
Objectives: The aim of this study was to assess the prognostic value of MR-proANP in patients with acute dyspnea in emergency department.
Method: An observational, prospective study was carried on 230 patients with acute dyspnea in emergency department. Patients were observed the survival within 12 months.
Results: The cut-off points for survival in 12 months of MR-proANP was 316 pmol/l with sensitivity and spedfidty as 82%> and 61%>, respectively. Multivariable Cox regression armlysis showed that MR-proANP had the indeperulEnt prognostic value for survival in 12 months. Furthermore, by analyzing AIC, we concluded that the model with MR-proANP above cut-point and ejection fradion (EF) < 30% was the best one in predicting survival Jbr patients.
Conclusions: MR-proANP was a value biomarker pr prognosis in acute dyspnea.
Key words: MR-proANP, acute dyspnea, prognostic, sensitivity, spedfidty.
DAT VAN DE ^ ^ - Nguyen nhan chii yeii la do cac benh ly tim va phoi chiem khoang 73% cac trudng hgp kho Khd tiid la mgt taxing nhung tinh trang cap ^^ ^ g p ^^^ ^ ^ ^ ^ap ciiuP'. Nhieu nghien oiu ciiu noi khoa thudng gap nhat tai cac don vi cap
* Dai hoc Y Duoc TP.HCM, ** NCS nien khoa 2013 - 2016 Tdcgid lien lac: PGS.TS.BS.Le Xuan T n r d n g DT. 01269872057 £m«'^: lxtruonsl957C..'gmail.com 16
Y Hpc TP. Hb Chi Minh * Tap 21 * So 2 * 2017 Nghien cmi Y hpc
tren the gidi da chi ra rang dau ah sinh hgc MR- proANP cd gia tri tien lugng tren nhiing doi tugng nay. That vay, Ravi V.Shah va cgng su<*>
ti&i hanh tren 560 benh nhan khd thd cap, nhan thay rang xet nghiem MR-proANP khong chi cd vai tid tiong chan doan ma cdn cd Ihe tien doan dugc du hliu ciia benh nhan. Hay trong nghien a i u tren 1740 benh nhan nhap vien vi viem phoi"'. tac gia cho thay rang MR-proANPcd gia cao tiong theo doi du hau cho benh nhan.Ty le tli vong dai hgn a i a nhdm benh nhan khd thd do suy tim, viem phoi cdn d miic caot*-^. Do do can phai xay dung md hinh tien lugng sao cho cd the du bao dugc nguy ca cho benh nhan mgt each dan gian, hi^u qua la rat can thiet.
Muc tieu nghien cmi
Xac dinh do nh?y, do d|c hieu cua xet nghiem MR-proANP trong tien lugng tii vong tai thdi diem 12 thang.
Xac djnh mo hinh tien lugng cd gia trj nhat tiong du bao nguy co tu vong cho benh nhan.
PHl/ONG PHAP NGHIEN CtTU Thiet ke ng^en cmi
Nghien ciiu tien ciiu, thiet ke kieu quan sat cat doc, khdng can thiep, hang loat ca.
Dan so nghien cmi
Benh nhan nhap khoa cap ciiu benh vien Chg Ray tir thang 06/20014 d m tiiang 06/2015 do khd thd cap.
Phtrong phap chpn mau Tieu chuan chgn benh
Benh nhan nhap vao khoa cap ciiu benh vien Chg Riy vdi trieu chiing khd thd cap. Tren 18 tuoiBenh nhan cd ho so theo doi tai cac khoa phdng.Benh nhan dugc cliati doan xac dinh nguyen nhan khd thd va theo ddi 12 tiiang sau khi xuat vien.
Tieu chuan lo^i trie
Ch&i thuong nggc do tai nan Hgi chung mach vanh cap Suy than (Creatinin > 2,5 mg/dl) Cudng aldosterol, hoi chiing cushing
Phirong phap thu ttiap so lieu Cdch thu thdp s&lieu
Benh nhan nhap khoa cap ciiu benh vien Chg Ray tiida tieu chuan chgn mau tren dugc dua vao nhdm nghien aiu. Cac xet nghiem thudng quy tiiuc h i ^ cdng thiic mau, BUN, creatinin, ion do, ECG, XQ nguc thiing dugc thuc hien tai.khoa cap cuu. 2ml mau finh mach xac dinh nong do MR-proANP. Theo doi diln ti&i, chan doan va dieu trj tai cac khoa phdng.
Xdc dirih dimt dodn Suy tim
Tieu chuan chan doan suy tim:
- Tieu chuan chSi doan suy tim cua hgi tim mach Chau Au, ket hgp sieu am tim.- Dap iing cac thuoc Igi tieu, giam tien tai, giam hau tai, tang siic co bop ca tim.
- Chan doan ciia bac si chuyen khoa liic xuat vien.- Do nang suy tim theo phan loai ciia do nang ciia Hiep Hgi Hoa Ky (NYHA).
Viim phoi
- Trieu chiing Iam sang: sot ho dam, khd thd, phdi cd rales am, nd. Miic do nang viem phoi dv tiieo thang diem CURB-65.- X-Quang nguc thang: tham nhiem nhu md ggi y viem phdi.
Cdng thiic mau: bach cau tang, CRP, Procalcitonin tang.
- Dap ling vdi dieu tri dac hieu: khang viem, khang sinh," •
- Chan doan ciia bac si chuyen khoa dteu tri.
Phan tich solieu
So lieu dugc nhap va phan tich bdi phan mem SPSS 16.0. Dimg phuong phap phan tich bieu do xac xuat song cdn tich luy Kaplan Meier de so sanh khac biet t u vong ciia 2 nhdm benh nhan khd thd cd gia tri MR-proANP tren va dudi diem c3t, bang phep kiein Logrank test. Ti so chenh (odd ratio, OR) va 95% khoang tin cay tuong ling dugc khao sat don b i a i cho cac bi&i so hen quan den tii vong. Dimg phuong phap hdi qui Cox de khao sat cac yeu to anh hudng
Nghi&n cuu Y hoc Y Hpc TP. Ho Chi M i n h * Tap 21 * So 2 * 2017
dffli tien lugng qua phan tich don WOT, da birai.
Ngoai ra, chiing toi cdn xay dung md hinh du bao xay ra bi&i cd (tii vong) tai tiidi dian 12 thang qua viec phan tich AIC (Akaike Information Criterion) trong phan mem R. Trong dd md hinh cd so lugng bi&i du bao (cac bien dgc lap) it nhat, chi so AIC thap nhat thi dugc
xem la md hinh tien lugng toi uu tiong danh gia nguy CO tli vong tren benh nhan khd thd cSp.
KETQUA
Trong qua trinh theo ddi, chiing tdi thu th|p dugc 230 benh nhan, mat dau 14 benh nhan, chiem ty 1§ 6,1%. Khi ket thiic nghien oiu, cd 35 benh nhan tti vong chion ty le 15,2%.
Dac diem nong dp MR-proANP trong nhom tix vong 1 nam Bdngl. Dqc diim tiong do MR-proANP (pmol/l) trin 2 nhbm benh nhan
N6ng d6 MR-proANP (fHnol/l)
Nhdm bfnh nhSn
X±SD Logarit nepe
Tmngvi Khoang ti> phdn vj
Tir vong (n = 35) 609.5 ±481.2
6,2 429 313,8-726,8
Cdns6ng{n = 181) 255,5 ±195,2
5,2 224 91,1-388,7
P
< 0,001
Ghi nhan: Ndng do MR-proANP huyet tiianh tien nhdm benh nhan t& vong cao hon
nhdm sdng sdt sau 1 nam; su khac biet nay cd y nghia thdng ke vdi p<0,001.
Do nhgy
Thoi gian (thang)
Bieii do 1. Dubng cong ROC nong do MR-proANP trong chan dodn tie vong 12 thdng.
^ Vii ptiSn VI inU nhk ^ ^
Tan suat ton sinh
u phan v| Ihir hai
''Tiiphflnviihiiba
• Tu phan vilhij tir
Log rank test = 37,5. P < 0,001
Bim do 2. Dubng biiit diin song con Kaplain mierce trin tieng mik phdn vi
Y Hpc TP. Hb Chi Minh * Tap 21 * So 2 * 2017 N g h i e n cmi Y hpc
Bdng 3. Cdc yiu to'dnh huong dm tu vong Phan tang cdc ylu t6 (n = 216)
m6 hinh 1
Phan tidi da biln m6 iiinli 2
Phan tich da bien mfl hinh 3
PhSn tich 3a biln mfl hinh 4
Tuoi £ 65 Gioi nif ti/lR-proANP > 316 pmol/l
EF£30%
NYHA IV CURB-66i3 lulR-proANP a 316 pmot/t
Tuoi £ 65 GiflinQ' MR-proANP()
Tuoi a 65 Gioi nij NYHA iV EF < 30%
liJR-proANP (*) Tuoi a 65
Gidi n&
CURB-65 2 3 H/lR-proANP (*)
Tuoi £ 65 Gifli nO' CURB-65 2 3 Suy tim l<em viem phoi Mo hinh tien tuvng
NYHA IV + EF < 30% + CURB-65 > 3 + IVlR-proANP > 316 pmoW CUR&«5 > 3 + EF < 30% + MR-proANP > 316 pmoifl
EF < 30% + r^R-proANP > 316 pmoW
HR 0,8 1.21 4.6 2.S 3.3 1.46 4,49 1,37 1,26 3,93 0.69 1,19 0,22 3,41 6.1 0,66 1,17 0,83 4,83 0,64 1,13 0,67 1,47
KTC 95%
0.4-1.61 0.61 -2.37
2.2-9.63 1.8-4.35 1.63-6.56 0.78-2 7 2,28-8,83 0,69-2,63 0.68-2,33 2,21-6,98 0,36-1,32 0,64-2,21 0,05-0,98 1,07-10,88 3,07-8,45 0,35-1,26 0,28-2,16 0,43-1,61 2,17-8,15 0,34-1,23 0,61-2,09 0,31-1,47 0,66-3,26
G i i trip 0.072
0.27
< 0.001 0.017 0.001 0 23
< 0,001 0,32 0,48
< 0,001 0,25 0,59 0,047 0,04
< 0,001 0,21 0,63 0,58
< 0,001 018 0,71 0,322 0,35 AIC 176,75 174,91 173,67 BAN LUAN
Khi danh gia vai trd ciia timg bien so trong van de du bao nguy co tii vong tren benh nhan khd thd cap, chung tdi da phan tich dua tren bon md hinh phan tich da bien. Bdi le, trong nghien cuu nay cd 3 nhdm benh nhan;
suy tim, viem phoi, suy tim kem viem pho'i, nen chung tdi chgn bien so phan tich sao cho phu hgp nhat, vi du n h u do nang viem phdi tiieo thang diem CURB-65 chi dimg trong md hinh cd c h ^ i doan la viem phoi. Tuong tg", phan do nang suy tim theo NYHA chi dimg h-ong md hinh cd chan doan la suy tim. Nhiing mo hmh phan tang nguy co la mgt cdng cu Iam sang quan trgng giup xac dinh nguy co cua benh nhan d 2 khia canh: nhting berth nhan cd nguy ca rat cao nen giam sat can than, chaji doan va dieu trj sdm nham cai thien ty Ie tli vong, trong khi benh nhan co nguy co thap
cd the theo doi, lam day du cac can lam sang khac can thiet. Ngoai ra, phan tang nguy ca cd tiie giup xac dinh muc tieu sinh ly benh cho dieu tri.Nghien ciiu cua tac gia Ravi V.Shah va cgng sij**' tren 560 benh nhan nhap vien vi khd tiid cap, trong do cd 180 benh nhan dugc ehab doan la suy tim. Qua md hinh phan tich da bieh gom tudi, nong do MR-proANP, sii dung thudc Igi tieu..., nhan thay MR-proANP la yeu to tien quan ddc lap vdi hi vong cho benh nhan. Ngoai ra, nghien ciiu ciia tac gia MillerWL va cdng su<^' tien 187 benh nhan nhap vien vi suy tim cap tir thang 06/2001 den tiiang 01/2004, da sd la NYHA III, IV, theo ddi moi 3 thang, va lam Iai xet nghiem MR- proANP khi tai kham, nhan thay nong do MR- proANP [a yeu td nguy co ddc lap ddi vdi bien CO hi vong hay phai ghep tim. Ngoai ra, trong nghien ciiu nay, tac gia con khao sat rd su thay
NgJiien cmi Y hpc Y Hpc TP. Hb Chi Minh * T$p 21 * So 2 * 2017
doi cua ndng do MR-proANP len bien co. Khi nong do MR-proANP thay ddi it hon 30%
(nhung khdng trd ve tri so binh thudng) thi nguy CO xay ra bieh co gap 5,79 lan. Tuy nhien, nguy co nay cao hon nhieu (10,07 Ian) khi su thay ddi tang vugt qua 30%. Kruger S va cdng su<'J nghien ciiu tien 728 benh nhan n h | p v i | n vi viem phoi. Cd 5,1% benh nhan tii vong trong vdng 180 ngay. Nhung doi tugng hi vong cd nong do trung vi MR-proANP cao horn nhdm cdn Iai d ca hai thdi diem, (175,9 pmoI/1 so vdi 86,6 pmol/l). Ngoai ra, trong nghien ciiu nay, tac gia ding sii dung phan tich hdi quy da b i a i vdi hai md hmh (md hinh 1: MR-proANP > 102 pmol/l, CRB-65 > 1, cd tinh trang suy tim sung huyet; md hinh 2:
gidng nhu md hinh 1, nhung dua them nhieu benh ly di kem) de tun yeu td nguy co ddc lap anh hudng den tii vong cua benh nhan. Tac gia nhan thay tai hai thdi diem, MR-proANP CO vai tro tien doan nguy co hi vong dgc lap.Nhu vay, qua phan tich mgt vai nghien Clhi, chiing tdi nhan thay rang gia tri tien doan dgc lap ddi vdi nguy co xay ra bien co hi vong cho benh nhan ciia MR-proANP tiong nghien cuu nay tuong t u nhu cac tac gia khac. Tuy nhien, ngudng nong do MR-proANP tiong nghien ciiu nay cao hon nhieu. Bdi le, dan so chgn mau cua chiing tdi gom nhiing doi tugng benh nang, viem phdi ngudi ldn tuoi chie'm da so (71%), cd yeu to suy tim kem theo, va sii dung chung ngudng nong do MR-proANP trong tien doan hi vong cho tat ca cac nhdm khao sat gom suy tim, viem phoi, suy tim kem viem phdi.Trong nghien ciiu nay, chiing tdi sii dung phuong phap phan tich chi so AIC de
xac dinh md hinh tien lugng lot nhat cho b | n h nhan, nhan thay d Ihdi diem 12 thang thi su gia tang MR-proANP tren miic 316 pmol/l va phan suat tong mau that tiai giam nang (<
30%) cd y nghia tot nhat trong du bao nguy co hi vong cho benh nhan.
KETLUAN
MR-proANP d miic 316 pmol/l cd gia tri tdt trong tien iugng tir vong tren benh nhan khd thd cap vdi do nhay va do dac hieu Ian lugt la 82%; 61%. Trong cac md hinh tien lugng, thi md hinh cd nong do MR-proANP cao va suy tim phan suat tong mau giam nang (EF<30%) la md hinh toi uu tiong d u bao nguy CO sau 12 thang tiieo ddi.
TAI U E U THAM KHAO
1 Kruger S, Ewig S, et al (2014), '•Pro-atrial ratnurebc peptide and pro-vasopressm for predicting short-teim and long-term survival in conununity-acquired pmeumonia: results from the German Competence Network CAPNETZ", Thorax, BMJ.pp.
20&-214.
2 Lighezan DF, U ^ e z a n R, el al P006), "Acute Dyspnea: from palhof^tyMology, evaluation to diagnoas", TM/, 56, pp. 235-242.
3 Milier WL, Hartman KA, el al (2011), "Serial measuremenb of nudregion proAMP and copeptin m ambulatory patioils with heart failure: incremental prognostic value of novel biomarkos in heart failure", Hairt £A^, p p 1-6
4 Ravi v s , Quynh A.Truong (2012), "Mid regional pn>atnal natriuretic peptide and pro-adrenDmedullin testing for diagnostic and progrrastic evaluadrai of patienls with acute dyspnea", European Heart jidlurejounial, 33, pp. 2197-2205 5 Wang X, Liu Y, et al (2015), "Short-term prognostic factors m the
patiails after acute heart ^ilure", Int ] Clm Exp Med, 8(1), pp 1515-1520.
Ngdy nhgn bM bdo: 10/11/2016 Ngdy phdn biin nhan xet bdi bdo: 18/11/2016 Ngdy bdi bdo dugc ddng- 01/03/2017
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