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 - oxigenare Hb
 - filtru (particule, bacterii)
 - eliminarea CO2 – echilibru acido-bazic
CIRCULATIA CIRCULATIA
PULMONARA BRONSICA
Sange venos sange arterial
a. pulmonara a. bronsice
Capilare Capilare
Vene pulmonare Vene sistemice
CIRCULATIA
PULMONARA NORMALA
PLAMANUL

 Sunt fiziologic dr-stg
(pana la 30% din DC)
- bronsiectazii
- fibroza chistica
- boli congenitale
cardio-vasculare
CIRCULATIA BRONSICA

NORMAL
A SISTEMICE – media 20-25% din diam. vasului
A. PULMONARE - media < 10- 5% din diam. vasului
Arteriolele pulmonare nu au tunica medie si nu contribuie
la rezistenta vasculara
VD – fluxul coronarian cel mai mare in sistola
- depinde de gradientul pres. pulm. – aorta
Pres. VD creste – gradientul scade – fluxul coronar drept
scade – ischemie VD
HIPERTENSIUNEA
PULMONARA (HTP)

NORMAL
PRES. A. PULMONARA - sist. 18-25 mm Hg
- diast. 6-10 mm Hg
- medie 12-16 mm Hg
PRES V. PULMONARE – 2-10 mm Hg
REZIST. VASC. PULM. = 1/10 din REZIST. SISTEMICA
HIPERTENSIUNEA PULMONARA (HTP)
PRES. A. PULMONARA - sist. > 30-35 mm Hg
- medie > 20-25 mm Hg
- diast. > 15 mm Hg
 Reducerea calibrului vaselor pulmonare
 Cresterea fluxului
HIPERTENSIUNEA
PULMONARA (HTP)

HIPOXIA VASOCONSTRICTIE PULMONARA
-histamina – receptori H1 vasculari
- endoteliu - echilibru NO – endoteline
- patrunderea Ca 2+ in celula musculara neteda
HIPOXIA CRONICA
1. Extensia musculaturii netede in peretele arterelor din
periferia plamanilor
2. Ingrosarea peretilor arterelor musculare
3. Reducerea nr. arterelor – cresterea raportului alveole/artere
REACTIVITATEA
VASCULARA PULMONARA
VASOCONSTRICTIE
Hipoxia
Acidoza
Prostaglandine F2α si A2
HISTAMINA – H1
SEROTONINA ?
ANGIOTENSINA A2
ALTITUDINE
VASODILATATIE
Alcaloza
PROSTAGLANDINE I2 si E
BLOCANTI α
STIMULARE β
(ISOPROTERENOL)
ACETILCOLINA (prin
EDRF)
HISTAMINA (prin H2 ?)
INDOMETACIN– creste rezistenta
pulmonara
La 10 000 m altitudine
TA pulmonara medie = 25 mm Hg in repaus
> 50 mm Hg in efort

1. HTP arteriala
1.1. Idiopatica
1.2. Ereditara
1.3. Indusa de droguri si toxine
1.4. Asociata cu:
Boli de colagen
HIV
Hipertensiune portala
Boli cardiace congenitale
Schistosomiaza
Anemie hemolitica cronica
1.5. HTP persistenta la nou nascut
1’ Boala venoocluziva pulmonara si/sau hemangiomatoza capilara pulmonara
CLASIFICAREA HTP
Dana Point, 2008

2. HTP prin suferinta ventriculului stang
2.1. Disfunctie sistolica
2.2. Disfunctie diastolica
2.3. Boli valvulare
CLASIFICAREA HTP
Dana Point, 2008

3. HTP prin boli pulmonare sau hipoxie
3.1. BPOC
3.2. Boli interstitiale
3.3. Alte boli cu restrictie si obstructie
3.4. Apneea de somn
3.5. Boli cu hipoventilatie alveolara
3.6. Expunerea cronica la mare altitudine
3.7. Anomalii de dezvoltare fizica
CLASIFICAREA HTP
Dana Point, 2008

4. HTP prin tromboembolism
5. HTP prin factori multipli neclari
5.1. Boli hematologice: mieloproliferare, hipersplenism
5.2. Boli sistemice: sarcoidoza, histiocitoza pulmonara
cu celule Langerhans
5.3. Boli metabolice: B. Gaucher, glicogenoze, disfunctii
tiroidiene
5.4. Altele: obstructii tumorale, mediastinita fibrozanta,,
IRC sau dializa
CLASIFICAREA HTP
Dana Point, 2008

In suferinta inimii stangi
PRESIUNE ATRIU STG = 7 mm Hg
scade rezistenta pulmonara (recrutare de vase)
>7 mmHg – creste presiunea in a. pulmonara (fluxul ramane
constant; gradientul ramane constant)
> 25 mmHg – crestere disproportionata de presiune in a.
pulmonara (gradientul creste; fluxul constant sau scade)
CATEVA MECANISME
FIZIOPATOLOGICE

Variabilitatea reactivitatii vasculare pulmonare:
 creste presiunea venoasa – distrugere sau inchidere de cai
aeriene – hipoxie – creste presiunea in a. pulmonara
 creste presiunea venoasa – edem interstitial – rigidizarea
vaselor – HTP
 drenajul limfatic creste
 starea VD
 normal
 hipertrofic
 insuficient
 miopatic (+ VS)
 hipoperfuzat (infarct)
 Volumul sanguin pulmonar (depinde de debitul celor 2
ventriculi si de distensibilitatea vaselor pulmonare)
CATEVA MECANISME
FIZIOPATOLOGICE

- Celule endoteliale capilare umflate
- Membrane bazale capilare ingrosate
- Edem interstitial
- Rupturi de membrane bazale – transudare de eritrocite –
hemosideroza
- Alveole fibroase
- Destindere de limfatice
MODIFICARI ANATOMICE
Test Notable Findings
Chest x-ray Enlargement of central pulmonary arteries reflects level of PA pressure
and duration.
Electrocardiography Right axis deviation and precordial T wave abnormalities are early signs.
Pulmonary function tests Elevated pulmonary artery pressure causes restrictive physiology.
Perfusion lung scan Nonsegmental perfusion abnormalities can occur from severe pulmonary
vascular disease.
Chest computed tomography scan Minor interstitial changes may reflect diffuse disease; mosaic perfusion
pattern indicates thromboembolism and/or left heart failure.
Echocardiography Right ventricular enlargement will parallel the severity of the pulmonary
hypertension.
Contrast echocardiography Minor right to left shunting rarely produces hypoxemia.
Doppler echocardiography This is too unreliable for following serial measurements to monitor
therapy.
Exercise testing This is very helpful to assess the efficacy of therapy. Severe exercise-
induced hypoxemia should cause consideration of a right-to-left shunt.
TABLE 73-2 -- Clues for Interpretation of Diagnostic Tests for Pulmonary
Hypertension

Toate sunturile sistemico-pulmonare rezultand din
mari defecte care duc la cresteri de presiune in VD si
la inversarea suntului (pulmonar-sistemic) sau sunt
bidirectional cu: cianoza, eritrocitoza si multiple
suferinte de organ
SINDROM
EISENMENGER

GR. I : hipertrofia mediei artereor mici musculare
GR. II : + proliferarea intimei
GR. III: + fibroza concentrica cu obliterare de vase
GR. IV: “leziuni plexiforme”, dilatatii, trombi
GR. V: complexe plexiforme, leziuni angiomatoase si cavernoase si hialinizaea
fibrozei intimale
GR. VI: arterita necrozanta
MODIFICARI ANATOMICE
Histopathology of endothelial cell lesions in
IPAH. A. Pulmonary artery showing medial
hypertrophy and lined by a single layer of
endothelial cells, as outlined by Factor VIII
related antigen immunostaining(arrow).
Plexiformlesion (outlined by the rim of
arrowheads) with the proximal vascular arterial
segment with marked intimal and medial
thickening by smooth muscle cells (arrow). Note
the proliferation of endothelial cells with the
outer edge (3–5 o’clock) occupied by dilated
blood vessel-like structures. C. Cross section of
a plexiformlesion, outlined by arrowheads. Note
perilesional inflammatory infiltrate (arrow). D.
High magnification histology of plexiformlesions
shown slit-like vascular channels lined by
hyperchromatic and cuboidal endothelial cells.
Cells in the core do not display distinct
cytoplamic borders. E. Low magnification
immunohistology with Factor VIII related antigen
immunohistochemistry of different endothelial
cell based vascular lesions. This area has re-
vascularized lesions (possibly an organized
thrombus), with well-formed and distinct small
capillaries/vessels (arrowhead), a plexiform
lesion (arrow), and dilated/angiomatoidlesions
(between arrowheads). F. High magnification
immunohistology of cellular plexiformlesion
stained with Factor VIII related antigen
(arrowheads). G and H. Histological
identification of plexiform and dilation lesions (G)
is markedly improved by Factor VIII related
antigen immunohistochemistry (H)
(arrowheads), while the parent vessel (arrow)
shows mild medial remodeling. I. Highlight of
vascular dilation/angiomatoidlesions with Factor
VIII related antigen immunohistochemistry. J.
Endothelial cells in plexiformlesion is
highlighted by CD34 immunohisochemistry
(arrowheads). Proximal pulmonary artery with
marked intima and medial thickening is
highlighted by the arrow. K and I. Endothelial
cells are highlighted by CD31
immunohistochemistyr (arrowheads). Note that
capillary endothelial cells express CD31 as well
(arrow in I),
A. Fibrotic, relatively paucicellular
intima thickening (outlined by
arrowheads) in a pulmonary artery
with the media highlighted with the
arrow. B. Marked intima remodeling
with almost complete obliteration by
fibrous tissue with a marked
intravascular and perivascular
inflammatory infiltrate (arrows). C.
Smooth muscle cell hypertrophy, with
prominent thickening of medial layer
(arrow). D. Highlight of medial
hypertrophy with smooth muscle α
actin immunohistochemistry. E.
Markedly remodeled pulmonary artery
with endothelial cell layer highlighted
by Factor VIII related antigen
immunohistochemistry. Note that the
intima and medial smooth muscle
cells are negative for Factor VIII
related antigen reactivity. F. Ingrowth
of smooth muscle cells in a plexiform
lesions, highlighted by smooth
muscle cell α actin
immunohistochemistry (arrow).
Veno-occlusive PH. A. Low-power histological view of thickened pulmonary veins running into the lung parenchyma from the
pleural surface (left edge) (arrows). Note marked vein wall thickening and decreased lumen. Adjacent alveoli are filled with blood
and show septal thickening with engorged capillaries (arrowhead). B. Marked vein thickening with intimal projection probably
representing organized thrombus (arrow). Alveolar hemorrhage and septal thickening are highlighted with arrowhead. C and D.
Movat stained pulmonary vein showing arterialization pattern with internal and external elastic layers (arrow). The vein shows
marked intima thickening with organized thrombus (arrowheads).



Normal
 Flux crescut in lobii inferiori
Gravitatie
Presiuni diferite intra –alveolare
Raport A/B = 1,2 : 1
CRESTEREA FLUXULUI PULMONAR
FLUX - Φ VASE x 8 (rezerva) +
 Φ vase - flux + presiune
- presiune
 Creste Φ venos
Rx – 1/3 ext. vascularizata
- Circ. Inf = circ. sup.
N – Φ a. pulm. desc. dr. = 10-15 mm la barbati si 9-14 mm la femei
Rx în HTP

HTP arteriala
- vasoconstrictie periferica
- vasospasm
- ingrosarea peretelui vascular
Rx
- scade circulatia (creste transparenta) in 1/3 ext.
- vasele centrale elastice se largesc
- calcificari ale vaselor centrale
Rx în HTP

HTP de origine venoasa
P venoasa > 8 – 12 mm Hg
 fluxul pulmonar este redistribuit spre lobii superiori
Rx – inversare a aspectului normal (cefalizarea fluxului arterial si venos)
P venoasa > 25 mm Hg
 Edem pulmonar
Rx în HTP

Mecanisme
 Sechestrarea de lichid interstitial in lobii inferiori

 Presiunea interstitiala ↑

 Complianta pulmonara ↓

 Fluxul spre lobii inferiori ↓
+
 Spasm arterial
 Fluxul este redistribuit spre lobii superiori
Rx în HTP

ETIOLOGIE
 Embolism pulmonar recurent, asimptomatic
 Embolism amniotic
 Tromboza in situ, tulburari de coagulare si fibrinoliza , contraceptive
 Vasoconstrictie cronica → necroza fibrinoida → leziuni plexiforme
 Vasculita generala cu fenomen Raynaud
 Hipersensibilitate la droguri
 Ingestia de fumarat de aminorex (anorexigen)
 Hormoni feminini
HTP IDIOPATICA

MODIFICARI HISTOLOGICE
Ingrosarea intimala a a. mici si arteriole cu fibroza in
“foi de ceapa”
Ingrosarea mediei a. musculare si muscularizarea
arteriolelor
Arterita necrozanta cu necroza fibrinoida
Leziuni plexiforme → arteriopatie pulmonara
plexogenica → umbre vasculare → reducerea patului
vascular
HTP IDIOPATICA

HIPOXIE → raspuns anormal → disfunctie endoteliala
Modificarea raportului EDRF - endoteline
Distrugeri de endoteliu
Tromboza
Vasoconstrictie → necroza fibrinoida
Leziuni plexiforme
HTP IDIOPATICA

ASPECTE CLINICE
 Femei tinere
4 simptome principale
 Dispnee de efort
 Accentuarea zgomotului II
 Modificari Rx – cardiomegalie
- a. pulmonara proeminenta
 Modificari ECG : - HVD
- deviatie axiala dr.
- HAD
Mai rar:
- Ameteli si sincope de efort
- Dureri toracice de efort
- Edeme
- Fenomene Raynaud
- Ciroza hepatica
- Istoric de tromboflebita superficiala
HTP IDIOPATICA

PROGNOSTIC
 Prost (supravietuire peste 5 ani – 21%)
 Anticoagulantele imbunatatesc prognosticul
MOARTEA
 Insuficienta cardiaca congestiva
 Pneumonie
 Moarte subita
 Moarte la cateterism
 Disectie de a pulmonara
HEMOPTIZIA IN STADII TARDIVE
 Ruptura de leziuni plexiforme
 Tromboze in situ
 Embolism pulmonar
DUREREA TORACICA
 Ischemia subendocardului VD
 Distensia a pulmonare
HTP IDIOPATICA

SEMNE CLINICE
 Zgomot II intarit la pulmonara
 Suflu sistolic la pulmonara
 Semne de insuficienta cardiaca dreapta
 Semne de regurgitare triscuspidiana
 Cianoza - tardiv prin deschidere de foramen ovale
 Paralizie de recurent (rara)
HTP IDIOPATICA

LABORATOR - Uneori defecte de coagulare si fibrinoliza
ECG: HVD, HAD
Rx: largirea a pulmonare; marirea atriului si ventriculului dr
CT – Φ a pulmonare
TESTE FUNCTIONALE - Disfunctie restrictiva
ECHOCARDIOGRAFIA
Marirea atriului si ventriculului drept
Cavitati stangi normale
Ingrosarea septului
Regurgitare tricuspidiana si prolaps de valva mitrala secundare dilatatiei
de VD
HTP IDIOPATICA

SCINTIGRAFIA PULMONARA - normala
In stadii avansate poate fi daunatoare – trasorul legat de albumina –
procoagulant
CATETERISMUL CARDIAC SI ANGIOGRAFIA
 RISCANTE
 Presiunea in VD egala sau chiar mai mare decit presiunea sistemica
 Rezistenta vasculara pulmonara depaseste uneori pe cea sistemica
 Uneori foramen ovale este patent
 Presiunile stg. sunt normale sau mici, dar uneori greu de determinat
BIOPSIA PULMONARA
HTP IDIOPATICA

HTP IDIOPATICA
DIAGNOSTIC DIFERENTIAL
HTP secundara (mai benigna si mai tratabila)

In sala de cateterism cardiac
PAPm dupa administrarea de NO inhalator (sau adenozina iv,
epoprostenol iv sau inhalator)
Test + = reducerea cu 20% a PAPm sau a rezistentei vasculare
pulmonare – bolnavul va primi vasodilatator indelungat
TESTUL
VASODILATATOR

Supravietuirea medie in HTP netratata = 2,8 ani
Factori de prognostic:
Varsta < 14 ani sau 65 ani – prognostic prost
Clasa NYHA: I – II: supravietuire 6 ani in medie
III: supravietuire 2,5 ani in medie
IV: supravietuire 0,5 ani in medie
Scaderea capacitatii de efort
Sincopa
Hemoptizie
Semne de insuficienta ventriculara dreapta
O2 in a pulmonara > 63 – 55% supravietuire la 5 ani
< 63 – 17% supravietuire la 5 ani
Indexul cardiac < 2,1 l/min/m2 supravietuire medie 17 luni
Presiunea in AD < 10 mmHg - supravietuire 4 ani in medie
> 20 mmHg - supravietuire medie o luna
Test de vasodilatatie negativ
PROGNOSTICUL

1. Anticoagulantele
Warfarina dubleaza supravietuirea in HPP
Indicatiile anticoagularii permanente: toti pacientii cu HTPI
Tromboembolismul pulmonar (INR = 2-3)
HTP secundare, daca nu exista contraindicatii
2. Oxigenoterapia
Se recomanda monitorizarea Sat O2 nocturna, Sat O2 < 90% in aerul
atmosferic corectabila la administrarea de O2, indica oxigenoterapia
nocturna
3. Tratamentul insuficientei ventriculare drepte:
- Diuretice
- Digoxinul creste DC in administrarea acuta in HTPI, efectul sau in
administrarea cronica este discutabil
TRATAMENTUL
MEDICAL

4. Tratamentul vasodilatator
Antagonistii de Ca (diltiazem sau nifedipina):
 HTP de tip arterial cu test vasodilatator pozitiv
 CI in : HTP venoasa (precipita EPA)
HTP hipoxica din bolile cronice pulmonare cu Sat O2 in sangele
venos < 63% (agraveaza hipoxemia)
PAD > 10 mm Hg
Index cardiac < 2,1 l/min/m2
TRATAMENTUL
MEDICAL

Responders: Ca.-blockers
 (if bradicardic)
Nifedipine :120 -240 mg
 (if tahicardic)
Diltiazem240-720 mg
Begin low dosage , increase weekly
Less than ½ of pts tolerate maximum dosage

5. Prostaglandinele – efectele pozitive ale tratamentului
indelungat (min 3 luni)
Reducerea rezistentei vasculare pulmonare
Cresterea indexului cardiac
Dublarea supravietuirii la 5 ani
Reducerea riscului si ameliorarea evolutiei dupa transplantul
pulmonar
TRATAMENTUL
MEDICAL (PG)

Indicatii
Bolnavii cu ICC cl III – IV, index cardiac < 2,1
l/min/m2 si/sau Sat O2 in artera pulmonara < 63%
si/sau PAD > 10 mmHg, indiferent de testul
vasodilatator
Toti bolnavii care nu raspund la tratamentul medical
conventional, in asteptarea transplantului pulmonar
TRATAMENTUL
MEDICAL

Efecte adverse:
Diaree, dureri abdominale, cefalee, flush, artralgii,
dureri musculare
Ascita, edem pumonar (prin cresterea permeabilitatii
vasculare)
Toleranta ce necesita cresterea dozelor
Rebound al HTP la intreruperea brusca a
tratamentului
Infectii de cateter
TRATAMENTUL
MEDICAL (PG)

Preparate folosite:
Epoprostenol = PGI2 iv. Se incepe cu 2 ng/kc/min in pev continua si se
creste doza dupa o saptamana pana la doza maxima tolerata de
pacient
Iloprost = analog al epoprostenolului, mai puternic iv (pev continua)
sau in aerosoli, 6-9 inhalatii/zi (50 -200 μg/zi)
Trepostenil (UT – 15) este analog de PGI2. Doza initiala este de 1,25
ng/kc/min si se creste cu 1,25 ng/kc/min la 7 zile pana la 9,3
ng/kc/min
TRATAMENTUL
MEDICAL (PG)

Beraprost: derivat stabil de PGI2, poate fi adminisrat
p.o. 1 tb = 20μg. Se incepe cu 1 tb/zi si dupa 6
saptamani de titrare, se ajunge la 6 tb/zi (studiul
ALPHABET). Rezultate bune in HTPI,
neconcludente in HTP sec. Se pare ca nu este eficient
in stadiile avansate de boala.
TRATAMENTUL
MEDICAL (PG)

Prostanoid analogues
CTD= boala de tesut conjunctiv
Epoprostenol
short HL, temp.-dependent , i- v (infusion pump ) , local facilities
2-4ng/kg/min ..20-40 ( tolerance , rebound , adverse reactions: common)
>100.000 $ /year
Rubin LJ Ann. Intern.Med. 1990;112:485-92
Barst RJ N.Engl. J Med 1996;334:296-304
Badesch DB Ann. Intern.Med. 2000;132:425-34
3 month results: indic. surv/altern
Conversion to oral agents ??
Treprostenil
sufficient chemical stability to be
administered at ambient temperature
allow iv / subcutaneous /oral ( bid )
and inhalatory adm.(6-9 d )
Beraprost
Orally :40-80microg qid/zi
efficacy does not appear to be sustained
with extended duration of therapy
Iloprost
Inhalations 6-12 times/d
(20-40 microg/d.)
Advant: selective to pulm.circ.
J Am CollCardiol. 2003 Jun 18;41(12): 2119–25

6. Antagonistii receptorilor de endotelina
Bosentan (ET1RA) po. Doze: 62,5 mg de 2 ori/zi, pana la 125 mg
de 2 ori/zi, timp de 16 saptamani.
TRATAMENTUL
MEDICAL (ARE)

Endothelin receptor antagonists
Type A receptor :
vasoconstriction, proliferation, fibrosis.
Type B receptor (endotelial):
increases the synthesis of nitric oxide
( vasodilation )
Type B receptor (SMC):
activates aldosterone,
thromboxane, norepinephrine.
( vasoconstriction )
Bosentan ( Tracleer ) available in Romania
dual ETA and ETB-receptor antagonist
125 mg bid BREATHE-1
BREATHE-3 (children )
10% liver enzimes > BREATHE -5
EARLY
Sitaxsentan
6500 times greater affinity for the ETA STRIDE I and II
Chest , 2008; 134(4): 775 - 782.
100-300 mg od 2004 : Level of evidence : B
Incl .HTP in congenitals/CTD aproved in Europe
Warfarine interference
Ambrisentan ARIES-2 . Am J Respir Cirt Care Med. 2006;173:
lower incidence of liver enzyme abnormality Ann. Pharmacother, 2008; 42(11):
1653
absence of significant drug interactions -
2004 : Level of evidence : C

7. Inhibitori de fosfodiesteraza (Sildenafil)
TRATAMENTUL
MEDICAL (IFD)

Phosphodiesterase inhibitors
Sildenafil ( REVATIO )
25 mg t.i.d.
Available in Romania
Humbert M N Engl J Med 2004;351: 1425–36.

Type 5 Phosphodiesterase inhibitors
 Vardenafil HCL ( Levitra ) Br J Pharmacol., 154(4):787-96. 2008 Apr
21
 Tadalafil ( Cialis )
longer half-life (17.50 hours )
marketing approval began in late 2008
J Am Coll Cardiol, 2004; 44:1488-1496
Circulation. 2004;110:3149-3155
The three PDE5 inhibitors differ markedly in :
 kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil)
 selectivity for the pulmonary circulation (sildenafil and tadalafil, but
not
vardenafil),
 impact on arterial oxygenation (improvement with sildenafil only).

Septostomie atriala. Procedeu paleativ ce scade presiunea
in inima dreapta.
 Indicatii:
 HTP severa, care nu raspunde la prostaglandine
 Se exclud pacientii cu Insuf Ventr dr severa, disfunctie de VS sau
in stare critica
Trombendarterectomie
Transplant pulmonar
TRATAMENTE
CHIRURGICALE

Indicatii transplant
HTPI simptomatica, progresiva in ciuda tratamentului
medical optim, cu test de mers de 6 min < 400 m, cu
index cardiac < 2,1 l/min/m2 si/sau Sat O2 in artera
pulmonara < 63% si/sau PAD > 10 mm Hg sau PAP
m > 55 mmHg
TRATAMENTE
CHIRURGICALE
Test vasodilatator acut
Raspuns +
Sv O2>63%, IC > 2,1
Raspuns -
NYHA I/II, Sv O2>63%,
IC > 2,1
NYHA III/IV, Sv O2<63%,
IC < 2,1
Blocanti de Ca
Nu raspund la tratament
Prostaglandine
+/- transplant
Warfarina + diuretic + digoxin



Frequently asked
questions
 At which level of pulm.pressure should we
begin pharmacological treatment in sec. PHT ?
Adapted to etiology ! Unknown borderline !
 Is it harmful to use CCB in nonresponders ?
Yes , at least for high doses
ACCP Gd.: Level of evidence: expert opinion; benefit: substantial;
grade of recommendation: E/A.
 Would it be better to use the more active drugs
for responders also ?
Probably yes , but economically unwise

Frequently asked
questions
 How useful is multiple drug therapy
Which order of introduction /doses ?
BREATHE -2
 Is atrial septostomy an option ?
Rarely (bridge to… ) ; 5-15% mortality

CONCLUSIONS
 PPHT pts to be treated in dedicated centers
 New therapies available ; debate on results
 Combination therapy in developpement
 Rapid change of recomandations /guidelines
 Cost –effectiveness analysis vital
 Hard end points-including mortality may be influenced