Recurrent Stroke in a Young Patient with Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Quo Vadis?
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SUBMITTER: Feil K
PROVIDER: S-EPMC7036551 | biostudies-literature | 2020 Jan-Apr
REPOSITORIES: biostudies-literature
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Recurrent Stroke in a Young Patient with Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Quo Vadis?
Feil Katharina K Heinrich Johanna J von Falkenhausen Aenne S AS Becker Regina R Küpper Clemens C Müller Katharina K Thunstedt Dennis C DC Sinner Moritz F MF Kääb Stefan S Kellert Lars L
Case reports in neurology 20200129 1
So far, there has been no generally accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). As recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation and the concept of ESUS comprises heterogeneous subgroups of patients, including a wide age range, concomitant patent foramen ovale (PFO), variable cardiovascular risk factors as well as a variable probability for atrial fibrillation (AF), a ...[more]
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Project description:BackgroundThe aim of this study was to develop a screening score system of non-contrast transthoracic echocardiography (TTE) for patent foramen ovale (PFO) in patients with embolic stroke of undetermined source (ESUS).MethodsWe performed a retrospective analysis of 218 consecutive patients with a recent ESUS from 2015 to 2018, who received TTE and transcranial Doppler (TCD) as routine examinations. PFO was diagnosed by the bubble test of TCD. Significant differences of the non-contrast TTE findings and patient characteristics between PFO group and non-PFO group were selected into a score.ResultsPFO was diagnosed in 35.8% (78/218) of the patients. Compared with non-PFO group, a larger median aortic root diameter (ARd) (34 mm vs. 32 mm, p = 0.005), a lower median peak E wave velocity (Em) (61.5 cm/s vs. 68 cm/s, p = 0.005) and a lower incidence rate of mitral regurgitation (34.6% vs. 50.7%, p = 0.022) were seen in PFO group. ARd>33 mm and Em < 72 cm/s were the best thresholds to predict PFO in ROC analysis. A four-point score system (MEAD) including TTE criteria (including ARd>33 mm, Em < 72 cm/s and without mitral regurgitation) and no history of diabetes predicted PFO with an area under curve of 0.67 (95%CI 0.57-0.72, p < 0.001). MEAD score ≥ 3 was the best threshold to predict PFO with an accuracy of 0.64 (95% CI 0.57-0.7), a sensitivity of 0.65 (95% CI 0.53-0.75) and a specificity of 0.63 (95% CI 0.55-0.71).ConclusionThe MEAD score measured with non-contrast TTE can be used to select patients for bubble test of TCD to increase the diagnostic yield of PFO after ESUS.
| S-EPMC8815249 | biostudies-literature
Project description:BACKGROUND:Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS:NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS:Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION:Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING:Bayer and Janssen.
| S-EPMC6662613 | biostudies-literature
Project description:Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.
| S-EPMC4635723 | biostudies-literature
Project description:Patent foramen ovale (PFO)-related stroke is increasingly recognized as an important etiology of ischemic embolic stroke-accounting for up to 50% of strokes previously considered 'cryptogenic' or with an unknown mechanism. As a 'back door to the brain,' PFO can allow venous clots to enter arterial circulation via interatrial right-to-left shunting, potentially resulting in ischemic stroke. We observe that clinically, PFO-related stroke affects women of childbearing age, and that pregnancy-owing to major changes in hemocoagulative, hormonal, and cardiovascular parameters-can enhance stroke risks. However, no systematic study has been performed and little is known regarding complications, pregnancy outcomes and treatment for PFO-related stroke during pregnancy. To identify and characterize the complications and clinical outcomes related to PFOs during pregnancy, we performed a literature review and analysis from all reported cases of pregnancy with PFO-related complications in the medical literature from 1970 to 2015. We find that during pregnancy and post-partum, PFO is associated with complications affecting multiple organs, including the brain, heart and lung. The three principal complications reported are stroke, pulmonary emboli and myocardial infarction. In contrast to other pregnancy-related stroke etiologies, which peak during later pregnancy and postpartum, PFO-related stroke peaks during early pregnancy (first and second trimester-60%), and most patients had good neurological outcome (77%). In patients with PFO with recurrent stroke during pregnancy, additional key factors include high-risk PFO morphology (atrial septal aneurysm), larger right-to-left shunt, multiple gestation and concurrent hypercoagulability. Compared to strokes of other etiologies during pregnancy, most PFO stroke patients experienced uneventful delivery (93%) of healthy babies with a good clinical outcome. We conclude with recommended clinical treatment strategies for pregnant patients with PFO suggested by the data from these cases, and the clinical experience of our Cardio-Neurology Clinic.
| S-EPMC6083869 | biostudies-literature
Project description:BackgroundPercutaneous patent foramen ovale (PFO) closure has been well established in the secondary prevention of cryptogenic stroke with overall low rates of procedural complications. One such complication is PFO closure device thrombus formation which is now rarely reported with newer generation devices.Case summaryWe present the unusual case of a 59-year-old woman with myelofibrosis who developed late-onset recurrent embolic strokes related to Amplatzer PFO closure device thrombus whilst therapeutically anticoagulated on Warfarin. Surgical management was deemed too high risk and our patient was conservatively managed with enoxaparin. Serial transthoracic echocardiography demonstrated a reduction in thrombus size and the patient had no further neurological events.DiscussionOverall, the risk of serious complications following percutaneous PFO closure, such as device-associated thrombus, remains low. The risk of thrombus formation in patients with hypercoagulable states is not well characterized. Despite good evidence for the efficacy in preventing recurrent cryptogenic stroke, the role of PFO closure in addition to anticoagulation is unclear. Given this uncertain benefit of PFO closure in anticoagulated patients and the unclear risk profile, patient selection, and thorough pre-procedural evaluation are vital when assessing the appropriateness of percutaneous PFO closure.
| S-EPMC8377246 | biostudies-literature
Project description:One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.
| S-EPMC7902455 | biostudies-literature
Project description: Not available
| S-EPMC8828961 | biostudies-literature
Project description:Background and purposePatent foramen ovale (PFO) is significantly associated with cryptogenic stroke (CS). However, even in patients with CS, a PFO can be an incidental finding. We sought to estimate the probability that a PFO in a patient with CS is incidental.MethodsA systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus control subjects with stroke of known cause. Using simple assumptions and Bayes' theorem, we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus control subjects in different age populations, with or without atrial septal aneurysms, and were used to summarize across studies the probability that a PFO in CS is incidental.ResultsThe summary OR (95% CIs) for PFO in CS versus control subjects was 2.9 (CI, 2.1 to 4.0). The corresponding ORs for young and old patients (< or >or=55 years) were 5.1 (3.3 to 7.8) and 2.0 (>1.0 to 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28% to 39%) in age-inclusive studies, 20% (16% to 25%) in younger patients, and 48% (34% to 66%) in older patients. These probabilities were much lower when an atrial septal aneurysm was present.ConclusionsIn patients with otherwise CS, approximately one third of discovered PFOs are likely to be incidental and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an atrial septal aneurysm, suggesting the importance of patient selection in therapeutic decision-making.
| S-EPMC2764355 | biostudies-literature
Project description:Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83-2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23-2.32]), male sex (HR, 1.60 [95% CI, 1.27-2.02]), and CHA2DS2-VASc ≥4 (HR, 1.55 [95% CI, 1.15-2.08] and HR, 1.66 [95% CI, 1.21-2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2-VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE-SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high-risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
| S-EPMC9238731 | biostudies-literature
Project description:Background: Randomized controlled trials indicate that patent foramen ovale (PFO) closure reduces risk of stroke recurrence in patients with cryptogenic stroke and PFO. However, the optimal time point for PFO closure is unknown and depends on the risk of stroke recurrence. Objective: We aimed to investigate risk of early new ischemic lesions on cerebral magnetic resonance imaging (MRI) in cryptogenic stroke patients with and without PFO. Methods: Cryptogenic stroke patients underwent serial MRI examinations within 1 week after symptom onset to detect early new ischemic lesions. Diffusion-weighted imaging (DWI) lesions were delineated, co-registered, and analyzed visually for new hyperintensities by raters blinded to clinical details. A PFO was classified as stroke-related in patients with PFO and a Risk of Paradoxical Embolism (RoPE) score >5 points. Results: Out of 80 cryptogenic stroke patients, risk of early recurrent DWI lesions was not significantly different in cryptogenic stroke patients with and without PFO. Similar results were observed in patients ?60 years of age. Patients with a stroke-related PFO even had a significantly lower risk of early recurrent ischemic lesions compared to all other patients with cryptogenic stroke (unadjusted odds ratio 0.23 [95% confidence interval 0.06-0.87], P = 0.030). Conclusion: Our data argue against a high risk of early stroke recurrence in patients with cryptogenic stroke and PFO.
| S-EPMC6262074 | biostudies-literature