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

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
David E Thaler ◽  
Robin Ruthazer ◽  
Emanuele Di Angelantonio ◽  
Marco R Di Tullio ◽  
Jennifer S Donovan ◽  
...  

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 >6, estimated PFO attributable fraction 72-99%, n=646) and others (RoPE Score of <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 (<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).

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
David E Thaler ◽  
Issa J Dahabreh ◽  
Robin Ruthazer ◽  
Anthony J Furlan ◽  
Mark Reisman ◽  
...  

Introduction: The Risk of Paradoxical Embolism (RoPE) Score can disaggregate patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) into those who are more likely to have a pathogenic PFO (high RoPE score) than an incidental PFO (low RoPE score). Those with higher RoPE scores have a lower risk of recurrent stroke and different recurrence predictors compared to those with low RoPE scores. Hypotheses: Patients with high RoPE scores benefit more from PFO closure than patients with low RoPE scores. Patients with high RoPE scores and risk factors for recurrence should benefit even more. Methods: The RoPE score was created from a database of CS patients with known PFO status to estimate stratum-specific PFO-attributable fraction and recurrence rates. Variables that predict stroke recurrence in high RoPE score groups (atrial septal aneurysm, history of stroke/TIA prior to index event) were added – the “RoPE Recurrence Score.” Using pooled individual patient data from all 3 RCTs of PFO closure vs. medical therapy (ITT populations; stroke outcome) we tested the ability of the scores to predict the heterogeneity of response to assigned treatment. Results: The mean RoPE score was significantly higher (6.8 vs. 6.3) with smaller variance (Stdev 1.5 vs. 1.9) in the pooled RCT population than in the original RoPE cohort (p<0.0001). Hazard ratios favoring closure were 0.82 (0.42-1.59, p=0.56) in the low RoPE score (<7) group and 0.31 (0.11-0.85, p=0.02) in the high RoPE score (≥7) group but the interaction p-value was not significant (p=0.12). The RoPE Recurrence score did not improve the prediction of treatment response (low score HR=0.65 (0.31-1.37), p=0.26; high score HR=0.58 (0.26-1.26), p=0.17; interaction p=0.82). Conclusion: As expected, the HR favoring closure trended lower in the high RoPE score group in the RCTs but missed statistical significance. The RoPE Recurrence score did not improve the prediction. This may be due to the narrow distribution of relatively high RoPE scores amongst RCT patients and so a low power to detect heterogeneity of treatment effect. Given that PFO closure can only prevent PFO-related recurrences, the treatment effect may also have been obscured by including recurrent strokes with non-PFO-related mechanisms.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Richard Jung ◽  
Benny Kim ◽  
Joseph Massaro ◽  
Anthony J Furlan

Background: Cryptogenic stroke may have several etiologies including paradoxical embolism through a patent foramen ovale (PFO). A cardiac source of embolism may be suggested by multiple infarcts, sometimes hemorrhagic, in different vascular distributions or a cortical wedge shaped infarct. We report the baseline diffusion weighted MRI (DWMRI) characteristics in patients with cryptogenic stroke and a patent foramen ovale (PFO) from the CLOSURE I trial. Methods: CLOSURE I compared device closure versus medical therapy for secondary prevention in patients with cryptogenic TIA or stroke and a PFO. Of 909 patients randomized, 562 patients demonstrated acute infarcts on baseline DWMRI and are included in this analysis. Multivariate proportional hazard Cox regression compared imaging subgroups with remaining randomized patients Results: Single infarcts were found in 62% of patients. Of these, 61% were anterior circulation, 30% posterior, and 8.5% were of uncertain territory. Of the anterior circulation infarcts, 40% were cortical, 36% subcortical, and 24% affected both the cortical and subcortical regions. Of the posterior circulation infarcts, 45% were thalamic or cerebellar. Of 562 patients, 18.5% had a single subcortical lesion <1.5cm in diameter and met the radiological definition of an acute lacunar infarct. Multiple infarcts were found in 38%. Infarcts in a single vascular territory were found in 23%, often in the anterior circulation (66%). Infarcts in multiple vascular territories were found in 15%. Hemorrhagic infarction was present in 9%. Adjusting for patient characteristics, no significant difference in 2 year rate of TIA, stroke or death was found compared to remaining randomized patients. Discussion: The specificity of infarct patterns for embolism in patients with cryptogenic stroke and a PFO is uncertain. We found no significant relationship between lacunar or subcortical infarction and the risk of recurrent TIA or stroke. Baseline infarct patterns on DWMRI in patients with cryptogenic stroke and PFO may not be useful in predicting recurrent stroke risk or determining best prevention therapy.


Stroke ◽  
2018 ◽  
Vol 49 (12) ◽  
pp. 2872-2876 ◽  
Author(s):  
Andrew J. Zhang ◽  
Parth Dhruv ◽  
Philip Choi ◽  
Caitlin Bakker ◽  
Jonathan Koffel ◽  
...  

Background and Purpose— Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods— Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results— Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16–85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0–97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients. Conclusions— CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Yeseon P Moon ◽  
Consuelo Mora-McLaughlin ◽  
Joshua Z Willey ◽  
Marco R Di Tullio ◽  
...  

Background: While left atrial (LA) enlargement increases incident stroke risk, the association with recurrent stroke is unclear. Our aim was to determine the association of LA enlargement (LAE) with stroke recurrence risk and recurrent stroke subtypes likely related to embolism (cryptogenic or cardioembolic). Methods: We enrolled 655 first ischemic stroke patients in the Northern Manhattan Stroke Study. LA size was measured by two-dimensional echocardiogram as part of the clinical evaluation and patients were followed annually for up to 5 years. LA size adjusted for sex and body surface area was categorized into three groups: normal (52.7%), mild LAE (31.6%), and moderate to severe LAE (15.7%). The outcomes were total recurrent stroke, and recurrent combined cryptogenic or cardioembolic stroke. Cox proportional hazard models assessed the association between LA size and risk of stroke recurrence. Results: Of 655 patients, LA size data was present in 529 (81%). Mean age was 69 ± 13 years; 46% were male and 18% had atrial fibrillation. Over a median of 4 years, recurrent stroke occurred in 83 patients (16%), 29 were cardioembolic or cryptogenic stroke. After adjusting for baseline demographics and risk factors including atrial fibrillation and congestive heart failure, compared to normal LA size, moderate to severe LAE was associated with greater risk of recurrent combined cardioembolic or cryptogenic stroke (adjusted HR 2. 99, 95% CI 1. 10 to 8.13), but not with risk of total stroke recurrence (adjusted HR 1.18, 95% CI 0.60 to 2.32). Mild LAE was not associated with either total stroke recurrence or the combined recurrent cryptogenic or cardioembolic stroke subtypes. Conclusion: Moderate to severe LAE is an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Future research is needed to determine if anticoagulant use reduces the risk of recurrence in ischemic stroke patients with moderate to severe LAE.


2020 ◽  
Vol 13 ◽  
pp. 175628642096467
Author(s):  
Ioanna Koutroulou ◽  
Georgios Tsivgoulis ◽  
Dimitris Karacostas ◽  
Ignatios Ikonomidis ◽  
Nikolaos Grigoriadis ◽  
...  

Background: The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely. Methods: Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11–20), and small (⩽10). Results: PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS ( p = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124); p = 0.1] and to nonCS [7.1% (4/56), p = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9–10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was <33%. Conclusions: PFO prevalence in the Greek population is much higher than the widely accepted 25%. PFO may be the cause of stroke in one out of nine Greek patients with CS. Among Greek CS patients who harbor a PFO, the latter is causal in one out of five. The established RoPE score cutoff of ⩾7 for having a probable PFO-associated stroke may overestimate the probability in patients deriving from populations with high PFO prevalence.


Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 3119-3123
Author(s):  
David M. Kent ◽  
Jeffrey L. Saver ◽  
Robin Ruthazer ◽  
Anthony J. Furlan ◽  
Mark Reisman ◽  
...  

Background and Purpose: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific “PFO-attributable fraction”—the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. Methods: We pooled data from 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), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial–compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. Results: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42–1.59] P =0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11–0.85] P =0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P =0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial ( r =0.95, P <0.001) and 2-trial ( r =0.92, P <0.001) analyses. Conclusions: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.


2016 ◽  
Vol 12 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Layan Akijian ◽  
Danielle Ní Chróinín ◽  
Elizabeth Callaly ◽  
Niamh Hannon ◽  
Michael Marnane ◽  
...  

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.


2021 ◽  
pp. 239698732110585
Author(s):  
Elora Basu ◽  
Setareh Salehi Omran ◽  
Hooman Kamel ◽  
Neal S Parikh

Background Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. Patients and methods We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (<60 versus >60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Results Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%–6.85%) compared to men (5.67%; 95% CI, 4.83%–6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80–1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients <60 years old, there was a non-significantly lower risk of recurrent stroke in women compared to men (HR 0.66; 95% CI 0.42–1.05). Last, sex did not modify the association between common stroke risk factors and recurrent stroke risk. Discussion and Conclusion Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.


VASA ◽  
2011 ◽  
Vol 40 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Lehmeyer ◽  
Lindhoff-Last

Paradoxical emboli have their origin in the low-pressure venous system and can cause ischemic stroke or peripheral arterial embolism through a cardiac or pulmonary shunt. In most cases, a patent foramen ovale (PFO) is found. About 20 % of the population has a patent foramen ovale. This review gives insight into publications concerning the association between the presence of a patent foramen ovale and cryptogenic stroke; the association of PFO, coagulation disorders and stroke; and recurrence rates of stroke in patients with PFO. Diagnostic features are discussed, as are the different therapy modalities, taking existing national and international guidelines into account. Also, our own recommendations are given. In addition some new information on the potential improvement of migraine after PFO closure is discussed. It is widely accepted that the optimal therapy for the prevention of recurrent stroke in patients with PFO and cryptogenic stroke has not yet been found. Randomized, controlled clinical studies are ongoing in the United States and will give even more insight and answer open questions in the future.


Author(s):  
Yilong Guo ◽  
Zhensu Shi ◽  
Yin Zheng ◽  
Caichan Xie ◽  
Jiao Yi ◽  
...  

Background: This study aimed to assess the short-term (12 months) results of PFO occlusion guided by transoesophageal echocardiography (TEE) and the results of regular transthoracic ultrasound foaming test (UFT). Methods: Data of 75 patients who underwent interventional therapy for PFO and CS were retrospectively analysed. The patients were grouped according to their preoperative UFT results: group A, small volume of right-to-left shunts; group B, moderate volume of right-to-left shunts; and group C, large volume of right-to-left shunts. All patients were treated with an Amplatzer occluder under TEE guidance. UFT follow-up was conducted regularly until 12 months after surgery. Results: No remarkable differences in preoperative data, length of hospital stay, or operative time were noted between the groups. Length of the PFO and diameter of the occluder differed between the groups: group A=group Bp<0.001). One patient in group C developed recurrent stroke 11 months postoperatively. Two patients in group C developed atrial arrhythmia, which improved after 3 months of antiarrhythmic treatment. However, 19 patients still had positive UFT results 12 months postoperatively. Furthermore, the positive UFT rate 12 months postoperatively differed between the groups: group A=group Bp<0.05). Conclusions: In patients with PFO and CS, interventional therapy guided by TEE could lead to satisfactory short-term (12 months) outcomes. A longer PFO and preoperative large-volume shunt were negatively associated with a negative UFT rate 12 months postoperatively. Further studies are required to clarify the relationship between positive UFT results postoperatively and stroke recurrence.


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