Eisenmenger Syndrome

Dr. Md.Toufiqur Rahman MBBS, FCPS, MD, FACC, FESC, FRCP, FSCAI,

FAPSC, FAPSIC, FAHA

Associate Professor of CardiologyNational Institute of Cardiovascular Diseases

Sher-e-Bangla Nagar, Dhaka-1207

drtoufiq19711@yahoo.com

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the causes? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the causes? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the complications? How can be managed?

What are the findings? What is the diagnosis? What are the causes? How can be managed?

• Eisenmenger syndrome is pulmonary hypertension with a reversed central shunt

• First used by Paul Wood, is defined as pulmonary vascular obstructive disease that develop as a consequence of a large preexisting left-to-right shunt such that pulmonary artery pressures approach systemic levels that direction of flow becomes bidirectional or right-to-left shunt

• The high pulmonary vascular resistance is usually established in infancy, and can sometimes be present from birth

• An uncorrected large left-to-right shunt causes irreversible rise in PVR leading to reversal of or bidirectional shunt flow with resultant hypoxemia

• Eisenmenger syndrome is not a congenital defect, but a pathophysiologic condition

• Around 12 different congenital intracardiac or extracardiac defects can cause Eisenmenger syndrome:

• Following 3 account for 70–80% of cases

• VSD• Atrioventricular septal defect• PDA

• Other congenital heart diseases which can cause Eisenmenger syndrome:

– ASD– Truncus arteriosus– Aortopulmonary window– Univentricular heart without PS– D-transposition of the great vessels with VSD– Surgically created aorto-pulmonary connections

Braunwald E. Heart Disease

• With large shunts, the PVR develops relatively quickly, usually within first two years of life

• In patient with ASD may have Eisenmenger syndrome in adulthood

Presentation and course in childhood

• Children may be asymptomatic or have only mild dyspnea

• Reduced exercise capacity, dyspnea and fatigue develop gradually as pulmonary blood flow decreases, and hypoxemia increases due to bidirectional shunting

Course in adulthood

• Many individuals with Eisenmenger syndrome survive into adulthood with 80% survival at 10 years, 77% survival at 15 years and 42% at 25 years after diagnosis

• Variables associated with poor prognosis include : - Syncope - Elevated RA pressure - Severe resting hypoxemia (<80% transcutaneous oxygen

saturation)

The causes of death in Eisenmenger pts:

• Sudden death (30%)

• Congestive heart failure (25%)

• Hemoptysis (15%)

The causes of death contd.Other (30%) including:

– Pregnancy

– Perioperative following non-cardiac surgery

– Infective endocarditis

– Brain abscess

– Non-cardiac causes

• While individuals with Eisenmenger syndrome may remain relatively stable for long periods of time, it is essential to appreciate that their hemodynamic state is very delicately balanced

• This balance is easily upset, often with disastrous results

Examination in Eisenmenger Syndrome

• Central cyanosis with digital clubbing

• May have differential cyanosis and clubbing

• Hypoxemia with resting oxygen saturation <90%

• Lungs are usually clear

• RV heave, palpable P2, right sided S4, and occasionally pulmonary ejection click

• Murmurs likely to be heard include a high-pitched diastolic decrescendo murmur of pulmonic insufficiency and a holosystolic murmur of TR

• Murmurs related to the defects connecting the systemic and pulmonary circulations are not usually heard

ComplicationsCongestive heart failure• Arrhythmias (atrial fibrillation/flutter)• Bleeding disorders• Brain abscess• Erythrocytosis• Hyperuricemia/gout• Infectious endocarditis• Paradoxical emboli• Pulmonary artery calcification & aneurysm • Progressive valvular disease• Renal dysfunction• Sudden death • Stroke or transient ischemic attack

Diagnostic 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

• It is important to be certain that the diagnosis of Eisenmenger syndrome is correct

• One does not want to miss the opportunity to identify individuals who have reversibility of their pulmonary vascular disease that may enable a surgical repair of the defect

• The cardiac catheterization is performed to establish that the PVR is elevated and responsiveness to administration of oxygen, nitric oxide, suldinafil , Ca Channel Blockers

Catheter and surgical management

• Once Eisenmenger physiology has developed, catheter or surgical interventions have a limited role in management

• Surgery to repair the underlying congenital anomaly is not recommended for two reasons:

1 - The risk of surgery is exceedingly high

2 – Those who survive the surgery have increased mortality

• Heart–lung transplantation is an option, but long waiting is a problem

• In some instances , lung transplantation with repair of the intracardiac defect may be an option

• Lung transplantation has the advantage of better donor availability, a shorter waiting period, and avoidance of problems associated with heart transplantation (vasculopathy and rejection)

The following may lead one to consider surgical or transcatheter options:

• Progressive deterioration of functional class

• Recurrent syncope

• Refractory right heart failure

• Supraventricular tachyarrhythmias

• Worsening hypoxemia

Summary of treatment Avoid factors that may destabilize the delicately balanced

physiology, in general, an approach of nonintervention is recommended.

Main interventions are directed toward preventing complications or to restore physiological balance

• Isovolumic phlebotomy unless iron deficiency anemia• Hypovolemia be avoided• Noncardiac surgery only when necessary without general

anesthesia • Hemoptysis commonly due to bronchial vessel or pulmonary

infarction• Influenza shots, antiarrhythmic management, salt restriction• Endocarditis prophylaxis is recommendedTransplantation

Expected abnormalities• A number of abnormal findings are expected in Eisenmenger

syndrome pts and should not raise undue concern unless they represent a significant change from past values

• Oxygen saturation at rest usually ranges in 80s

• If checked shortly after exertion , it will be lower (mid 70% range)

• The baseline value should be established after a few minutes of rest

• Hct , PLt

• INR and APTT are mildly prolonged

• Uric acid and bilirubin are elevated

• Proteinuria , usually less than 1 G/24 hours (this is glomerular in origin and related to the hypoxemia)

• Mildly elevated serum Cr and hematuria can also be found

Recommendations for Medical Therapy ofEisenmenger Physiology

Class I

1. It is recommended that patients with Eisenmenger syndrome avoid the following activities or exposures, which carry increased risks:

a. Pregnancy. (Level of Evidence: B)

b. Dehydration. (Level of Evidence: C)

c. Moderate and severe strenuous exercise, particularly isometric exercise (Level of Evidence: C)

d. Acute exposure to excessive heat (eg, hot tub or sauna). (Level of Evidence: C)

e. Chronic high-altitude exposure (particularly at an elevation greater than 5000 feet above sea level). (Level of Evidence: C)

f. Iron deficiency. (Level of Evidence: B)

Recommendations for Medical Therapy ofEisenmenger Physiology cont:

2. Patients with Eisenmenger syndrome should seek prompt therapy for arrhythmias and infections. (Level of Evidence: C)

3. Should have hemoglobin, platelet count, iron stores, creatinine, and uric acid assessed at least yearly. (Level of Evidence: C)

4. Should have assessment of digital oximetry, both with and without supplemental oxygen therapy, at least yearly. The presence of oxygen-responsive hypoxemia should be investigated further. (Level of Evidence: C)

Recommendations for Medical Therapy ofEisenmenger Physiology cont:

5. Exclusion of air bubbles in intravenous tubing is recommended as essential during treatment of adults with Eisenmenger syndrome. (Level of Evidence: C)

6. These pts should undergo noncardiac surgery and cardiac catheterization only in centers with expertise in the care of such patients (Level of Evidence: C)

Medical Therapy ofEisenmenger Physiology cont:

Hypoxemia: • While it seems obvious that inhaled O2 would help, no studies

show a mortality or morbidity benefit from chronic O2 administration

• Inhaled O2 can be used if the patient feels comfortable with it (reduced dyspnea, reduced fatigue, improved sleep)

• However, the adverse effects of mucosal dryness leading to mucous bleeding and the cumbersome equipment cause most patients to chose not to chronically use O2

Hyperviscosity syndrome:

• Viscosity is affected by the concentration of RBCs and their deformability

• A high Hct alone may not cause these symptoms

• The major etiology for reduced deformity is thought to be iron deficiency which causes RBCs to change from deformable biconcave disks to more rigid microspheres

• Blood loss related to phlebotomy, hemoptysis, epistaxis and menses are common causes of iron deficiency

Important considerations in individuals with symptoms suggestive of hyperviscosity syndrome

• High Hct in the absence of symptoms does not require phlebotomy

• Exclude dehydration as a cause of Hct

• Exclude iron deficiency , If present, treat with oral iron

• Phlebotomy may be appropriate if symptoms are severe and none of the above factors apply

Phlebotomy

• The goal of phlebotomy is to treat the symptoms of the hyperviscosity syndrome and not to obtain a specific Hct

• Prompt relief of symptoms after the phlebotomy confirms that hyperviscosity was the likely etiology

• If the symptoms do not resolve promptly, consider other alternative causes and do not repeat the phlebotomy

Medical Therapy ofEisenmenger Physiology cont:

Bleeding:

• These pts are at risk of bleeding from the relatively benign easy bruising to life-threatening massive intra-pulmonary hemorrhage and hemoptysis

• Most bleeding is, however minor, involves the mucocutaneous tissues, and responds to conservative management

• Significant bleeding can be treated with vitamin K, FFPs, platelets or cryoprecipitate

• Phlebotomy may improve platelet function, increase platelet count and improve various coagulation abnormalities

• Phlebotomy can be considered prior to elective surgery to decrease the risk of bleeding

Cerebrovascular and other embolic events:

• Mechanisms include hemorrhage, emboli and infection with formation of a cerebral abscess

• Iron deficiency is the major risk factor for cerebrovascular events

• The risk–benefit ratio of aspirin or warfarin needs to be considered in each patient

Gout• Rare• Pathophysiology ??– Increase resorption of uric acid– Increase production of uric acid and impaired excretion

• Treatment

– Colchicine

– Avoid NSAIDs

Pulmonary hypertension

• Pulmonary vasodilator agents such as prostacyclin analogs, endothelin antagonists and phosphodiesterase inhibitors have been found to reduce PVR and improve functional capacity

• Limited data cite some individuals so responsive to these agents that surgical correction of the defect was possible

• Alternatively, in patients with progressive heart failure, these agents have been used as part of a bridge to transplantation

Recommendations for Follow-Up

Class I1. Patients with CHD-related PAH should:

a. Have coordinated care under the supervision of a trained CHD and PAH care provider and be seen by such individuals at least yearly (Level of Evidence: C)

b. Have yearly comprehensive evaluation of functional capacity and assessment of secondary complications (Level of Evidence: C)

c. Discuss all medication changes or planned interventions with their CHD-related PAH caregiver(Level of Evidence: C)

Recommendations for Reproduction

Class I1. Women with severe CHD-PAH, especially those with

Eisenmenger physiology, and their partners should be counseled about the absolute avoidance of pregnancy in view of the high risk of maternal death, and they should be educated regarding safe and appropriate methods of contraception. (Level of Evidence: B)

2. Women with CHD-PAH who become pregnant should:

a. Receive individualized counseling from cardiovascular and obstetric caregivers collaborating in care and with expertise in management of CHD-PAH. (Level of Evidence: C)

b. Undergo the earliest possible pregnancy termination after such counseling. (Level of Evidence: C)

3. Surgical sterilization carries some operative risk for women with CHD-PAH but is a safer option than pregnancy (Level of Evidence: C)

Class IIb

1. Pregnancy termination in the last 2 trimesters of pregnancy poses a high risk to the mother

- It may be reasonable, however, after the risks of termination are balanced against the risks of continuation of the pregnancy (Level of Evidence: C)

During pregnancy deaths are commonly due to:

• Thromboembolism (44%)• Hypovolemia (25%)• Pre-eclampsia (18%)• Worsening heart failure• Progressive hypoxemia

Non-cardiac surgery in Eisenmenger patients

• Non-cardiac surgery in Eisenmenger patients carries a high morbidity and mortality risk (up to 19%)

• Surgery should be avoided when possible, but is commonly needed for acute cholecystitis (due to bilirubin stone formation from the hyperbilirubinemia)

• Necessary operations should be done in a center familiar with the high risks of performing surgery on these patients

Perioperative morbidity and mortality

The mortality and morbidity are related to:• Sudden fall in SVR leading to worsening hypoxemia due to

progressive right to left shunting

• Hypovolemia and dehydration

• Excessive bleeding

• Perioperative arrhythmias

• Thrombophlebitis/DVT/paradoxical emboli

Risks for Eisenmenger Syndrome• Pregnancy (contraindicated)• General anesthesia• Dehydration• Hemorrhage• Cardiac and noncardiac surgery• Drugs (vasodilator, diuretics,oral pill, nonsteroidal anti-

inflammatory drugs)• Anemia commonly due to iron deficiency• Intravenous lines (air embolism,infection)• Altitute exposure• Pulmonary infection

Take Home Messages

• Eisenmenger syndrome is a pulmonary hypertensive disease caused by left-to-right shunting of blood

• The severity of pulmonary vascular resistance is a important prognostic factor

• Corrective surgery may cause pulmonary crisis. It should be performed in selected patients

• The principle of intervention is non-intervention

• For quality of life, complications must be managed

• Pregnancy, noncardiac surgery, travelling: be cautious

• Transplantation is an effective choice of treatment