Transesophageal echocardiography in patients with cryptogenic cerebral ischemia.
ABSTRACT: BACKGROUND: In about one third of all patients with cerebral ischemia, no definite cause can be identified (cryptogenic stroke). In many patients with initially suspected cryptogenic stroke, however, a cardiogenic etiology can eventually be determined. Hence, the aim of this study was to describe the prevalence of abnormal echocardiographic findings in a large number of these patients. METHOD: Patients with cryptogenic cerebral ischemia (ischemic stroke, IS, and transient ischemic attack, TIA) were included. The initial work-up included a neurological examination, EEG, cCT, cMRT, 12-lead ECG, Holter-ECG, Doppler ultrasound of the extracranial arteries, and transthoracic echocardiography. A multiplane transeophageal echocardiography (TEE, including i.v. contrast medium application [Echovist], Valsalva maneuver) was performed in all patients RESULTS: 702 consecutive patients (380 male, 383 IS, 319 TIA, age 18-90 years) were included. In 52.6% of all patients, TEE examination revealed relevant findings. Overall, the most common findings in all patients were: patent foramen ovale (21.7%), previously undiagnosed valvular disease (15.8%), aortic plaques, aortic valve sclerosis, atrial septal aneurysms, regional myocardial dyskinesia, dilated left atrium and atrial septal defects. Older patients (> 55 years, n = 291) and patients with IS had more relevant echocardiographic findings than younger patients or patients with TIA, respectively (p = 0.002, p = 0.003). The prevalence rates of PFO or ASD were higher in younger patients (PFO: 26.8% vs. 18.0%, p = 0.005, ASD: 9.6% vs. 4.9%, p = 0.014). CONCLUSION: A TEE examination in cryptogenic stroke reveals contributing cardiogenic factors in about half of all patients. Younger patients had a higher prevalence of PFO, whereas older patients had more frequently atherosclerotic findings. Therefore, TEE examinations seem indicated in all patients with cryptogenic stroke - irrespective of age - because of specific therapeutic consequences.
Project description: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.
Project description:To provide a comprehensive comparison of patent foramen ovale (PFO) closure versus medical therapy in patients with cryptogenic stroke or transient ischaemic attack (TIA) and demonstrated PFO.Systematic review with complete case meta-analysis and sensitivity analyses. Data sources included MEDLINE and EMBASE from 1980 up to May 2013. All randomised controlled trials (RCTs) comparing treatment with percutaneous catheter-based closure of PFO to anticoagulant or antiplatelet therapy in patients with cryptogenic stroke or TIA and echocardiographically confirmed PFO or atrial septal defect (ASD) were eligible.1967 participants with prior stroke or TIA and echocardiographically confirmed PFO or ASD.The primary outcome of interest was recurrence of ischaemic stroke. We utilised data from complete cases only for the primary endpoint and combined data from trials to estimate the pooled risk ratio (RR) and associated 95% CIs calculated using random effects models.We identified 284 potentially eligible articles of which three RCTs including 2303 patients proved eligible and 1967 patients had complete data. Of the 1026 patients randomised to PFO closure and followed to study conclusion 22 experienced non-fatal ischaemic strokes, as did 34 of 941 patients randomised to medical therapy (risk ratio (RR) 0.61, 95% CI 0.34 to 1.07; heterogeneity: p=0.34, I(2)=8%, confidence in estimates low due to risk of bias and imprecision). Analyses for ischaemic stroke restricted to 'per-protocol' patients or patients with concomitant atrial septal aneurysm did not substantially change the observed RRs. Complication rates associated with either PFO closure or medical therapy were low.Pooled data from three RCTs provides insufficient support that PFO closure is preferable to medical therapy for secondary prevention of cryptogenic stroke in patients with PFO.
Project description:Importance:Patent foramen ovale (PFO) closure may prevent recurrent stroke after cryptogenic transient ischemic attack (TIA) or stroke (TIA/stroke) in patients aged 60 years or younger. Patent foramen ovale is associated with cryptogenic stroke in the older population, but risk of recurrence is unknown. Data on prognosis of patients receiving medical treatment at older ages (?60 years) are essential to justify trials of PFO closure. Objective:To examine the age-specific risk of recurrence in patients with cryptogenic TIA/stroke with PFO. Design, Setting, and Participants:A prospective study was nested in the population-based Oxford Vascular Study between September 1, 2014, and March 31, 2019, with face-to-face follow-up for 5 years. A total of 416 consecutive patients with a diagnosis of cryptogenic TIA or nondisabling stroke, screened for PFO at a rapid-access TIA/stroke clinic, were included. A systematic review and meta-analysis of cohort studies reporting on ischemic stroke recurrence after cryptogenic TIA/stroke in patients with PFO who were receiving medical therapy alone, or with PFO vs no-PFO was conducted. Sample size calculation for future trials on PFO closure was performed for patients aged 60 years or older. Exposures:Patent foramen ovale and age as modifiers of risk of recurrent stroke after cryptogenic TIA/stroke in patients receiving only medical therapy. Main Outcomes and Measures:Risk of ischemic stroke recurrence in patients with cryptogenic TIA/stroke and PFO receiving medical therapy only, and in patients with vs without PFO, stratified by age (<65 vs ?65 years), as well as sample-size calculation for future trials of PFO closure in patients aged 60 years or older. Results:Among the 153 Oxford Vascular Study patients with PFO (mean [SD] age, 66.7 [13.7] years; 80 [52.3%] men), recurrent ischemic stroke risk (2.05 per 100 patient-years) was similar to the pooled estimate from a systematic review of 23 other studies (9 trials and 14 observational studies) (2.00 per 100 patient-years; 95% CI, 1.55-2.58). However, there was heterogeneity between studies (P?<?.001 for heterogeneity), owing mainly to risk increasing with mean cohort age (meta-regression: R2?=?0.31; P?=?.003). In the pooled analysis of 4 studies including patients with or without PFO, increased risk of stroke recurrence with PFO was seen only at age 65 years or older (odds ratio, 2.5; 95% CI, 1.4-4.2; P?=?.001 for difference; P?=?.39 for heterogeneity). The pooled ischemic stroke risk was 3.27 per 100 patient-years (95% CI, 2.59-4.13) in 4 cohorts with mean age 60 years or older. Assuming the more conservative 2.0 per 100 patient-years ischemic stroke risk in the PFO nonclosure arms of future trials in patients aged 60 years or older, projected sample sizes were 1080 per arm for 80% power to detect a 33% relative risk reduction. Conclusions and Relevance:The findings of this study suggest that age is a determinant of risk of ischemic stroke after cryptogenic TIA/stroke in patients with PFO, such that trials of PFO closure at older ages are justified; however, projected sample sizes are large.
Project description:We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation.The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings.A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use.Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.
Project description:BACKGROUND:Previous review from randomized controlled trials (RCT) showed that patients with cryptogenic stroke may benefit from patent foramen ovale (PFO) closure. However, the findings from the systematic review were not clear when observational studies were also included. METHODS:We searched MEDLINE, Embase, and Cochrane databases. The primary endpoints were recurrent stroke or transient ischemic attack (TIA). The secondary outcomes were all-cause death, atrial fibrillation (AF), and hemorrhagic events. RESULTS:Five randomized trials and fourteen observational studies (6301 participants) were eligible. PFO closure was superior to medical therapy for stroke prevention risk ratios ([RR], 0.38; 95% CI, 0.24-0.60), but showed increased risk of AF (RR, 4.96; 95% CI, 2.31-10.7). There was no significant difference in TIA recurrence, death, and hemorrhagic events. Subgroup analyses showed that patients with factors such as substantial residual shunt, the presence of atrial septal aneurysm (ASA), male, and age <45 years had a lower risk of recurrent stroke when PFOs were closed. CONCLUSIONS:In patients with cryptogenic stroke, PFO closure does appeared to be superior to medical therapy in stroke prevention, with an increased incidence of AF. Male, age <45 years, substantial residual shunt, and the history of ASA are the factors that will predict the benefit when PFO is closed.
Project description:There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke.A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs).A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n = 1150) and medical therapy (n = 1153). Mean follow-up was 2.5 years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01; p = 0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98; p = 0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96; p = 0.038).In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.
Project description:<b>Background and purpose: </b>Ischemic stroke is a widespread disease carrying high morbidity and mortality. Transesophageal echocardiography (TEE) is considered an important tool in the work-up of patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients; its utility is limited by a semi-invasive nature. The purpose of this study was to evaluate the probability of treatment change due to TEE findings (yield) in the work-up of AIS and TIA patients.<br><br><b>Methods: </b>Retrospective data on patients with AIS or TIA who underwent TEE examination between 2000-2013 were collected from the institutional registry.<br><br><b>Results: </b>The average age of 1284 patients who were included in the study was 57±10.4, 66% of patients were male. The most frequent TEE findings included aortic plaques in 54% and patent foramen ovale (PFO) in 15%. TEE findings led to treatment change in 135 (10.5%) patients; anticoagulant treatment was initiated in 110 of them (81%). Most common etiology for switch to anticoagulation was aortic plaques (71 patients); PFO was second most common reason (26 patients). Significant TEE findings (thrombus, endocarditis, tumor) were found in 1.9% of patients, they were more common in young patients (<55; 56% of the patients).<br><br><b>Conclusions: </b>The beginning of anticoagulation treatment in patients with thick and complicated plaques was found frequently in our study. Significant TEE findings, were infrequent, constituted an absolute indication for treatment change and were more common in younger patients.
Project description:<h4>Objective</h4>We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.<h4>Methods</h4>Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.<h4>Results</h4>Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest.<h4>Conclusion</h4>Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.
Project description:It was under debate whether cryptogenic stroke patients benefited from patent foramen ovale (PFO) closure. We sought to determine secondary prevention strategy in these patients.Scientific databases were searched for randomized controlled trials enrolling cryptogenic stroke patients with PFO who underwent PFO closure or medical therapy. The random-effect model was used to analyze the outcomes.We identified 6 trials enrolling 3630 participants in this meta-analysis. When compared with medical therapy, PFO closure reduced risks of recurrent stroke (risk ratio [RR] 0.52, 95% confidence interval [CI] 0.29-0.93) and composite of stroke and transient ischemic attack (TIA) (RR 0.60, 95% CI 0.46-0.80). And no differences in all-cause death (RR 0.80, 95% CI 0.37-1.72) and cardiovascular death (RR 1.47, 95% CI 0.36-5.94) between 2 groups were observed. The risks of major bleeding (RR 0.96, 95% CI 0.47-1.96) and any serious adverse event (RR 1.03, 95% CI 0.92-1.16) did not differ between 2 groups. Yet, PFO closure increased risk of atrial fibrillation (RR 4.25, 95% CI 2.10-8.60).PFO closure, as compared with medical therapy, was associated with decreased risk of recurrent stroke and increased risk of atrial fibrillation in cryptogenic stroke patients with PFO.
Project description: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.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.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.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.