Letter by Schuchlenz Regarding Article, “Transesophageal Echocardiography in Cryptogenic Stroke and Patent Foramen Ovale Analysis of Putative High-Risk Features From 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 >6, estimated PFO attributable fraction 72-99%, n=637) than in those with lower RoPE Scores (<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.

Download Full-text

Importance of Contrast Transthoracic Echocardiography for Evaluating Large Right-to-Left Shunt in Patent Foramen Ovale Associated with Cryptogenic Stroke

10.21203/rs.3.rs-760835/v1 ◽

2021 ◽

Author(s):

Yoichi Takaya ◽

Rie Nakayama ◽

Teiji Akagi ◽

Fumi Yokohama ◽

Takashi Miki ◽

...

Keyword(s):

High Risk ◽

Transesophageal Echocardiography ◽

Transthoracic Echocardiography ◽

Patent Foramen Ovale ◽

Transcatheter Closure ◽

Cryptogenic Stroke ◽

Effective Therapy ◽

Foramen Ovale

Abstract Transcatheter closure of patent foramen ovale (PFO) is an effective therapy for preventing cryptogenic stroke (CS). The identification of high-risk PFO, which is more likely to be linked to CS, is essential. This study aimed to assess the accuracy of contrast transthoracic echocardiography (TTE) for evaluating large right-to-left (RL) shunt. We enrolled 119 patients with or without CS who were confirmed to have PFO. The severity of RL shunt evaluated by contrast TTE and transesophageal echocardiography (TEE) was classified as follows: small (<10 microbubbles), moderate (10–20 microbubbles), and large (>20 microbubbles). With contrast TTE, large RL shunt was observed in 94 (79%) of 119 patients, including 66 of 74 with CS and 28 of 45 without CS. With contrast TEE, large RL shunt was observed in 33 (28%) patients, including 26 with CS and 7 without CS. Contrast TTE showed large RL shunt more frequently than contrast TEE (p < 0.01). Large RL shunt evaluated by contrast TTE had a sensitivity of 89% and an accuracy of 70% for the association with CS, whereas large RL shunt evaluated by contrast TEE had a sensitivity of 35% and an accuracy of 56%. Accuracy was significantly greater in contrast TTE than in contrast TEE (p = 0.02). In conclusion, contrast TTE identified large RL shunt more frequently. Large RL shunt evaluated by contrast TTE provided greater accuracy for the association with CS. Our findings suggest that contrast TTE is valuable for evaluating large RL shunt as high-risk PFO.

Download Full-text

Importance of contrast transthoracic echocardiography for evaluating large right-to-left shunt in patent foramen ovale associated with cryptogenic stroke

10.22541/au.162376891.16321495/v1 ◽

2021 ◽

Author(s):

Yoichi Takaya ◽

Rie Nakayama ◽

Teiji Akagi ◽

Fumi Yokohama ◽

Takashi Miki ◽

...

Keyword(s):

High Risk ◽

Transesophageal Echocardiography ◽

Transthoracic Echocardiography ◽

Patent Foramen Ovale ◽

Transcatheter Closure ◽

Cryptogenic Stroke ◽

Effective Therapy ◽

Foramen Ovale

Background: Transcatheter closure of patent foramen ovale (PFO) is an effective therapy for preventing cryptogenic stroke (CS). The identification of high-risk PFO, which is more likely to be linked to CS, is essential. This study aimed to assess the accuracy of contrast transthoracic echocardiography (TTE) for evaluating large right-to-left (RL) shunt. Methods: We enrolled 119 patients with or without CS who were confirmed to have PFO. The severity of RL shunt evaluated by contrast TTE and transesophageal echocardiography (TEE) was classified as follows: small (<10 microbubbles), moderate (10–20 microbubbles), and large (>20 microbubbles). Results: With contrast TTE, large RL shunt was observed in 94 (79%) of 119 patients, including 66 of 74 with CS and 28 of 45 without CS. With contrast TEE, large RL shunt was observed in 33 (28%) patients, including 26 with CS and 7 without CS. Contrast TTE showed large RL shunt more frequently than contrast TEE (P < .01). Large RL shunt evaluated by contrast TTE had a sensitivity of 89% and an accuracy of 70% for the association with CS, whereas large RL shunt evaluated by contrast TEE had a sensitivity of 35% and an accuracy of 56%. Accuracy was significantly greater in contrast TTE than in contrast TEE (P = .02). Conclusion: Contrast TTE identified large RL shunt more frequently. Large RL shunt evaluated by contrast TTE provided greater accuracy for the association with CS. Our findings suggest that contrast TTE is valuable for evaluating large RL shunt as high-risk PFO.

Download Full-text

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

Cerebrovascular Diseases ◽

10.1159/000430998 ◽

2015 ◽

Vol 40 (1-2) ◽

pp. 52-58 ◽

Cited By ~ 12

Author(s):

Benjamin S. Wessler ◽

David M. Kent ◽

David E. Thaler ◽

Robin Ruthazer ◽

Jennifer S. Lutz ◽

...

Keyword(s):

Transesophageal Echocardiography ◽

Multicenter Study ◽

Transcranial Doppler ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Rank Correlation ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

C Statistic

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.

Download Full-text

Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200203111641 ◽

2020 ◽

Vol 18 (2) ◽

pp. 135-150

Author(s):

Harsha S. Nagarajarao ◽

Chandra P. Ojha ◽

Archana Kedar ◽

Debabrata Mukherjee

Keyword(s):

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Narrow Channel ◽

Paradoxical Embolism ◽

Current Evidence ◽

Foramen Ovale ◽

The Right ◽

The Relationship ◽

Current Guidelines

: Cryptogenic stroke and its relation to the Patent Foramen Ovale (PFO) is a long-debated topic. Recent clinical trials have unequivocally established the relationship between cryptogenic strokes and paradoxical embolism across the PFO. This slit-like communication exists in everyone before birth, but most often closes shortly after birth. PFO may persist as a narrow channel of communication between the right and left atria in approximately 25-27% of adults. : In this review, we examine the clinical relevance of the PFO with analysis of the latest trials evaluating catheter-based closure of PFO’s for cryptogenic stroke. We also review the current evidence examining the use of antiplatelet medications versus anticoagulants for stroke prevention in those patients with PFO who do not qualify for closure per current guidelines.

Download Full-text

Residual Shunt after Patent Foramen Ovale Device Closure in Patients With Cryptogenic Stroke: Serial Bubble Contrast Transesophageal Echocardiography Data

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2018.10.006 ◽

2019 ◽

Vol 28 (2) ◽

pp. 347-353 ◽

Cited By ~ 3

Author(s):

Jeonggeun Moon ◽

Minsu Kim ◽

Pyung Chun Oh ◽

Dong Hoon Shin ◽

Hyeon-MI Park ◽

...

Keyword(s):

Transesophageal Echocardiography ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Foramen Ovale ◽

Device Closure ◽

Residual Shunt

Download Full-text

Patent Foramen Ovale Device Closure in a 27 Years Old Young Lady with Cryptogenic Ischaemic Stroke - First Case Report from Bangladesh

Cardiovascular Journal ◽

10.3329/cardio.v13i2.52978 ◽

2021 ◽

Vol 13 (2) ◽

pp. 227-234

Author(s):

AQM Reza ◽

Aparajita Karim ◽

Mahmood Hasan Khan ◽

Kazi Atiqur Rahman ◽

Md Aliuzzaman Joarder ◽

...

Keyword(s):

Ischaemic Stroke ◽

Patent Foramen Ovale ◽

Incidental Finding ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

Coagulation Therapy ◽

First Case ◽

Treatment Paradigm ◽

Meta Analyses

A patent foramen ovale (PFO) is highly prevalent in patients with strokes of unknown cause or cryptogenic strokes (CSs). It has been remained an unsolved question as to whether a PFO should be closed or not to prevent recurrent strokes in patients diagnosed with cryptogenic stroke (CS). A paradoxical embolism through a PFO is pointed as a leading cause of CS, especially in younger patients with low risk factors for stroke. It also remains an unsolved matter on type of anti-coagulation therapy, which would be better for patients with CS and a PFO. In addition, surgical and transcutaneous closure of a PFO has been proposed for the secondary prevention of stroke in patients with CS with PFO. Several randomized controlled trials have been conducted in recent years to test whether a PFO closure gives a significant benefit in the management of CS. Many investigators believed that a PFO was an incidental finding in patients with CS. However, meta-analyses and more recent specific trials have eliminated several confounding factors and possible biases and have also emphasized the use of a shunt closure over medical therapy in patients with CS. Therefore, these latest studies can possibly change the treatment paradigm in the near future. We are reporting a case of cryptogenic ischaemic stroke in middle cerebral artery territory due to paradoxical embolism through a PFO which was successfully closed with a device solely by a Bangladeshi Consultant & his team first time in Bangladesh. Cardiovasc. j. 2021; 13(2): 227-234

Download Full-text

Abstract WP264: Frequency of Hypercoagulability in Patients With Embolic Stroke of Undetermined Source and Patent Foramen Ovale

Stroke ◽

10.1161/str.51.suppl_1.wp264 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Michael Liu ◽

Srikant Rangaraju ◽

Alexander Duncan ◽

Samir Belagaje ◽

Trina Belair ◽

...

Keyword(s):

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Paradoxical Embolism ◽

Embolic Stroke ◽

Composite Outcome ◽

Foramen Ovale ◽

Primary Mechanism ◽

Detailed Evaluation ◽

D Dimer

Introduction: Patent foramen ovale (PFO) is more commonly found in patients with cryptogenic stroke and paradoxical embolism is commonly assumed to be the primary mechanism. Our objective was to determine the frequency of hypercoagulability in cryptogenic stroke patients and PFO. Methods: Consecutive patients with embolic stroke of undetermined source (ESUS) seen at the Emory Clinic from January 1, 2017 to June 30, 2019 who underwent echocardiogram with bubble study and markers of coagulation and hemostatic activation (MOCHA) testing (serum d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) were included; abnormal MOCHA was defined as ≥ 2 elevated markers. Venous thromboembolism, malignancy, other defined hypercoagulable state, and the composite outcome were assessed at routine follow-up and compared across groups based on PFO status. Results: Of 172 patients (mean age 63 ± 16 years, 60% female), 40 (23%) had a PFO. Compared to the PFO- group, the PFO+ group was younger (p=<0.001), less likely to have hypertension (p<0.001) and diabetes (p=0.011), and had a higher ROPE score (p=0.007) (Table 1). There was no difference in the frequency of abnormal MOCHA between groups and the composite outcome was less frequent in PFO+ versus PFO- patients (p=0.017). In the subgroup of patients <60 years old, there was no difference in the frequency of abnormal MOCHA and the composite outcome. Conclusion: Hypercoagulability as measured by MOCHA was not associated with the presence of PFO in ESUS patients. Based on our results, ESUS patients should undergo a detailed evaluation for alternative causes of stroke other than paradoxical embolism.

Download Full-text

Abstract TMP13: Baseline DWMRI Characteristics In Patients With Cryptogenic Stroke And Patent Foramen Ovale: Results From The Closure I Trial

Stroke ◽

10.1161/str.44.suppl_1.atmp13 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Richard Jung ◽

Benny Kim ◽

Joseph Massaro ◽

Anthony J Furlan

Keyword(s):

Patent Foramen Ovale ◽

Cox Regression ◽

Recurrent Stroke ◽

Cryptogenic Stroke ◽

Patient Characteristics ◽

Paradoxical Embolism ◽

Foramen Ovale ◽

Anterior Circulation ◽

Significant Difference ◽

Multivariate Proportional Hazard

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.

Download Full-text