Pulmonary Embolism And Impending Paradoxical Embolism: A Case Report

Adefinitive diagnosis of paradoxical embolism is based on the evidence that a thrombus crosses through the right-to-left shunting. We report a case of impending paradoxical embolism in a patient with pulmonary embolism diagnosed by echocardiography and proved by operation later. CASE REPORT A 44-year-old man with slurred speech and left hemiplegia was admitted to the CCU of this hospital after onset of dyspnea and tarchycardia. The patient had been well until four weeks previously, when he had a sudden onset of slurred speech and was found unable to move his right arm and leg after getting drunk the preceding night. The patient had a history of uncontrolled hypertension, a borderline blood glucose level and was obese. He has been smoking for 20 years and drinking alcohol for 20 years before his hospitalization. There was no history of atrial fibrillation, blood clotting disorders or cardiac valvular disease. CT and MRI of the brain in another hospital suggested the presence of thrombosis in the right middle cerebral artery. After the appearance of above mentioned symptoms his family members found his left leg was more edematous and bulky than the other leg, but they did not pay much attention to it. The medications he received then were nimodipine 30 mg tid, lumbrokinase 600 kU tid, DengZhanXiXin 40 mg qd (a herb medication for vasodilatation). The patient was hospitalized in the department of rehabilitation for exercise training. On the 18th day of the hospitalization he caught a cold, had fever of 39°C at 3 am and was given antibiotics. Later, at 2 pm the same day, the patient was sweating, palpitating and breathing quickly when he did some exercises. He was given oxygen and advised to rest. The symptoms did not subside. At 9 pm he had shortness of breath and palpitation; blood pressure was 110–140/70–90 mmHg and heart rate was 125 beats per minute. Arterial blood gas analysis showed pH 7.474, PCO2 24.3 mmHg, PO2 46.2 mmHg and SaO2 83.7%. An electrocardiogram showed sinus rhythm at a rate of 125 beats per minute with lead I having S wave, lead III QS wave and T-wave abnormalities. Chest radiogram showed heart shadow enlarged and pulmonary segment prominent. Chest spiral CT showed there were multiple filling defects in bilateral pulmonary arteries (Figure 1).Figure 1.: Multiple filling defects in bilateral pulmonary arteries.After clinical diagnosis of pulmonary embolism, the patient was transferred to the coronary care unit immediately. His temperature was 35.5°C, blood pressure 100/60 mmHg, heart rate 90 beats per minute and respiratory rate 33 per minute. He did not receive thrombolysis therapy because of recent cerebral thrombosis with hemorrhagic complications. The patient was given heparin, which was then changed to low molecular weight heparin and herbesser to decrease the pulmonary pressure. Oxygen saturation was around 90 percent, when the concentration of inspired oxygen was kept above 70 percent. Several hours later, bedside transthoracic and transesophageal echocardiography revealed a large “snake-like” mass floating in the right atrium and a similar mobile mass in the left atrium connected through a patent foramen ovale (PFO), as well as a thrombus in the pulmonary artery and a patent interatrial communication (Figure 2). Enlargement and hypokinesis of the right ventricle with moderate tricuspid insufficiency were also seen. The estimated pulmonary artery systolic pressure was 63 mmHg. The left ventricle was of “D” shape, and there was no evidence of pericardial tamponade.Figure 2.: Transesophageal echocardiogram revealed a large waving tubular thrombus present in the right atrium and left atrium crossing through a patent foramen ovale (PFO) several hours after the onset of symptoms.The patient underwent an emergent pulmonary thromboembolectomy the next day with cardiopulmonary bypass. Right and left atriotomy revealed a large thrombus traversing the patent foramen ovale (Figure 3). An additional 13-cm thrombus was retrieved from the saddle portion of the main and right pulmonary arteries. Evacuation of the multiple clots from bilateral pulmonary arteries was carried out. The PFO was closed by direct suture.Figure 3.: Intraoperative exploration demonstrated a large thrombus traversing the patent foramen ovale.Repeat Doppler examination of the lower extremities revealed right popliteal vein thrombus extending to the right femoral vein. An inferior vena cava filter was placed and on the next day the patient was treated with heparin which was later shifted to warfarin. Another transthoracic echocardiogram obtained 14 days after the operation showed that the heart size and structure were normalized. The patient was discharged on the 40th postoperative day with daily warfarin and instruction to continue taking it with a target international normalized ratio (INR) of 2 to 3. The final diagnosis was pulmonary embolus with impending paradoxical embolism. CLINICAL OVERVIEW History Cohnheim initially described the term paradoxical embolism in 1877. 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. Prior to the new examination echocardiography, impending paradoxical embolism was usually discovered only on postmortem examination. Although paradoxical embolism had been described 100 years earlier, only 150 cases had been reported by 1975, most of them post mortem, and only 20 cases had been detected in live patients.1 Epidemiology There were some case reports of paradoxical embolism but little epidemiology data about this situation. Paradoxical embolism may be common, but the actual frequency of paradoxical embolism is unknown because most cases are presumed rather than proven. A patent foramen ovale is present in 17% to 35% of the cases at autopsy in all age groups and it is associated with potential paradoxical embolism in 16% of the cases.2 According to the estimates by Bridges et al,3 in United States each year from 20 000 to 50 000 strokes may be attributable to the presence of a patent foramen ovale. There are little data about pulmonary embolism morbidity and mortality in China. Considering pulmonary embolism, a one-centre study had shown that during the 1970s, 0.27% of patients in a cardiovascular hospital had PTE (<5 cases per year); while so far this century the proportion is 0.94% (48 to 113 per year). The mortality of hospitalized pulmonary embolism patients fell from 20.00% in the 1970s to 4.10% this century. Prior to 1990, the mortality of hospitalized pulmonary embolism patients was 12.50%, and in the years after 1990 only 3.40%.4 But there are no data to help predict the number of strokes due to paradoxical embolism. Pathogenesis Paradoxical embolism usually originates from a venous thrombosis. The thrombus is composed of platelets, fibrin, and, eventually, red blood cells. The thrombus tends to propagate in the direction of the blood flow. In most cases, the source is in the deep veins of the lower extremities. Many conditions increased risk for deep venous thrombosis (DVT), including hypercoagulable states, immobilization, pregnancy, estrogen use, previous DVT, trauma, neoplasms and surgery; especially orthopedic, abdominal, and genitourinary procedures. The intracardiac shunt between the pulmonary and systemic circulation can be a PFO, atrial septal defect (ASD), ventricular septal defect (VSD), a patent ductus arteriosus (PDA), Ebstein anomaly, endocardial cushions, aortopulmonary septal defect, tetralogy of Fallot, coronary arterio-pulmonary artery fistula, arteriovenous anastomosis or a pulmonary arteriovenous malformation. STRATEGIES Diagnosis A definitive diagnosis of paradoxical embolism is based on the evidence that a thrombus crosses through the right-to-left shunting. Paradoxical embolism can be presumed in the following criteria: (1) Deep venous thrombosis (DVT) with or without PE; (2) Abnormal communication between right (venous) and left (systemic) circulation; (3) Clinical, angiographic, or pathologic evidence for systemic embolism; (4) Presence of a favorable pressure gradient, promoting right-to-left shunting.5 The clinical manifestations of paradoxical embolism are based on the embolism site of the embolus. DVT manifestations include unilateral leg pain; leg swelling; unilateral leg redness; a positive history of previous DVT. PE is present in most reported cases of paradoxical embolism; while pulmonary embolism is not an essential condition for paradoxical embolism. PE symptoms include: dyspnea; chest pain; hemoptysis; syncope. Clinical symptoms associated with multiorgan arterial embolism depend on the location of the embolism (e.g., embolic stroke, extremity artery, retinal artery, mesenteric artery and splenic artery). Chronically elevated pressures of the right side of the heart depend on the size of the embolus, the proportion of pulmonary arterial being involved and the right side of heart compensation. The clinical findings of paradoxical embolism are arterial embolic manifestations that include cerebral (37%), peripheral (49%), coronary (9%), renal (1%) and splenic (1%) ischemia or infarction.6 Examinations which help to make a diagnosis include clinical and investigations made with noninvasive studies, such as duplex venous ultrasonography, to find DVT, CT scan with intravenous contrast or MR venogram to rule out iliac vein thrombosis. Spiral computed tomography (CT) scan with intravenous contrast is used commonly to help diagnose PE. It has a sensitivity close to that of pulmonary angiography, which has been the criterion standard for PE. Noncontrast CT scans of the head are important in evaluating any intracranial bleeding, space-occupying lesions, midline shifts, or herniation, which are contraindications to thrombolytics treatment and anticoagulation. Transthoracic and transesophageal echocardiography had high sensitivity and specificity for PFO and other right-to-left shunts. The bedside echocardiography is invaluable because it may reveal many findings in major pulmonary embolism and can rule out other important disorders that need totally different treatment, such as pericardial tamponade, aortic dissection and acute myocardial infarction. The laboratory studies in PDE are performed to evaluate hypercoagulability that increases the risk of DVT. The quantitative plasma D-dimer is elevated (>500 ng/ml) in more than 90% of patients with PE. This test will help to rule out pulmonary embolism. Paradoxical embolism is an exclusion diagnosis. Cerebral and peripheral arterial embolisms caused by other diseases with thrombus that form on the left side of the heart could be the same as paradoxical embolism. Other causes include atrial fibrillation, ischemic cardiomyopathy, myocardial infarction, mitral stenosis with or without atrial fibrillation, prosthetic valves, septic endocarditis, atrial myxoma, fat emboli, septal aneurysm, ascending aortic atherosclerosis, stenosis of artery, emboli from left atrium or ventrium, dissecting aneurysm of aorta, alcohol abuse and pregnancy. All of these situations may cause thrombosis from the left side of heart or systemic circulation and should be differentiated carefully before making a diagnosis of paradoxical embolism. Paradoxical embolism may be associated with a hypercoagulable state, factor C or S deficiency, resistance to activated protein C, prothrombin mutations and carcinoma. Deep venous thrombosis 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. Treatments Patients having a very high risk of thrombosis are stratified as also having a high risk of pulmonary embolism, for which a plan of care based on thrombolysis or thromboembolectomy, in addition to heparin anticoagulation, should be undertaken.7 There was no evidence-based result to show which is better for paradoxical embolism patients between thrombolysis or thromboembolectomy. Medical care The initial treatment is anticoagulation to prevent propagation of an intracardiac clot. Anticoagulation can be in the form of heparin, low molecular-weight heparin. Thrombolytics are another alternative available therapy when acute cor pulmonale or hemodynamic instability is present. Anticoagulation and thrombolytics can be used separately or at the same time, when there are no contraindications. Thrombolytics include the recombinant tissue-type plasminogen activator (tPA), reteplase and TNKase. Contraindications include intracranial disease, recent surgery or trauma. It has additional advantage of treating associated PE and acute arterial occlusion of the extremities. This can lead to immediate decrease in pulmonary artery pressure and can reduce the incidence of recurrent paradoxical embolism. Treatment of the underlying disease which increased right atrial pressure is intended to reverse the right-to-left shunt, restoring the hemodynamic homeostasis. DVT and PE in conjunction with paradoxical embolism can be treated with long-term anticoagulation in the form of warfarin when surgical intervention is not an option. Antiplatelet therapy may be beneficial if anticoagulants are contraindicated. They also are beneficial in the treatment of TIA, which can be a presentation of paradoxical embolism. Surgical care Surgical therapies include embolectomy and closure of the intracardiac communication (usually a PFO). Surgical embolectomy with closure of a PFO or ASD appears to be the best treatment option for patients with an impending paradoxical embolism; except in fixed pulmonary hypertension where indefinite anticoagulation is an acceptable option. For those with indications of surgery, pulmonary thromboembolectomy started before the deterioration of hemodynamic indices may have a better outcome.8 Interventional therapeutic procedures Interventional therapeutic procedures can be used in several steps in the treatment of paradoxical embolism; selective transcatheter thrombolytic and thrombus fragmentation therapy, inferior vena cava filter and transcatheter closure of intracardiac communication. Wang et al9 reported thrombus fragmentation and transcatheter thrombolytic therapy should be used especially in severe cases of operation-induced acute cardiogenic shock type of pulmonary embolism or acute cor pulmonale type of pulmonary embolism. And it produces significant results. Inferior vena cava interruption with caval filters, such as a Greenfield filter, can be used. However, they are not protective against emboli which are too small. Transcatheter closure of intracardiac communication is an alternative option to surgical closure. Wahl et al10 reported a multi-center study of transcatheter treatment of atrial septal aneurysm associated with patent foramen ovale as safe and effective in patients with paradoxical embolism. The procedure effectively abolishes right-to-left shunt and decreases atrial septal mobility. Long-term prevention of recurrent events appears favorable when compared to patients with PFO alone. Transcatheter closure of PFO or ASD has been a promising alternative to surgical closure and a promising treatment for patients who are unable to tolerate long-term anticoagulation or who are poor surgical candidates. Complications of nonsurgical closure of PFO or ASD for paradoxical embolism include risks of recurrent neurologic events due to significant residual shunting and the development of a displaced fractured device-arm friction lesion. Residual shunting eventually may lead to surgical closure when recurrent neurologic deficit or stroke complicates transcatheter PFO or ASD closure. CLINICAL DIFFICULTIES The clinical difficulties of paradoxical embolisms are listed as follows: (1) Difficulties in diagnosis: as mentioned above, paradoxical embolism had no peculiar clinical symptoms, so the diagnosis mainly depended on clinical history of arterial obstruction and examination such as duplex venous ultrasonography, spiral computed tomography (CT) scan and transthoracic and transesophageal echocardiography for right to left channel. Some of the emboli are too small to be detected or have been spontaneously lysed and fragmented. Acute pulmonary embolism is a common disease but easy to be misdiagnosed. In order to decrease the rate of misdiagnosis and missed diagnosis it is necessary to raise the consciousness of diagnosis.11 (2) Devastating outcome may be a concern to complications such as neurological deficits, gangrene of extremities, amputation, blindness and renal infarction with eventual renal insufficiency depending on where the emboli arrived. (3) Adverse reactions from intravenous contrast agents may occur. (4) Some effective treatments can lead to morbidity and mortality. Thrombolysis may cause severe hemorrhage. An inferior vena cava filter may cause new thrombosis resulting from the device. Transcatheter closure of PFO may lead to residual shunting.12 (5) For surgical embolectomy and closure of PFO, operative mortality of pulmonary thromboembolectomy ranges from 8% to 75%, related to resuscitation history, hemodynamic stability and, possibly, the need for life support.7 The benefits should be weighed against the risks when choosing a treatment strategy. Patients and their families should be provided with a thorough explanation about the outcome of the intervention. PERSONAL OPINIONS In this case, the patient was bedridden because of hemiplegia. The symptoms of fever, dyspnea, tachycardia and sweating suggested the possibility of pulmonary embolism. CT scan supported the clinical diagnosis of pulmonary embolism. Bedside transthoracic and transesophageal echocardiography showed a large tubular thrombus waving in the right and left atrium across the patent foramen ovale. Impending paradoxical embolism could be diagnosed and it was proven by operation later.13 With regard to the diagnosis of the stroke in this case, it is difficult to differentiate between embolism and thrombosis of the cerebral artery clinically or with imaging. Young patients, who had less or no stroke risk factors such as high blood pressure, diabetes, smoking, drinking etc, could be thought of as having an embolism rather than thrombosis. This patient had several risk factors and his onset of hemiplegia was found after getting drunk in the preceding night. More over, CT and MRI in another hospital suggested cerebral thrombosis. The diagnosis of thrombosis of cerebral artery was thus entertained and it is possible that the bed-ridden state resulting from hemiplegia predisposed him to the risk of deep vein thrombosis. For this patient with impending paradoxical embolism, who recently had the presence of a thrombosis in the right middle cerebral artery with some signs of brain bleeding, thrombolysis might cause brain bleeding to become more severe and embolectomy and closure of the right to left shunt could be a better choice.