This document provides information on Eisenmenger syndrome (ES), including its etiology, pathophysiology, natural history, clinical features, and management. ES is defined as severe pulmonary hypertension developing as a consequence of a large pre-existing left-to-right shunt that has reversed flow or become bidirectional. The causes of ES include simple defects like atrial septal defects (ASDs) or complex defects. Clinical features include fatigue, syncope, chest pain, stroke, and sudden cardiac death. Management focuses on treating secondary erythrocytosis, thrombotic diathesis, hemoptysis, arrhythmias, and using targeted therapies like endothelin receptor antagonists, phosphodiesterase 5 inhibitors, prost

1. EISENMENGER SYNDROME (ES)
Preceptor :- Dr Asst. Prof B.K.DASH
Presented by – Dr Vedprakash Verma

2. ETIOLOGY,PATHOPHYSIOLOGY
NATURAL HISTORY OF EISENMENGER
SYNDROME
CLINICAL FEATURES
MANAGEMENT

3. Eisenmenger syndrome (ES)
Victor Eisenmenger (1897)- First described ES. Austrian
physician

4. Mr PAUlWOOD
He was born in Coonoor . Studied in Australia . But
celebrated as the Gale force of British Cardiology

5. What is Eisenmenger syndrome?
• Defined as pulmonary vascular obstructive disease that
develops as a consequence of a large pre-existing left-to-right
shunt due to High PVR with reversal or bidirectional shunt.
• Hemodynamically ES is defined as an elevation of the PVR
to > 10 Wood units or
• PVR/SVR ratio equal to or greater than 1.0.

6. • Eisenmenger Reaction- It is the gradual proces of development
of pulmonary hypertension & PVR in a large left to right shunt
lesion sooner or later leading to bidirectional shunt or reversal of
shunt
• Eisenmenger’s complex- VSD with reversed shunt in the absence
of PS. Term coined by MAUDE ABOTT (1927)
• Eisenmengers syndrome- Includes all defects.

7. Causes of ES
1. SIMPLE :
• PRETRICUSPID- ASD/TAPVC/PAPVC
• POST TRICUSPID- VSD/PDA/AP WINDOW
2. COMPLEX :
• VENTRICULAR-SINGLE VENTRICLE,DORV
• GREAT VESSELS-TRUNCUS ARTERIOSUS
• D-TGA
3. POST PALLIATION SURGERY :
• WATERSTON SHUNT
• POTTS SHUNT

8. CAUSES AND FREQUENCY OF ES (PAUL WOOD SERIES)

9. INDIAN DATA FROM SRI CHITRA 1972-1992

12. Clinical classification of congenital systemic-to-pulmonary shunts
associated to pulmonary arterial hypertension
4 subsets
NICE / Dana point classification

14. CLINICAL FEATURES OF ES
CLINICAL FEATURES DUE TO
FATIGUE LOW/FIXED CARDIAC OUTPUT
SYNCOPE ARRHYTHMIA/LOW CO
CHEST PAIN RV ISCHEMIA
STROKE PARADOXICAL EMBOLISM/
ICH/
THROMBOSIS
PALPITATIONS ARRHYTHMIA
SUDDEN CARDIAC DEATH ARRHYTHMIA

15. SHUNT ESTABLISHED AT PRESENTATION AT
PDA >2 YRS 19 YRS
VSD >2 YRS 22 YRS
ASD >20 35 YRS
AVSD MUCH EARLIER
COMPARATIVE ANALYSIS

16. • Pretricuspid lesion :
• Soon after birth, shunting of low pressure blood occurs into the non compliant
neonatal RV.
• Low pressure shunt flow at rest is not sufficient to maintain the pulmonary
pressure at systemic level.
• PVR falls to normal before the relatively slow involution of the right ventricle
after birth.
• So after RV involution L→ R shunted high volume blood now actually goes into
a low resistance compliant pulmonary circulation, and does not promote
hypertensive changes till late in life.
• Once the PVR falls appreciably, much larger flows are necessary to maintain
high pulmonary pressure.

17. • Post tricuspid lesion :
• Soon after birth , direct shunting of blood at systemic arterial pressure before
neonatal PAH has regressed.
• Lowering of PVR to normal is prevented by a sufficient increase of flow to keep
the pressure at systemic level.
• So long as pulmonary hypertension is maintained, vasoconstrictor tone is not
inhibited and the muscular pulmonary arteries do not involute.
• This Not only delays the natural fall in pulmonary vascular resistance,
• But also promotes hypertensive changes.

18. ASD VSD PDA
ANGINA + + +
SYNCOPE + + +
HEMOPTYSIS + ++ ++
HEART FAILURE ++ + +
SQUATTING - + -
COMPARATIVE ANALYSIS

19. • NATURAL HISTORY
• In the absence of complications, these patients generally have a good
functional capacity up to their third decade and thereafter usually experience
a slowly progressive decline in their physical abilities.
>Most patients survive to adulthood, with reported survival rates of 77% at 15
years of age and 42% at 25 years of age.
>Congestive heart failure in patients with Eisenmenger syndrome usually occurs
after 40 years of age.
>The most common modes of death are
• sudden death (≈30%),
• congestive heart failure (≈25%), and
• pulmonary hemorrhage/Hemoptysis (≈15%).
• Pregnancy, perioperative death at the time of noncardiac surgery, and
infectious causes (brain abscesses and endocarditis) account for most of the
remainder.
• Hemoptysis is usually due to bleeding bronchial vessels or pulmonary
infarction.
Physical examination reveals central cyanosis and clubbing of the nail beds

21. Pregnancy carries 30-50%
maternal mortality (commonly
due to):

22. ASD VSD PDA
GENDER RATIO
(F:M)
3:1 1:1 2:1
PRESENTATION 3RD DECADE 2ND DECADE 2ND DECADE
CYANOSIS UNIFORM UNIFORM DIFFERENTIAL
JVP
VERY PROMINANT
A/V
PROMINANT A/V PROMINANT A/V
CARDIOMEGALY
GROSS
CARDIOMEGALY
NORMAL NORMAL
LT PS HEAVE PROMINANT PRESENT PRESENT
S2 WIDE & FIXED MOSTLY SINGLE
CLOSELY
SPLIT/SINGLE
TR MURMUR PROMINANT LESS LESS
ESM (LT 2ND ICS) 80 % 80 % 80 %
EDM (PR) 50 % 50 % 50 %
COMPARATIVE ANALYSIS

23. COMPARATIVE ANALYSIS ECG
ASD VSD PDA
RAE 50 % 50 % 50 %
RAD + + +
RVH + + +
q R IN V1 25 % - -
SV ARRHYTHMIAS + - -

24. COMPARATIVE ANALYSIS CXR
ASD VSD PDA
CARDIOMEGALY + - -
LARGE MPA + + +
RDPA ++ + +
DUCTAL
CALCIFICATION - - +
AORTA SMALL NORMAL LARGE

25. • Chest Radiography.
• Chest radiography shows dilated central pulmonary arteries with rapid tapering
of the peripheral pulmonary vasculature (the radiographic hallmarks of
Eisenmenger syndrome).
• Pulmonary artery calcification may be seen and is diagnostic of long-standing
pulmonary hypertension.
• Eisenmenger syndrome due to an ASD typically has a large cardiothoracic ratio
because of right atrial and ventricular dilation.

26. VSD ES vs ASD ES

27. • Echocardiography.
• The intracardiac defect should be seen readily, along with bidirectional shunting.
• Evidence of pulmonary hypertension is found.
• Assessment of right ventricular function adds prognostic value.

28. • Cardiac Catheterization.
• Cardiac catheterization not only provides direct measurement of the
pulmonary artery pressure, documenting the existence of severe pulmonary
hypertension, but can also allow assessment of the reactivity of the pulmonary
vasculature.
• Administration of pulmonary arterial vasodilators (O2, nitric oxide,
prostaglandin I2 [epoprostenol]) can determine which patients have
contraindications to surgical repair and which patients have reversible
pulmonary hypertension and may benefit from surgical or even catheter repair.

29. • Open-Lung Biopsy.
• Open-lung biopsy is seldom used in the current era, and should be considered
only when reversibility of the pulmonary hypertension is uncertain from the
hemodynamic data.
• An expert opinion will be necessary to determine the severity of the changes,
often using the Heath-Edwards classification.

30. • MANAGEMENT
• Secondary erythrocytosis-
No place for routine venesections
In patients with hemoglobin >22 g/dL and hematocrit >65% presenting
with severe hyperviscosity symptoms in the absence of dehydration
At small volumes (250-500 mL) with simultaneous fluid replacement to
avoid hemodynamic imbalance .
Iron deficiency
• Transferrin saturation <20% is the best marker & peripheral microcytosis
Oral iron supplementation
Intravenous supplementation (Administer at a slow rate).
• Thrombotic diathesis
Oral anticoagulation should be recommended only in cases of atrial arrythmia and
in the presence of PA thrombus or emboli.
Vitamin K antagonists remain the oral anticoagulants of choice pending
safety and efficacy data on direct oral anticoagulants

31. • Hemoptysis
• Anticoagulation is not recommended in patients with active or recurrent
hemoptysis & Supportive treatment to be given
Manage concomitant respiratory tract infections, suppress coughing,
reduce physical activity, treat hypovolemia and (relative) anemia
CTPA to determine the presence and location/origin of intrapulmonary
hemorrhage
• Coil embolization of causative bronchial arteries in selected patients
Inhaled tranexamic acid may be considered
• Arrhythmias
Prompt restoration and maintenance of sinus rhythm recommended
Catheter ablation in specialized centers may be considered in patients with
intractable arrhythmia
ICD may be considered for secondary prevention of sudden cardiac death

32. • OPERABLE / INOPERABLE ?
• BASELINE VALUES –
• QP/QS >1.5/1
• PVR < 4 WOOD
• PVR/SVR<0.3
• ON THE BASIS OF PVR
• PVR <4 WOOD – OPERABLE
• PVR >8 WOOD–INOPERABLE
• PVR 4-8 WOOD - INDIVIDUALIZE
MANAGEMENT

48. • TARGETED THERAPY

50. • Endothelin receptor antagonists )ERA):
• Ambrisentan, Bosentan, Macitentan
• BOSENTAN
• Competitive antagonist of endothelin-1;
• Blocks endothelin receptors on vascular endothelium and smooth muscle
resulting in inhibition of vasoconstriction
• BREATH-5 trial showed improved hemodynamics, exercise capacity & functional
class.
• Ambrisentan & Sitaxentan are also used but evidence is less.
• Bosentan (non selevtive)-1Mg/Kg twice daily
• Ambrisentan (selective)- 5 Mg once daily

51. • PHOSPHODIESTERASE 5 INHIBITORS (PDE5-I) :
• Inhibits PDE-5, increasing cyclic guanosine monophosphate cGMP to allow
smooth-muscle relaxation.
• Reduces PVR, Mean PA pressre, Improves 6MWD,SpO2
• Sildenafil & Tadalafil.
• STARTS 1 study showed improved functional class and hemodynamics with
medium to high doses OF SILDENAFIL.
• STARTS 2 showed decreased survival with high dose of sildenafil.
• Sildenafil-0.2- 0.3 mg/kg P.O in 6-8 hrly
• IV-2.5-10 mg bolus TID
• Tadalafil- 40mg daily (adult)

52. • Prostanoids
• PGI2 and its analogues bind the IP receptor on the cell surface membrane.
Once engaged, the IP receptor couples the G-protein Gs and activates adenylyl
cyclase, producing cyclic adenosine monophosphate (cAMP) and leading to
relaxation in smooth muscle cells and antithrombosis in platelets.
• Beyond vasodilation, PGI2 also has proapoptotic properties via
the IP receptor
• Epoprostenol, a synthetic prostacyclin, and iloprost and treprostinil, synthetic
prostacyclin analogues, are currently used to treat patients with Eisenmenger
Syndrome.
• Continuous i.v. infusion of prostacyclin, continuous s.c. infusion of treprostinil,
p.o. application of beraprost, and inhaled application of iloprost.
• 0.25 ng/kg/min for inhaled iloprost
• 30–50 ng/kg/min for i.v. prostacyclin.
• 60 mcg/day in 3 divides doses of oral Beraprost

53. • Soluble guanylate cyclase (sGC) stimulators
• Riociguat sensitizes sGC to endogenous NO, and it directly stimulates sGC
receptors independent of NO availability, resulting in vasorelaxation and
antiproliferative effects.
• Riociguat significantly reduced PVR, mean pulmonary arterial pressure, systolic
blood pressure, and systemic vascular resistance in addition to increasing the
cardiac index in a dose-dependent manner.
• Doses of 1 mg or 2.5 mg tid p.o

54. • IP Receptor Agonists
• The novel oral IP receptor agonist selexipag was tested in the multicenter
GRIPHON study of patients who were either treatment naïve or on stable
background therapy of an ERA, PDE-5i, or both.
• It demonstrated a 40% reduction in a composite endpoint of death or
worsening PAH for selexipag versus placebo.

56. THANKS !!!