Paradoxical Embolism 

The clinical manifestations of paradoxical embolism (PDE) are nonspecific, and the diagnosis is difficult to establish. Patients with PDE may present with neurologic abnormalities or features suggesting arterial embolism. The disease starts with the formation of emboli within the venous system, which traverse a patent foramen ovale (PFO) and enter the systemic circulation.^{[1, 2, 3]} PFOs have been found on autopsy in up to 35% of the healthy population.

PDE originates in the veins of the lower extremities and occasionally in the pelvic veins. Emboli may be of various types, such as clots, air, tumor, fat, and amniotic fluid.^[4] Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet). See the image below.

The management of PDE is both medical and surgical in nature. PDE is considered the major cause of cerebral ischemic events in young patients. On rare occasions, it may occlude the pelvic aortic bifurcation. The largest documented thrombus in a PFO (impending PDE) was 25 cm in length.

PDE is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. It may be presumed in the presence of arterial embolism with no evidence of left-side circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO.^[5]

PDE originates from a venous thrombosis (see the image below). In most cases, the source is in the deep veins of the lower extremities; thrombosis occurs less frequently in the upper extremities than in the lower extremities. The thrombus is composed of platelets, fibrin, and, eventually, red blood cells (RBCs). It tends to propagate in the direction of the blood flow.

Many conditions predispose individuals to increased risk for development of venous thrombosis, including the following:

• Hypercoagulable states, such as factor V Leiden (resistance to activated protein C)
• Antithrombin III, protein C, or protein S deficiencies
• Antiphospholipid antibody syndrome
• Prothrombin mutation
• Dysfibrinogenemia

Risk factors include the following:

• Immobilization
• Pregnancy
• Estrogen use
• Previous DVT
• Trauma
• Neoplasms (ie, breast, pelvic malignancy, stomach, pancreas, lung)
• Surgery (especially orthopedic, abdominal, and genitourinary procedures)
• Thromboangiitis obliterans and homocystinuria – These 2 types of venulitis are among the least common risk factors

The intracardiac communication between the venous and arterial circulations can be in the form of a PFO, an atrial septal defect (ASD), a pulmonary arteriovenous malformation, a ventricular septal defect, an Ebstein anomaly, or a patent ductus arteriosus.

A PFO is defined as a valvelike opening between the septum primum and the septum secundum without evidence of an anatomic septal defect. PFO is significant in the etiology of PDE if associated right-to-left shunting is present. Causes of right-to-left shunting include the following:

• Right atrial hypertension
• Right ventricular hypertension
• Right ventricular failure with increased end-diastolic pressure; positive-pressure ventilation
• Positive end-expiratory pressure
• Pulmonary hypertension from hypoxemia
• Myocardial infarction (MI) of the right side of the heart
• Valsalva-type maneuvers (forced expiration against a closed glottis), including urination, defecation, and sneezing

The clinical manifestations are based on complications of embolism and depend on the site of the embolus; multiorgan ischemia and infarction can occur. PE is a prerequisite for PDE. If the left pulmonary artery is occluded suddenly, the mean pulmonary artery pressure increases by 30% from the baseline. According to estimates, PE may lead to PDE only if it produces a rise in mean pulmonary artery pressure greater than 30 mm Hg, facilitating an increase in right atrial pressure above left atrial pressure that results in right-to-left shunting.

The PFO increases in size with advancing age, from a mean of 3 mm in the first decade to 6 mm in the 10th decade.

Many conditions predispose individuals to increased risk for DVT, including the following:

• Hypercoagulable states, such as factor V Leiden (resistance to activated protein C); antithrombin III, protein C, and protein S deficiencies; antiphospholipid antibody syndrome; prothrombin mutation; and dysfibrinogenemia
• Previous DVT
• Immobilization
• Pregnancy and estrogen use
• Neoplasms (eg, of the breast, pelvis, or stomach)
• Abdominal and thoracic surgical procedures
• Orthopedic and genitourinary surgical procedures
• Trauma
• Venulitis (eg, thromboangiitis obliterans and homocystinuria)

Intracardiac communication of the venous and arterial circulations can lead to PDE and may occur via the following:

• PFO
• ASD
• Pulmonary arteriovenous malformation
• Ventricular septal defect
• Ebstein anomaly
• Patent ductus arteriosus

The actual frequency of PDE is not known, because most cases are presumed rather than proved and most cryptogenic strokes are not investigated.

PDE may be common. The incidence of stroke in the United States is approximately 500,000 per year. Of all strokes, 35-40% are cryptogenic (ie, without an identifiable source). PFOs are found in approximately 20-30% of those who sustain cryptogenic strokes. Autopsy data suggest that PFO may be present in 25-35% of the normal population. Right-to-left atrial shunts in PDE are associated with an underlying PFO in approximately 70% of case series and autopsy reports.

DVT may escape clinical detection in more than 50% of cases. Venous thrombosis may occur in more than 50% of orthopedic surgical procedures and in more than 20% of patients who undergo abdominal or thoracic surgical procedures.

The clinical findings of PDE are arterial embolic manifestations that include cerebral (40%), peripheral (50%), coronary (8%), renal (1%), and splenic (1%) ischemia or infarction. PE has been demonstrated in as many as 85% of diagnosed cases of PDE. Chronically elevated pressures of the right side of the heart are associated with 5% of PDE cases.

Age-, sex-, and race-related demographics

Elderly patients are commonly affected; PDE is not common in children. The risk of DVT is increased in the elderly population; this is correlated with the increased incidence of PDE in patients older than 55 years. Elderly patients may be at increased risk for the passage of thrombus through a PFO. The size of the PFO is usually greater in this age group than in younger populations; the average size of a PFO is 3 mm in the first decade of life versus 6 mm in the 10th decade of life.

PDEs do occur in individuals younger than 55 years when an intracardiac communication is present with risk of DVT and right-to-left atrial shunting. PFO with atrial right-to-left shunting is the most frequent cardiac finding in patients younger than 55 years with an otherwise unexplained ischemic cerebral insult or cryptogenic stroke.

The sexes are equally represented in the demographics of the disease because there is no sex-related difference in the incidence of PFO in the normal population. [#Clinical] No established differences exist across racial or ethnic groups.

PDE generally has a good prognosis when it is not complicated. Morbidity and mortality are increased in patients with PDE and PE, depending on the size of the embolus and end-organ lodgment. When impending paradoxical embolism (PDE) occurs, the choice of treatment involves open-heart surgery.

Some p atients with PDE experience devastating outcomes with complications such as neurologic deficits, blindness, gangrene of extremities, and amputation, depending on whether the limb is salvageable or not. Organ damage may include renal infarction with eventual renal insufficiency.

Patients on long-term anticoagulant therapy should be educated in the importance of compliance with their medication regimen for prevention of recurrent thromboembolic events. They should also be instructed to avoid vitamin K–containing foods such as green leafy vegetables (eg, spinach, broccoli, and cauliflower).

Varicose veins coexist commonly with cyanotic congenital heart disease, and these may predispose to thromboembolic phenomena. Accordingly, patients with varicose veins should avoid passive standing, should avoid crossing their legs when sitting, and should not allow their legs to be dependent.

To prevent elevation of the right atrial pressure above the left atrial pressure, which can lead to transient right-to-left shunting in patients with risk factors for PDE, Valsalva maneuvers should be avoided.

Patients should be educated regarding the adverse reactions from IV contrast agents that may occur in studies such as venography, arteriography, angiography, and cardiac catheterization (see Workup). Obtaining an informed consent after providing full explanation of the indications, implications, and complications of the procedure and the possibility of contrast-associated adverse reactions is important.

For patient education resources, see the Circulatory Problems Center, as well as Blood Clot in the Legs.