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