Paradoxical embolism is an uncommon cause for acute arterial occlusion. Paradoxical Embolism (PDE) occurs when a thrombus crosses an intracardiac defect into the systemic circulation.[1][2] Patients may present with symptoms based on the site of the resultant embolization. These sites can include the brain, heart, gastrointestinal tract, or extremities[1][3]. Patients may present with a cerebrovascular event, chest pain, migraine, cold extremity, or mesenteric ischemia. The emboli is usually a blood clot but maybe a fat particle, air, amniotic fluid, or tumor.[1][3] The management of paradoxical embolism is medical and/or surgery, depending on the location of the embolus. Many physicians treat their patients based on a presumptive diagnosis of PDEgiven the challenge of obtaining a definitive diagnosis.[2]
Patent foramen ovale (PFO) is a left to right shunt that occurs between the septum primum and septum secundum. The magnitude of the right to left shunt may be associated with an increased risk of cryptogenic stroke. [4] Valsalva maneuvers such as coughing, squatting, or defecating can transiently increase right atrial pressure leading to a transient shunt reversal and the transfer of potential thrombi into the systemic circulation. [1]
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. A transient reversal of blood flow can reverse the shunt. ASDs are associated with a paradoxical embolism in up to 14% of patients[5].
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[6].
Cerebrovascular accidents are the second most common cause of mortality worldwide and are the most frequent and relevant sequela of paradoxical embolism.[1] Up to 45% of ischemic strokes do not have identifiable causes, such as atrial fibrillation, and are referred to as cryptogenic strokes. The prevalence of paradoxical embolism is difficult to quantify because of the difficulty in diagnosing proven or impending embolic events[1]. A PFO may be found in up to 30% of the population and studies have suggested that the annual risk of cryptogenic and recurrent strokes in patients with a PFO is 0.1% and 1% respectively. [1][4] ASDs are 2 to 3 times more common in females and are responsible for over 30% of congenital heart defects in adults.[1] Paradoxical embolism should be suspected in all patients with an ischemic stroke without an identifiable cause.
A paradoxical embolism can occur when a thrombus in the deep venous circulation embolizes through an intracardiac shunt or pulmonary artery venous malformation (PAVM) into the systemic circulation. [1] Deep venous thrombosis is a risk factor for paradoxical embolism. Studies have shown that cryptogenic stroke is 5 times more likely with pelvic vein thrombosis.[7][8] The pathophysiological mechanism of a paradoxical embolism does vary. In the setting of a PFO, any permanent increase in right-sided cardiac pressures can increase the risk of a paradoxical embolism.[1]
Paradoxical Embolism can be difficult to diagnose and have an insidious onset. Physicians should strongly suspect paradoxical embolism in patients with an embolic event with a non-identifiable source, such as atrial fibrillation, and when a concomitant intracardiac shunt or PAVM is known or suspected.[1] A thorough history and physical examination are paramount. Depending on the organ affected, the symptoms may vary.
Physical Examination Findings:[3][4][1]
The diagnosis of paradoxical embolism is one of exclusion. Other causes for the patient's signs and symptoms should be considered first.
The evaluation should include:[9][1][3][4][2]
The treatment of paradoxical embolism is based on both medical and surgical approaches. The treatment pathways are divided into three general approaches:[1][4][3]
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.
Complications include:
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]
[1] | Windecker S,Stortecky S,Meier B, Paradoxical embolism. Journal of the American College of Cardiology. 2014 Jul 29; [PubMed PMID: 25060377] |
[2] | Saremi F,Emmanuel N,Wu PF,Ihde L,Shavelle D,Go JL,Sánchez-Quintana D, Paradoxical embolism: role of imaging in diagnosis and treatment planning. Radiographics : a review publication of the Radiological Society of North America, Inc. 2014 Oct [PubMed PMID: 25310418] |
[3] | Geng J,Tian HY,Zhang YM,He S,Ma Q,Zhang JB,Liu Y,Tian H,Zhang D,Meng Y, Paradoxical embolism: A report of 2 cases. Medicine. 2017 Jun; [PubMed PMID: 28658147] |
[4] | Maron BA,Shekar PS,Goldhaber SZ, Paradoxical embolism. Circulation. 2010 Nov 9; [PubMed PMID: 21060086] |
[5] | Bannan A,Shen R,Silvestry FE,Herrmann HC, Characteristics of adult patients with atrial septal defects presenting with paradoxical embolism. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography [PubMed PMID: 19670302] |
[6] | Kjeldsen AD,Oxhøj H,Andersen PE,Green A,Vase P, Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT). Journal of internal medicine. 2000 Sep; [PubMed PMID: 10971793] |
[7] | Osgood M,Budman E,Carandang R,Goddeau RP Jr,Henninger N, Prevalence of Pelvic Vein Pathology in Patients with Cryptogenic Stroke and Patent Foramen Ovale Undergoing MRV Pelvis. Cerebrovascular diseases (Basel, Switzerland). 2015 [PubMed PMID: 25791718] |
[8] | Cramer SC,Rordorf G,Maki JH,Kramer LA,Grotta JC,Burgin WS,Hinchey JA,Benesch C,Furie KL,Lutsep HL,Kelly E,Longstreth WT Jr, Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study. Stroke. 2004 Jan [PubMed PMID: 14657451] |
[9] | Karttunen V,Ventilä M,Ikäheimo M,Niemelä M,Hillbom M, Ear oximetry: a noninvasive method for detection of patent foramen ovale: a study comparing dye dilution method and oximetry with contrast transesophageal echocardiography. Stroke. 2001 Feb; [PubMed PMID: 11157181] |