1. Eisenmenger Syndrome Anita Saxena Department of Cardiology,
All India Institute of Medical Sciences
New Delhi, India

2. Eisenmenger Syndrome
1887 : Victor Eisenmenger described history and postmortem details of 32 year old man with VSD and pathological features of PAH

3. Eisenmenger Syndrome
1958: Paul Wood’s Croonian Lectures coined the term “Eisenmenger Syndrome”

4. Eisenmenger Syndrome Definition:
Pulmonary hypertension at or near systemic level with reversed or bidirectional shunt between the pulmonary and systemic circulation and pulmonary vascular resistance above 800dyn/cm-5 (10 Wood Units)
Paul Wood, Br Med J, 1958

5. Eisenmenger Syndrome Underlying Basic Lesions
Type of lesion Somerville ‘98 Daliento et al ‘98
(n=132) (n=188)
Ventricular Septal Defect
Atrial Septal Defect
Patent ductus arteriosus
Atrio ventricular septal defect
Truncus arteriosus
Single ventricle
Transposition of great arteries 5 8
Others

6. Eisenmenger Syndrome – A progressive disease

7. Exact mechanism not clear
Eisenmenger Syndrome
Mechanism of abnormal pulm vascular response
Stimulation of insulin like growth factor
Impaired relaxation of pulmonary arterioles
Increased endothelin production
Elevated plasma thromboxane B2
Exact mechanism not clear

8. Pulmonary Arterial Hypertension
Hyperkinetic Obstructive
(Eisenmenger’s)
Heart Size Large Normal
Parasternal
impulse Hyperkinetic Forcible
Click Absent Present
S2 ASD wide & fixed wide & fixed
VSD wide & variable Single
PDA paradoxic split normal split
Shunt murmur present short/absent
Flow murmur Present Absent

10. At what age a large VSD Eisenmengerize?1
Question 1
At what age a large VSD Eisenmengerize?
< 6 months
2 years
10 years
20 years

11. Eisenmenger Syndrome Clinical Groups
Cyanosis since birth: TGA, Truncus, Univentricular hearts
Failure to thrive in infancy – A settled phase – Symptomatic adolescent: Large VSD, PDA, AVSD
Insidious presentation: AP Window

12. Eisenmenger Syndrome Clinical Evaluation
History of symptoms of L R shunt in infancy
Cyanosis, erythrocytosis, headache
Mildly symptomatic with dyspnoea, fatigue
History of syncope, hemoptysis,CVA

13. Question 2
ES - Underlying CHD
Which one of the following clinical sign is unlikely in VSD ES (uncomplicated)
Single S2
Palpable second sound
Cardiomegaly
Absent parasternal heave

14. Eisenmenger’s Physiology: Clinical Assessment
Cyanosis: generally mild
Absence of cardiomegaly, heart failure
Minimal left parasternal lift
Constant ejection click of PAH
Absence of significant shunt murmurs
Pulmonary regurgitation murmur may be audible

15. ES: Underlying CHD Characteristic VSD PDA ASD Usual age of ES
< 2 years
20 – 40 years
Differential Cyanosis -
Yes (50%)
Cardiomegaly
Yes
Second H S (S2)
Single
Narrow/normal
Wide & fixed
Parasternal heave
TR murmur
PR murmur

16. Noninvasive Assessment

18. Eisenmenger Syndrome Noninvasive Evaluation
Echocardiography is very useful
Defines the large defect (PDA may be difficult)
Estimates PA pressure by TR/PR jets
Contrast echo demonstrates R L shunting
TEE is safe and may be required in adults for precise delineation of the abnormality

19. Eisenmenger Syndrome: Invasive Evaluation
Cardiac cath can be safely performed
It must be done in borderline cases to assess operability
Response of pulmonary vasculature to pulmonary vasodilators like 02, tolazoline and nitric oxide should be assessed
Limit the use of contrast agent to minimal

20. Eisenmenger Syndrome: Natural history
Question 4
Eisenmenger Syndrome: Natural history
Identify the false statement
Prognosis of ES is good
Survival better than IPAH
With recent advances, pregnancy better tolerated
Heart failure most common cause of death

21. Eisenmenger Syndrome Natural History
Life expectancy reduced by about 20 years
Survival Pattern:
At one year 97%
At 5 years 87%
At 10 years 80%
At 15 years 77%
At 25 years %

22. 22

23. Policy of “non-intervention”, unless absolutely necessary
Life expectancy reduced by about 20 years
Unwarranted surgical closure hastens death
Policy of “non-intervention”, unless absolutely necessary
Avoid destabilizing the “balanced physiology”

24. ES – Survival better than IPAH

25. Landzberg, M. J. et al. J Am Coll Cardiol 2006;47:D33-D36
Impact of left ventricular dysfunction on survival in Eisenmenger syndrome
Landzberg, M. J. et al. J Am Coll Cardiol 2006;47:D33-D36

26. Cumulative mortality rate curve (with 95% CIs)
Overall population (n=229)
According to functional class
Dimopoulos, K. et al. Circulation 2010;121:20-25

27. Long Term Survival in Eisenmenger physiology
Survival prospects of patients with Eisenmenger physiology when compared with an age- and gender-matched healthy population showing reduced life expectancy in patients with Eisenmenger syndrome. The survival curve appears to be shifted leftwards by ∼20 years in patients with simple underlying lesions and ∼40 years in those with complex lesions. †Predicted survival is based on the life tables for UK and Wales (2001–2003 interim life tables) published by the Government Actuary's Department. *Comparison between Eisenmenger patients with simple and complex lesions. Patients with complex lesions had a significantly worse outcome compared with those with simple lesions.
Diller G et al. Eur Heart J 2006;27:

28. Eisenmenger Syndrome Predictors of Poor outcome History of syncope
Elevated right heart filling pressure
Severe hypoxemia (Sa02<85%)
Lange RA et al, 1998

29. Eisenmenger’s
Syndrome
Is Preventable

30. Eisenmenger Syndrome Management Strategies
Drug treatment
Phlebotomy
Transplantation : Heart lung / lung
Counsel against special risks
Pregnancy
Hormone contraceptives
Noncardiac surgery
High altitude/flying
Sudden emotional upset 30

31. Conventional Therapy Digitalis, diuretics Anti-arrhythmic drugs
Anticoagulants
Long term oxygen therapy
Avoidance of dehydration, high altitude, infections and IV lines
Avoidance of pregnancy

32. Targeted Therapy: Pulmonary Vasodilators
Prostanoids: Epoprostenol infusion
Phosphodiesterase-5 inhibitors: Sildenafil, tadalafil
Endothelin receptor antagonists: Bosentan (BREATH-5 trial)
Fernandes SM, et al 2003
Chou EM, et al 2007
Mukhopadhyay S, et al 2006
Galie N, et al 2006
Gatzoulis MA, et al 2008

33. Survival in Eisenmenger Syndrome Patients on Advanced Therapy (n=287)
Dimopoulos, K. et al. Circulation 2010;121:20-25

34. Bosentan in ES

35. Bosentan in ES: BREATH 5
Gatzoulis MA, Int J Cardio 2008

36. Eisenmenger Syndrome: Role of Phlebotomy
Indication for Isovolumic Phlebotomy
Symptomatic hyper viscosity (PCV >0.65, Hb>20gm%)
Important issues to remember
Symptoms of hyper viscosity resemble those of iron deficiency
Phlebotomy may result in iron deficiency anemia and cerebrovascular accidents
Discourage routine phlebotomy

37. Management of Eisenmenger Syndrome
Transplantation
1982 : Combined heart-lung transplantation
introduced by Reitz et al
1990 : Single lung transplantation with repair of
cardiac defect successfully performed by
Fremes et al
Lung transplant has advantages of
better donor availability
Avoidance of cardiac allograft rejection
Absence of coronary vasculopathy

38. Management of Eisenmenger Syndrome
Lung Transplantation
Actuarial survival rates : At 1 year 70-80%,
At 4 years <50%, At 10 years <30%
Indications for transplant
History of syncope
Refractory right heart failure
Poor exercise tolerance
Severe hypoxemia

39. Perioperative Risk for Noncardiac Surgery
High risk conditions
Pulm hypertension
Cyanotic CHD
NYHA class III or IV
Severe ventricular dysfuntion (EF<35%)
Severe left heart obstructive obstruction
Moderate risk conditions
Intracardiac shunt lesions
ACC/AHA guidelines 2008

40. Perioperative Risk for Noncardiac Surgery in Eisenmenger Syndrome
Associated with a mortality rate of 14% -19%
Local anesthesia is preferred to general anesthesia
Prolonged fasting and volume depletion should be avoided
Small air bubbles in IV lines should be removed
Early ambulation is encouraged
Antibodies given to prevent infective endocarditis

41. Pregnancy and congenital heart disease
Risk to Fetus: if Sao2 < 85%, chances of live fetus only 12%
Caesarian section only for obstetric reasons

42. Complications During Pregnancy in Women with CHD
Drenthen W, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007;49:

43. Complications During Pregnancy in Women with CHD
Drenthen W, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007;49:

44. Management of Eisenmenger Syndrome
Avoidance of Pregnancy
Pregnancy is absolutely contraindicated
Maternal mortality is 36%-45%
Mortality often occurs in post-partum period
Fetal loss occurs in over 60%
Termination is indicated in early gestation
Outcome of pregnant women with Eisenmenger syndrome has not changed in last three decades

45. Eisenmenger Syndrome Management of Pregnancy
Prolonged bed rest after 20th wks gestation
Oxygen therapy
Digoxin and diuretics if CHF present
Prolonged use of anticoagulants - Heparin
Careful monitoring of volume status, oxygen saturation and hematocrit is necessary

46. Eisenmenger Syndrome Basic Events Leading to Death
Right ventricular failure 30%
Sudden death?vent arrhythmia 25%
Cardiovascular surgery %
Cerebrovascular accidents/abscess 10%
Hemoptysis %
Noncardiac surgery 6%
Pregnancy related 5%
Heart lung/lung transplants 4%

47. Carefully managed, most patients lead useful lives
Eisenmenger Syndrome
Is generally established by 2-4 yrs of age
Accelerated onset in Down’s, Cyanotic CHD
Median survival is yrs of age
Anesthesia, surgery, dehydration poorly tolerated
Pregnancy carries 30-50% maternal mortality
Closure of the defect is detrimental once obstructive PAH has developed
Carefully managed, most patients lead useful lives

48. “Doing nothing may be a positive action for
Eisenmenger Syndrome
Conclusion
Patients with Eisenmenger syndrome can live upto fifth and sixth decades with informed medical care, patient education and protection from special risks
20% of death are related to avoidable errors
“Doing nothing may be a positive action for
good in such patients”
Jane Somerville, 1998