tang ap mach phoi mayoclinic
TRANSCRIPT
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TNG P MCH PHI:TNG P MCH PHI:
Chin lc chn onChin lc chn on
v iu tr mi nhtv iu tr mi nht
Michael D. McGoonMichael D. McGoonProfessor of MedicineProfessor of Medicine
Consultant, Cardiovascular DiseasesConsultant, Cardiovascular Diseases
Mayo ClinicMayo Clinic
Rochester, MNRochester, MN
H Ni 4/2009
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p dng cho tt ccc tr-ng hp tng
p mch phi
Cc nh ngha huyt ngCc nh ngha huyt ng
> 3 USc cn mchphi
> 30 mm HgALMP trung bnhkhi gng sc
< 15 mm HgPCWP, LAP, LVEDP
> 25 mm HgALMP trung bnhkhi ngh
>15 mm HgALMP tm tr-ng khi ngh
>35 mm HgALMP tm thukhi ngh
p dng cho cctrng hp tng p
lc ng mchphi
kin chuyngia
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Bnh th-ng
Mch mu
Trung mc
Ni mc
Thi gianThi gian
PAPPAP
PVRPVR
COCO
IINYHANYHA
TAMP: TiTAMP: Tin trin huyt ng v lm sngn trin huyt ng v lm sng
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Bnh thng
Mch mu
Trung mc
Nimc
Ph i t bo c
trn
Dy ni mcsm
Tn thng cn bo tn
Thi gianThi gian
PAPPAP
PVRPVR
COCO
II IIII IIIIII
BNPBNP
NYHANYHA
TALMP: Tin trin huyt ng v lm sngTALMP: Tin trin huyt ng v lm sng
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Bnh thng
Mch mu
Trung mc
Ni mc
Ph i lp t bo
c trn
Dy ni mcsm
Tn thng c th hi phc Tn thng khng th hi phc
Tn thngtnh co gin
Huyt khi
Tng sinh mchmu v lp ni mc
Ph i t bo ctrn
Thi gianThi gian
PAPPAP
PVRPVR
COCO
II IIII IIIIII IVIV
BNPBNP
NYHANYHA
TALMP: Din bin huyt ng v lm sngTALMP: Din bin huyt ng v lm sng
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Cc bnh khc c nh hng n h mch mu phiNhm 5:
Nhi mu phi hoc bnh phi tc nghn mn tnhNhm 4:
Thiu oxy hoc bnh phiNhm 3:
Bnh tim triNhm2:
TALMP TALMP tin pht (IPAH) TALMP c tnh cht gia nh (FPAH) TALMP c nh tr s sinh (PPHN)
Bnh tc nghn tnh mch phi (PVOD) TALMP v cc bnh lin quan (APAH)
Nhm 1:
PhPhn loi TALMPn loi TALMP33rdrd World Conference on Pulmonary Hypertension, Venice 2003World Conference on Pulmonary Hypertension, Venice 2003
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L nhm TALMP trc mao mchL nhm TALMP trc mao mch T l mc bnh n/nam 4:1T l mc bnh n/nam 4:1
Tui trung bnh 50 tuiTui trung bnh 50 tui
T l mc 6/million; mc ph bin ca bnhT l mc 6/million; mc ph bin ca bnh15/million15/million
Thi gian sng trung bnh bnh nhn khng c iuThi gian sng trung bnh bnh nhn khng c iu
tr: 2.8 nmtr: 2.8 nm
Thi gian t khi xut hin triu chng n khi cThi gian t khi xut hin triu chng n khi cchn on: >2 nmchn on: >2 nm
NhNhmm 1: TAL1: TALMP tin phtMP tin pht((IPAHIPAH))
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TALMP trc mao mchTALMP trc mao mch Ri lon nhim sc thRi lon nhim sc th
Ri lon genRi lon gen
c pht hin sm hn v nng hnc pht hin sm hn v nng hn Tn thng thm nhim khng hon tonTn thng thm nhim khng hon ton
2020% cc trng hp t bin tin trin thnh TALMP% cc trng hp t bin tin trin thnh TALMP
Gen m ho th th 2 ca protein Bone MorphogeneticGen m ho th th 2 ca protein Bone Morphogenetic(BMPR2)(BMPR2)
Quan trQuan trng trong kim sot cht t bo theo chngng trong kim sot cht t bo theo chngtrnhtrnh
NhNhmm 1: TAL1: TALMP c yu t gia nhMP c yu t gia nh ((FPAHFPAH))
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Bnh m lin ktBnh m lin kt
Shunt ch-phi bm sinhShunt ch-phi bm sinh TALTM caTALTM ca Nhim HIVNhim HIV Thuc v nhim cThuc v nhim c
Cc bnh l khc:Cc bnh l khc:
Tn thng tuyn gipTn thng tuyn gip
Bnh tch lu glycogenBnh tch lu glycogen
Bnh GaucherBnh Gaucher
Bnh gin mch xut huyt di truyn (Bnh Osler WeberBnh gin mch xut huyt di truyn (Bnh Osler WeberRendu)Rendu)
Bnh l Hemoglobin (Bnh hng cu hnh lim)Bnh l Hemoglobin (Bnh hng cu hnh lim)
Hi chng tng sinh tuHi chng tng sinh tu
Ct lchCt lch
NhNhmm1: TAL1: TALMP v cc bnh lin quanMP v cc bnh lin quan ((APAHAPAH))
Bnh thng gp nht lx cng b (CREST);TALMP l nguyn nhndn n t vong nhtthng gp nht
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NhNhmm 1: Ng1: Ng c c
Fenfluramine/Phentermine,Fenfluramine/Phentermine,Dexfenfluramine, MethamphetamineDexfenfluramine, Methamphetamine
Tng lin kt caTALMP 23XTng lin kt caTALMP 23X
CH3
NH2
C2H5
Fenfluramine
NH2
Aminorex
O
NCH3
NH2
Phentermine
CH3CH3
NH2
Amphetamine
CH3
NH2
CH3
Methamphetamine
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Chin lc chn onChin lc chn on
Pht hin triu chngPht hin triu chng Tm hiu (hoc loi tr) cc nguyn nhn.Tm hiu (hoc loi tr) cc nguyn nhn.
Xc nh kiu huyt ngXc nh kiu huyt ng
Mc nngMc nng Kiu trc/sau mao mchKiu trc/sau mao mch p ng vi thuc gin mchp ng vi thuc gin mch
Xc nh kh nng gng scXc nh kh nng gng sc
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Hng dn chn onHng dn chn on
Siu m timSiu m tim PFTsPFTs Thm d khi ngThm d khi ng
Chp CT thng khChp CT thng khti mu phi,ti mu phi,Chp CT c cnChp CT c cnquang,quang,
Chp mchChp mch
XN min dchXN min dchXN HIVXN HIV
LFTs v bngLFTs v bngchng LSchng LSca x ganca x ganhay TALTMChay TALTMC
RVE, RAE,RVE, RAE, RVSPRVSPBnh tim triBnh tim tri
VHDVHDCHDCHD
Kh ph thng vKh ph thng v
cc bt thng v lng ngccc bt thng v lng ngc Ri lon khi ngRi lon khi ng
Huyt khiHuyt khitc mch mn tnhtc mch mn tnh
X cng bX cng bLupusLupus
RARAVim mchVim mch
HIVHIVTAL ca phiTAL ca phi
Test chc nngTest chc nngBNPBNPThng tim phiThng tim phi
Test gin mchTest gin mch
Khm LSKhm LSX. QuangX. Quang
TT
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Siu m v thng tim phi Cc thng tin b sungSiu m v thng tim phi Cc thng tin b sung
Siu m timSiu m tim
nh gi bnh nnnh gi bnh nn
nh gi RVSP, Pam, Pad,nh gi RVSP, Pam, Pad,SV/PP, RV dP/dt, PVRSV/PP, RV dP/dt, PVR
Chc nng tht phiChc nng tht phiQuan stQuan st
RV-IMPRV-IMP
Siu m Doppler mSiu m Doppler m
TAPSETAPSE
Strain, Strain RateStrain, Strain Rate
Isovolumic AccelIsovolumic Accel
RHCRHC
nh gi huyt ngnh gi huyt ng
AL mao mch phi btAL mao mch phi bt
PBFPBF
ALMP trung bnhALMP trung bnh
p ng vi cht gin mchp ng vi cht gin mch
bo ho Oxy bo ho Oxy
nh gi tnh trng shuntnh gi tnh trng shunt
Sng lc v theo diSng lc v theo di
Chn on xcChn on xc
nhnh
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Cc yu t chi phi mch phiCc yu t chi phi mch phi
argininearginine
NONO
GTPGTP
cGMPcGMP
eNOSeNOS
GCGC
AAAA
PGIPGI22
ATPATP
cAMPcAMP
PSPS
ACAC
Big-ETBig-ET
ETET11
ECEECE
ETETAA ETETBB
Gin mch, Chng tng sinhGin mch, Chng tng sinh Co mch, tng sinhCo mch, tng sinh
5`GMP5`GMP
PDEPDEPDE5iPDE5i
PGIPGI22ETRAETRA ETRAETRA
Tboni
Tboni
mc
mc
Tbo
c
Tbo
c
trntrn
Con ngNitrite oxide
Con ngProstacyclin
Con ngEndothelin
CaCa++++
CCBsCCBs
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Chn knh CalciumChn knh Calcium
Rich S, Kaufmann E, Levy PS: Tc dng ca thuc chn knh canxiliu cao ln t l sng cn ca TALMP tin pht.
N Engl J Med 327:76-81, 1992
N=17N=17
N=47N=47
N=187N=187
30
40
50
60
70
80
90
100
0 6 12 18 24 30 36 42 48 54 60
Thng
Tlsngc
n,%
p ng vi iu tr
Khng p ng vi iu tr
NIH Registry
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Nn iu tr thuc chn knhcni cho nhng bnh nhn cp ng vi cht gin mch.
557 bnh nhn c test chtgin mch c tc dng ngn:
70 (12%) gim ALMPTB vsc cn phi >20% v c
iu tr thuc chn knh Ca.
54% bnh nhn p ng (6%tng s BN) c chng
minh c ci thin lu di khi
iu tr chn knh Ca.
Sitbon O, Humbert M, Jais X, et al. Circ 2005;111:3105-11.Sitbon O, Humbert M, Jais X, et al. Circ 2005;111:3105-11.
Chn knh CalciumChn knh Calcium
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Sitbon O, Humbert M, Jais X, et al. Circ 2005;111:3105-11.Sitbon O, Humbert M, Jais X, et al. Circ 2005;111:3105-11.
Chn knh CalciumChn knh Calcium
p ng gin mchp ng gin mch
Gim ALMPTB trnGim ALMPTB trn 10 mm Hg10 mm Hg
Gim ALMPTM cnGim ALMPTM cn 40 mmHg40 mmHg
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Cc cht tng t ProstacyclinCc cht tng t Prostacyclin
Ci thin kh nng gng scCi thin kh nng gng scKhong 15 - 50 met trong nghim php 6 pht i bKhong 15 - 50 met trong nghim php 6 pht i b
Ci thin triu chngCi thin triu chng Gim PVR > PAPGim PVR > PAP Li ch trn t l sng cnLi ch trn t l sng cn
McLaughlin VV et al. Circulation.McLaughlin VV et al. Circulation.2002;106:1477-1482.2002;106:1477-1482.
ThngThng
0.20.2
0.40.4
0.60.6
0.80.8
11
%Tl
sng
%Tl
sng
cncn
1212 2424 3636
ExpectedExpected
Observed (n=162)Observed (n=162)
**
**
***p*p
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860 PAH pts
87
7871
68
Tc dng ca Treprostinil tiTc dng ca Treprostinil tim di dam di daln t l sng cnln t l sng cn
Barst RJ et al. Eur Respir J 2006;28(6):1195-203.Barst RJ et al. Eur Respir J 2006;28(6):1195-203.
n tr liu 332 IPAH pts
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Cc cht tng t ProstacyclinCc cht tng t Prostacyclin
Tim TM, Tim di da hoc kh dungTim TM, Tim di da hoc kh dung Mt s tc dng phMt s tc dng ph Tn kmTn km
Epoprostenol (FlolanEpoprostenol (Flolan))
Treprostinil (RemodulinTreprostinil (Remodulin
))
Treprostinil (RemodulinTreprostinil (Remodulin))
Iloprost (VentavisIloprost (Ventavis))tepoprostenol = 6 mintreprostinil = 4.5 hr
au hmBng mt
au chna chyQu liu
Ho
auNhim trngngc dng
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NghiNghin cun cu Treprostinil PivotalTreprostinil Pivotal
Mt
Mt
-5-5
00
55
1010
1515
2020
2525
3030
3535
4040Trung bnh SE thay i so vi ng c bn(met)Trung bnh SE thay i so vi ng c bn(met)
1st Quartile1st Quartile< 5.0< 5.0
(2.5 0.2)(2.5 0.2)
-4 12-4 12(N=34)(N=34)
2nd Quartile2nd Quartile5 to
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Cht i khngCht i khng Endothelin - BosentanEndothelin - Bosentan
BREATHE-1 (PAH):BREATHE-1 (PAH):
Theo di 12 week soTheo di 12 week sosnh vi placebosnh vi placebo
CICI 1.0 L/min/m1.0 L/min/m22 mPAPmPAP 7 mmHg7 mmHg PVRPVR 5 U5 U Ci thin khong cchCi thin khong cch
i b trong ti b trong test i best i b 66pht.pht. -40-40
-20-20
00
2020
4040
6060BosentanBosentan(n=144)(n=144)
PlaceboPlacebo(n=69)(n=69)
BaselineBaseline 44 88 1616
PP=0.0002=0.0002
BREATHE-1BREATHE-1
TunTun
Rubin LJ et al. NEJM 2002;346(12):896-903.Rubin LJ et al. NEJM 2002;346(12):896-903.
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BREATHE-5: Eisenmenger PAH (16 weeks):BREATHE-5: Eisenmenger PAH (16 weeks): Tiu ch nh gi u tin: huyt ng (placebo-hiu chnh)Tiu ch nh gi u tin: huyt ng (placebo-hiu chnh)
mPAP (-5.5 mmHg); PVR (-472 dmPAP (-5.5 mmHg); PVR (-472 dsscmcm-5-5) both p
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ng ungng ung Bosentan cht i khng receptor (khng chnBosentan cht i khng receptor (khng chn
lc)lc)
Tc dng ph:Tc dng ph: Ng c ganNg c gan Tng tc thucTng tc thuc TeratogenTeratogen
Ambrisentan chn lc (ET-A affinity 4000x ET-Ambrisentan chn lc (ET-A affinity 4000x ET-B)B)
Sitaxsentan khng c dng MSitaxsentan khng c dng M
10% pht trin thnh bt thng LFT10% pht trin thnh bt thng LFTv phi dng li, cn kim tra li hngv phi dng li, cn kim tra li hngthngthng
Bosentan gim AUC ca sildenafil AUC khongBosentan gim AUC ca sildenafil AUC khong50%50%
Paul, G. A., J. S. Gibbs, et al. (2005).Paul, G. A., J. S. Gibbs, et al. (2005)."Bosentan lm gim tp trung huyt"Bosentan lm gim tp trung huyttng ca sildenafil khi phi hp iu trtng ca sildenafil khi phi hp iu trTALMP."TALMP." British Journal of ClinicalBritish Journal of ClinicalPharmacologyPharmacology 60(1): 107-112.60(1): 107-112.
Glyburide Tng nhim c ganGlyburide Tng nhim c ganLm gim nng hp thu CyclosporinLm gim nng hp thu Cyclosporin
PhPh2% pht trin thnh bt thng LFT v2% pht trin thnh bt thng LFT vphi dng thuc, cn kim tra li hngphi dng thuc, cn kim tra li hngthngthng
Cht i khng EndothelinCht i khng Endothelin
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1.1.McLaughlin VV et al. Eur Respir J. 2005;25:244-249.McLaughlin VV et al. Eur Respir J. 2005;25:244-249.
2.2.Provencher S et al. Eur Heart J. 2006;27:589-595.Provencher S et al. Eur Heart J. 2006;27:589-595.
T l sngT l sngcn (%)cn (%)
ThThi gian (thng)(thng)
100100
8080
6060
4040
2020
00
T l sng cn c quan st (McLaughlin et alT l sng cn c quan st (McLaughlin et al11))T l sng cn(Provencher v cslT l sng cn(Provencher v csl22))T l sng cn d onT l sng cn d on
00 66 1212 1818 2424 3030 3636 4242 4848 5454 6060
TTc dng cac dng ca BosentanBosentan ln t l sng cnln t l sng cn ccaaTALMP tin phtTALMP tin pht (IPAH)(IPAH)
Based on historicalBased on historicalcontrolcontrol
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*C*Cc tiu ch nh gi kt hp; t l t vong, thay phi, ti nhp vin hoc khng tip tc tham gia nghinc tiu ch nh gi kt hp; t l t vong, thay phi, ti nhp vin hoc khng tip tc tham gia nghincu do bnh TALMP nng lncu do bnh TALMP nng ln, c, cn iu trn iu tr epoprostenol , hoepoprostenol , hoc ph vch lin nhc ph vch lin nh..Adapted from Rubin LJAdapted from Rubin LJet al, N Engl J Med. 2002;346;896-903et al, N Engl J Med. 2002;346;896-903..
Time (weeks)Time (weeks)
00
2525
5050
7575
100100
00 44 88 1212 1616 2020 2424 2828
PP=0.0015=0.0015PP=0.0038=0.0038
89%89%
63%63%
Event-freeEvent-free(%)(%)
Bosentan (144)Bosentan (144)
Placebo (n=69)Placebo (n=69)
Bosentan (n=35)Bosentan (n=35)
Placebo (n=13)Placebo (n=13)
Bosentan: ThBosentan: Thi gian triu chng lm sng xu ii gian triu chng lm sng xu i(BREATHE-1)*(BREATHE-1)*
n=144n=144
n=69n=69
n=103n=103
n=48n=48
n=13n=13
n=3n=3
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AmbrisentanAmbrisentanARIES-1 and 2: Sau 12 tuARIES-1 and 2: Sau 12 tunn
Ambrisentan ci thin ng k:Ambrisentan ci thin ng k:
Khong cch i b 6 phtKhong cch i b 6 pht
Thi gian triu chng lm sng xu iThi gian triu chng lm sng xu i
Phn loi triu chng c nng WHOPhn loi triu chng c nng WHO
Ch s kh th gng sc BorgCh s kh th gng sc Borg
SF-36SF-36 Health SurveyHealth Survey B-type natriuretic peptideB-type natriuretic peptide
Galie N et al. Circulation 2008;117(23):3010-9.Galie N et al. Circulation 2008;117(23):3010-9.
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N=132 N=127 N=115 N=94N=132 N=127 N=115 N=94N=64 N=62 N=61 N=50N=64 N=62 N=61 N=50N=130 N=124 N=119 N=98N=130 N=124 N=119 N=98N=67 N=65 N=63 N=51N=67 N=65 N=63 N=51
PlaceboPlacebo
2.5 mg2.5 mg5 mg5 mg
2.5 + 5.0 mg2.5 + 5.0 mg
7070
8080
9090
100100
00 44 88 1212WeeksWeeks
Event-Free(%)
Event-Free(%)
P-values represent log-rank comparison to placeboP-values represent log-rank comparison to placebo
71% relative risk gim71% relative risk gimtriu chng lm sngtriu chng lm sng
xu ixu i
CCi thini thin BDIBDI c quan st thy sau 12 tun iu trc quan st thy sau 12 tun iu tr ambrisentan so vambrisentan so viiplaceboplacebo CCi thin sau 12 tun xut hin nhm >10mgi thin sau 12 tun xut hin nhm >10mg
AmbrisentanAmbrisentanARIES-2: ThARIES-2: Thi gian triu chng lm sng xu ii gian triu chng lm sng xu i
Galie N et al. Circulation 2008;117(23):3010-9Galie N et al. Circulation 2008;117(23):3010-9
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00
1010
2020
3030
4040
5050
00 1212 2424 3636 4848Changein6MWD
(meters)
Changein6MWD
(meters)
Trung bnhTrung bnh 95% Kho 95% Khong tin cyng tin cy
TunTunn=383n=383 n=338n=338 n=248n=248 n=193n=193 n=146n=146
CCithin
ithin
+36.4 met+36.4 met
sau 48 tunsau 48 tun
Ambrisentan 2.5 10 mg once dailyAmbrisentan 2.5 10 mg once daily
Oudiz RJ, et al. Oral presentation, American Thoracic Society Annual Meeting, 2007.Oudiz RJ, et al. Oral presentation, American Thoracic Society Annual Meeting, 2007.
ARIES-E: Test i b 6 phtARIES-E: Test i b 6 phtso vi ng c bnso vi ng c bn
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AMB 222: ALT/AST >3xULNAMB 222: ALT/AST >3xULNNg c gan do bosentan hoc sitaxsentanNg c gan do bosentan hoc sitaxsentan
00
2525
5050
7575
100100
00 1212 2424 3636 4848
TunTun
Khngc
binc(%)
Khngc
binc(%)
N = 36N = 36 N = 34N = 34 N = 32N = 32 N = 31N = 31 N = 30N = 30
Ch 1 bnh nhn c ALT/AST >3xULNCh 1 bnh nhn c ALT/AST >3xULN
McGoon MD et al. Chest 2008;http://chestjournal.org/cgi/content/abstract/chest.08-McGoon MD et al. Chest 2008;http://chestjournal.org/cgi/content/abstract/chest.08-1028v1:Published online Sept 23, 2008.1028v1:Published online Sept 23, 2008.
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Cc thuc c ch PhosphodiesteraseCc thuc c ch Phosphodiesterase
SildenafilSildenafil Dng ung, thi gian bn hu 5 gi, 20 mg TIDDng ung, thi gian bn hu 5 gi, 20 mg TID
Dng liu duy nht *Dng liu duy nht *
Ci thin 6MWD, kh nng gng sc, huyt ng, ch sCi thin 6MWD, kh nng gng sc, huyt ng, ch scht lng cuc sngcht lng cuc sng
Gy gin mch, Chy mu camGy gin mch, Chy mu cam
c FDA khuyn co Khng hn ch trn cc mc c FDA khuyn co Khng hn ch trn cc mc phn loi triu chng c nngphn loi triu chng c nng
**Galie N, et al. N Engl J Med. 2005;353:2148-2157.Galie N, et al. N Engl J Med. 2005;353:2148-2157.
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Cc thuc c ch PhosphodiesteraseCc thuc c ch Phosphodiesterase
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
0.5
mPAP (mmHg)
CI (l/min/m2)
PVR (U)
RAP (mmHg)
**Galie N, et al. N Engl J Med. 2005;353:2148-2157Galie N, et al. N Engl J Med. 2005;353:2148-2157
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Test gin mch cpTest gin mch cpChng ngChng ng ++ Li tiuLi tiu ++ oxyoxy ++
digoxindigoxin
Chn knh caChn knh cang ungng ung
Tip tcTip tciu triu tr
chn knhchn knhCaCa
Nguy c cao
p ng kop ng kodidi
DngDngtnhtnh
Nguy c thp
CC
m tnhm tnh
RAP cao, CI thpHuyt ngRAP v CI bnh thng/gn bnh thng
Trn dch mng timSuy tht phi ng k
Siu m timSuy chc nng tht phit
Tng nhiuBNPTng t
Ngn hn (400 m)
IVPhn loi theo WHOII, III
NhanhMc tin trinT t
CBng chng lm sngca suy tht phi
Khng
Xc nh mc nguyc
Chin lc iu trChin lc iu tr
ACCP Consensus: modified from Chest, 126,1(supp), July 2004 inACCP Consensus: modified from Chest, 126,1(supp), July 2004 inMcLaughlin VV, McGoon MD. Circulation 2006;114(13):1417-31.McLaughlin VV, McGoon MD. Circulation 2006;114(13):1417-31.
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Test gin mch cpTest gin mch cpChng ng + Li tiu +Chng ng + Li tiu +
oxy + digoxinoxy + digoxin
Chn CaChn Caungung
Tip tcTip tcdung chndung chnCa ungCa ung
Nguy c cao
EpoprostenolEpoprostenolTreprostinilTreprostinil
IloprostIloprostETRAETRA
c ch PDE-5c ch PDE-5
ETRAETRAc ch PDE-5c ch PDE-5EpoprostenolEpoprostenolTreprostinilTreprostinil
p ng lup ng ludidi
Dngtnh
Nguy c thpNguy c thp
Yes
NoNo
Protocol nhProtocol nhgigi
m tnh
nh gi li xem xt ktnh gi li xem xt kthp iu trhp iu tr
Chin lc iu trChin lc iu tr
ACCP Consensus: modified from Chest, 126,1(supp), July 2004 inACCP Consensus: modified from Chest, 126,1(supp), July 2004 inMcLaughlin VV, McGoon MD. Circulation 2006;114(13):1417-31.McLaughlin VV, McGoon MD. Circulation 2006;114(13):1417-31.
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BosentanBosentan ng ungng ung && EpoprostenolEpoprostenoltruytruyn tnh mchn tnh mch::
BREATHE-2BREATHE-2 CC xu hng ci thin xu hng ci thin
huyt ng v lm sng,huyt ng v lm sng,nhng khng c nghanhng khng c ngha
thng kthng k TiTiu ch nh gi u tinu ch nh gi u tin
= TPR,= TPR, c thay i:c thay i:
-36% bosentan-36% bosentan
-22% placebo-22% placebo
p = 0.08%p = 0.08%
6MWD6MWD
68
74
0
10
20
30
40
50
60
70
80
Bosentan +
Epoprostenol
Placebo +
EpoprostenolMedianChang
efrom
Baselinein6-minuteWal
(m)
Humbert M, et al. Eur Respir J. 2004;24:353-359Humbert M, et al. Eur Respir J. 2004;24:353-359
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7575
5050
2525
00
-25-25
-50-50
-75-75BaselineBaseline Week 4Week 4 Week 8Week 8 Week 12Week 12
Changefro
mBaselinein6MWD
Changefro
mBaselinein6MWD
Bosentan + Iloprost (N = 34)Bosentan + Iloprost (N = 34)Bosentan + Placebo (N = 33)Bosentan + Placebo (N = 33)
McLaughlin VV, et al. Am J Respir Crit Care Med. 2006;174:1257-1263McLaughlin VV, et al. Am J Respir Crit Care Med. 2006;174:1257-1263
STEP: Kh dung Iloprost phi hp Bosentan ungSTEP: Kh dung Iloprost phi hp Bosentan ung
Nhng bnh nhn n nh khi dng bosentan ti thiu 3
thng c la chn ngu nhin vo nhm placebo vkh dung iloprost
An ton, ci thin 6MWD, FC, thi gian n khi triuchng lm sng xu i
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IV Epoprostenol phIV Epoprostenol phi hpi hp Sildenafil: PACES-1Sildenafil: PACES-1
m 95% CI
-20
0
20
40
60
Baseline Week 4 Week 8 Week 12 Week 16
Placebo Sildenafil
Changein6MWDfrom
Baseline(m)
*
30.1
4.1
Treatment Effect 26m
*p=0.0009
Simonneau G et al.. Ann Intern Med 2008;149(8):521-30Simonneau G et al.. Ann Intern Med 2008;149(8):521-30
(n = 267)
6 Minute Walk Test6 Minute Walk Test
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iu tr sm c tt hn khng?iu tr sm c tt hn khng?
Galie N et al: Treatment of patients with mildly symptomatic pulmonary arterial hypertension withGalie N et al: Treatment of patients with mildly symptomatic pulmonary arterial hypertension withbosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371:2093-100, 2008bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371:2093-100, 2008
Nghin cu EARLY- BosentanNghin cu EARLY- Bosentan
vv ci thin ci thin TTCW hTTCW hnn 32 tu32 tunnp = 0.0114p = 0.0114
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Cc thuc ang tip tc nghin cu ?Cc thuc ang tip tc nghin cu ?
Kh dung treprostinil (TRIUMPH-1; Viveta)Kh dung treprostinil (TRIUMPH-1; Viveta) Ung treprostinil, beraprostUng treprostinil, beraprost c ch PDE5 ko di (tadalafil)c ch PDE5 ko di (tadalafil)
Genetically modified PAECsGenetically modified PAECs c ch Tyrosine kinase (imatinib, sorafenib)c ch Tyrosine kinase (imatinib, sorafenib) c ch Rho-Kinase (fasudil)c ch Rho-Kinase (fasudil) Hot ho PPAR (rosiglitazone, pioglitazone)Hot ho PPAR (rosiglitazone, pioglitazone)
Vasoactive intestinal peptideVasoactive intestinal peptide SSRIs, statins, aspirinSSRIs, statins, aspirin Khc CO, c ch elastase, dichloroacetateKhc CO, c ch elastase, dichloroacetate
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The EndThe End