Comparative analysis of the diagnostic value of several methods for the diagnosis of patent foramen ovale.

The aim of this research was to compare the sensitivity and positive predictive value of contrast transcranial Doppler (c-TCD), contrast transthoracic echocardiography (c-TTE), and contrast transesophageal echocardiography (c-TEE), to determine the best method for diagnosing patent foramen ovale (PFO) and to provide a reference for the further improvement of clinical practice. We investigated 161 patients who suffered from migraines, cryptogenic stroke, TIA, and cerebral infarction of unknown cause. All patients underwent transcatheter examination, and the results of the right heart catheterization (RHC) were considered the gold standard for PFO diagnosis. The present study revealed that c-TTE with the Valsalva maneuver had a higher sensitivity in detecting PFO related right-to-left shunt (PFO-RLS), c-TCD performed similarly to c-TEE but maybe produce more false positives. Moreover, when we observed color shunt from the slit-like channel between the septum primum and the septum secundum on TEE, the positive predictive value was the highest. Patients with suspected PFO should be examined with c-TTE and c-TEE for confirmation. When there were a large number of bubbles in the left heart, especially in the presence of color shunt, the positive predictive value was the highest. The positive results of c-TCD only point out the presence of right-to-left shunt and cannot exclude extracardiac shunt, so c-TCD should not be used as a screen for PFO, additional measures such as c-TTE and c-TEE should be used.

Tumor Embolism Through Right-to-Left Shunt Due to Venous Invasion of Esophageal Carcinoma.

A 69-year-old man was admitted to the hospital with right hemiparesis and global aphasia. Perfusion computed tomography imaging revealed ischemic penumbra in the middle cerebral artery territory. Angiography showed left middle cerebral artery occlusion. Mechanical thrombectomy with one pass was performed, and successful recanalization was obtained. Embolic material was retrieved; it contained tumor fragments with atypical keratinizing squamous cell carcinoma. Contrast computed tomography imaging indicated tumor invasion into the superior vena cava, and contrast transcranial Doppler indicated the presence of a right-to-left shunt after the Valsalva maneuver. We diagnosed the patient with acute ischemic stroke of large vessel occlusion due to venous invasion of esophageal carcinoma via a right-to-left shunt. To the best of our knowledge, this is the first case of embolic occlusion resulting from an extracardiac tumor via a right-to-left shunt. Contrast transcranial Doppler potentially detects right-to-left shunts in patients who cannot undergo transesophageal echocardiography.

Latin American Consensus Statement for the Use of Contrast-Enhanced Transcranial Ultrasound as a Diagnostic Test for Detection of Right-to-Left Shunt.

BACKGROUND: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients' management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. SUMMARY: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis.

Purpose: To evaluate and compare the diagnostic value of contrast-enhanced transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) for right to left shunt (RLS) in patent foramen ovale (PFO) by meta-analysis. Methods: The literature included in the Cochrane Library, PubMed, and Embase were searched by using "contrast-enhanced transcranial Doppler (c-TCD), contrast-enhanced transthoracic echocardiography (c-TTE), patent foramen ovale (PFO), and right to left shunt (RLS)" as the keywords from inception through April 30, 2024. The diagnostic accuracy research quality assessment tool (QUADAS-2) was used to evaluate the quality of the included literature. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and Diagnostic odds ratio (DOR) were pooled, and a comprehensive ROC curve analysis was performed. Statistical software StataSE 12.0 and Meta-Disc 1.4 were used for data analysis. Results: A total of 8,536 articles were retrieved, and 9 articles that met all inclusion criteria were included in this meta-analysis. The meta-analysis results show that the combined sensitivity, specificity, PLR, NLR, DOR, and area under the SROC curve of c-TCD for the diagnose of PFO-RLS were 0.91 (95% CI, 0.88-0.93), 0.87 (95% CI: 0.84-0.91), 6.0 (95% CI, 2.78-12.96), 0.10 (95% CI, 0.06-0.18), 91.61 (95% CI, 26.55-316.10), and 0.9681, respectively; the corresponding values of c-TTE were 0.86 (95% CI, 0.84-0.89), 0.88 (95% CI, 0.84-0.91), 5.21 (95% CI, 2.55-10.63), 0.16 (95% CI, 0.09-0.31), 71.43 (95% CI, 22.85-223.23), and 0.9532. The ROC curve shows that c-TCD has slightly higher diagnostic value for PFO than c-TTE, but there is no significant statistical difference (Z = 0.622, p > 0.05). Deek funnel pattern showed no significant publication bias. Conclusion: Both c-TCD and c-TTE have high diagnostic values for PFO-RLS. However, c-TCD has slightly higher sensitivity and lower specificity in diagnosing PFO-RLS compared to c-TTE.Systematic review registration: identifier [CRD42024544169].

Relationship between right-to-left shunt and white matter lesions in patients with migraine: a single-center study.

Background: Migraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs. Methods: In this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs). Results: Among the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p < 0. 001) and a shorter disease duration (6.76 vs. 8.34 years, p = 0.024). The overall proportion of RLS patients was 41.9%, with a greater proportion of RLS patients in the MA group than in the MO group (55.8% vs. 41. 1%, p = 0.037). The percentage of RLS-positive patients with no/small shunt was greater in the MO group than in the MA group (81.5% vs. 65.4%, p = 0.004), whereas the percentage of RLS-positive patients with moderate/large shunt was greater in the MA group (34.6% vs. 18.5%, p = 0.024). The proportion of RLS patients was lower in the WML-positive group (n = 173) than in the WML-negative group (n = 332), but the difference was not significant (40.5% vs. 45.8%, p = 0.253). Conclusion: This study revealed that 41.9% of migraine patients had RLS, and the proportion of RLS patients was 41. 1% in the MO group and 55.8% in the MA group. The rate of RLS positivity in migraine patients may not be related to the incidence of WMLs.

PFO-spectrum disorder: two different cerebrovascular diseases in patients with PFO as detected by AI brain imaging software.

Background: Patent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions. Patients and methods: Retrospective, case-control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume. Results: Of the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03-0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02-0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes. Discussion: We suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and "silent" WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the "at-risk" PFOs and gain deeper insights into their clinical implications.

Synchronous multimode ultrasound for assessing right-to-left shunt: a prospective clinical study.

Background: Right-to-left shunt (RLS) is associated with several conditions and causes morbidity. In this study, we aimed to evaluate the effectiveness of synchronous multimode ultrasonography in detecting RLS. Methods: We prospectively enrolled 423 patients with high clinical suspicion of RLS and divided them into the contrast transcranial Doppler (cTCD) group and synchronous multimode ultrasound group, in which both cTCD and contrast transthoracic echocardiography (cTTE) were performed during the same process of contrast-enhanced ultrasound imaging. The simultaneous test results were compared with those of cTCD alone. Results: The positive rates of grade II (22.0%:10.0%) and III (12.7%:10.8%) shunts and the total positive rate (82.1748%) in the synchronous multimode ultrasound group were higher than those in the cTCD alone group. Among patients with RLS grade I in the synchronous multimode ultrasound group, 23 had RLS grade I in cTCD but grade 0 in synchronous cTTE, whereas four had grade I in cTCD but grade 0 in synchronous cTTE. Among patients with RLS grade II in the synchronous multimode ultrasound group, 28 had RLS grade I in cTCD but grade II in synchronous cTTE. Among patients with RLS grade III in the synchronous multimode ultrasound group, four had RLS grade I in cTCD but grade III in synchronous cTTE. Synchronous multimode ultrasound had a sensitivity of 87.5% and specificity of 60.6% in the patent foramen ovale (PFO) diagnosis. Binary logistic regression analyses showed that age (odds ratio [OR] = 1.041) and risk of paradoxical embolism score ≥ 7 (OR = 7.798) were risk factors for stroke recurrence, whereas antiplatelets (OR = 0.590) and PFO closure with antiplatelets (OR = 0.109) were protective factors. Conclusion: Synchronous multimodal ultrasound significantly improves the detection rate and test efficiency, quantifies RLS more accurately, and reduces testing risks and medical costs. We conclude that synchronous multimodal ultrasound has significant potential for clinical applications.

PFO morphology for evaluation of c-TCD and c-TTE RLS grades.

PURPOSE: The purpose of this study was to observe the morphologic characteristics of patent foramen ovale (PFO) by transesophageal echocardiography (TEE), and to analyze its correlation with right-to-left shunt (RLS) of contrast-transthoracic echocardiography (c-TTE) and contrast-transcranial Doppler ultrasonography (c-TCD). METHODS: 124 patients with PFO were divided into four groups according to the morphological characteristics of PFO. RLS grade of each group PFO with c-TTE and c-TCD in resting and Valsalva manoeuvre was measured. Anatomical structures influencing RLS grade were analyzed statistically through multivariate logistic analyses and predictive models. RESULTS: The 124 cases of PFO were divided into four groups: 55 cases (44.4%) with smooth uniform tubular tunnel (SUT), 21 cases (16.9%) with granule uniform tubular tunnel (GUT), 23 cases (18.5%) of right funnelform, 25 cases (20.2%) of left funnelform. Between group comparisons and multivariate logistic analyses revealed that PFO morphotype and interatrial septum(IAS) mobility were influencing factors of RLS degree. During Valsalva, the probability of c-TCD RLS ≥ 2 for the right funnelform PFO was 13.428 times that of the GUT, one unit increase in IAS mobility increased the probability of c-TCD RLS ≥ 2 by a factor of 2.029, model predicted c-TCD RLS ≥ 2 with 78.1% sensitivity and 94.7% specificity; During Valsalva, the probability of c-TCD RLS ≥ 2 for the SUT PFO was 4.244 times that of the GUT, one unit increase in IAS mobility increased the probability of c-TTE RLS ≥ 2 by a factor of 2.392, model predicted c-TTE RLS ≥ 2 with 80.2% sensitivity and 87.9% specificity. CONCLUSIONS: Studies have shown that the morphological structure of PFO is an influencing factor of RLS, and TEE can observe the specific morphological characteristics of PFO, which can further predict the level of RLS, help predict the occurrence of Cryptogenic stroke (CS). The above provides more evidences and surgical options for Interventional device closure indications.

A comparison of contrast transthoracic echocardiography and contrast transcranial Doppler in cryptogenic stroke patients with patent foramen ovale.

OBJECTIVE: In recent years, increasing attention has been paid to cryptogenic stroke (CS) caused by the patent foramen ovale (PFO). This study aims to compare contrast transthoracic echocardiography (cTTE) and contrast transcranial Doppler (cTCD) to determine whether cTTE is more suitable and reliable than cTCD for clinical use. METHODS: From March 2017 to May 2018, patients who suffered from migraines, stroke, hypomnesis, or asymptomatic stroke found casually were included in our study. Patients with CS were semirandomly divided into two groups (cTTE and cTCD) according to the date of the outpatient visit. Patients with either of the examination above found positive were selected to finish transesophageal echocardiography (TEE). RESULTS: In our study, the sensitivities of group cTTE positive (group cTTE+) and group cTCD positive (group cTCD+) did not have any statistical difference (89% vs. 80%, p = 0.236). Focusing on group cTCD+, we discovered that the semiquantitative shunt grading was not correlated with whether a PFO was present or not (p = 0.194). However, once the PFO has been diagnosed, the shunt grading was shown to be related to the width of the gaps (p = 0.032, pdeviation  = 0.03). CONCLUSION: Both cTTE and the cTCD can be used for preliminary PFO findings. The semiquantitative shunt grading of cTCD and cTTE can suggest the size of the PFO and the next course of treatment. The cTTE may be more significant to a safe PFO (a PFO does not have right-to-left shunts, RLSs). Combining cTTE and TEE could help diagnose PFO and assess CS risk.

Different Valsalva Manoeuvre Procedures for the Diagnosis of Right-to-Left Shunt by Contrast-Transcranial Doppler.

The main purpose of this study was to compare two contrast agent injection times during the Valsalva manoeuvre (VM) for the diagnosis of right-to-left shunt using contrast-transcranial Doppler (c-TCD). In total, 992 consecutive patients underwent testing. All patients underwent step 1, and then a coin toss was used to determine the order of steps 2 and 3. The following testing steps were repeated twice: (1) a contrast agent (CA) was infused at rest (CA at rest testing); (2) the VM was initiated immediately after CA injection and released 10 s after CA injection (CA pre-VM testing); and (3) a CA was injected 5 s after initiating the VM, which was released 5 s after CA injection (CA mid-VM testing). For the CA at rest, pre-VM and mid-VM groups, significant differences were observed in the positive right-to-left shunt diagnosis rates (11.49% vs. 23.08% vs. 26.11%, respectively, with an inter-group significance of p < 0.05) and grade classifications (p < 0.05). Although the times to first microbubble appearance were similar between the CA at rest and the CA pre-VM groups (8.96 ± 3.40 s vs. 8.42 ± 3.72 s, p > 0.05), it was shorter (6.4 ± 2.75 s, p < 0.05) for the CA mid-VM group than for the other two groups. For the c-TCD testing, the CA mid-VM group yielded different results for diagnosing right-to-left shunts relative to the CA pre-VM group.

Body positions in the diagnosis of right-to-left shunt by contrast transcranial Doppler.

Contrast transcranial Doppler (c-TCD) is sensitive in detecting right-to-left shunt (RLS). However, the methodology and ideal posture are controversial. Consecutive migraine patients were prospectively examined for RLS using c-TCD. Each patient was examined while at rest and subsequently with the Valsalva maneuver (VM) in three positions: supine, left lateral decubitus and right lateral decubitus. RLS was diagnosed with at least one microbubble detected at any position. RLS was highest in the left lateral decubitus position, both during rest and with VM. The left lateral decubitus position was associated with the highest total number of microbubbles and greater shunt grades. Patients who tested positive in the other two positions had the lowest index position failure rate during rest in the left lateral decubitus position. In some patients in whom RLS is detected at rest, it may not be detected (false negative) under VM. To ensure c-TCD's the sensitivity to RLS, testing in the left lateral decubitus position at rest and under VM is suggested; testing in other positions is necessary to avoid false negatives.