Characteristics of adult patients with atrial septal defects presenting with paradoxical embolism

Background : The association between patent foramen ovale (PFO), atrial septal aneurysm, and cryptogenic stroke due to paradoxical embolism has been established. The correlation between atrial septal defect (ASD) in adults and paradoxical embolism is less well defined. Methods : We examined our single center experience with 329 adult patients undergoing percutaneous device closure of interatrial communication defects to identify clinical and morphologic differences among adult patients with ASDs who presented with or without paradoxical embolism. Comparison was made with patients with PFO. Results : Although a significant left‐to‐right shunt was the predominant indication for ASD closure, 20 patients (14%) presented with a paradoxical embolism. These patients tended to be younger and had smaller defects (both by size and shunt ratio) than ASD patients without paradoxical embolism, and were more likely to be female than PFO patients. Conclusions : The incidence of adult patients with ASD who presented with paradoxical embolism is higher than expected and suggests that this diagnosis should be considered in patients with cryptogenic stroke. © 2009 Wiley‐Liss, Inc.     

Closing patent foramen ovale in cryptogenic stroke: The underscored importance of other interatrial shunt variants

Recent trials and metanalysis even not fully conclusive and still debated, at least suggested that mechanical device-based closure of patent foramen ovale (PFO) is more effective than medical therapy in prevent recurrence of stroke. In a proportion ranging from 20% to nearly 40% of patients in literature, PFO is associated to atrial septal aneurysm (ASA): ASA is a well-known entity often associated with additional fenestration. Additionally small atrial septal defects (“Flat ASD”) can present with signs of paradoxical embolism and cannot be easily detected by transthoracic echocardiography or even by transesophageal echocardiography and are usually discovered by intracardiac echocardiography at the moment of transcatheter closure. This evidence might change potentially the anatomical diagnosis from PFO to fenestrated ASA or as we called it to “hybrid defect”, being a bidirectional flow through a small ASD or/and an additional fenestration, often present. Despite the differences in anatomy, pathophysiology and haemodynamic paradoxical embolism may occur in both entities and also may be the first appearance of fenestrated ASA. Because some overlapping do really exist between PFO and hybrid defects, which are often not clearly differentiable by standard diagnostic tools, it is likely that a proportion of patients evaluated for potential transcatheter closure of PFO had actually a different anatomical substrate. These different anatomical and pathophysiologic entities have not been address in any of the previous trials, potentially having an impact on overall results despite the similar mechanical treatment. Neurologists and general cardiologists in charge of clinical management of PFO-related cryptogenic stroke should be aware of the role of hybrid defects in the pathophysiology of paradoxical embolism - mediated cerebral ischemic events in order to apply the correct decision - making process and avoid downgrading of patients with paradoxical embolism-related interatrial shunt variants different from PFO.     

Paradoxical peripheral embolism coincident with acute pulmonary thromboembolism

Paradoxical embolism may occur in patients with acute pulmonary thromboembolism, when patent foramen ovale (PFO) coexists with pulmonary hypertension (right-left shunt). There have been few case reports of paradoxical embolism in peripheral arteries coincident with acute pulmonary thromboembolism. Here, we describe a case of paradoxical peripheral embolism associated with PFO complicated by acute pulmonary thromboembolism. The patient had severe peripheral ischemia due to a massive thrombus and was treated successfully by peripheral thrombectomy, thrombolysis, implantation of a permanent inferior vena cava filter and anticoagulation.     

Multiple Intracardiac and Paradoxical Thrombi Caused by a Thrombus Entrapped in a Patent Foramen Ovale

Patent foramen ovale (PFO) usually represents a benign incidental finding. Occasionally, a PFO can open widely, resulting in paradoxical embolism, with potentially devastating consequence. Floating intracardiac thrombi and thrombus straddling a PFO are 2 extremely rare conditions associated with a dismal prognosis and encountered almost exclusively in the setting of pulmonary embolism (PE). We report the unusual case of a 47-year-old man with an unremarkable medical history who presented with a bilateral PE and multiple paradoxical and intracardiac floating thrombi in the setting of a thrombus entrapped in a PFO.     

Exclusion of patients with arteriosclerosis reduces long-term recurrence rate of presumed arterial embolism after PFO closure

BACKGROUND: Percutaneous transcatheter closure of patent interatrial communications after presumed paradoxical embolism is used as an alternative to surgery or long-term anticoagulation for the treatment of patients who are at risk for recurrent thromboembolism. To avoid atherosclerotic events to be judged as recurrent paradoxical embolism, we prospectively excluded all patients with detectable arteriosclerosis from our series and investigated long-term results. METHODS AND RESULTS: We report the outcome of 180 patients who underwent percutaneous transcatheter closure of patent foramen ovale (PFO), PFO like atrial septal defect (ASD), or an ASD because of paradoxical embolism. One hundred four patients had cerebral embolism, 57 had transient ischemic attacks, 16 coronary embolism, and 3 had peripheral embolism. Twenty-three patients experienced multilocal arterial embolism. One hundred twenty-five patients had a PFO, 63 of them with an atrial septal aneurysm (ASA), 24 a PFO-like ASD (7 of them with an ASA), and 31 had an ASD. After 18 months, only 5 patients (2.8%) showed a trivial residual shunt. At a mean follow-up of 40 months (range 4 to 88), resulting in 602 observed patient-years, only 1 patient experienced a presumed paradoxical (coronary) embolism (calculated annual risk to suffer a recurrent thromboembolic event: 0.16%). CONCLUSIONS: Percutaneous transcatheter closure of PFO/ASD is a safe and effective therapeutic option for the secondary prevention of presumed paradoxical embolism. It is associated with a high success rate, low incidence of hospital complications, and very low frequency of recurrent systemic embolic events.     

Caught in the act: serial, real time images of a thrombus traversing from the right to left atrium across a patent foramen ovale.

AIMS: To illustrate the association between a patent foramen ovale (PFO) and paradoxical embolization. METHODS AND RESULTS: We report a unique case of a paradoxical embolization across a PFO noted during a transesophageal echocardiographic study. Serial images demonstrate the thrombus migrating from the superior vena cava to the left atrium across the PFO. CONCLUSIONS: This case establishes the association between the PFO and paradoxical embolism unequivocally.     

Is stroke a paradoxical embolism in patients with patent foramen ovale?

OBJECTIVE: Purpose was to assess the stroke mechanism in patients with patent foramen ovale (PFO). METHODS: We reviewed the medical records of 111 stroke patients with PFO and sinus rhythm (PFO-S group), 25 with PFO and atrial fibrillation (AF) (PFO-AF group) and 67 with AF but not PFO (AF group), who had received contrast transesophageal echocardiography. The clinical and neuroradiological findings were then compared among the three groups. Deep vein thrombosis was investigated in 93 patients with PFO. We determined the number of patients with definite paradoxical embolism who met three criteria: deep vein thrombosis, neuroradiological features indicating embolic stroke, and the absence of other sources of emboli. We also evaluated those with probable paradoxical embolism who met two of the three criteria. RESULTS: The PFO-S group more frequently exhibited hypercholesterolemia (p<0.0001) and lesions limited to the posterior circulation (p<0.0004), and less frequently exhibited large or cortical lesions in the anterior circulation (p=0.0008, p<0.0001, respectively), than the PFO-AF and AF groups. In the PFO-S and PFO-AF groups, other sources of emboli such as a cardiac source of emboli, cerebral artery stenosis > or =50%, or complicated atheroma in the aortic arch were identified in 72 cases (52.9%). In the 93 patients with examination for deep vein thrombosis, the definite and probable criteria of paradoxical embolism were fulfilled only in three (3.2%) and 33 cases (35.5%), respectively. CONCLUSION: In stroke patients with PFO, not only paradoxical brain embolism through the PFO but also other causes of stroke may contribute to the development of stroke.     

Paradoxical embolization in an adult cystic fibrosis patient

Cystic fibrosis patients with an implantable venous access device (IVAD) and a patent foramen ovale (PFO) are at an increased risk of developing paradoxical embolism. A 33-year-old patient who had a cerebrovascular accident in the above setting is described. She had been anticoagulated because she had thrombosis of the tip of the indwelling catheter, and her PFO was closed percutaneuosly followed by replacement of her IVAD. She made a full neurological recovery. Echocardiography and prophylactic closure of the PFO, when present, as primary prevention for paradoxical embolism may be warranted in cystic fibrosis patients before placement of an IVAD.     

卵圆孔未闭与原因不明性卒中

流行病学研究显示,原因不明性卒中患者中的卵圆孔未闭(patent foramen ovale,PFO)患病率显著高于普通人群,二者之间的密切联系支持反常性栓塞为卒中病因的假说.然而,在原因不明性卒中患者中,单纯检测到PFO并不能确立反常性栓塞的诊断.当PFO与其他一些因素共存时,会显著增高缺血性卒中风险.一些研究显示,伴有PFO的原因不明性卒中患者的MRI病灶模式与无PFO者并无显著差异,特别是多发性缺血灶,因此不支持反常性栓塞作为PFO患者卒中病因的理论.PFO的检测方法包括经胸壁超声心动图、经食管超声心动图(transesophageal echocardiography,TEE)和经颅多普勒(transcranial Doppler,TCD).TCD与TEE具有良好的一致性,因此应被推荐为一种简单、无创和可靠的技术,而TEE仅应在经过选择的患者中进行.PFO的治疗选择包括抗血小板药、抗凝药、经皮血管内封堵术和开胸手术.在几项重要的大样本随机对照试验完成之前,对于伴有PFO的原因不明性卒中患者,经皮封堵术仅应考虑用于治疗在接受内科治疗过程中仍然出现复发性事件、对内科治疗存在禁忌证以及某些高危解剖学风险的PFO.     

Patent foramen ovale and unexplained ischemic cerebrovascular events in children.

OBJECTIVES: To consider the role of patent foramen ovale (PFO) in ischemic cerebrovascular event of unknown cause in children. BACKGROUND: Data regarding the possibility of paradoxical embolism in unexplained ischemic cerebrovascular event in children are lacking. METHODS: Between January 2005 and March 2007, all consecutive children evaluated due to ischemic cerebrovascular event were included in the retrospective study. In addition to the standard diagnostic protocol, a contrast transcranial Doppler (TCD) with Valsalva maneuver (VM) was performed in patients with unexplained events. Percutaneous PFO closure was offered to all patients with ischemic cerebrovascular event of unknown cause and presumed paradoxical embolism. RESULTS: Eighteen patients aged between 2 and 17 years (median 11.5 years) were included in the study: 12 patients suffered ischemic stroke and six with transient ischemic attack (TIA). In six patients, ischemic stroke was of unknown cause and contrast TCD with VM was positive in four of them. In addition, TCD study was positive in five patients evaluated because of TIA. Nine patients with presumed paradoxical embolism underwent an attempt at the percutaneous PFO closure. CONCLUSIONS: It appears that the role of PFO in ischemic cerebrovascular event of unknown cause in children may be underestimated. Contrast TCD with VM is a sensitive, noninvasive method for PFO detection, proved in our experience particularly suitable for children. In children with unexplained ischemic cerebrovascular event and presumed paradoxical embolism, percutaneous PFO closure should be considered.     

Impending paradoxical embolism through a patent foramen ovale in an octogenarian with pulmonary embolism: detection by transesophageal echocardiography and successful treatment by anticoagulation

Paradoxical embolism through a patent foramen ovale (PFO), an increasingly recognized cause of cryptogenic stroke and peripheral embolism, is believed to play little role in the elderly, mainly based on retrospective studies on selected populations. Paradoxical embolism is mostly a presumptive diagnosis, while definite demonstration of a thrombus crossing a PFO is rare. We describe the case of an 84-year-old patient with pulmonary embolism in whom a thrombus in transit through a PFO was found by transesophageal echocardiography (TEE). Treatment with anticoagulants allowed thrombus resolution without evidence of further embolic events. This finding demonstrates that (impending) paradoxical embolism may be present in the ;oldest old'. Its prompt diagnosis may allow effective treatment even with medical therapy alone. We suggest that paradoxical embolism may be not so rare in the elderly. The apparent decline in prevalence with age may be the result of less extensive diagnostic assessment in the elderly, as compared to younger patients.     

Transcatheter closure of interatrial communications for secondary prevention of paradoxical embolism: single-center experience

BACKGROUND: Patients with a patent foramen ovale (PFO) after cerebral, coronary, or systemic embolic events of presumed paradoxical origin are at risk for recurrent thromboembolism. We report our single-center experience of interventional closure of interatrial communications for secondary prevention of presumed paradoxical embolism. Methods and Results- Since 1997, percutaneous closure of interatrial communications was performed at our institution in 66 patients (mean age 47.8+/-12.7 years; 31 males) with a PFO or an atrial septal defect and at least 1 documented presumed paradoxical thromboembolic event. Fifty-eight patients had cerebral embolism, 10 had coronary embolism, and 3 had peripheral embolism. Several patients experienced multilocal arterial embolism. Fifty-four patients had a PFO, 33 of them with an atrial septal aneurysm, and 12 had an atrial septal defect. The implantation procedure was successful and without complication in all patients. After 3 months, only 2 patients showed a residual shunt, which disappeared in both cases after 12 months. In 112.2 patient-years of follow-up (range, 5 weeks to 3.5 years), we have not seen any recurrent thromboembolic event. CONCLUSIONS: Interventional closure of interatrial communications is a safe and effective therapeutic option for the secondary prevention of presumed paradoxical embolism. To further evaluate this strategy, randomized trials comparing interventional closure with anticoagulation have been initiated by us and others.     

卵圆孔未闭与原因不明性卒中

流行病学研究显示,原因不明性卒中患者中的卵圆孔未闭(patent foramen ovale,PFO)患病率显著高于普通人群,二者之间的密切联系支持反常性栓塞为卒中病因的假说.然而,在原因不明性卒中患者中,单纯检测到PFO并不能确立反常性栓塞的诊断.当PFO与其他一些因素共存时,会显著增高缺血性卒中风险.一些研究显示,伴有PFO的原因不明性卒中患者的MRI病灶模式与无PFO者并无显著差异,特别是多发性缺血灶,因此不支持反常性栓塞作为PFO患者卒中病因的理论.PFO的检测方法包括经胸壁超声心动图、经食管超声心动图(transesophageal echocardiography,TEE)和经颅多普勒(transcranial Doppler,TCD).TCD与TEE具有良好的一致性,因此应被推荐为一种简单、无创和可靠的技术,而TEE仅应在经过选择的患者中进行.PFO的治疗选择包括抗血小板药、抗凝药、经皮血管内封堵术和开胸手术.在几项重要的大样本随机对照试验完成之前,对于伴有PFO的原因不明性卒中患者,经皮封堵术仅应考虑用于治疗在接受内科治疗过程中仍然出现复发性事件、对内科治疗存在禁忌证以及某些高危解剖学风险的PFO.     

PFO and paradoxical embolism producing events other than stroke

Background: A patent foramen ovale (PFO) is a risk factor for cerebral events such as cryptogenic stroke, transient ischemic attacks, and migraine headaches. Far less commonly, PFO is associated with non‐cerebral, paradoxical systemic embolic events such as myocardial infarction (MI), renal infarct, and limb ischemia. This report details the incidence of systemic paradoxical emboli at our institution. Methods: 416 patients were referred for evaluation of PFO related conditions from 2001 to 2009. Clinical history and medical records of the patients were reviewed for incidence of cryptogenic stroke, transient ischemic attack (TIA), migraine headache, arterial desaturation, and noncerebral systemic embolism. Results: As the primary presenting symptom, 219 patients had a diagnosis of cryptogenic stroke, 38 patients had migraine headaches, and 80 patients had transient neurologic deficits consistent with a TIA or complex headache. Twelve patients (2.9% of the total population) presented with a presumptive diagnosis of systemic embolism. Eight of these patients had acute MI diagnosed by elevated cardiac biomarkers, electrocardiogram changes, and/or imaging evidence of a left ventricular wall motion abnormality, without evidence of obstructive coronary disease on angiography. Four patients had evidence of peripheral embolism to a systemic artery, including the popliteal artery, ophthalmic artery, and brachial artery. PFO closure was performed in 197 patients (47.4% of the total population), including eight patients in the systemic embolism group. All closure procedures were successful. Conclusion: Although most paradoxical emboli travel to the brain, noncerebral paradoxical embolism is also associated with PFO. In addition to embolism of thrombus, there may be paradoxical passage of vasoactive chemicals that induce intense coronary spasm and myocardial infarction. Diagnosis is often challenging, given the lack of definitive criteria and the need to exclude other potential etiologies. © 2011 Wiley‐Liss, Inc.     

Hypercoagulable States in patients with patent foramen ovale

A patent foramen ovale (PFO) is a risk factor for stroke with the presumed mechanism being paradoxical embolism. Hypercoagulable states have been associated with the propensity to develop venous thromboses and have been separately associated with the risk for ischemic stroke. A PFO could provide the missing link. Having a PFO and a hypercoagulable state may place a person at an increased risk for paradoxical embolism. However, the prevalence of PFO in patients with hypercoagulable states and vice versa is unknown, and the best therapeutic strategy for these patients is unelucidated. This review assesses the literature, provides some insight on these topics, and identifies areas for further investigation.     

Echocardiographically guided closure of a patent foramen ovale during pregnancy after recurrent strokes

BACKGROUND: Stroke during pregnancy and puerperium is a severe complication that causes high morbidity and mortality. A patent foramen ovale (PFO) allowing paradoxical embolism is one identified risk factor. CASE: A 25-year-old pregnant woman with PFO suffered from recurrent cerebral embolism. To prevent recurrent cerebral embolism during pregnancy, delivery, and puerperium, interventional closure of the PFO was performed without fluoroscopy under echocardiographic guidance. The postinterventional course was uneventful. CONCLUSION: Percutaneous transvenous closure of a PFO during pregnancy is feasible without the use of fluoroscopy.     

Transcatheter treatment of atrial septal aneurysm associated with patent foramen ovale for prevention of recurrent paradoxical embolism in high-risk patients

OBJECTIVES: This study sought to investigate the safety and efficacy of transcatheter treatment of atrial septal aneurysm (ASA) associated with patent foramen ovale (PFO). BACKGROUND: Patients with both ASA and PFO are at high risk for recurrent paradoxical embolism. METHODS: The procedural, echocardiographic, and clinical outcomes of 141 patients with ASA + PFO and > or =1 paradoxical embolic event undergoing transcatheter treatment were compared with 220 patients with PFO alone. RESULTS: Device success (ASA + PFO, 99.3%; PFO alone, 99.5%; p = 0.75) and procedural complications (ASA + PFO, 0.7%; PFO alone, 3.2%; p = 0.12) were similar in both groups. Maximal atrial septal excursion in patients with ASA + PFO decreased from 16 +/- 4 mm before to 4 +/- 3 mm after the intervention (p < 0.0001). At 6 months follow-up, right-to-left shunt was abolished in 120 (86%) patients with ASA + PFO, compared to 187 (85%) patients with PFO alone (p = 0.80). Freedom from recurrent transient ischemic attack, stroke, and peripheral embolism at 4 years was 95% (ASA + PFO) and 94% (PFO alone, p = 0.70), respectively. A residual right-to-left shunt after the intervention was the only predictor for recurrence (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.3 to 36.9, p < 0.03) in patients with ASA + PFO. CONCLUSIONS: Transcatheter treatment of ASA + PFO is 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.     

Percutaneous closure of patent foramen ovale in symptomatic patients

BACKGROUND: Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been associated with stroke in young adults. Patients with PFO suffering from paradoxical embolism are at increased risk for recurrent events. Percutaneous PFO closure is a new treatment modality aimed at secondary prevention. METHODS AND RESULTS: Since April 1994, 132 consecutive patients, aged 51 +/- 12 years with PFO and with at least one paradoxical embolic event, underwent percutaneous PFO closure using six different device types. The embolic index event was an ischemic stroke in 62% of patients, a transient ischemic attack (TIA) in 33% of patients, and a peripheral embolism in 5% of patients. Thirty-six (27%) patients had PFO associated with ASA, whereas 96 (73%) patients had PFO only. The implantation procedure was successful in 130 (98%) patients. During and up to 6 years of follow-up (mean 1.8 +/- 1.6 years, 231 patient years), a total of eight recurrent embolic events were observed, with six TIAs, two peripheral emboli, and no ischemic stroke. The actuarial freedom from recurrence of the combined end point of TIA, ischemic stroke, and peripheral embolism was 95.3% (95% confidence interval [CI], 91.0%-96.4%) at 1 year and 90.5% (95% CI, 83.6%-97.2%) at 6 years. CONCLUSIONS: Percutaneous PFO closure can be performed with a high success rate. The procedure appears a promising therapeutic modality for secondary prevention of recurrent embolism in patients with PFO. Randomized trials must define its therapeutic value.     

Patent foramen ovale: conservative or surgical therapy?

Notwithstanding the difficulties in definitely confirming paradoxical embolism, the association between patent foramen ovale (PFO) and cryptogenic stroke has repeatedly been demonstrated in clinical studies. Moreover, the recurrence rate of cerebral ischemia in patients with PFO and an unexplained stroke was found to be 3-4% per year in two recently published series. With the exception of right atrial pressure elevation in the setting of major pulmonary embolism, a reliable risk stratification of patients with PFO based on clinical or echocardiographic findings is not yet possible. The presence of atrial septal aneurysm, a wide opening of the defect during the cardiac cycle and a large atrial shunt have been implicated as risk factors by some investigators. Long-term prevention of paradoxical embolism with oral anticoagulants seems to be of questionable benefit. Besides, these agents are poorly tolerated and carry the risk of significant or fatal bleeding at a rate of 2-5% per year. Surgery of the atrial septum has been performed for many decades in patients with atrial septal defect and evidence accumulates that it is a safe and highly effective procedure in patients with PFO. At present, surgical closure of the PFO appears to be the treatment of choice for secondary prevention of paradoxical embolism. However, further studies are needed to define the appropriate candidates for surgical treatment. Devices for catheter-based sealing of PFO are also available and are currently being evaluated in clinical trials. However, experience with their use remains confined to specialized centers. Furthermore, further technical improvements of these systems are needed in order to optimize successful delivery and positioning, increase their long-term stability, and reduce periprocedural complications.     

Outcome after percutaneous closure of a patent foramen ovale using the Intrasept™ device

Objectives : This multi‐centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept? device. Background : PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo‐embolism. Currently, different devices are used for PFO closure. Methods : Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo‐embolism. Peri‐procedural and mid‐term complications were reported. Results : Four‐hundred thirty patients (mean age 50.7 ± 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow‐up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri‐procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid‐term follow‐up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04). Conclusion : This multi‐centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo‐embolic events. © 2008 Wiley‐Liss, Inc.