Title: Eisenmenger Syndrome
1Eisenmenger Syndrome
2Outline 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
3Eisenmenger 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
4Eisenmenger 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
5NEJM 2000 342(5) 334-342
6Eisenmenger 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
7Eisenmenger 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
8Eisenmenger 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
9Eisenmenger 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
10Eisenmenger 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
11Eisenmenger 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
12Eisenmenger 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.
13Eisenmenger 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
14Eisenmenger 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?
15Pulmonary 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
16Eisenmenger 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
17Eisenmenger 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
18Eisenmenger 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.
19Eisenmenger 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
20Eisenmenger 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?
21Eisenmenger 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!!
22Eisenmenger 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)
23Eisenmenger 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
24Eisenmenger SyndromeComplications
Ann Intern Med 1998 128 745-755
25Eisenmenger 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
26Eisenmenger 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
27Eisenmenger SyndromePhlebotomy
Ann Intern Med 1998 128 745-755
28Eisenmenger 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
29Eisenmenger SyndromeHemoptysis cause and therapy
Ann Intern Med 1998 128 745-755
30Eisenmenger 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
31Eisenmenger 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
32Eisenmenger 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
33Eisenmenger 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
34Eisenmenger SyndromeNot discuss in this
presentation
- Pregnancy
- Non-cardiac surgery
- Traveling
35Eisenmenger 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
36Thanks for your attention