Download pulmonary hypertension

Prof. S. Shanmuga Sundaram
K.S. Hospital, Chennai
PULMONARY HYPERTENSION AT SYSTEMIC
LEVEL, DUE TO HIGH PULMONARY VASCULAR
RESISTANCE ( > 800 dynes sec cm-5 ) WITH
REVERSED OR BIDIRECTIONAL SHUNT…..
8% (1950) → → → → 4%
Complications associated with the Eisenmenger syndrome
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
DEATH: Sudden death 30% , Heart failure 23% , Hemoptysis
11%
Death during noncardiac surgery & pregnancy
DISSECTION OF PULMONARY
ARTERY
PROXIMAL PA THROMBOSIS
PULMONARY ARTERIAL HYPERTENSION
IN SHUNT LESIONS
mPAP > 25 mmHg at rest / > 30 mm Hg post exercise
PAWP < 15 mm Hg ; PVR > 3 Wood Units
• TRANSMISSION OF SYSTEMIC ARTERIAL PRESSURE
• VASOCONSTRICTION
• VASCULAR OBLITERATION – MEDIAL HYPERTROPHY
FIBROSIS
INTIMAL PROLIF +
ARTERIAL THROMBI
OBLITERATIVE
PVR
PA PP/PA SP
HYPERKINETIC
< 5 W.U
> 60%
> 5 W.U
< 40%
ASD
CA, APVC
APWINDOW
VSD
PDA
TGA VSD, DORV
SINGLE VENTRICLE
TRUNCUS
> 2 cm
> 1 cm
> 1 cm
PULMONARY CIRCULATION - STRUCTURAL REMODELING
Elastic > Fully muscular > Partially muscular > Non
muscular
 At birth the smallest muscular arteries dilate with medial
thinning
 By 4 months, this process involves larger arteries & get
completed
 Alveoli and Arteries grow both in number & size Al : Art =
20:1 > 8:1
 With shunt lesions resulting in increased flow ± pressure,
proximal arteries dilate, distal arteries reduce in number
and size bcause of extension of muscle in media of partially
or non muscular arteries
NORMAL
VSD
MATURATION OF
PULMONARY VASCULAR BED
Lucas R. Am J Dis Child
PAH IN L > R SHUNTS
 NONRESTRICTIVE VSD = 15 % < 2 yrs of life
MODERATE DEFECTS = 3% ; LARGE DEFECTS (1.5cm) =
50%
 LARGE PDA
= similar incidence
 LARGE ASD
= 6-10% > 3rd decade
Frequent in SVC, partial AV Canal defects & in
Lutembacher’s
 TGA = 8% (intact IVS ) 40% ( VSD/PDA ) < 1 yr
75% at 2 yrs
 COMMON AV CANAL
all develop PAH
 TRUNCUS ARTERIOSUS
by 1-2 yrs
 SYSTEMIC - PA SHUNTS: BT Shunt (<10%)
Waterston / Pott’s ~ 30%
MECHANISMS OF PAH IN L>R SHUNTS
LESION
ASD
VSD
PDA
AV CANAL
TGA, TA
↑Qp ↑PAP
+
+
+
+
+
+
+
+
+
↑PVP ↓ pH ↑ Ht
+
+
++
+
+
+
ENDOTHELIAL DYSFUNCTION
↑ ET, TXA2 , SEROTONIN ↓ NO
,PGI2,VIP
PLATELET ADHESION +
THROMBUS
GENETIC SUSCEPTIBIILITY
BMPR2 MUTATION = 6 % 26%(IPAH) 50%
(FPAH)
MORPHOMETRIC GRADING
Rabinovitch M
Grade A : Extension of muscle into small peripheral arteries
Wall thickness increased but < 1.5 times the normal
↑ PBF ↑ PA PP + NORMAL MEAN PAP
Grade B : Mild : medial thickness 1.5 – 2.0 times the normal
Severe : medial thickness > 2 times the normal
PAH - MEAN PAP > 50 % OF SYSTEMIC LEVEL
Grade C : Size and number of arteries reduced
PAH - PVR > 3.5 - 6.0 u.m2
CLINICAL RECOGNITION
• Apparent improvement of neonatal HF
• Reduction of frequency of respiratory infections
• Precordium becomes less tumultous
• Flow murmur decreases > disappears
• Shunt murmur decreases in intensity & duration
• S2 split decreases and P2 increases in intensity
EISENMENGER’S SYNDROME
SYMPTOMS:
1) Low C.O + Hypoxia > DOE, Dizziness, Syncope, Fatigue
2) Hemoptysis : Rupture of plexiform, dilatation lesions,
pulmonary arterioles, Broncho Pulmonary connexions,
Pulmonary Embolism / in situ thrombosis
3) Hyperviscosity: Headache, dizziness, Visual sx
4) Right Heart failure : Edema, RHC pain
5) CVA : Hyperviscosity, Parad. emboli, Cerebral abscess
6) Sudden cardiac death: Arrhythmia
EISENMENGER’S SYNDROME
SIGNS :
1) Cyanosis and Clubbing
2) JVP inconspicuous
3) Pulmonary Ejection Sound
4) 2-3/6 Ejection Systolic Murmur
5) Loud P2
6) Murmurs of TR and PR
EISENMENGER’S SYNDROME
FEATURE
ASD
Neonatal HF
-
Age
30-40
-
-
Single
-
Differential
±
+
Fixed
-
2-12
Uniform
-
Prominent ‘a’ JVP
S2 split
Long PR murmur
2-12
+
PDA
+
±
Uniform
Cardiomegaly,PSH
Wide pulse pressure
+
±
Syncope
Cyanosis
VSD
Normal
+
-
PAH
GROWING
PDA
DOPPLER
PATTERN
S
PULSATILE
CLOSING
CLOSED
DOPPLER IN
PDA
SHUNT LESIONS - OPERABILITY
 Qp : Qs = > 2:1 No or mild PAH
 Qp : Qs = < 1.5:1 Severe PAH -
INOPERABLE
Qp = O2 Consumption / PV – PA O2 content
Qs = O2 consumption / SA - MV O2 content
O2 content = O2 saturation x O2 carrying capacity x Hb
Qp : Qs = SA – MV O2 sat / PV – PA O2 sat
Why to assess operability ?
CHD PAH – REVERSIBILITY TESTING
HIGH SURGICAL RISK ( 20% )
RIGHT VENTRICULAR FAILURE ( IPAH like ! )
PROGRESSION OF PAH
AGENTS
CRITERIA
100% OXYGEN (10 mts)
↓Rp /Rs > 20%
NITRIC OXIDE (10-80ppm)
Rp:Rs < 0.33
02 + N.O (Se 97% Sp 90%)
Rp < 8 u.m2
ADENOSINE (50-500µg/kg/mt)
EPOPROSTENOL (2-10 ng/kg/mt)
ILOPROST (2.5-5.0 µg )
ASSESSING OPERABILITY BASED ON PVR
MISTAKES & MISCONCEPTIONS
22 to
44%
40
to
60%
60 to
100%
Expecting PAP to decline ( ↓ PVR > ↑ FLOW )
Assuming O2 consumption
Ignoring dissolved O2 in calculating PVR
O2 sat x 1.36 x Hb =
60 x 1.36 x 12 = 98 ml/L ( 0.03 x 55 = 1.7ml )
98 x 1.36 x 12 = 160 ml/L ( 0.03 x 95 = 2.9ml )
PVR = 60 – 8 = 52 / 3.2 = 16 units ( 16.5 units )
After 100% oxygen : 72 x 1.36 x 12 = 118 ml/L ( 0.03 x 100 = 3 ml )
98 x 1.36 x 12 = 160 ml/L ( 0.03 x 500 = 15 ml)
PVR = 55 – 8 = 47 / 4.8 = 9.8 units ( 12.7 units )
PVR INDEXED TO BODY SURFACE AREA
A child of BSA of 0.5 m2 has a PBF of 2 l/mt
PA mean pressure = 20 mmHg ; mean LAP = 8
mmHg
PVR absolute value = 20-8/2 = 6 units
If corrected for BSA = 6/0.5 = 12 units
PBF corrected to BSA = 2/0.5 = 4
l/mt/m2
PVR indexed to BSA = 20-8/4 = 3 u.m2
ROLE OF ECHOCARDIOGRAPHY
• Qp/Qs by doppler, PAcT not reliable
• PA peak velocity > 1.0 m/s predictive
• PVR = TR Velocity/ TVI RVOT x 10 + 0.16
• Vp > 18 cm/s = PVR < 6 units
4 WU
8.8 W.U
12.4
cm/s
16.4 W.U
23.1 cm/s
PULMONARY
WEDGE
ANGIO
PREDICTION OF PVOD
Wilson NJ CCVD 1993;28:22
PREDICTING HEATH EDWARDS Grade III - IV
Sensitivity
Specificity
PVR > 6 units
100%
94%
Monopedial count<3 83%
100%
Abnormal blush
83%
69%
Combination of all
100%
100%
LUNG BIOPSY
MORPHOMETRIC GRADING
Rabinovitch M
Grade A : Extension of muscle into small peripheral arteries
Wall thickness increased but < 1.5 times the normal
↑ PBF ↑ PA PP + NORMAL MEAN PAP
Grade B : Mild : medial thickness 1.5 – 2.0 times the normal
Severe : medial thickness > 2 times the normal
PAH - MEAN PAP > 50 % OF SYSTEMIC LEVEL
Grade C : Size and number of arteries reduced
PAH - PVR > 3.5 - 6.0 u.m2
CARDIAC MR
 DEFECT SIZE & LOCATION
 PA SIZE ↑ WITH PAH
 RV FUNCTION
 Qp/Qs RATIO Phase contrast
velocity mapping
 MR OXIMETRY ( T2 relaxation
time)
 DEGREE OF PAH
BALLOON OCCLUSION IN HYPERTENSIVE DUCTUS
Roy A IHJ 2005;57:332
Fall in
m/d PAP
> 20
mmHg
TRIAL OCCLUSION OF PDA
Yan C Heart 2007;93:514
Trial occlusion for 30 mts with ADO
Reduction of mPAP 78 ± 19.3 to 41 ± 13.8 mm Hg
FU for 3 to 6 months – clinical improvement
PAH IN ATRIAL SEPTAL DEFECT
• 6% ( Mayo clinic); 9% - half were below 20 yrs(CMC)
• PAH (mPAP>30 mmHg) 26% SVC (9% FO)
↑PVR 16% SVC (4% FO ) ; at younger age
• 85 % were women ( overall F:M = 2:1 )
• PVR > 15 units do poorly – death / progression of PAH
• PVR < 10 units do well with surgery
• PVR 10 – 15 units – if SPO2 is < 90% surgery not useful
DEVICE CLOSURE IN ASD + PAH
Balint OH Heart 2008;94:1189
PAH Moderate Severe
PASP 50-59
>60
At 3 m
PASP ↓ 57± 11 to 51±17
At 3 yrs
PASP ↓ to 44 ±16
Only in 43.6% PAP
normalised
15.4% had persistent
severe PAH
EISENMENGER’S SYNDROME
MANAGEMENT
 Avoid
dehydration, livingISSUES
at high altitude
 Air travel safe (supplemental O2)
 Avoid pregnancy ( No OCP – tubal
ligation/vasectomy)
 Treat Iron deficiency ( MCV < 82 ) ; hyperuricemia
 Vensection for hyperviscosity syndrome
 Antiplatelet / Anticoagulants ?
 Disease targeting therapies : Prostacyclin &
analogues, sildenafil, bosentan
 Surgery: Correction after PA banding, prolonged
vasodilator therapy, Heart Lung Transplant
Management of the patient with the Eisenmenger syndrome and erythrocytosis
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
Causes of and Therapy for Hemoptysis in Patients with the Eisenmenger
Syndrome
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
BOSENTAN IN CHD + PAH
Diller GP Heart 2007;93:974
BOSENTAN IN CHD + PAH
2007;93:621
Alto MD, Heart
PROGNOSIS
EISENMENGER SYNDROME ~ IPH
ACTUARIAL
SURVIVAL
1 yr
2 yr
3 yr
E.S
97 %
89 %
77 %
IPAH
77 %
69 %
35 %
MORPHOMETRIC GRADING
Rabinovitch M
Grade A : Extension of muscle into small peripheral arteries
Wall thickness increased but < 1.5 times the normal
↑ PBF ↑ PA PP + NORMAL MEAN PAP
Grade B : Mild : medial thickness 1.5 – 2.0 times the normal
Severe : medial thickness > 2 times the normal
PAH - MEAN PAP > 50 % OF SYSTEMIC LEVEL
Grade C : Size and number of arteries reduced
PAH - PVR > 3.5 - 6.0 u.m2
Pooled Data from Studies of Pregnant Patients with the Eisenmenger
Syndrome*
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
VENTRICULAR SEPTAL DEFECT
PATENT DUCTUS ARTERIOSUS