Download - PULMONARY HYPERTENSION
Prof. S. Shanmuga SundaramK.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%
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
Complications associated with the Eisenmenger syndrome
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 LESIONSmPAP > 25 mmHg at rest / > 30 mm Hg post exercisePAWP < 15 mm Hg ; PVR > 3 Wood Units• TRANSMISSION OF SYSTEMIC ARTERIAL PRESSURE • VASOCONSTRICTION• VASCULAR OBLITERATION – MEDIAL HYPERTROPHY INTIMAL
PROLIF + FIBROSIS ARTERIAL
THROMBI
HYPERKINETIC OBLITERATIVE
PVR < 5 W.U > 5 W.U
PA PP/PA SP > 60% < 40%
ASD VSD PDA CA, APVC TGA VSD, DORV APWINDOW 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 SHUNTSNONRESTRICTIVE VSD = 15 % < 2 yrs of life
MODERATE DEFECTS = 3% ; LARGE DEFECTS (1.5cm) = 50%
LARGE PDA = similar incidenceLARGE ASD = 6-10% > 3rd
decade Frequent in SVC, partial AV Canal defects & in
Lutembacher’sTGA = 8% (intact IVS ) 40% ( VSD/PDA ) < 1 yr 75% at 2 yrsCOMMON AV CANAL all develop PAHTRUNCUS ARTERIOSUS by 1-2 yrsSYSTEMIC - PA SHUNTS: BT Shunt (<10%) Waterston / Pott’s ~
30%
MECHANISMS OF PAH IN L>R SHUNTS LESION ↑Qp ↑PAP ↑PVP ↓ pH
↑ Ht ASD + - - -
- VSD + + + -
- PDA + + + -
- AV CANAL + + ++ -
- TGA, TA + + +
+ +
PLATELET ADHESION + THROMBUS
ENDOTHELIAL DYSFUNCTION↑ ET, TXA2 , SEROTONIN ↓
NO ,PGI2,VIP
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 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 PAH - MEAN PAP > 50 % OF
SYSTEMIC LEVELSYSTEMIC LEVEL Grade C : Size and number of arteries reduced PAH - PVR > 3.5 - 6.0 u.m2PAH - 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 SYNDROMESYMPTOMS:
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 SYNDROMESIGNS : 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 VSD PDA
Neonatal HF - + + Age 30-40 2-12 2-12
Syncope ± ± -
Cyanosis Uniform Uniform Differential
Cardiomegaly,PSH + - - Wide pulse pressure - - ± Prominent ‘a’ JVP + -
- S2 split Fixed Single Normal Long PR murmur - - +
PDA
DOPPLER
PATTERNS
PAH
PULSATILE CLOSING CLOSED
GROWING
DOPPLER IN PDA
SHUNT LESIONS - OPERABILITY
Qp : Qs = > 2:1 No or mild PAHQp : 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
Expecting PAP to decline ( ↓ PVR > ↑ FLOW )Assuming O2 consumptionIgnoring 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 )
22 to
44%40 to60%
60 to 100%
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
12.4 cm/s
23.1 cm/s
4 WU8.8 W.U
16.4 W.U
PULMONARY WEDGEANGIO
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 BIOPSYMORPHOMETRIC 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 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 PAH - MEAN PAP > 50 % OF
SYSTEMIC LEVELSYSTEMIC LEVEL Grade C : Size and number of arteries reduced PAH - PVR > 3.5 - 6.0 u.m2PAH - PVR > 3.5 - 6.0 u.m2
CARDIAC MRDEFECT SIZE &
LOCATIONPA SIZE ↑ WITH PAHRV FUNCTIONQp/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 SYNDROMEMANAGEMENT ISSUESAvoid dehydration, living at high altitude
Air travel safe (supplemental O2) Avoid pregnancy ( No OCP – tubal
ligation/vasectomy)Treat Iron deficiency ( MCV < 82 ) ;
hyperuricemiaVensection for hyperviscosity syndromeAntiplatelet / Anticoagulants ?Disease targeting therapies : Prostacyclin &
analogues, sildenafil, bosentanSurgery: Correction after PA banding,
prolonged vasodilator therapy, Heart Lung Transplant
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
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
BOSENTAN IN CHD + PAH Diller GP Heart 2007;93:974
BOSENTAN IN CHD + PAH Alto MD, Heart
2007;93:621
PROGNOSIS EISENMENGER SYNDROME ~ IPH
ACTUARIAL
SURVIVAL
E.S IPAH
1 yr 97 % 77 %
2 yr 89 % 69 %
3 yr 77 % 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 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 PAH - MEAN PAP > 50 % OF
SYSTEMIC LEVELSYSTEMIC LEVEL Grade C : Size and number of arteries reduced PAH - PVR > 3.5 - 6.0 u.m2PAH - PVR > 3.5 - 6.0 u.m2
Vongpatanasin, W. et. al. Ann Intern Med 1998;128:745-755
Pooled Data from Studies of Pregnant Patients with the Eisenmenger Syndrome*
VENTRICULAR SEPTAL DEFECT
PATENT DUCTUS ARTERIOSUS