Eisenmenger Syndrome

Introduction
Background

In 1897, Eisenmenger reported the case of a 32-year-old man who had showed exercise intolerance, cyanosis, heart failure, and hemoptysis prior to death. Autopsy showed a large ventricular septal defect (VSD) and overriding aorta. This was the first description of a link between a large congenital cardiac shunt defect and the development of pulmonary hypertension.
Pathophysiology

Eisenmenger syndrome occurs in patients with large congenital cardiac or surgically created extracardiac left-to-right shunts. These shunts initially cause increased pulmonary blood flow. Subsequently, usually before puberty, pulmonary vascular disease causes pulmonary hypertension, ultimately resulting in reversed or bidirectional shunt flow with variable degrees of cyanosis.

For more information, see Medscape CME activity, Eisenmenger's Syndrome: Pathophysiologic Insights and Pharmacologic Treatment Rationales.
Frequency
International
The frequency of pulmonary hypertension and the subsequent development of reversed shunting vary depending on the specific heart defect and operative interventions.
Approximately 50% of infants with a large, nonrestrictive VSD or patent ductus arteriosus (PDA) develop pulmonary hypertension by early childhood.
Forty percent of patients with VSD or PDA and transposition of the great arteries develop pulmonary hypertension within the first year of life.
The natural history of a large secundum atrial septal defect (ASD) differs in that the 10% of cases that progress to pulmonary hypertension do so more slowly and usually not until after the third decade of life.
All patients with persistent truncus arteriosus and unrestricted pulmonary blood flow, and almost all patients with common atrioventricular canal, develop severe pulmonary hypertension by the second year of life.
The frequency of pulmonary hypertension in surgically created systemic-to-pulmonary shunts varies depending on size and anatomy.
Ten percent of those with a Blalock-Taussig anastomosis (subclavian artery to pulmonary artery) develop pulmonary hypertension compared to 30% of those with a Waterston (ascending aorta to pulmonary artery) or a Potts (descending aorta to pulmonary artery) shunt.
Mortality/Morbidity
Exercise tolerance is severely impaired due to an inability to increase pulmonary blood flow, thereby limiting oxygen uptake. The systemic vascular bed is prone to vasodilation and subsequent systemic arterial hypotension, which can cause syncope.
Long-term survival depends on the age at onset of pulmonary hypertension and the coexistence of additional adverse features, such as Down syndrome. Survival predominantly depends on right ventricular function. These patients usually do not survive beyond the second or third decade. The most frequent terminal event is a combination of hypoxemia and arrhythmia in the setting of rapid increases in pulmonary vascular resistance or decreases in systemic vascular resistance (SVR).
The complications of chronic cyanotic heart disease affect multiple organ systems, including hematologic, skeletal, renal, and neurologic, causing significant morbidity and mortality.
Sex

No overall sex predilection has been reported.
Age

Eisenmenger syndrome usually develops before puberty but may develop in adolescence and early adulthood.
Clinical
History

Symptoms related specifically to pulmonary hypertension result from the inability to increase pulmonary blood flow in response to physiological stress. Other symptoms are caused by the variety of multisystem complications associated with cyanotic congenital heart disease.

Pulmonary hypertension
Breathlessness
Fatigue
Lethargy
Severely reduced exercise tolerance with a prolonged recovery phase
Presyncope
Syncope
Heart failure
Exertional dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Edema
Ascites
Anorexia
Nausea
Erythrocytosis
Myalgias
Muscle weakness
Anorexia
Fatigue
Lassitude
Paresthesias of the digits and lips
Tinnitus
Blurred or double vision
Scotomata
Headache
Dizziness
Slowed mentation
Decreased alertness
Irritability
Bleeding tendency
Mild mucocutaneous bleeding
Epistaxis
Menorrhagia
Pulmonary hemorrhage
Vasodilation
Presyncope
Syncope
Cholelithiasis
Right upper quadrant pain
Biliary colic
Fever
Pale stools
Jaundice
Nephrolithiasis
Renal colic
Secondary gout
Joint pain and swelling
Paradoxical embolus can cause symptoms of localized vascular insufficiency end-organ ischemia.
Hypertrophic osteoarthropathy can cause long bone pain and tenderness.
Retinal complications include episodes of transient visual loss and spontaneous hyphemas.

For more information, see Medscape CME activity Uncovering Complications of Congenital Heart Disease: Eisenmenger's Syndrome and Beyond.

Physical
Cardiovascular
Central cyanosis (differential cyanosis in the case of a PDA)
Clubbing
Jugular venous pulse wave may be A-wave dominant, and, in the presence of a significant tricuspid regurgitation, the V wave may be prominent; central venous pressure may be elevated.
Precordial palpation reveals a right ventricular heave and, frequently, a palpable S2.
Loud P2
High-pitched early diastolic murmur of pulmonic insufficiency
Right-sided fourth heart sound
Pulmonary ejection click
Single S2
As the pulmonary vascular resistance progressively rises, the holosystolic murmur of nonrestrictive VSD shortens and softens, first becoming early systolic in timing, before disappearing entirely as the shunt is reversed.
The continuous murmur of a PDA disappears when Eisenmenger physiology develops; a short systolic murmur may remain audible.
Other signs
Respiratory signs include cyanosis and tachypnea.
Hematologic signs include bruising and bleeding; funduscopic abnormalities related to erythrocytosis include engorged vessels, papilledema, microaneurysms, and blot hemorrhages.
Abdominal signs include jaundice, right upper quadrant tenderness, and positive Murphy sign (acute cholecystitis).
Vascular signs include postural hypotension and focal ischaemia (paradoxical embolus).
Musculoskeletal signs include clubbing, tenderness over the metacarpal or metatarsal joints (hypertrophic osteoarthropathy), and joint effusions.
Skin demonstrates fewer urate deposits than commonly observed in primary gout.
Ocular signs include conjunctival injection, rubeosis iridis, and retinal hyperviscosity changes (see Hematological signs).
Causes
Large uncorrected cardiac shunts or palliative, surgically created systemic-to-pulmonary shunts for congenital heart disease
Large nonrestrictive VSD
Nonrestrictive PDA
Atrioventricular septal defect, including large ostium primum ASD without ventricular component
Aortopulmonary window
Palliative, surgically created systemic-to-pulmonary anastomosis for treatment of congenital heart disease

http://emedicine.medscape.com/article/154555-overview