Patent Foramen Ovale and its Significance in the Perioperative Period

Patent foramen ovale (PFO), usually a benign and silent lesion (Fig. 1), can cause hypoxemia and embolic phenomena under circumstances when right atrial (RA) pressure exceeds left atrial (LA) pressure or when preferential flow from the inferior vena cava (IVC) toward the PFO persists, as in the prenatal circulation (1–3). These circumstances may occur during the perioperative period as a result of the effect of mechanical ventilation, thromboembolism or air embolism, the altered anatomic relationship between the IVC and interatrial septum, or an increase in intraabdominal pressure. Although not extensively studied, numerous case reports implicate PFO as a causative factor for hypoxemia and systemic thromboembolism in the perioperative period. In the following review, we describe the epidemiology, pathogenesis, modern methods of detection, and general clinical importance of PFO. In particular, we highlight the significance of PFO in the perioperative period.Figure 1: Patent foramen ovale.Development, Epidemiology, Pathogenesis, Detection, and Management Development During prenatal life, PFO is a fenestration in the septum secundum, bordered on the left side by the septum primum, which allows blood flow from the RA to the LA. After birth, when LA pressure exceeds RA pressure, the PFO closes functionally with permanent closure caused by adhesion occurring within the first year of life (4). Although a large PFO is sometimes a functional atrial septal defect (ASD), this should not be confused with true ASD, particularly of secundum type (Table 1).Table 1: Atrial Septum Defects versus Patent Foramen OvaleEpidemiology A PFO is a common finding in approximately 25% of postmortem examinations. For example, Hagen et al. (5) identified PFOs in 263 of 965 autopsies. PFOs were found to range from 1 to 19 mm, with the size increasing with age, whereas prevalence declined. There was no significant difference in the incidence and size of PFO between men and women. In another study, Thompson (6) found a “pencil patent” PFO (0.6–1 cm) in 6% of cases and a “probe patent” PFO (0.2–0.6 cm) in 29% of cases among 1000 random autopsies. The presence of a PFO is highly associated with atrial septal aneurysm. This association was demonstrated in the multicenter study of Mugge et al. (7), in which 54% of patients with atrial septal aneurysm (protruding >10 mm beyond the plane of the intraatrial septum) showed intraatrial shunting, in the majority of cases through a PFO. Pathogenesis Three factors are important in determining the likelihood that a PFO will be of clinical significance: (a) its size, (b) the pressure gradient between the RA and LA, and (c) the direction of IVC flow. A large PFO in combination with a transient or persistent right-to-left pressure gradient or IVC flow directed through the PFO will allow unwelcome material, such as deoxygenated blood, thrombi, or air, to enter the systemic circulation. The size of a PFO probably does not change over time, with the exception of smaller lesions, which can undergo spontaneous closure (5). The RA pressure can increase as part of everyday life, e.g., coughing, retching, or hypoxic pulmonary vasoconstriction at high altitude (8), or it can result from specific clinical situations, as will be described later. In addition, the direction of the blood flow in the RA may change in situations such as right lung resection when, as a result of postoperative shift of the mediastinum, the angle between the IVC flow and the intraatrial septum may be altered and preferential flow through a PFO may develop (3). Detection Modern methods of PFO detection include transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), and transcranial Doppler imaging. TEE is now considered to be the “gold standard” on the basis of comparison with postmortem studies and with other methods (Table 2) (9–11). The resolution of two-dimensional ultrasound technology is not yet high enough, however, to identify an actual defect except where a PFO is very large. Therefore, passage of contrast material or color flow through the defect should be demonstrated to establish the diagnosis. Under normal circumstances, LA pressure is higher than RA pressure; hence, a provocative procedure that temporarily reverses this relationship needs to be applied to demonstrate the passage of the contrast (usually agitated saline) through the interatrial septum. Provocative procedures include a Valsalva maneuver or coughing. Either maneuver results in a reduction of blood flow into the thorax because of an increase in intrathoracic pressure. Upon sudden release of the intrathoracic pressure, blood rapidly enters the thoracic cavity and fills the RA, creating a temporary transatrial pressure gradient (RA > LA), which remains until flow equilibrates. Agitated saline or blood injected IV at this time will “cross” the PFO from right to left, demonstrating its presence and confirming the diagnosis (Fig. 2). Contrast-based methods may lead to false-negative results when LA pressure far exceeds RA pressure and a pressure gradient cannot be reversed with any provocative maneuver. Assessment of flow through the PFO with color Doppler imaging (Fig. 3) avoids this limitation, but it assumes continuous left-to-right flow (unless a provocative maneuver is used). Continuous left-to-right flow is not seen in PFOs unless they are both anatomically and functionally open.Table 2: Sensitivity and Specificity of Standard Diagnostic Tests for PFO DetectionFigure 2: Air bubbles seen in the left atrium (arrow) of the patient with patent foramen ovale after IV injection of agitated saline.Figure 3: Left-to-right shunt through the patent foramen ovale (arrow) demonstrated with color Doppler imaging.With respect to the TEE diagnosis of PFO, Schneider et al. (9) validated the use of TEE for PFO detection by comparison with autopsy finding in 35 consecutive patients. All PFOs were correctly identified by the color Doppler imaging, but only eight of nine were diagnosed by means of a contrast study. This corresponds to sensitivities of 100% and 89%, respectively. The specificity of both methods was 100%. In contrast, Konstadt et al. (12), by using TEE for PFO detection in 50 patients undergoing elective cardiac surgery, were able to identify PFO in 11 patients (22%). Color flow through the shunt was seen in only three patients. However, in two of these patients, contrast studies failed to identify a PFO. Luotolahti et al. (10) found similar results in patients who had experienced cryptogenic stroke. Contrast TEE identified a PFO in 21 of 28 patients, whereas color Doppler imaging was positive in only 17 of these 28 patients. The combination of both methods allowed the identification of a PFO in 24 of 28 patients with cryptogenic stroke. Di Tullio et al. (11) compared TTE and transcranial Doppler imaging with TEE for PFO detection and found that transcranial Doppler imaging was more sensitive than TTE (68% and 47%, respectively), but both methods were 100% specific. The transcranial Doppler technique to detect PFO is based on the transient enhancement of an ultrasound signal reflected from air bubbles passing through cerebral arteries. It is a blind technique and, as with contrast echocardiography, it also relies on the creation of a temporary pressure gradient between the RA and LA with a provocative maneuver. An indicator dilution technique and pulse oximetry have also been used in combination with a provocative maneuver to detect a transient left-to-right shunt (13). Karttunen et al. (14) have recently validated these methods in 103 cryptogenic stroke patients. They compared pulse oximetry and indicator dilution technique with contrast TEE and found that pulse oximetry had a sensitivity and specificity of 85% and 100%, whereas with indicator dilution technique these were 76% and 100%, respectively. In contrast, Sukernik et al. (15) evaluated pulse oximetry in 42 patients before coronary artery bypass grafting (CABG) and found a sensitivity of 27% and a specificity of 83%. Sensitivity for large PFO (more than 20 bubbles crossed) was slightly higher (40%). The difference in these results can probably be partly attributed to differences in the target populations, difference in pulse oximetry probe placement (ear versus finger), and the sophistication of the computer algorithm used by Karttunen et al. (14). More work needs to be done before this promising technique can be recommended as a screening method for PFO detection. Ay et al. (16) reported that an M-shaped bifid notch, an electrocardiographic sign of ostium secundum ASD, can be seen in patients with PFO. The sensitivity and specificity of this method were 36% and 91%, respectively. Management Asymptomatic PFO does not usually require any intervention. However, if hypoxemia develops or a patient experiences paradoxical embolism, treatment is usually indicated. This may include measures directed toward decreasing RA pressure (inotropes, nitric oxide, or thrombolysis) (17–19), prevention of thrombus formation (anticoagulation), or PFO closure. PFO closure may be accomplished at open heart surgery or as a percutaneous procedure (20) (Fig. 4).Figure 4: Percutaneous closure of the patent foramen ovale (courtesy of AGA Medical Corporation, Golden Valley, MN).Pathologic Consequences of a PFO in Patients with Normal RA Pressure In certain situations, despite normal RA pressure, right-to-left shunt may develop. These situations may be caused by transient, rather than mean, interatrial right-to-left pressure gradients resulting from a Valsalva-like activity, such as coughing, or they may be caused by contraction of the RA against a stiff right ventricle. Further preferential flow from the IVC toward the fossa ovalis may be the mechanism responsible for right-to-left shunt in some cases (1). For example, Gallaher et al. (21) described three patients with a PFO, normal RA pressure, and a large eustachian valve and postulated that the eustachian valve was responsible for directing IVC flow toward the PFO, as is the case in prenatal life. Several other case reports describe hypoxemia occurring in association with a PFO in otherwise healthy subjects. Strunk et al. (1) described four patients with PFO who experienced decreased oxygen saturation and dyspnea. One patient had mild chronic obstructive pulmonary disease, and the others had no associated pulmonary or cardiac involvement. Contrast echocardiography revealed a right-to-left intraatrial shunt in all four subjects. Three of these four patients underwent surgical closure of the PFO, with a resultant increase in oxygen saturation and symptomatic improvement. Godart et al. (22) reported 11 cases of hypoxemia in the presence of normal RA pressure in patients with PFO or a small ASD. All of these patients were treated by percutaneous closure of the defect. There were no episodes of desaturation in the 30-day follow-up period in any of these patients. PFO was found almost twice as often in young patients who experienced cryptogenic embolic stroke when compared with the general population (23,24). This observation suggests an underlying mechanism of paradoxical embolism. Lechat et al. (23) used TEE to study the prevalence of PFO in 60 patients under 55 yr old who had an ischemic stroke and a normal cardiac examination. They found a PFO in 40% of these patients and in only 10% of controls. In addition, Van Camp et al. (24) found a significant relationship between stroke and early and massive passage of contrast into the LA on TEE evaluation. Kozelj et al. (25) published a case report of a stroke in the postpartum period in a patient with a PFO and no other significant risk factors. Migraine with an aura, transient amnesia, and retinal thrombosis are other manifestations of possible paradoxical embolism that have been described. Anzola et al. (26) compared the prevalence of PFO in 113 patients who had migraine with aura with 53 patients who had migraine without aura. The prevalence of PFO was 48% vs 23%, respectively. This finding suggests that paradoxical microembolization in the terminal vertebrobasilar territory might cause some cases of migraine with aura. Klotzsch et al. (27) evaluated 53 consecutive patients with transient global by use of transcranial Doppler imaging. They found a PFO in of the patients and in 27% of controls. a study of et al. revealed a possible association between PFO and of the and Patients with PFO and a of paradoxical embolism are at risk for embolic stroke in patients with a PFO may be as as and PFO closure have been for stroke prevention in these patients et al. by using a that if the stroke exceeds which is the case in paradoxical embolism, or closure of the defect is a in comparison with Although the clinical of these are yet to be percutaneous PFO closure et al. (20) patients with a of at of paradoxical embolism after percutaneous closure of PFO for yr The incidence for was for transient ischemic was and for was shunt was a of paradoxical embolism. another in which a PFO can result in an likelihood of The suggests that with a PFO are at risk of bubbles that develop during and are in the pulmonary may cause an increase in pulmonary artery pressure. These in combination with a Valsalva by to pressure, can right-to-left intraatrial and systemic embolism. the risk of on the basis of the of three studies and that PFO the for this PFO may also be important in the of et al. TTE on a who hypoxemia after to on They demonstrated significant pulmonary in this patient with continuous right-to-left flow through a PFO. after the patient to a TTE was and showed no pulmonary and no of right-to-left They that hypoxic pulmonary vasoconstriction in patients with PFO may a and result in PFO in with RA Pressure Continuous right-to-left shunt a PFO with hypoxemia been described in cardiac with significant and and it been associated with right et al. found that PFO was associated with in patients with pulmonary embolism. stroke and embolism were more among patients found to have a PFO with an risk of such PFO in approximately of patients with chronic pulmonary and obstructive and may to hypoxemia and the of pulmonary to et al. described a case of hypoxemia that after in a healthy patient with PFO. A revealed pulmonary and right The patient was treated with an after the of an of the pulmonary pressure decreased from 50 to mm and oxygen saturation from 85% to that right-to-left of blood et al. described a case of by and The patient despite postmortem a large PFO was that the cause of was a right-to-left shunt from pulmonary et al. published a case of and hypoxemia in a with and a PFO. underwent percutaneous closure of PFO with resolution of PFO in the study been to the possible significance of PFO in the perioperative an of case reports suggests an association between PFO and perioperative hypoxemia and embolism with a to right-to-left shunt through the PFO are in 3: with a the air embolism resulting in paradoxical embolism during placement or of or been described in case reports to et al. passage of the air through the pulmonary circulation is a possible in PFO was in 40% of reported been used to such of blood been described during the from general when to the may to a temporary positive pressure gradient between the RA and the LA. et al. published an a case of in a the of surgery, despite the use of 100% desaturation from 100% to was during of was and the oxygen saturation TTE with color flow Doppler imaging revealed a small left-to-right The was and the patient to the by During this oxygen saturation decreased and color flow Doppler imaging demonstrated of the small left-to-right shunt to a right-to-left with 100% oxygen in a of oxygen saturation to 100%, and the patient was et al. compared the effect of of positive pressure on shunt in patients who had a PFO with patients who not have a PFO. They found that shunt in the majority of patients with a PFO when was whereas it decreased in patients without a PFO. In a case report by et al. right-to-left shunt through a PFO, by TEE in the early of mechanical ventilation, continuous after the of of Although the mechanism of right-to-left shunt is not these that the increase in pulmonary might be responsible for this The studies that hypoxemia should not be treated with in patients with PFO. fossa surgery in the may patients with a PFO to risk from paradoxical air embolism. In these patients it is to the patient a PFO because the incidence of air embolism during fossa surgery from 25% to 100%, on the method of detection used et al. by using found that paradoxical air embolism air embolism in of 21 patients during in the cases of paradoxical air embolism were described by et al. during procedures in the with to possible of cerebral or coronary arteries. et al. by using identified a PFO in of patients for fossa surgery or in the In this patients with PFO were from surgery in the of 17 patients undergoing fossa paradoxical air embolism. the basis of the that air embolism was in 76% of fossa and in 25% of the that the for a PFO should be for all in the and if a PFO is the should be They also that a risk of paradoxical air embolism despite by Patients with a PFO undergoing a procedure are probably at risk for the of perioperative paradoxical embolism compared with the general surgical This difference in risk may to the incidence of thrombosis associated with this surgery and the of embolism. et al. described a case of paradoxical embolism after case of cerebral resulting from paradoxical embolism was reported by and in a patient from the of a et al. described two cases in which pulmonary embolism cerebral after patients were diagnosed with PFO by These that the increase of RA pressure as a result of in pulmonary might be an important factor for paradoxical embolism in patients with PFO because these may open a right-to-left They that the diagnosis of paradoxical embolism should be considered in the presence of right-to-left shunt (PFO), and embolism without of Several case reports have been published the of oxygen desaturation after or in patients with PFO in the is usually by of when the patient is through a PFO often develops in the of a pressure gradient between the RA and LA, in the case of a right to the altered anatomic which results in preferential flow from the IVC through the PFO (3). PFO closure in these patients and of Although it been that and are of thoracic surgery, the actual of these are not and have probably been because and oxygen saturation are often attributed to pulmonary embolism, heart or lung rather than to (3). et al. reported three cases of the or of a right-to-left shunt in patients diagnosed with PFO after an otherwise The postulated for this increase in were the of a right a small pulmonary transient right or a of the right et al. reported a case of hypoxemia caused by PFO in a who right after surgical closure of an an The after the of nitric A case of pulmonary embolism that right-to-left through a PFO and desaturation on the postoperative after was described by et al. The patient was and treated with with of within The patient was on and from the without bypass is a more can be in patients with PFO because of the heart may lead to an increase of RA pressure, with the of and published a case report a patient with and coronary artery in was the heart was by a under the oxygen saturation decreased to pressure decreased to mm and the RA pressure from to mm of the reversed the hypoxemia and TEE was and showed no defect. However, when the was under the RA pressure and a significant right-to-left shunt was demonstrated through the PFO by bypass was was and the PFO was et al. two patients with right-to-left shunt from a PFO who after valve The shunt in patient and decreased in another after 1 and yr of respectively. embolic was in these patients. All patients undergoing left placement should be for the presence of PFO. PFO should be in this because the left heart will a permanent right-to-left shunt through the PFO, with hypoxemia resulting from a silent PFO was described after heart the heart usually high pulmonary in the and this can right-to-left shunting, a for a PFO needs to be and, if the PFO needs to be air embolism with paradoxical embolism also been reported in that the of PFO in these patients may also be important et al. reported a case of right-to-left shunt through a PFO during for by The patient had a of valve with They that an intraabdominal pressure of mm might have to intraatrial Although the mechanism for this is not they that an increase of intrathoracic pressure to might be a PFO in the Although the prevalence of PFO in patients undergoing surgery is very the presence of PFO is probably of significance in patients. However, the of a PFO should be in in the diagnosis of perioperative when hypoxemia is of to pulmonary or and cannot be by increasing oxygen or with may be a to the presence of PFO. embolism without an should the of a possible PFO for PFO the basis of the we that screening for PFO is only in situations in which its may be and a is e.g., fossa Although TEE the it is and an The procedure is if on patients. TTE and transcranial Doppler are and may also be used for the screening with the that PFOs be oximetry is an and which some as a screening but needs evaluation. In cardiac surgery when TEE is a for a PFO should be The fossa ovalis of the septum can be from the usually in a Color flow of this should be first without a Valsalva-like maneuver to for a a positive pressure of 20 should be to the and color flow is of the intraatrial septum toward the LA after pressure release the of a right-to-left pressure gradient to identify a right-to-left A contrast study should the for a right-to-left This is by the injection of of agitated saline and positive pressure release as as the contrast material is in the of In patients with a of paradoxical embolism associated with PFO, PFO closure or perioperative should be when an with a incidence of postoperative thrombosis is for the method of prevention of paradoxical embolism have not yet been the results of clinical these results are a on or PFO closure is the method of treatment should be this this should be by a the and Management of The of a right-to-left shunt can be accomplished by the of positive nitric oxide, or both in the of right or pulmonary the of or in cardiac in pulmonary embolism not if other methods PFO closure. PFO closure should be considered when hypoxemia does not with time, as in after In cardiac surgery, we that PFO should be if the intraatrial septum is for other such as for or valve surgery, or when the of hypoxemia are very as in left In other cardiac such as coronary or valve the to a PFO needs to be During heart the heart should be for a PFO and, if the PFO should be before the heart is In the of paradoxical embolism of air, can be considered to the size of the air bubbles and a large oxygen to ischemic develop on the perioperative of studies by clinical to be These studies should include patients with right-to-left shunt or of paradoxical embolism or who undergo surgery in the lung or The results of clinical on prevention of paradoxical embolism and cryptogenic embolism PFO in cryptogenic stroke should on the of methods of paradoxical embolism and PFO closure.