Transcranial Doppler With Microbubbles: Screening Test to Detect and Grade Right-to-Left Shunt After an Ischemic Stroke: A Literature Review.

Right-to-left shunt, mainly due to patent foramen ovale (PFO), is likely responsible for ≈5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Randomized clinical trials demonstrated that, in selected young and middle-aged patients with otherwise cryptogenic acute ischemic stroke and high-risk PFO, percutaneous PFO closure is more effective than antiplatelet therapy alone in preventing recurrence. However, PFO is generally a benign finding and is present in about one-quarter of the population. Therefore, in clinical practice, identifying PFOs that are likely to be pathogenetic is crucial for selecting suitable patients for PFO closure to prevent recurrent stroke and to avoid potentially harmful and costly overtreatment. Contrast transthoracic echocardiography has a relatively low sensitivity in detecting PFO, whereas transesophageal echocardiography is currently considered the gold standard for PFO detection. However, it is a relatively invasive procedure and may not always be easily feasible in the subacute setting. Contrast transcranial Doppler is a noninvasive, inexpensive, accurate tool for the detection of right-to-left shunt. We conducted a literature review on the use of contrast transcranial Doppler to detect and grade right-to-left shunt after an acute ischemic stroke and present a clinical workflow proposal for young and middle-aged patients.

Advances in Recurrent Stroke Prevention: Focus on Antithrombotic Therapies.

The past decade has seen significant advances in stroke prevention. These advances include new antithrombotic agents, new options for dyslipidemia treatment, and novel techniques for surgical stroke prevention. In addition, there is greater recognition of the benefits of multifaceted interventions, including the role of physical activity and dietary modification. Despite these advances, the aging of the population and the high prevalence of key vascular risk factors pose challenges to reducing the burden of stroke. Using a cause-based framework, current approaches to prevention of cardioembolic, cryptogenic, atherosclerotic, and small vessel disease stroke are outlined in this paper. Special emphasis is given to recent trials of antithrombotic agents, including studies that have tested combination treatments and responses according to genetic factors.

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease.

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.

Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Cardiac ultrasound to identify sources of cardioembolism is part of the diagnostic workup of acute ischemic stroke. Recommendations on whether transesophageal echocardiography (TEE) should be performed in addition to transthoracic echocardiography (TTE) are controversial. We aimed to determine the incremental diagnostic yield of TEE in addition to TTE in patients with acute ischemic stroke with undetermined cause. METHODS: In a prospective, observational, pragmatic multicenter cohort study, patients with acute ischemic stroke or transient ischemic attack with undetermined cause before cardiac ultrasound were studied by TTE and TEE. The primary outcome was the rate of treatment-relevant findings in TTE and TEE as defined by a panel of experts based on current evidence. Further outcomes included the rate of changes in the assessment of stroke cause after TEE. RESULTS: Between July 1, 2017, and June 30, 2019, we enrolled 494 patients, of whom 492 (99.6%) received TTE and 454 (91.9%) received TEE. Mean age was 64.7 years, and 204 (41.3%) were women. TEE showed a higher rate of treatment-relevant findings than TTE (86 [18.9%] versus 64 [14.1%], P<0.001). TEE in addition to TTE resulted in 29 (6.4%) additional patients with treatment-relevant findings. Among 191 patients ≤60 years additional treatment-relevant findings by TEE were observed in 27 (14.1%) patients. Classification of stroke cause changed after TEE in 52 of 453 patients (11.5%), resulting in a significant difference in the distribution of stroke cause before and after TEE (P<0.001). CONCLUSIONS: In patients with undetermined cause of stroke, TEE yielded a higher number of treatment-relevant findings than TTE. TEE appears especially useful in younger patients with stroke, with treatment-relevant findings in one out of seven patients ≤60 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03411642.

Severe hypoxemia in a patient with right ventricular myocardial infarction and SARS-CoV-2 infection.

BACKGROUND: Refractory hypoxemia after right ventricular myocardial infarction and concomitant SARS-CoV-2 infection represents an uncommon, yet particularly challenging clinical scenario. We report a challenging diagnostic case of refractory hypoxemia due to right-to-left shunt highlighting contemporary challenges and pitfalls in acute cardiovascular care associated with the current COVID-19 pandemic. CASE PRESENTATION: A 52-year-old patient admitted for inferior acute myocardial infarction developed rapidly worsening hypoxemia shortly after primary percutaneous coronary intervention. RT-PCR screening for SARS-CoV-2 was positive, even though the patient had no prior symptoms. A computed tomography pulmonary angiogram excluded pulmonary embolism and showed only mild interstitial pulmonary involvement of the virus. Transthoracic echocardiogram showed severe right ventricular dysfunction and significant right-to-left shunt at the atrial level after agitated saline injection. Progressive improvement of right ventricular function allowed weaning from supplementary oxygen support. Patient was latter discharged with marked symptomatic improvement. CONCLUSION: Refractory hypoxemia after RV myocardial infarction should be carefully addressed, even in the setting of other more common and tempting diagnoses. After exclusion of usual etiologies, right-to-left shunting at the atrial level should always be suspected, as this may avoid unnecessary and sometimes harmful interventions.

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. METHODS: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (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) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. RESULTS: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO (P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke. CONCLUSIONS: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.

Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction.

Background and Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score. Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score's calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO. Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score's area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, P=0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients. Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up.

Atrial Fibrillation Following Patent Foramen Ovale Closure: Systematic Review and Meta-Analysis of Observational Studies and Clinical Trials.

Background and Purpose: Multiple studies evaluated whether patent foramen ovale (PFO) closure reduces the risk of ischemic stroke. One commonly reported complication of PFO closure is the development of atrial fibrillation (AF), which is itself a powerful stroke risk factor that requires specific management. This study aims to evaluate the frequency of AF in patients post-percutaneous closure of PFO and the clinical factors that predict AF detection. Methods: Studies were identified by systematically searching EMBASE and MEDLINE databases on July 11, 2019. Meta-analysis of proportions was performed, assuming a random-effects model. Results: A total of 6 randomized controlled trials and 26 observational studies were included, comprising 3737 and 9126 patients, respectively. After PFO closure, the rate of AF development was 3.7 patients per 100 patient-years of follow-up (95% CI, 2.6­4.9). The risk of AF development is concentrated in the first 45 days post-procedure (27.2 patients per 100 patient-years [95% CI, 20.1­34.81], compared with 1.3 patients per 100 patient-years [95% CI, 0.3­2.7]) after 45 days. Meta-regression by age suggested that studies with older patients reported higher rate of AF (P=0.001).In medically treated patients, the rate of AF development was 0.1 per 100 patient-years of follow-up (95% CI, 0.0­0.4). Closure of PFO is associated with increased risk of AF compared with medical management (odds ratio, 5.3 [95% CI, 2.5­11.41]; P<0.001). Conclusions: AF is more common in PFO patients who had percutaneous closure compared with those who were medically treated. The risk of AF was higher in the first 45 days post-closure and in studies that included patients with increased age.

The role of cardiac CT throughout the full cardiac cycle in diagnosing patent foramen ovale in patients with acute stroke.

OBJECTIVES: We explored the hypothesis that the diagnostic performance of cardiac computed tomography (CT) throughout the full cardiac cycle would be superior to single-phase CT and comparable to transesophageal echocardiography (TEE) in diagnosing patent foramen ovale (PFO). METHODS AND RESULTS: From May 2011 to April 2015, 978 patients with stroke were diagnosed with PFO by TEE. In patients with stroke, cardiac CT was performed if the patients had more than two cardiovascular risk factors. We prospectively enrolled 70 patients with an indication for cardiac CT. Cardiac CT images were reconstructed at 10% increments of the R-R interval. The sensitivity of cardiac CT throughout the full cardiac cycle in diagnosing PFO was compared to that for TEE and single-phase cardiac CT. To evaluate the specificity of cardiac CT, we analyzed patients without PFO confirmed by TEE who underwent cardiac CT within 1 month of pre-cardiac surgery. Sixty-six patients with cardiac CT and TEE were included in the final analysis. Throughout the full cardiac cycle, cardiac CT had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing PFO, compared to TEE as a reference. PFO was primarily detected in the 60% and 70% intervals in 10-phase reconstructed images. The sensitivity of PFO diagnosis with cardiac CT was 81.8% when analyzing both the 60% and 70% intervals instead of the full cardiac cycle. CONCLUSION: Cardiac CT throughout the full cardiac cycle outperforms single-phase cardiac CT in detecting PFO. Cardiac CT can be used as an alternative method to TEE for detecting PFO in stroke patients. KEY POINTS: • Throughout the full cardiac cycle, cardiac computed tomography (CT) had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing patent foramen ovale (PFO), compared to transesophageal echocardiography. • The sensitivity of diagnosing patent foramen ovale with cardiac CT was 81.8% when analyzing 60% and 70% R-R intervals instead of the full cardiac cycle. • Cardiac CT with retrospective electrocardiographic gating throughout the full cardiac cycle can increase the detectability of PFO, compared to single-phase cardiac CT.

Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials.

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.

Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Previous systematic reviews and meta-analyses compared the efficacy and safety of patent foramen ovale (PFO) closure versus medical treatment in patients with cryptogenic stroke or transient ischemic attack (TIA). Recently, new evidence from randomized trials became available. METHODS: We searched PubMed until September 24, 2017, for trials comparing PFO closure with medical treatment in patients with cryptogenic stroke/TIA using the items: stroke or cerebrovascular accident or TIA and patent foramen ovale or paradoxical embolism and trial or study. RESULTS: Among 851 identified articles, 5 were eligible. In 3627 patients with 3.7-year mean follow-up, there was significant difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years, respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90; relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR, 0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100 patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per 100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in 72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus 0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR, 1.07; 95% CI, 0.92-1.25) were similar. CONCLUSIONS: In patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient. There is no difference in TIA, all-cause mortality, or myocardial infarction.

[Neuroimaging characteristics of cryptogenic stroke with and without patent foramen ovale].

Objective: To explore the neuroimaging characteristics associated with the presence of patent foramen ovale(PFO) for patients with cryptogenic stroke. Methods: We retrospectively collected the clinical and imaging data of cryptogenic stroke patients with PFO and without PFO from Henan Province People's Hospital from January 1, 2013 to June 30, 2017. Lesion patterns and pertinent vascular territory were compared between the two groups. Multivariate logistic regression analysis was used to explore the independent predictors for the presence of PFO. Results: A total of 54 cryptogenic stroke patients with PFO and 50 cases without PFO were recruited. Compared with PFO(-) stroke group, more patients in PFO(+ ) stroke group had migraine(P=0.036), and patients in PFO(+ ) stroke group had higher Risk of Paradoxical Embolism(RoPE) score(P=0.030). The lesion pattern of PFO(+ ) stroke was more frequently observed as multiple lesions in multicirculatory (P=0.035), and infarcts were more likely to be distributed in the vertebrobasilar artery territory (P=0.041); the most frequently involved vessel was the posterior cerebral artery region (P=0.006). More patients with PFO(+ ) stroke had old silent stroke lesion(P=0.021). On multivariate analysis, infarction distributed in the posterior cerebral artery region(OR=4.292, 95% CI 1.469-12.543, P=0.008), silent stroke lesion (OR=6.688, 95% CI 1.277-35.029, P=0.024), and high RoPE score (OR=1.393, 95% CI 1.026-1.893, P=0.034) were independent parameters that could predict the presence of PFO. Conclusions: Multiple lesions in multicirculatory and the posterior predominance are neuroimaging characteristics of cryptogenic stroke with PFO. Infarction distributed in the posterior cerebral artery region, silent stroke lesion and high RoPE score are independent predictors of the presence of PFO.

[Acute treatment and secondary prophylaxis of ischemic stroke : An excellent example for personalized medicine]. / Akuttherapie und Sekundärprophylaxe des ischämischen Schlaganfalls : Ein Musterbeispiel für personalisierte Medizin.

About a quarter of a million people in Germany suffer a stroke every year. Stroke is the most dreaded cardiovascular disease, even before myocardial infarction and heart failure. In the last two to three years, significant progress has been made in acute treatment, secondary prophylaxis in patients with patent foramen ovale, and the interdisciplinary evaluation of atrial fibrillation as the cause of the stroke. These new findings allow for more precise treatment.

[Efficacy and outcome of transcatheter closure of patent foramen ovale in patients with cryptogenic stroke].

Objective: To investigate the efficacy and outcome of transcatheter patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS). Methods: Sixty consecutive patients with cryptogenic stroke who undertook transcatheter PFO closure between May 2015 and September 2017 in Beijing Tiantan Hospital were enrolled in this prospective study.Transcranial Doppler (TCD) bubble test was performed and right-left shunt(RLS) was confirmed in all patients.Closure success rate,effective closure rate, complications, recurrence of ischemic stroke and new onset atrial fibrillation were evaluated. Results: A total of 60 patients (42 male,age range 24-68 (47±11)years) were included in the study.PFO size (motionless state) was (1.6±0.6)mm.RLS before closure was graded and 11 patients had moderate RLS and 48 patients had large RLS (include 41 patients who experienced shower or curtain effect).Closure success rate was 100% (60/60).No severe complications were observed.At 6 months,45 patients completed TCD bubble test.Of these, 4 patients suffered from moderate to large residual and thus effective closure rate was 91%(41/45).The mean follow-up period was 2-29 (median 12) months. During the follow-up, only 1 patient experienced recurrent cerebral infarction.New onset atrial fibrillation was not detected. Conclusion: Transcatheter PFO closure is effective,safe and related with a good outcome in reduction of recurrent CS for patients with PFO.

[Comparison on the efficacy and safety of different occlusion devices for the treatment of patients with patent foramen ovale].

Objective: To compare the efficacy and safety of Cardi-O-fix patent foramen ovale (PFO) occluder and Amplatzer PFO occluder for the treatment of patients with PFO. Methods: A total of 246 consecutive patients (105 males and 141 females) with PFO were prospectively enrolled from May 30, 2013 to March 30, 2015 in our hospital. PFO interventional closure was applied according to the anatomical structure of the disease and patients' wishes.Cardi-O-fix PFO occluder was used in 180 cases (COF group), Amplatzer PFO occluder was used in the remaining 66 cases (Amp group). Post-procedure safety including recurrent stroke, transient ischemic attack, death, and complete closure rate, and efficacy including procedure related complications of different devices were compared during the 12 months follow-up. Results: (1) Rate of transient ischemic attack was similar between COF group and Amp group at 12 months after procedure(1.1%(2/180) vs. 1.5%(1/66), P=1.000). There was no recurrent stroke and death during the 12 months follow-up period.Complete closure rate was similar between COF group and Amp group at 12 months after the procedure(90.6%(163/180)vs. 86.4%(57/66), P=0.355). (2) Three cases(1.7%) of paroxysmal atrial fibrillation were observed in COF group during the 12 months follow-up period, 1 patient converted spontaneously to sinus rhythm and 2 patients received successful pharmacologic conversion and converted to sinus rhythm. One patient(1.5%)developed paroxysmal atrial fibrillation and was pharmacologically converted to sinus rhythm in the Amp group. There was no significant difference in rate of paroxysmal atrial fibrillation between the two groups(P=1.000). There was no complications such as occluder translocation, erosion, pericardial effusion and puncture site bleeding in the 2 groups during the 12 months follow-up. Conclusion: Efficacy and safety are similar for PFO treatment with Cardi-O-fix PFO occluder or Amplatzer PFO occluder in this patient cohort.

Stroke in Commercial Flights.

BACKGROUND AND PURPOSE: Stroke on board aircraft has been reported in retrospective case series, mainly focusing on economy class stroke syndrome. Data on the actual incidence, pathogenesis, and prognosis of stroke in commercial flights are lacking. METHODS: A prospective registry was designed to include all consecutive patients referred from an international airport (40 million passengers a year) to our hospital with a diagnosis of ischemic stroke or transient ischemic attack and onset of symptoms during a flight or immediately after landing. RESULTS: Forty-four patients (32 ischemic strokes and 12 transient ischemic attacks) were included over a 76-month period (January 2008 to April 2014). The estimated incidence of stroke was 1 stroke in 35 000 flights. Pathogeneses of stroke or transient ischemic attack were atherothrombotic in 16 (36%), economy class stroke syndrome in 8 (18%), cardioembolic in 7 (16%), arterial dissection in 4 (9%), lacunar stroke in 4 (9%), and undetermined in 5 (12%) patients. Carotid stenosis >70% was found in 12 (27%) of the patients. Overall prognosis was good, and thrombolysis was applied in 44% of the cases. The most common reason for not treating patients who had experienced stroke onset midflight was the delay in reaching the hospital. Only 1 patient with symptom onset during the flight prompted a flight diversion. CONCLUSIONS: We found a low incidence of stroke in the setting of air travel. Economy class stroke syndrome and arterial dissection were well represented in our sample. However, the main pathogenesis was atherothrombosis with a high proportion of patients with high carotid stenosis.

Platypnoea-orthodeoxia syndrome, an underdiagnosed cause of hypoxaemia: four cases and the possible underlying mechanisms.

Cardiac platypnoea-orthodeoxia syndrome (POS) is a position-dependent condition of dyspnoea and hypoxaemia due to right-to-left shunting. It often remains unrecognised in clinical practice, possibly because of its complex underlying pathophysiology. We present four consecutive patients with POS and patent foramen ovale (PFO) who underwent a successful percutaneous PFO closure, describe the mechanism of their POS and provide a review of the literature.