Risk Of Paradoxical Embolism Research Articles

66. Clinical profile of adult Ebstein’s anomaly

Adults often present with arrhythmias. In the presence of an interatrial communication, the risk of paradoxical embolization, brain abscess, and sudden death increases. 10% cases WPW syndrome, junctional rhythm with intermittent sinus pauses (20%) and ventricular trigeminy (10%). Overt cardiac failure was the initial presentation in (10% patients), whereas 20% patients presented with NYHA functional class II dyspnoea and easy fatiguability. Rheumatic fever was present coexisting with Ebsteins anomaly in (5%). Two patients presented with congenital rubella syndrome with patent ductus arteriosus with Ebsteins anomaly. 5% patients who presented with inferior wall myocardial infarction on routine echocardiographic evaluation had Ebsteins anomaly. Two patients had cyanosis. Associated defects in these patients included ASD (25%), ASD with VSD (20%), PDA (5%), RVOT aneurysm (5%), pericardial effusion (10%). All patients had low pressure tricuspid regurgitation (TR). Posterior leaflet displacement more than septal leaflet displacement was present in 20% patients. Anterior leaflet was not displaced in any of these patients. Celemajors index in most of the patients was in the range of (0.6–0.97). 3 patients had celemajor index of 1.5. Carpentier type I in 20% patients, in type II in 65% patients, type III in 10% patients, type IV in 5% patients. Cardiothoracic ratio ranged from 0.61 to 0.71 and only one patient had a ratio of 0.85. 10% cases WPW syndrome , junctional rhythm with intermittent sinus pauses (20%) and ventricular trigeminy (10%). Overt cardiac failure was the initial presentation in (10%patients), whereas 20% patients presented with NYHA functional class II dyspnoea and easy fatiguability. Rheumatic fever was present coexisting with Ebsteins anomaly in (5%). Two patients presented with congenital rubella syndrome with patent ductus arteriosus with Ebsteins anomaly. 5% patients who presented with inferior wall myocardial infarction on routine echocardiographic evaluation had Ebsteins anomaly. Two patients had cyanosis. Associated defects in these patients included ASD (25%), ASD with VSD (20%), PDA(5%), RVOT aneurysm (5%), pericardial effusion (10%). All patients had low pressure tricuspid regurgitation (TR). Posterior leaflet displacement more than septal leaflet displacement was present in 20% patients. Anterior leaflet was not displaced in any of these patients. Celemajors index in most of the patients was in the range of (0.6–0.97). 3 patients had celemajor index of 1.5. Carpentier type I in 20% patients, in type II in 65% patients, type III in 10% patients, type IV in 5% patients. Cardiothoracic ratio ranged from 0.61 to 0.71 and only one patient had a ratio of 0.85. Ebsteins anomaly in adults can have diverse presentations. Symptoms due to Electrophysiological events were more prevalent than due to hemodynamic disturbances.

Abstract WP228: Stratification of Patent Foramen Ovale (PFO) Pathogenicity Using the RoPE Score Differs in Women and Men

Background: A patent foramen ovale (PFO) discovered in patients with cryptogenic stroke (CS) may be incidental or pathogenic. Recently, a Risk of Paradoxical Embolism (RoPE) score has been proposed to stratify patients by their PFO pathogenicity. Based on this score, the probability that a PFO is incidental (rather than pathogenic) increases with advancing age, deep stroke location, or the presence of cardiovascular risk factors (RF). Given that RF accumulate at a later age in women than in men, we hypothesize that there are gender differences in the variables used for RoPE score calculation. Methods: The distribution of RF (history of hypertension, diabetes or stroke/TIA, current smoking, and age categories as defined in the original RoPE score publication) was compared by sex in the entire cohort of 1044 CS patients as well as within the groups with low (0-5) and high (7-10) RoPE scores (due to lacking information on cortical versus deep stroke location, we excluded all patients with a RoPE score of 6, since they could be either classified with low or high RoPE score depending on stroke location). Furthermore, for each patient we calculated the age impact ratio (AIR): the points assigned for the corresponding age category divided by the RoPE score. Gender comparisons of AIR were drawn in the entire cohort and within the RoPE score strata. Results: Average age was 55.5 years and 635 patients (61%) were male. In the entire cohort, the distribution of age categories and RF as well as AIR did not differ between men and women. In the higher RoPE stratum (PFO likely pathogenic), women were younger than men (median, 38 years vs 45 years, P=0.036). The distribution of RF and the AIR did not differ between sexes. In the lower PFO stratum (PFO likely incidental), men were younger than women (median, 62 years vs 66 years, P=0.011). The AIR was lower in women than in men (mean, 0.24 vs 0.29, P=0.013). There were no gender differences in the distribution of RF. Conclusions: There are significant gender differences in age among patients with CS and PFO, with women being younger than men in the higher RoPE stratum and vice versa in the lower RoPE stratum. More women than men are classified as having an incidental PFO because of their advancing age rather than the accumulation of RF.

Abstract 205: Preceding Valsalva Maneuver Significantly Associated With Pathogenic Patent Foramen Ovale (PFO) in Patients With Cryptogenic Stroke

Background: In patients with cryptogenic stroke (CS), a patent foramen ovale (PFO) can be incidental or pathogenic. The Risk of Paradoxical Embolism (RoPE) score has been developed to determine the likelihood that a PFO is pathogenic or incidental using clinical variables. We hypothesize that echocardiographic features and conditions promoting paradoxical embolism differ between patients with pathogenic and incidental PFOs. Methods: The International PFO Consortium collects clinical, radiological and echocardiographic data of patients with CS and PFO. In the original RoPE score, a value of 0-6 was classified as a low RoPE score and 7-10 as a high score. Since information on cortical versus deep stroke location (one of the items on the RoPE score) was not available, we used two alternative approaches to stratify for PFO pathogenicity. In a first approach, we used a 9-point score and lowered the cut-off for dichotomization by 1 point (RoPE score 0-5 vs 6-9). In a second approach, patients with a RoPE score of 6 were excluded since they could either be classified as low or high RoPE score depending on stroke location. The associations between RoPE stratum and echocardiographic features (atrial septal aneurysm (ASA), right-to-left shunt (RLS) at rest and large RLS) as well as conditions promoting paradoxical embolism (deep vein thrombosis (DVT), pulmonary embolism (PE) and Valsalva maneuver (VM) were studied. Results: We analyzed 1044 CS patients with a PFO. Average age was 55 (SD 16) and 635 patients (61%) were male. Preceding VM was more frequent in patients with a high vs low RoPE score in both analyses: 11% vs 5% (OR: 2.1 95%CI 1.3-4.3) and 10% vs 5% (OR: 2.0 95%CI 1.2-3.6). The distribution of ASA (35% vs 34% and 32% vs 34%, in the first and the second analysis respectively), RLS at rest (28% vs 28% and 29% vs 28%), large RLS (67% vs 66% and 65% vs 66%), PE (2% vs 2% and 1% vs 2%), and DVT (4% vs 4% and 3% vs 4%) did not differ by RoPE stratum. Conclusion: In patients with CS, preceding VM was significantly associated with pathogenic PFO, while echocardiographic features or conditions promoting paradoxical embolism were not. The formation of a significant right-to-left pressure gradient at the atrial septum level appears to play a substantial role in the pathogenicity of PFO.

Abstract 16261: Risk of Stroke or Systemic Embolism After Transseptal Ablation in Patients With Implanted Cardiac Devices

Introduction: Mobile thrombi are commonly observed on endovascular leads at the time of catheter ablation. Transseptal puncture poses a risk of paradoxical embolism. We sought to examine the risk of stroke or systemic embolism after transseptal ablation in patients with and without cardiac implantable electronic devices (CIEDs). Methods: Using a large, national administrative claims database we identified 31,720 patients who underwent a catheter ablation requiring transseptal puncture between 1/1/2004 and 9/30/2014. We created two propensity-matched cohorts, matching on age, gender, race, household income, region, Charlson index, CHADS-Vasc score, and year and indication for ablation (5,533 patients with CIEDs and 11,300 patients without devices). Incidence rates (events/100 patient-years) and propensity score-matched cox proportional hazards models (with 95% confidence intervals) were used to estimate risk of stroke, transient ischemic attack, or systemic embolism for patients with or without CIEDs. We also examined the impact of presence of a CIED and oral anticoagulation (OAC) use on risk of stroke or systemic embolism within the matched cohort. Average follow up was 2.1 years. Results: The event rate was 1.5 per 100 person years in patients without device, and 1.9 per 100 person years in patients with device. Among patients not on OAC, presence of a cardiac device was associated with an increased risk of stroke or systemic embolism (HR 1.71 [1.24-2.35], P<0.01) whereas there was no association among patients treated with OAC (0.98 [0.75_1.28], p=ns) (Figure). Conclusions: Cardiac devices are associated with an increased risk of stroke or systemic embolism after transseptal ablation, but this risk is attenuated with post ablation OAC use. Anticoagulation should be considered for all patients with CIEDs post transseptal ablation, regardless of the presence of another compelling indication for anticoagulation.

The RoPE Score and Right-to-Left Shunt Severity by Transcranial Doppler in the CODICIA Study

Background: For patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), it is unknown whether the magnitude of right-to-left shunt (RLSh) measured by contrast transcranial Doppler (c-TCD) is correlated with the likelihood an identified PFO is related to CS as determined by the Risk of Paradoxical Embolism (RoPE) score. Additionally, for patients with CS, it is unknown whether PFO assessment by c-TCD is more sensitive for identifying RLSh compared with transesophageal echocardiography (TEE). Our aim was to determine the significance of RLSh grade by c-TCD in patients with PFO and CS. Methods: We evaluated patients with CS who had RLSh quantified by c-TCD in the Multicenter Study into RLSh in Cryptogenic Stroke (CODICIA) to determine whether there is an association between c-TCD shunt grade and the RoPE Score. For patients who underwent c-TCD and TEE, we determined whether there is agreement in identifying and grading RLSh between these two modalities. Results: The RoPE score predicted the presence versus the absence of RLSh documented by c-TCD (c-statistic = 0.66). For patients with documented RLSh by c-TCD, shunt severity was correlated with increasing RoPE score (rank correlation (r) = 0.15, p = 0.01). Among 293 patients who had both c-TCD and TEE performed, c-TCD was more sensitive (98.7%) for detecting RLSh. Of the 97 patients with no PFO identified on TEE, 28 (29%) had a large amount of RLSh seen on c-TCD. Conclusions: For patients with CS, severity of RLSh by c-TCD is positively correlated with the RoPE score, indicating that this technique for shunt grading identifies patients more likely to have pathogenic rather than incidental PFOs. c-TCD is also more sensitive in detecting RLSh than TEE. These findings suggest an important role for c-TCD in the evaluation of PFO in the setting of CS.

Abstract 208: Vascular Risk Factors But Not Transesophageal Echocardiography (TEE) Features Are Associated With Stroke Recurrence in Patients With Cryptogenic Stroke (CS) and Patent Foramen Ovale (PFO)

Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.

Predictors of Recurrent Events in Patients With Cryptogenic Stroke and Patent Foramen Ovale Within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) Trial

ObjectivesThis study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial. BackgroundThe CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO. MethodsThe CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort. ResultsIn 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001). ConclusionsThese findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461)

Recurrent stroke predictors differ in medically treated patients with pathogenic vs. other PFOs.

To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score. Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of ≤6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant. Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group. Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

Acute right ventricular failure caused by concomitant coronary and pulmonary embolism: successful treatment with endovascular coronary and pulmonary thrombectomy

Patent foramen ovale (PFO) is present in approximately 25% of the general population. PFO is characterized by intermittent shunting of blood from the right to the left atrium, especially in the context of increased right-sided filling pressures, with risk of paradoxical embolism. We describe a 69-year-old woman presenting with acute chest pain, severe dyspnoea, and acute inferolateral ST-segment elevation on the electrocardiogram. The patient was diagnosed with myocardial infarction and failure of the right cardiac ventricle, which was considered to be secondary to extensive pulmonary embolism leading to increased filling pressures and paradoxical coronary embolism. The patient underwent emergent percutaneous interventions with coronary thrombus extraction and pulmonary thrombus fragmentation and local thrombolysis. The patient was free of symptoms at follow up 6 months later and echocardiography showed substantially improved right ventricular function. We discuss issues related to the diagnosis, treatment, and secondary prevention for patients with concomitant pulmonary and coronary arterial thrombosis.

Abstract 198: PFO and Recurrent Stroke: Predictors Differ In Patients With “Probable Pathogenic” Versus Other PFOs

Background The “RoPE Score” is a predictive model created to stratify patients by the likelihood that a patent foramen ovale (PFO) is incidental or pathogenic using clinical variables. We hypothesized that the predictors of recurrent stroke differ between patients with pathogenic and incidental PFOs. Methods Patients in the Risk of Paradoxical Embolism (RoPE) database with cryptogenic stroke (CS) and PFO were classified as having a probable pathogenic PFO (RoPE Score of &gt;6, estimated PFO attributable fraction 72-99%, n=646) and others (RoPE Score of &lt;6 points estimated PFO attributable fraction 0-72%, n=678). We tested 15 clinical, 5 radiological, and 3 echo variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant. Results Follow-up was available for 91%, 80%, and 58% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA, not being on a statin at baseline, and having a prior radiological stroke. For the low RoPE score group, older age, male sex, high cholesterol and antiplatelet (vs warfarin) treatment predicted recurrence. For those with high RoPE scores, predictors were prior (clinical) stroke/TIA and 2 echo features: septal hypermobility and a small shunt (&lt;10 bubbles). Conclusions Predictors of recurrence differ when PFO relatedness is classified by the RoPE Score. The hypothesis that patients with CS and PFO form a heterogenous group with different stroke mechanisms is supported. Conventional stroke risk factors were strong predictors among patients with lower RoPE scores. Echocardiographic features - including a counterintuitive association between smaller shunts and increased recurrence risk - were uniquely predictive in the high RoPE score group (likely pathogenic PFO).

Abstract 33: PFO in Cryptogenic Stroke: An Analysis of “High Risk” Features on Transesophageal Echocardiography in the Risk of Paradoxical Embolism Database

Introduction: A patent foramen ovale (PFO) discovered in the setting of a cryptogenic stroke (CS) may be stroke-related or incidental. We have developed a score to stratify CS patients according to the probability that the event is attributable to a PFO (the Risk of Paradoxical Embolism (RoPE) Score), based on easily obtainable clinical and neuroradiological (but not transesophageal echocardiographic (TEE) variables. In this study, we examined whether putative “high risk” TEE features - shunt size, presence of a hypermobile septum, and presence of a right-to-left shunt at rest - vary across RoPE Score strata. Methods and Results: The RoPE Study combined existing cohort studies to create a pooled database of patients with CS and PFO. We dichotomized patients into groups and examined whether putative high risk TEE features are seen more frequently in those with “probable stroke-related” PFOs (RoPE Score of &gt;6, estimated PFO attributable fraction 72-99%, n=637) than in those with lower RoPE Scores (&lt;6, PFO attributable fraction 0-71%, n=657). None of the TEE features differed between the groups (large physiologic size, p=0.53; hypermobile septum, p=0.44; shunt at rest, p=0.11). Extensive additional exploratory analyses did not reveal any consistent associations between different RoPE Score strata and presumptive high risk echocardiographic features. Conclusion: We found no evidence that proposed TEE markers for “high risk” PFOs correlate with the estimated likelihood that a PFO is related to an index CS. Additional imaging tools or better standardization of imaging techniques are needed to determine whether specific anatomic features are associated with whether a discovered PFO is likely to be related to CS.

Abstract WP185: Cryptogenic Stroke and Patent Foramen Ovale: Posterior Circulation Strokes Are More Common In Men Than In Women

Background Stroke databanks have consistently found a high ratio of anterior circulation (AC) to posterior circulation (PC) strokes without significant differences when compared for vascular risk factors, stroke etiology, treatments and outcome. One study suggested that there was a deviation from this consistent observation when comparing men and women with cryptogenic stroke (CS) and patent foramen ovale (PFO). We tested these associations using the RoPE database. Methods The Risk of Paradoxical Embolism (RoPE) Study is an international collaboration of 12 merged cohort studies of patients with CS and known PFO status (n=3674). This analysis was restricted to those subjects in the RoPE database with index strokes in the AC or PC (excluding both or unknown) from the 7 databases that had data for CS with, and without, PFO. We compared the effect of sex on infarct location among patients with versus without PFO. We used generalized linear mixed models to examine whether PFO status modified the gender effect on infarct location adjusting for study cohort as a random effect. Results Among cryptogenic stroke patients both with and without PFO, AC strokes were more common (61%) than PC overall (n=1535). Among patients with PFO, PC stroke was higher in men than in women (50% vs. 33%, OR 2.23, 95% CI: 1.58-3.13). This gender effect was attenuated in those without PFO (38% vs. 31%; OR 1.32, 95% CI: 0.98-1.77). The gender-by-PFO-status interaction was significant (p= 0.0224) and was highly consistent across study cohorts. Conclusions These data confirm that males with CS and PFO contravene the otherwise consistent pattern that AC strokes are more commonly observed than PC strokes in stroke populations. The potential mechanisms underlying this interaction between gender and PFO-status remain to be elucidated.

Neuroimaging Findings in Cryptogenic Stroke Patients With and Without Patent Foramen Ovale

Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

Migräne und kardiale Shunts - gibt es Zusammenhänge?

Recently an association between migraine and cardiac shunts (e.g. through a patent foramen ovale, PFO) has been described. There is evidence from mostly retrospective case series that PFO closure can significantly improve migraine. On the other hand an increase in attack frequency or de novo migraine after percutaneous closure of an atrial septal defect has been described. Animal experiments showed that microemboli in the cerebral circulation can trigger a cortical spreading depression, which is believed the pathophysiological substrate of migraine aura. A randomized controlled trial that investigated PFO closure for treatment resistant migraine with aura was negative. It is currently discussed whether certain subgroups, who have a high risk for paradoxical embolism, might improve after PFO closer.

The Risk of Paradoxical Embolism (RoPE) Study: Initial Description of the Completed Database

Detecting a benefit from closure of patent foramen ovale in patients with cryptogenic stroke is hampered by low rates of stroke recurrence and uncertainty about the causal role of patent foramen ovale in the index event. A method to predict patent foramen ovale-attributable recurrence risk is needed. However, individual databases generally have too few stroke recurrences to support risk modeling. Prior studies of this population have been limited by low statistical power for examining factors related to recurrence. The aim of this study was to develop a database to support modeling of patent foramen ovale-attributable recurrence risk by combining extant data sets. We identified investigators with extant databases including subjects with cryptogenic stroke investigated for patent foramen ovale, determined the availability and characteristics of data in each database, collaboratively specified the variables to be included in the Risk of Paradoxical Embolism database, harmonized the variables across databases, and collected new primary data when necessary and feasible. The Risk of Paradoxical Embolism database has individual clinical, radiologic, and echocardiographic data from 12 component databases, including subjects with cryptogenic stroke both with (n = 1925) and without (n = 1749) patent foramen ovale. In the patent foramen ovale subjects, a total of 381 outcomes (stroke, transient ischemic attack, death) occurred (median follow-up 2·2 years). While there were substantial variations in data collection between studies, there was sufficient overlap to define a common set of variables suitable for risk modeling. While individual studies are inadequate for modeling patent foramen ovale-attributable recurrence risk, collaboration between investigators has yielded a database with sufficient power to identify those patients at highest risk for a patent foramen ovale-related stroke recurrence who may have the greatest potential benefit from patent foramen ovale closure.

Abstract 84: An Index to Identify Cryptogenic Stroke Patients whose Stroke is likely Attributable to Patent Foramen Ovale

Background: A patent foramen ovale (PFO) discovered in the setting of a cryptogenic stroke (CS) may be incidental or pathogenic. Based on Bayes theorem, the proportion of CS that is PFO-attributable among patients found to have a PFO has been shown to be related to PFO prevalence in CS versus control patients. However, the prevalence of PFO in CS patients is itself dependent on the presence or absence of other risk factors. We exploited this relationship to create an index to stratify CS patients with PFO by their likelihood that the CS is PFO-attributable. Methods This project is part of the Risk of Paradoxical Embolism (RoPE) Study, an international, multicenter collaboration that has combined data for patients with CS and cryptogenic TIA who have known PFO status from 12 component studies (n=3665). For this study, we included those subjects within the 7 databases enrolling subjects both with and without PFO (n=3023). We used generalized linear mixed models to identify variables associated with the presence of a PFO, accounting for clustering within study. Based on this model, we created a simple index. Bayes theorem was used to estimate the PFO-attributable fraction in each stratum assuming a PFO prevalence in the general population of ∼25%. Results: Variables negatively associated with the presence of a PFO included: age (odds ratio [OR] = 0.97 per 1 year increase, p &lt;0.0001); diabetes (OR= 0.65, p &lt; 0.001); hypertension (OR =0.68, p &lt; 0.0001); smoking (OR = 0.70, p&lt;0.60); prior stroke or TIA (OR = 0.78, p=0.04). Cortical stroke on neuroimaging (OR = 1.46, p &lt; 0.001) was also associated with PFO. Based on this, a simple index was created in which the absence of each stroke risk factor was assigned a point, with age dichotomized at 50 years. PFO prevalence in each stratum is shown in the table for patients &lt; age 60, i.e. the subset of patients likely to be considered for PFO closure trials. Conclusion: Even among CS patients in the younger age range considered eligible for closure trials, there is considerable heterogeneity in the distribution of risk factors for stroke and other characteristics that identify subgroups of CS patients with variation in PFO prevalence. This reflects substantial and clinically important variation in the probability that a discovered PFO is likely to be pathogenic rather than incidental. This score may be useful in selecting patients for closure trials, or for stratification within trials, particularly if combined with a recurrence risk model.

Abstract 3430: Superficial and Large Infarcts on Neuroimaging in Patients with Cryptogenic Stroke are Associated with the Presence or Absence of Patent Foramen Ovale

Introduction We aim to determine whether radiological findings are associated with patent foramen ovale (PFO) among patients with cryptogenic stroke (CS). Radiological findings associated with the presence of a PFO may represent stroke patterns typical of paradoxical embolism which may be distinct from other mechanisms of CS. Methods This project is part of the Risk of Paradoxical Embolism (RoPE) Study, an international collaboration that has combined individual-level data for subjects with CS and TIA who have known PFO status from 12 component studies (n=3665). For this study 7 databases (n=3023) were used that included subjects with and without PFO, and with radiologic data. Five variables were tested for their relationship with PFO status: 1) protocol-defined large vs. small infarct , 2) Index stroke seen on imaging, 3) superficial vs. deep infarct, 4) multiple index lesions, 5) Prior stroke, i.e. chronic infarct on index imaging. Results are presented in the table . Odds ratios and p-values are adjusted for age, database, sex, diabetes, hypertension, smoking, and history of stroke/TIA. This is the largest study to report the radiological characteristics of patients with CS who are known to have, or not to have, a PFO. Some prior studies had null findings but were limited by small sample size and low statistical power. Because CS unrelated to PFO may also be embolic, the radiological pattern of paradoxical embolism may not be expected to be different from other cryptogenic emboli. Despite this, PFOs were significantly more common in CS patients with large and with superficial infarcts. Conversely, infarcts that were small and deep were associated with PFO absence. This suggests that lacunar disease may account for some non-PFO related CS. Conclusion Participants were significantly more likely to have a PFO if they had 1) an index stroke seen on neuroimaging, 2) a large stroke, 3) a superficial stroke; there was no effect of the variables prior ( i.e. chronic) infarct or multiple vs. single infarcts. Further analyses may help to clarify the ability of neuroimaging to predict the finding of a PFO.

Transvenous Extraction of Pacemaker Leads in Infective Endocarditis With Vegetations ≥20 mm: Our Experience

According to published evidence, treatment of infective endocarditis (IE) associated with cardiovascular implantable electronic devices (CIEDs) should include complete removal of the system. Several publications have shown that transvenous removal is an effective and safe nonthoracotomy approach in patients with large vegetations, but experiences with vegetations larger than 20 mm have rarely been reported. Our aim was to describe our experience in percutaneous removal of CIEDs in patients with IE with large vegetations. The data were collected retrospectively and analyzed prospectively. We evaluated in-hospital morbidity and mortality related to percutaneous removal of vegetations ≥20 mm. This included 8 cases with a follow-up period of 20 months. We removed 100% of leads in the study population. Two patients experienced minor complications. No patient experienced subclavian vein laceration, hemothorax and lead fracture, or severe tricuspid regurgitation. After the removal procedure, 2 patients had symptoms compatible with pulmonary embolism. Both in-hospital mortality and mortality at follow-up were zero. Transvenous extraction of pacing leads with larger vegetations is a feasible technique. There was a tendency toward symptomatic pulmonary embolism in patients with vegetations larger than 20 mm; however, morbidity and mortality were not influenced. We agree with the consensus that this procedure is highly useful and that the selection of the removal techniques will depend not only on the size of vegetation but also on prior cardiopulmonary conditions, concomitant cardiac surgery, atrial septal defect with risk of paradoxical embolism, center experience, and the possibility of complete removal of the device.

Renal cell carcinoma with right atrial extension with associated atrial septal defect: a case report

We present a case of locally advanced renal cell carcinoma with tumor thrombus in the inferior vena-cava extending into the right atrium with associated atrial septal defect. Tumor removal posed a unique challenge in this patient as there was a risk of paradoxical embolism during the surgery.

Oclusão percutânea da fenestração no pós-operatório tardio da cirurgia de Fontan

INTRODUCAO: A fenestracao na cirurgia de Fontan (CF) melhora o resultado imediato no pos-operatorio, por descompressao do circuito venoso-pulmonar e aumento do debito cardiaco, a despeito da dessaturacao arterial de oxigenio e do risco de embolia paradoxal. Geralmente as fenestracoes sao ocluidas percutaneamente no seguimento a medio prazo. Este estudo teve como objetivo relatar a experiencia institucional na oclusao percutânea da fenestracao. METODOS: Estudo descritivo longitudinal, observacional, retrospectivo, de uma coorte nao-consecutiva de pacientes. O procedimento foi realizado sob anestesia geral com a ajuda de ecocardiograma transesofagico. O teste de oclusao da fenestracao com cateter Bermann angiografico foi realizado antes da intervencao. Diferentes tecnicas e dispositivos foram empregados para a oclusao da fenestracao. RESULTADOS: Entre abril de 2004 e dezembro de 2010, 12 pacientes (media de idade, 103,1 ± 88,6 meses; peso, 29,9 ± 12,7 kg) submetidos a CF (10 tubos extracardiacos, 2 tuneis intra-atriais) foram tratados 44,1 ± 26,7 meses apos a CF. Um paciente nao tolerou o teste de oclusao com o balao, sendo contraindicado o procedimento. As proteses utilizadas foram: HelexTM (4 pacientes), AmplatzerTM (2 pacientes), Cardia AtriaseptTM (2 pacientes), FigullaTM (1 paciente), CeraTM (1 paciente), e 1 stent coberto Cheatham-PlatinumTM. Apos a oclusao da fenestracao, a saturacao de oxigenio aumentou significativamente (82,1 ± 6,5% para 95,2 ± 3,2%), sem aumento significativo da pressao venosa central (12,4 ± 2,6 mmHg para 14,5 ± 2,3 mmHg) nem queda do debito cardiaco. Apos o procedimento foi observado shunt residual imediato em 5 pacientes, que desapareceu antes da alta. CONCLUSOES: A oclusao percutânea das fenestracoes apos CF pode ser realizada com varias opcoes de proteses e tecnicas, sendo um procedimento seguro e efetivo e que resulta em normalizacao dos niveis de saturacao.