Eisenmenger Syndrome

1
Eisenmenger Syndrome

• Presented by Ri ???

2
Outline of Presentation

• Eisenmenger syndrome introduction
• Definition, manifestation, natural courses,
  diagnosis, differential, diagnostic tests
• Prognostic factors, especially for corrective
  surgery
• Intervention medical and surgical
• Management of complications

3
Eisenmenger Syndrome

• Definition
• Pulmonary vascular obstructive disease that
  develops as a consequence of a large preexisting
  left-to-right shunt that pulmonary artery
  pressures approach systemic levels and the
  direction of the flow becomes bidirectional or
  right to left.

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 - 1616
4
Eisenmenger SyndromePathophysiology
Heath-Edwards Classifications Circulation
195818533-47 Grade I Arteriolar medial
hypertrophy Grade II Intimal proliferation Grade
III intimal fibrosis, occlusion Grade IV
Plexiform lesions Grade V Hemosiderin-filled
macrophage Grade VI Necrotizing arteritis
Ann Intern Med 1998 128 745-755
5
NEJM 2000 342(5) 334-342
6
Eisenmenger Syndrome

• Precipitating congenital heart diseases
• Ventricular septal defect
• Atrial septal defect
• Patent ductus arteriosis
• Atrio-ventricular septal defect
• Truncus arteriosus
• Aortopulmonary window
• Univentricular heart
• D-transposition of the great vessels
• Surgically created aorto-pulmonary connections

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
7
Eisenmenger SyndromeClinical Manifestations

• Right to left shunt
• Cyanosis (general or differential)
• Low cardiac output, congestive heart failure
• Exertional dyspnea, fatigue, syncope, orthopnea,
  PND, peripheral edema
• Neurologic symptoms (hyperviscosity)
• Headache, dizziness, Congestive heart failure
• Others
• Hemoptysis, arthralgia, gout, renal dysfunctions

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
8
Eisenmenger SyndromeNatural course and prognosis

• Age second or third decade of age
• Factors determining the likelihoods of
  Eisenmenger syndrome
• Size and location of heart defects
• PDA, VSD early onset (80 in childhood)
• ASD delay onset (80 in adulthood)
• The rate of survival
• 10 years 80
• 15 years 77
• 25 years 42
• Poor prognostic factors
• High pulmonary artery resistance
• Syncope
• Elevated right heart filling pressure
• Severe hypoxemia
• NOT influenced by types of heart defects

Ann Intern Med 1998 128 745-755 NEJM 1993
329864-872
9
Eisenmenger SyndromeCauses of death

• Sudden death (30)
• Congestive heart failure (25)
• Hemoptysis (15)
• Pregnancy
• Perioperative mortality of non-cardiac surgery
• Infectious diseases

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
10
Eisenmenger SyndromeDiagnostic Testing

• Goals
• For the diagnosis of heart defect
• For evaluating the severity
• For stratification, predictable prognostic
  factors? For surgery?
• Choices
• Electrocardiography
• RAE, RVH, right axis deviation, arrhythmia
• Chest X ray
• Cardiomegaly, dilated pulmonary arteries,
  pulmonary artery calcification
• Echocardiography TEE is preferred
• Heart defect, direction of shunting, pulmonary
  hypertension
• Cardiac catheterization
• Open lung biopsy

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
11
Eisenmenger SyndromeCardiac catheterization

• Goals to detect, localize, and quantitate
  intracardiac shunting and to determine the
  severity of pulmonary vascular disease
• What can we measure?
• Qp / Qs
• Rp / Rs
• Pulmonary arteriolar vasodilator in cardiac
  catheterization
• What we want to know? ? reversibility
• Agents 100 oxygen, nitric oxide, tolazoline,
  adenosine triphosphate, prostacyclin
• 100 O2 Circulation 19592066-73 / NEJM 1993
  329(12)864-872
• A fall to less than 80 of base line 80
  survival after surgery
• Remain higher than 80 27 survival after
  surgery
• Nitric oxide Am J Cardiol. 199677532-5
• ATP Circulation. 1994901287-93
• NO and ATP Cut point? Prognosis? Difficult to
  intervention
• Contrast media should be avoided
• It may cause hypotension, which could be lethal
  in these patients

12
Eisenmenger Syndrome Cardiac catheterization

• Cautions NEJM 1993 329(12)864-872
• Oxygen consumption should be measured directly
  rather than assumed
• Agitated patient ? systemic blood pressure higher
  than before
• polycythemia can independently elevate resistance
  due to an increase in viscosity
• In infant, Hct 50 -gt 40 viscosity decrease 30
• Measure the blood pressure and partial pressure
  of oxygen completely, before and after the
  administration of vesodilators.

13
Eisenmenger SyndromeSurgical Criteria ASD

• Qp/Qs gt 1.5
• Rp/Rs lt 0.7 (or 2/3, or 0.5)
• Rp/Rs gt 2/3, but Qp/Qs gt 1.5, significant
  left-to-right shunt, reversibility(), lung
  biopsy?
• Pulmonary vascular resistance lt 10 (or 15)
  units/m2 (lt 7 in vasodilators)
• Systemic arterial oxygen concentration
• gt 92 92 of long-term survival
• lt92 50 of long-term survival

Braunwald E. Heart Disease 6th, 1526 1527, 1594
- 1595 Park Pediatric Cardiology for
Practitioners, 4th ed. P132 NEJM 1993
329(12)864-872
14
Eisenmenger SyndromeOpen lung biopsy

• Pathological results
• Cardovasc Pathol. 2002 11(4) 221-8
• 20 cases with or without corrective surgery
• Fatal outcome is frequently associated with
  fibrinoid necrosis of small pulmonary arteries
• Kyobu Geka. 2001 54(5) 374-8
• Single case report 10 m/o, Down, VSD,
  Eisenmenger
• Lung biopsy Grade 2 Heath Edwards
  classificationResult Survived
• Conclusion evidence is weak!
• High grade lesions may be missed in a random
  biopsy
• Progression of structural changes can occur even
  in the absence of high grade changes
• Risk for biopsy?

15
Pulmonary Hypertension Differential diagnosis

• Pulmonary thrombo-embolism (a. or v.)
• Congenital heart diseases
• mitral or aortic valve diseases, LV dysfunction,
  systemic HTN
• Pulmonary airway disease
• Hypoxic pulmonary hypertension
• Interstitial lung disease
• Collagen-vascular disease
• Parasitic disease (ex. schistosomiasis)
• Peripheral pulmonary artery stenosis (ex.
  Takayasu)
• Cirrhosis with portal hypertension
• Sickle cell disease
• Primary pulmonary hypertension

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1922
16
Eisenmenger SyndromeInterventions

• Principles
• To avoid any factors that may destabilize the
  delicately balanced physiology
• An approach of nonintervention is recommended.
• Indications for intervention
• Preventing complications
• Flu vaccines, IE prophylaxis
• Restore the physiological balance
• Iron deficiency anemia, anti-arrhythmic
  management, digoxin and diuretics for right-side
  heart failure

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
17
Eisenmenger SyndromeInterventions

• Medical managements under investigations
• Nifedipine
• Oxygen therapy
• Prostacyclin
• Nitric oxide
• Managements of complications
• Corrective or palliative surgery
• Lung or heart-lung transplantation

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1614 1616 Ann Intern
Med 1998 128 745-755
18
Eisenmenger Syndrome corrective or palliative
surgerySurgery How to do?

• Pulmonary banding
• Arq Bras Cardiol. 1997 69(5) 369-72
• Pulmonary banding in one patient with
  biopsy-proven irreversible pulmonary vascular
  changes led to regression of pulmonary vascular
  changes, which made surgical closure of the
  defects possible.

19
Eisenmenger Syndrome Medical treatmentNifedipine

• Cardiovascular Drugs and Therapy 1992 6(2)
  183-6
• 10 children, 3-12 years of age, VSD, AVSD,
  Eisenmenger
• Nifedipine had a relaxing effect on the pulmonary
  bed, especially in the younger child with
  Eisenmengers mechanism.
• Clinical Cardiology 199114(12)957-61
• 4 patients, age? VSD, Eisenmenger
• Increase right to left shunt, without compromise
  SpO2
• Chronic (4 weeks) nifedipine therapy increases
  SaO2 on exercise and improves maximal exercise
  capacity in patients with Eisenmenger syndrome.
• Ann Intern Med 1998 128 745-755
• Do not suggest due to worries of syncope and
  sudden death
• Braunwald Heart Disease 6th 1614-1616
• Should be keep in investigation

20
Eisenmenger Syndrome Medical treatmentOxygen
Therapy

• Br Heart J 1986 55385-90
• 15 childrens with pulmonary disease, not
  randomized
• Treatment long term domiciliary oxygen for a
  minimum of 12 hours a day for up to 5 years
• Results nine treated children survived. Sixed
  untreated children died.
• AJRCCM 2001 164(9) 1682-7
• 23 patients (mean age 32 /- 6) with
  post-tricuspid congenital heart defects (VSD 10,
  PDA 13) and Eisenmenger.
• Severity pulmonary hypertension, erythrocytosis,
  limited exercise endurance
• Randomized trial. 2 years follow up
• Treatment nocturnal oxygen therapy, at least 8
  hrs a day
• Results it did not modify the natural history of
  patients with advanced Eisenmenger Syndrome
• Conclusions
• Evidence small case size, nonrandomized vs
  randomized, controversial
• Good for children, not good for adults?

21
Eisenmenger Syndrome Medical treatmentInhaled
Nitric Oxide

• Inhaled NO in pulmonary hypertension secondary to
  congenital heart diseases
• Heart 200186553558
• 23 patients enrolled.
• Mean Qp/Qs 1.1 (SD 0.9)
• Mean SBP / PAP 89 (22) / 72 (30)
• ASD, VSD, PDA, TGA, TOF, DORV, truncus arteriosis
• Inhaled NO, at 20 ppm and 80 ppm
• Results
• What determines effective? ? Total pulmonary
  vascular resistance was reduced by more than 20
• 20 ppm18, 95 CI 2 to 34
• 80 ppm 29, 95 CI 10 to 38
• Qp/Qs lt 1 remained unchanged!!

22
Eisenmenger Syndrome Medical treatmentInhaled
Nitric Oxide Pregnancy

• Only 2 cases was reported
• Am J Obstet Gynecol. 1999 Jan180(1 Pt 1)64-7.
• Am J Obstet Gynecol. 1999 Aug181(2)419-23.
• Inhaled NO during labor
• 2 cases delivered successfully, but died
  thereafter (21 days and 2 days postpartum)

23
Eisenmenger Syndrome Medical treatmentInhaled
Nitric Oxide

• Inhaled NO is effective in primary pulmonary
  hypertension (NEJM 1997336111-117) and neonatal
  PPHN (NEJM 1997336605-610)
• Inhaled NO may not be effective in patients Qp/Qs
  lt1
• Inhaled NO may be helpful for pregnant woman in
  delivery

24
Eisenmenger SyndromeComplications
Ann Intern Med 1998 128 745-755
25
Eisenmenger Syndrome ComplicationsHemostatic
problems

• Common Problems
• Thrombocytopenia
• Prolonged bleeding time, PT/PTT
• Deficiency in Vit. K dependent clotting factors
• Increased fibrinolytic activity
• Common Manifestations
• Mucocutaneous bleeding
• Epistaxis, hemoptysis, massive bleeding
• Pathogenesis
• Not fully understood
• Management
• Blood component therapy
• Avoidance of NSAIDs, heparin

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
26
Eisenmenger Syndrome ComplicationsHyperviscosity
Syndrome

• Manifestations
• Headaches, altered mentation, visual
  disturbances, tinnitus, paresthesis, fatigue,
  dizziness, myalgia
• Hct gt 65, or Hct lt 65 with iron deficiency or
  microcytic anemia
• Treatment
• Correct dehydration
• Iron supplement
• Phlebotomy if symptomatic
• Prophylactic phlebotomy is not suggested
• May cause iron deficiency anemia

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
27
Eisenmenger SyndromePhlebotomy
Ann Intern Med 1998 128 745-755
28
Eisenmenger Syndrome ComplicationsCerebrovascula
r events

• Hyperviscosity ? thrombosis, emboli
• Abnormal hemostasis ? hemorrhage
• Right to left shunt ? brain abscess, paradoxical
  emboli
• Prevention
• Phlebotomy has no rule in prevention
• Correct microcytic anemia
• Avoid air in peripheral IV intervention
• Control atrial fibrillation

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
29
Eisenmenger SyndromeHemoptysis cause and therapy
Ann Intern Med 1998 128 745-755
30
Eisenmenger Syndrome ComplicationsRenal
dysfunctions

• More than 1/3 of patients
• Manifestations
• Proteinuria, elevated serum creatinine, diminish
  GFR, hyperuricemia, renal failure
• Preventions avoid nephrotoxic drugs

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
31
Eisenmenger Syndrome ComplicationsGout

• Rare
• Pathophysiology ??
• Increase resorption of uric acid
• Increase production of uric acid and impaired
  excretion
• Treatment
• Colchicine
• Avoid NSAIDs

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
32
Eisenmenger Syndrome ComplicationsHypertrophic
Osteoarthropathy

• Mechanism
• Megakaryocytes bypass the lung (due to right to
  left shunt) ? induce PDRF in peripheral ?
  promoting local cell proliferation ? osseous
  formation ? bone pain, arthralgia
• Management
• Salsalate nonacetylated analog of aspirin

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
33
Eisenmenger Syndrome ComplicationsCholethiasis

• Elevated unconjugated bilirubin in bile
  secretions as a results of the increased
  erythrocyte mass ? increasing risk for
  developing gall stone.
• Management
• Asymptomatic cholelithiasis conservative
• Symptomatic cholelithiasis not known
• Cholecystitis surgery

Braunwald E. Heart Disease A Textbook of
Cardiovascular Medicine, P 1617-1618 Ann Intern
Med 1998 128 745-755
34
Eisenmenger SyndromeNot discuss in this
presentation

• Pregnancy
• Non-cardiac surgery
• Traveling

35
Eisenmenger SyndromeTake Home Messages

• Eisenmenger syndrome is a pulmonary hypertensive
  disease caused by left-to-right congenital heart
  disease.
• The severity of pulmonary vascular resistance is
  a important prognostic factors.
• Corrective surgery may cause pulmonary crisis. It
  should be performed in selected patients.
• The principle of intervention is
  non-intervention.
• No medical interventions are proved effectively
  so far. It should be kept in investigation.
• For quality of life, complications must be
  managed.
• Pregnancy, noncardiac surgery, travelling be
  cautious
• Transplantation is an effective choice of
  treatment

36
Thanks for your attention