Paradoxical Embolism 

In 1877, Cohnheim initially described the term paradoxical embolism (PDE).^[1] It illustrates a condition in which emboli from the venous system reach the systemic arterial circulation by passing through an abnormal communication between the chambers of the heart, leading to a systemic manifestation such as stroke, kidney infarction, or acute limb infarction.

Zahn reported a case in 1885 in which autopsy revealed thrombosis in the pelvic veins, multiple systemic emboli, and a thrombus passing through a patent foramen ovale (PFO).

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

Paradoxical embolism (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.^[3] Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet).

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

Paradoxical embolism (PDE) is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. Paradoxical embolism (PDE) can be presumed in the presence of arterial embolism with no evidence of left-sided circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO.^[4]

Paradoxical embolism (PDE) originates from a venous thrombosis. 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.

Many conditions predispose individuals to increased risk for development of venous thrombosis, including 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; and dysfibrinogenemia.

Immobilization, pregnancy, estrogen use, previous DVT, trauma, and neoplasms (ie, breast, pelvic malignancy, stomach, pancreas, lung) are risk factors. Surgery is also a common risk factor for DVT, especially orthopedic, abdominal, and genitourinary procedures. Thromboangiitis obliterans and homocystinuria, 2 types of venulitis, are among the least common risk factors. The thrombus is composed of platelets, fibrin, and, eventually, red blood cells. The thrombus tends to propagate in the direction of the blood flow.

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

A PFO is defined as a valvelike opening between the septum primum and the septum secundum without evidence of an anatomic defect in the septa. PFO is significant in the etiology of paradoxical embolism (PDE) if associated right-to-left shunting is present. Some causes of right-to-left shunting are 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 of the right side of the heart; and 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 paradoxical embolism (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 paradoxical embolism (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, resulting 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.

Frequency

United States

The actual frequency of paradoxical embolism (PDE) is unknown because most cases are presumed rather than proved and most cryptogenic strokes are not investigated.

Paradoxical embolism (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). PFO prevalence is approximately 20-30% in cryptogenic strokes. Autopsy data suggest that PFO may be present in 25-35% of the normal population. Right-to-left atrial shunts in paradoxical embolism (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 paradoxical embolism (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 paradoxical embolism (PDE). Chronically elevated pressures of the right side of the heart are associated with 5% of paradoxical embolism (PDE) cases.

Mortality/Morbidity

• Morbidity and mortality are increased in patients with paradoxical embolism (PDE) and PE, depending on the size of the embolus and end-organ lodgment.
• Patients with paradoxical embolism (PDE) can have permanent neurological damage with residual physical incapability.

Race

No established differences exist across racial or ethnic groups.

Sex

Both sexes are equally represented in the demographics of the disease because no sex difference exists in the incidence of PFO in the normal population.

Age

• Elderly patients are commonly affected. Risk of DVT is increased in the elderly population. This correlates to the increased incidence of paradoxical embolism (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 in this age group is usually larger when compared with 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.
• Paradoxical embolisms (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 shunt is the most frequent cardiac finding in patients younger than 55 years with an otherwise unexplained ischemic cerebral insult or cryptogenic stroke.