Catheterization and Cardiovascular Diagnosis 2:137-142 (1976)

CINE ANGIOGRAPHIC DIAGNOSIS OF PATENT FORAMEN OVALE IN PARADOXICAL EMBOLISM Gerald P. Tracy, M.D., HaroldSmulyan, M.D., James L. Potts, M.D., Robert H. Eich, M.D., and Lewis W. Johnson, M.D. A case of paradoxical embolism is presented in which the antemoflem diagnosis was facilitated by a new simple angiographictechnique that demonstrateda patent foramen ovale. An additional 14 patients were studied by this technique, and one had a patent foramen ovale. The mechanism of reversal of the normal intraatrlal pressure gradient and subsequent right to left shunt through a patent foramen ovale is discussed. This angiographictechnique may be readily applied in any diagnostic catheterizationlaboratory and complements existing methods for detecting patency of the foramen ovale in patients with suspected paradoxical embolism. Key words: paradoxical embolism, patent foramen ovale

INTRODUCTION

Conheim (1) first demonstrated that a venous embolus could traverse an intracardiac defect to cause arterial occlusion. Since then numerous cases of paradoxical embolism have been reported, but only 16 have been diagnosed during life ( 2 4 ) . The diagnosis is made by the presence of venous thromboembolism, arterial embolism, and a communication by which an embolus can pass from the venous to the arterial system. Most often the shunt is through a patent foramen ovale, hence the importance of documenting this lesion. The purpose of this report is to present an illustrativecase, describe a new, simple angiographic technique to identify a patent foramen ovale, and to discuss the pathophysiology of paradoxical embolism. From the State University of New York, Upstate Medical Center Syracuse, New York

Reprint requests to: Dr. L. W. Johnson, State University Hospital, 750 East Adams Street, Syracuse, New York 13210. Received June 5, 1975, accepted October 2. 1975.

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CASE REPORT A 33-year-old female was admitted to the hospital because of cough, dyspnea, and left precordial and right calf pain of 1 week duration. There was no antecedent phlebitis, cardiac disease, trauma, recent surgery, or prolonged bed rest. She had had 1 1 pregnancies, and a tuba1 ligation was performed one year ago. Physical examination revealed an obese woman in moderate respiratory distress. The pulse was 100/min and regular, blood pressure was 158/88 mm Hg, respiratory rate was 36/min, and temperature 36.6" C. Carotid pulses were normal, and the neck veins could not be evaluated because of obesity. The lungs were clear. There was a right ventricular lift, and the pulmonic component of the second heart sound was accentuated. There were no murmurs, gallops, or rubs. The abdomen was soft and nontender. Peripheral pulses were decreased in the right lower extremity, and the dorsalis pedis pulses were not palpable in either foot. The right leg was tender over the anterior compartment of the calf with a positive Homan's sign, and the left leg was slightly warmer than the right. There was no appreciable difference in calf size. Chest Xray showed borderline cardiomegaly and clear lung fields. The electrocardiogram revealed sinus tachycardia, low voltage, QRS frontal plane axis of +90", and nonspecific repolarization abnormalities. The hematocrit was 45%. and the hemoglobin was 15.6 gm%. Arterial blood gas analysis on samples obtained while breathing room air showed: pH, 7.48; P O 2 , 42 mm Hg; oxygen saturation, 82%; PCOz, 24 mm Hg. A lung scan showed multiple perfusion defects involving both lung fields. The initial diagnoses were thrombophlebitis of the lower extremities, pulmonary embolism, and an anterior compartment syndrome of unknown etiology involving the right calf. Anticoagulation with heparin was begun. Three days later she underwent fasciotomy of the right anterior compartment with some improvement over the next few days. However, she continued to have leg pain, with no posterior tibia1 o r dorsalis pedis pulses present. Ten days after admission the right foot appeared cool and mottled. An arteriogram showed multiple peripheral arterial emboli to the lower extremities. A bilateral embolectomy was performed, and the extracted clot was later reported to have the microscopic structure of a venous thrombus. The diagnosis of paradoxical embolism was suspected. Right heart catheterization and pulmonary arteriography were performed. Pressures in mm Hg were: brachial artery 200/113, right atrial mean 5, right ventricle 81/11, pulmonary artery 76/22, and pulmonary capillary wedge mean 6. There was no oxygen step-up in the right heart chambers. The pulmonary angiogram showed multiple large bilateral filling defects. A right atrial angiogram documented the presence of a patent foramen ovale with right to left shuntingof the contrast agent utilizing the technique described below. She was continued on intravenous heparin. The following day the inferior vena cava was ligated just below the renal veins. She was discharged 8 days later on maintenance warfarin sodium. Five months later the patient was admitted for reevaluation. The pulmonary artery pressure at rest was 30/11 mm Hg and increased to 44/13 after angiography. The intraatrial defect with right to left shunting was again demonstrated by right atrial angiography. Subsequent oximetry was

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performed and showed right to left shunting after release of the Valsalva maneuver. Because of chronic predisposition to venous thrombosis, persistence of the shunt with a Valsalva maneuver, and a repeat lung scan which suggested further pulmonary embolism after IVC ligation, it was elected to close the defect. At surgery a patent foramen ovale with a diameter of I cm was closed. She was discharged after an uneventful recovery. METHODS Fourteen additional patients, aged 2 7 6 7 years, undergoing diagnostic right and left heart catheterization were studied. Right atrial cine angiograms were performed after completion of the diagnostic study. Using a rotating cradle, the patient was placed in a 45" left anterior oblique position, thus putting the intraatrial septum in profile. The angiographic catheter tip was positioned at the junction of the superior vena cava and right atrium and 40 cc of meglumine diatrizoate were injected over a 2-sec period. Cine angiograms were recorded on 35 mm film at 60 fps and on videotape. In 5 patients the hemodynamics of a standardized Valsalva maneuver were studied. A no. 7 Cournand catheter was placed in the pulmonary capillary wedge position and in each instance confirmed by oxygen saturation and analysis of wave form. A second no. 7 NIH angiographic catheter was positioned in the midright atrium. Simultaneous right atrial and pulmonary capillary wedge pressures were recorded during a Valsalva maneuver. Patients with angiographic evidence of a right to left shunt through a patent foramen ovale were further studied. A small polyethylene catheter was introduced percutaneously into the right o r left brachial artery. Oxygen saturations of samples from venous and arterial blood were determined on an American Optical oximeter for standardization. A Valsalva maneuver was standardized to produce a 40 mm Hg pressure over a 10-15 sec interval. Blood was continuously withdrawn from the brachial artery during the Valsalva maneuver and passed through a Gilford oximeter with a 630 m p filter while oxygen saturation was continuously recorded on a DR-8Electronics for Medicine recorder. RESULTS Of the 15 patients who had right atrial cine angiograms 2 were found to have definite evidence of a right to left shunt through a patent foramen ovale. In the presence of a patent foramen ovale, contrast may be seen under the membrane covering the foramen ovale and then crossing through the foramen into the left atrium. This angiographic appearance differs markedly from a patient without a patent foramen ovale (Fig. 1). In the 5 patients studied hemodynamically the pulmonary capillary wedge pressure exceeded right atrial pressure at rest. In each instance both the right atrial pressure and pulmonary capillary wedge pressure increased during the Valsalva maneuver. However, by the end of o r directly after the release of the Valsalva maneuver, right atrial pressure transiently equaled o r exceeded wedge pressure (Fig. 2). The two patients with definite right to left shunting through a patent foramen ovale also had a drop in arterial saturation after the release of the Valsalva maneuver.

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Fig. 1. The upper panel (A) shows a single frame from a normalcineangiogramwith an intact atrial septum. The lower panel ( 6 )shows contrast agent passing from the right atrium into the left atrium via a patent foramen ovale. IVC = inferior vena cava; RA = right atrium; SVC = superior vena cava. '

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VALSALVAFig. 2. An example of the effect of a Valsalva maneuver on the simultaneously recorded right atrial and pulmonary capillary wedge pressures. Before and after Valsalva wedge pressure exceeds right atrial pressure. During the Valsalva they equalize. EKG = electrocardiogram; PCW = pulmonary capillary wedge pressure; RA = right atrial pressure.

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DISCUSSION

Paradoxical embolism, although potentially lethal or disabling, is rarely diagnosed during life. The hallmarks of the diagnosis are unexplained arterial embolism, venous thromboembolism, and an intracardiac communication. In a review of 82 consecutive cases of peripheral arterial embolism, 94% could be accounted for by associated mitral stenosis, atrial fibrillation, or a previous myocardial infarction (7). The intracardiac defect and right to left shunt are usually through a patent foramen ovale. A drop in oxygen saturation during the Valsalva maneuver was first used to prove right to left shunting across an intraatrial communication (8). Later various substances including ascorbate (9), hydrogen (lo), krypton (1 11, freon (121, and indocyanine green (13) were injected into the right side of the circulation with the early appearance of the indicator on the arterial side signifying a right to left shunt. Indocyanine green is probably the least complicated technique and has been used for diagnosis of small atrial defects in animals and man (13). Angiography has not previously been used to identify a patent foramen ovale in suspected paradoxical embolism. The left anterior oblique projection at approximately45" waschosen to place the intraatrial septum in profile. In 1 ofthe additional 14 patients studied contrast agent definitely passed through a large patent foramen ovale and to the left atrium. The presence of a large patent foramen ovale in 1 of 14 adults is the expected incidence of this abnormality (14,15). The mechanism allowing the passage of an embolus from the right to the left side of the circulation involves the reversal of the usual gradient in which left atrial pressure exceeds right atrial pressure. Right heart failure, either due to obstructive lung disease or due to massive pulmonary embolism, may cause right atrial pressure to exceed left atrial pressure. During a Valsalva maneuver, even in normal individuals, the right atrial pressure transiently exceeds or equals the left atrial pressure. When right atrial pressure exceeds left atrial pressure a right to left shunt may occur if there is an associated anatomical defect. In our patients this reversal of pressure gradient occurred either by the end of a Valsalva maneuver or immediately after. The pressure in these cases remained reversed for several seconds. This was even seen in one patient with marked elevation of wedge pressure secondary to mitral stenosis. All patients perform a modified Valsalva maneuver during breath holding for angiography. This is the probable mechanism for the right to left shunt seen on cine angiography in our cases. In the 2 patients with angiographic demonstration of a right to left shunt we were subsequently able to show a drop in arterial oxygen saturation after Valsalva release. This further confirmed the presence of a shunt. Our patient is the 17th reported case of paradoxical embolism diagnosed during life. To our knowledge she is the first to have angiographic preoperative identification of a patent foramen ovale and operative confirmation of this finding. She was initially treated in the usual fashion with anticoagulation and interruption of the inferior vena cava. Recently the advisability of caval interruption alone has been questioned (16). Because of a chronic predisposition to thrombophlebitis, possible embolization through venous collateral channels, and persistent pulmonary hypertension. closure of the patent foramen ovale was advised.

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The advantages of the cine angiographic method are: ( I ) ease of performance during the right heart catheterization and pulmonary angiography without significant increased risk to the patient: ( 2 ) immediate anatomical demonstration on video tape. The following approach is suggested in a patient with suspected paradoxical embolism: ( I ) anticoagulation with heparin if the diagnosis is seriously considered and there are no contraindications; (2) exclusion of other causes of arterial embolism such as previous myocardial infarction, atrial fibrillation, mitral stenosis, or left atrial myxoma; (3) lung scan to document pulmonary embolism; (4)right heart catheterization with cut film pulmonary angiography and right atrial cine angiography as described. Treatment must be individualized but should include anticoagulation and probably inferior vena caval ligation. Recommendation for closure of the patent foramen ovale depends on the presence of a chronic predisposition to pulmonary embolism and/or persistent right atrial hypertension. REFERENCES J: Thrombose und Embolie. Vorlesungen Uber Allgemeine Pathologie. Zv Berlin. Hirschwald 1:134, 1877. Meister SG, Grossman W, Dexter L. et al: Paradoxical embolism. Amer J Med 53:292-298. 1972. Gazzaniga AB and Dalen JE: Paradoxical embolism: its pathophysiology and clinical recognition. Ann Surg 171:137-142, 1970. Hunter DD: Pulmonary arteriovenous malformation. Canad Med Ass J 93:662-665. 1965. Sisel RJ. Parker BM and Bahl OP: Cerebral symptoms in pulmonary arteriovenous fistula. Circulation 41:123-128. 1970. Steiger BW, Libanoff AJ and Springer EB: Myocardial infarction due to paradoxical embolism. Amer J Med 4 7 9 5 - 9 9 8 . 1969. Edwards EA, Tihey N and Lindquist RC: Causes of peripheral embolism and their significance. JAMA 196:119-124. 1966. Lee G and Gimlette T: A simple test for interatrial communication. Brit Med J 1:1278-1281, 1957. Levy A. Monroe R, Hugenholtz P. et al: Clinical use of ascorbic acid as an indicator of right to left shunt. Brit Heart J 29:22-29. 1967. Clark L. Bargeron L , Lyons C. et al: Detection of right to left shunts with an arterial potentiometric electrode. Circulation 22949-955, 1960. Long R. Braunwald E and Morrow A: Intracardiac injection of radioactive krypton. Circulation 21:I 126-1 133. 1960. Amplatz K. Jeffery R. Gobel F. et al: The freon test. Circulation 39551-556, 1969. Banas J , Meister S. Gazzaniga A, et al: A simple technique for detecting small defects of the atrial septum. Amer J Cardiol 28:467-471. 1971. Thompson T, Evans W: Paradoxical embolism. Quart J Med 23:135-150. 1930. Johnson BI: Paradoxical embolism. J Clin Path 4:316-332, 1951. Editorial. Brit Med J 1:630-631, 1973.

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Cine angiographic diagnosis of patent foramen ovale in paradoxical embolism,.

Catheterization and Cardiovascular Diagnosis 2:137-142 (1976) CINE ANGIOGRAPHIC DIAGNOSIS OF PATENT FORAMEN OVALE IN PARADOXICAL EMBOLISM Gerald P. T...
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