Paradoxical embolism follows a temporal sequence of events that begin with the dislodgment of a venous thrombus that courses its way into systemic circulation via an intracardiac shunt or pulmonary arteriovenous malformation (PAVM). Patients may present with symptoms based on the site of the resultant paradoxical embolization. These sites can include the brain, heart, gastrointestinal tract, or extremities.
Patients may present with a cerebrovascular event, cold leg, or mesenteric ischemia. The emboli is usually a blood clot but maybe a fat particle, air, amniotic fluid, or tumor.
The management of paradoxical embolism is medical and/or surgery, depending on the location of the embolus.
Patent foramen ovale (PFO) is a left to right shunt that occurs between the septum primum and septum secundum. However, Valsalva maneuvers such as coughing, squatting, or defecating can transiently increase right atrial pressure leading to a transient shunt reversal, resulting in the transferring of potential thrombi into the systemic circulation.
Atrial septal defects (ASD) are congenital defects that vary in size and location, with clinical manifestations that range from atrial tachyarrhythmias to dyspnea. ASDs lead to a left to right shunt as well as a fixed split S2 on cardiac exam, however transient reversal in flow can reverse the shunt. ASDs are associated with a paradoxical embolism in up to 14% of patients.
Ventricular septal defects commonly result in left to right shunts, however certain conditions that increase right atrial pressure like Eisenmenger syndrome can reverse the shunt, allowing for paradoxical embolism.
Pulmonary arteriovenous malformations are usually hereditary and are a pathological connection between the pulmonary arteries to the pulmonary veins returning to the left atrium. This leads to a permanent right to left shunt. Patients with a history of hereditary hemorrhagic telangiectasia are at increased risk for PAVM and subsequent paradoxical embolism.
The actual cause-effect relationship of paradoxical embolism is difficult to correlate since additional mechanisms of strokes have not yet been fully studied. Further, the prevalence of paradoxical embolism is not fully known because paradoxical embolism is underdiagnosed. However, ischemic stroke is the most common complication of paradoxical embolism. Stroke is the second most common cause of mortality worldwide. Up to 45% of ischemic strokes do not have identifiable causes, such as atrial fibrillation, and are referred to as cryptogenic strokes. A Patent foramen ovale may be found in up to 30% of the population. Although most patients with PFO are asymptomatic, a cryptogenic stroke can be an important clinical manifestation. Therefore, paradoxical embolism should be suspected in patients with an ischemic stroke without an identifiable cause.
A deep venous thrombus (DVT) will propagate when there is either stasis of blood flow, endothelial injury, or if the patient is in a hypercoagulable state. Under physiological conditions, a dislodged DVT will predictably settle in the pulmonary arteries causing a pulmonary embolism. However, a DVT in the presence of an intracardiac shunt or PAVM can paradoxically cause an embolism in branches of the aorta. The pathophysiological mechanism varies depending on the etiology of the paradoxical embolism. For instance, in a paradoxical embolism due to a PFO, a DVT gets dislodged and enters the right atrium where a transient increase in right atrial pressure during a Valsalva maneuver can force the embolism through the PFO and into the left atrium where it will travel to the left ventricle, and out through the aorta where it can occlude coronary, cerebral, renal, mesenteric, or peripheral arteries. This occlusion will lead to ischemia and eventual infarction of affected tissues. The location of the affected tissue contributes to the clinical manifestation such as neurological deficits, chest pain, abdominal pain, or a cold limb. In the setting of a PAVM, the mechanism of a paradoxical embolism is a result of a permanent right to left shunt. When a dislodged embolus from a DVT enters the right atrium, it goes through the right ventricle and into the pulmonary artery where the embolus will bypass the lungs through the congenital fistula and enter the pulmonary vein and return to the left atrium and ventricle where it can then enter the systemic circulation.
The intracardiac communication that allows connection between the arterial and venous systems may be a patent foramen ovale, atrial septal defect, ventricular septal defect, or a pulmonary AVM. Factors that lead right to left shunts and increase the risk of paradoxical embolism include:
Physicians should strongly suspect paradoxical embolism in patients with an embolic event with a non-identifiable source such as atrial fibrillation, and a concomitant intracardiac shunt or PAVM. Physicians should be suspicious for paradoxical embolism when patients present with a systemic cryptogenic embolism with a recent or current history of DVT. Physicians should gather a history of factors that lead to the event such as coughing or straining. Physicians should also gather a history screening for DVT, CVD, and stroke. History of migraines occurs in up to 50% of patients with an intracardiac shunt. Physicians should look for signs of congenital heart defects such as right ventricular hypertrophy, digital clubbing, or fixed S2 splitting.
Depending on the organ affected, the symptoms may vary.
A CNS event may present with speech and visual abnormality, unilateral weakness, seizures, or swallowing difficulties. If the extremity is involved, it may present with a sudden onset of a cold leg that is pulseless and painful.
Diagnosis of paradoxical embolism is that of exclusion, and other common causes of stroke should be ruled out first. EKG should be performed to assess for atrial fibrillation. Transthoracic echocardiogram (TTE) with color-flow Doppler is the diagnostic imaging modality for the evaluation of intracardiac shunts, cardiac myxomas, and thrombus formations. Agitated saline or contrast can also be injected during TTE to help visualize and diagnose an intracardiac shunt. However, to accurately diagnose a PFO, the saline or contrast needs to be injected at the end of a Valsalva maneuver where the left of right shunt transiently reverses. The TTE can also evaluate the presence of aortic plaques in the ascending aorta, which can be a cause of systemic embolization. While TTE is limited to evaluating intracardiac shunts, transcranial Doppler sonography (TCD) can be used to detect any shunt, including PAVM. TCD is non-invasive and can be done at the bedside by injecting agitated contrast into a peripheral line and looking for microemboli in the middle cerebral artery. Ear oximetry is a simple screening tool for intracardiac shunts that can be utilized with high sensitivity and specificity. When the patient performs a Valsalva maneuver, the left to right shunt transiently turns into a right to left shunt, resulting in a transient decrease in the arterial oxygen saturation, which the ear oximeter can detect.
Coagulation parameters should be obtained, including tests for protein C and S antigen levels. If pulmonary embolism is suspected, d-dimer levels are necessary.
An arterial blood gas will help determine the oxygenation and ventilation status.
An ultrasound should be done to look for a DVT, and a spiral CT should be done to assess for a pulmonary embolus.
Noncontrast CT scan of the brain will reveal the presence of intracranial bleeding. If the patient has acute occlusion of the extremity, kidneys, or bowel, one may order a CT angiogram or MRI.
Treatment of paradoxical embolism is based on medical and surgical treatment. The choice of either and its specific plan is dependent on the risk of stroke recurrence, the lifelong benefit/risk ratio between antithrombotic therapy and surgery, as well as the cost of each intervention. The surgical approach includes occlusion of intracardiac shunts and PAVMs. Medical therapy is comprised of antithrombotic therapy, which includes aspirin, or clopidogrel as monotherapy or taken in combination with warfarin for the prevention of thrombotic events.
The initial treatment is always anticoagulation. If the patient has an intracardiac communication, it may be closed percutaneously or with open-heart surgery. Today, many types of devices are available to close cardiac shunts percutaneously with minimal morbidity.
Thrombolysis is often used in acute cases where the patient is hemodynamically unstable. Both DVT and pulmonary embolus need long term anticoagulation treatment. Some patients may need to be on antiplatelet therapy for life.
The prognosis after paradoxical embolism depends on the organ affected and the extent of the injury. Patients with CNS events usually tend to fare worse. Those who suffer mesenteric ischemia or a cold leg may be salvaged with surgery. On the other hand, renal infarction usually never recovers.
Most patients with a paradoxical embolus usually require admission and a prolonged hospital stay. Some may even require admission to the ICU for closer monitoring. In most patients, anticoagulation is necessary for six months if a DVT or a PE has been confirmed. The INR needs to be closely monitored to avoid a recurrent event.
A paradoxical embolism is a rare event with high morbidity and mortality. An interprofessional team best manages the disorder because of the diverse manifestations.
Reliance on team members working together from different disciplines is vital in order to diagnose, treat, and minimize negative outcomes in patients with a paradoxical embolism. For example, strong ultrasound skills are needed in order to identify an intracardiac shunt. The utilization of a pharmacist is important to achieve proper anticoagulation and prevent the formation of blood clots. Nursing staff should be proactive in looking for adverse effects of anticoagulation as well as performing timely neurological checks. Suspicion for a shunt should be high in the presence of venous pathology and an arterial event. Patients need to be educated on the prevention of blood clots by avoiding a sedentary lifestyle, wearing compression stockings if they have varicose veins, and taking the oral anticoagulants as prescribed. Pharmacists review medications, check for interactions and provide patient and family education. Women who are on the birth control pill should discontinue smoking and remain physically active.
The team needs to communicate and work together to produce the best outcomes. [Level 5]
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