Cryptogenic Stroke Research Articles (Page 1)

The aim was to evaluate the differential effects of right-to-left shunts (RLS) linked to patent foramen ovale (PFO) on left atrial strain using two-dimensional speckle tracking imaging (2D-STI), and to investigate the prognostic value of left atrial strain in predicting the risk of cryptogenic stroke (CS) related to PFO-RLS. This study involved 81 PFO patients and 45 healthy controls (HCs), who were divided into three groups: the permanent RLS, the latent RLS, and the HC group. Clinical characteristics, conventional echocardiographic parameters, and left atrial strains, such as left atrial reservoir strain (LASr), left atrial conduit strain (LAScd), left atrial contraction strain (LASct), and left atrial stiffness index (LASI) were collected and compared among the three groups. The PFO patients with RLS were subsequently stratified into a CS group and a non-CS group. To identify the predictors of CS in PFO patients with RLS, logistic regression analysis and receiver operating characteristic (ROC) curves were performed. There were no significant differences in left atrial structural parameters among the three groups (all P > 0.05). Compared to the HC group, both the permanent and latent RLS groups demonstrated significantly higher rates of CS (63.4% vs. 35.0% vs. 8.9%, P < 0.001) and migraine (73.2% vs. 60.0% vs. 8.9%, P < 0.001). A graded impairment in left atrial functional parameters was observed across the three groups: LASr (35.40 ± 2.65 vs. 39.18 ± 2.57 vs. 40.19 ± 2.16, P < 0.001), LAScd (-21.55 ± 2.61 vs. -23.99 ± 3.02 vs. -24.86 ± 3.33, P < 0.001), and LASct (-13.86 ± 1.82 vs. -15.19 ± 2.13 vs. -15.33 ± 2.39, P = 0.003). Subgroup analyses revealed reduced LASr (35.29 ± 1.89 vs. 39.20 ± 3.07, P < 0.001) and LAScd (-21.18 ± 2.24 vs. -24.29 ± 2.99, P < 0.001) in the CS group compared to the non-CS group, while LASct showed no statistically significant intergroup difference (P > 0.05). LASr (OR (95%CI): 0.38(0.25-0.57), P < 0.001) and LAScd (OR(95%CI): 1.78(1.33-2.40), P < 0.001) were independent factors for predicting risk of CS related to PFO-RLS. ROC curves analysis demonstrated strong predictive performance of LASr and LAScd for the CS occurrence related to PFO-RLS (LASr: AUC = 0.85, 95%CI = 0.76-0.94, P < 0.001; LAScd: AUC = 0.80, 95%CI = 0.70-0.89, P < 0.001). PFO patients with RLS, especially those with permanent RLS, had impaired left atrial function and an increased risk of CS. The LASr and LAScd were strong predictors and effective indicators of CS in PFO patients with RLS.

This study compares right heart contrast transthoracic echocardiography (c-TTE) and contrast transesophageal echocardiography (c-TEE) at different states for detecting and grading the right-to-left shunt (RLS) in patients with cryptogenic stroke (CS). A total of 150 CS patients were enrolled. All patients underwent c-TTE and c-TEE at 3 different states: the Rest, the Valsalva Maneuver, and the state of rest shortly after the Valsalva Maneuver (referred to as "Curtain effect"). Right-to-left shunt due to patent foramen ovale (PFO-RLS) or pulmonary right-to-left shunt was identified by the microbubble characteristics in the left atrium. The detection rates and semiquantitative grades of RLS were compared between c-TTE and c-TEE under different states. c-TTE at Valsalva Maneuver detected more RLS than c-TEE (83.3% vs 65.3%, P < .05). c-TTE at "Curtain effect" revealed more PFO-RLS and higher grades of PFO-RLS than c-TTE at Rest (91.8% vs 72.7%, P < .05). c-TTE showed higher grades of PFO-RLS compared to c-TEE at any state (P < .05). c-TTE at Valsalva Maneuver or "Curtain effect" has superiority in detecting RLS and grading PFO-RLS compared to c-TEE; it can be a practical screening approach for suspected RLS in CS patients.

BackgroundTimely identification of stroke etiology is crucial in managing large vessel occlusion (LVO) strokes. However, a substantial proportion remain cryptogenic despite comprehensive workup, raising concern about underdiagnosed cardioembolic sources. This study assessed the diagnostic contribution of early combined brain-cardiac CT imaging in patients with LVO stroke and explored imaging markers associated with each etiological subtype.Methods252 consecutive patients admitted for LVO stroke who underwent standardized acute-phase brain and cardiac CT imaging were included. Patients were classified as atheromatous, cardioembolic, or cryptogenic LVO stroke before and after consideration of cardiac CT results. Clinical and imaging characteristics of patients were compared according to final causes of stroke.ResultsCardiac CT led to etiological reclassification in 8 patients (3.2%), including 7 cryptogenic cases upgraded to cardioembolic due to detection of intracardiac thrombi in the absence of atrial fibrillation. Patients with cardioembolic LVO stroke (n=137,54%) were older, more frequently women, and had higher left atrial surface areas and volumes compared to atheromatous (n=40,16%) and cryptogenic cases (n=75, 30%). Epicardial adipose tissue volume was highest in atheromatous strokes while cryptogenic cases lacked markers of atrial cardiomyopathy. At follow-up, mortality was highest in the cardioembolic group.ConclusionsEarly brain-cardiac CT imaging enhances etiological classification in LVO strokes by identifying intracardiac thrombi and other cardioembolic markers missed by standard workup. A substantial subset of cryptogenic LVO strokes may represent a distinct pathophysiological entity. Broader adoption of cardiac CT could inform targeted stroke prevention strategies.

Rationale Detection of atrial fibrillation (AFib) and subsequent anticoagulation therapy reduce the risk of recurrent stroke, while prolonged rhythm monitoring significantly increases AFib detection. Thus, prolonged smartwatch-based ECG monitoring after cryptogenic ischemic stroke or transient ischemic attack (TIA) could lead to a reduction of recurrent stroke by prompting adequate anticoagulation therapy. Aim WATCH AFib investigates the accuracy of smartwatches for AFib detection in patients with cryptogenic TIA or ischemic stroke compared to an implantable event recorder. Sample size 40 cases of AFib are required to estimate the sensitivity for AFib detection per patient with a precision of about 10%. As AFib is observed in 9%−16% of cryptogenic strokes, we intend to enroll 400 patients. Methods WATCH AFib is a prospective, intraindividual-controlled, multicentre clinical study in patients with cryptogenic ischemic stroke or TIA. ECG-data from smartwatches and event recorders is continuously monitored by two independent cardiologists for a follow-up period of 6 months. If AFib is detected, therapeutic options are discussed at the including center. Primary outcome To compare smartwatch- and event recorder- based sensitivity and specificity of AFib detection per patient after 6 months. Discussion Prolonged AFib screening after stroke is currently suboptimal. Smartwatches might be a non-invasive, cost-effective, widely available alternative for prolonged rhythm monitoring. Usability in severely affected patients and patients with persisting neurological deficits might be limited. Trial registration The study is registered on clinicaltrials.gov . Registration number: 20230726.

Management of device-detected subclinical atrial fibrillation: A european heart rhythm association survey.

Background/Purpose: Cryptogenic stroke (CS) is defined as an ischemic stroke with no identifiable cause. We investigate the burden of obstructive and non-obstructive coronary artery disease (CAD) in patients with CS and the impact of CAD on new vascular events and mortality during a 6-year follow up. Methods: A total of 103 patients were enrolled in the present prospective observational NORSTROKE (Norwegian Stroke Research Registry) sub-study of patients ≥50 years with a documented CS (Figure). Clinical characteristics, echocardiographic, coronary imaging, vascular ultrasound, and 24-hour Holter-monitoring data were analysed. Results: The mean age was 67.9 (±8.2) years, with 70.9% (n=73) males. CAD was present in 81.5% (n=84), (non-obstructive 56.3% (n=58) and obstructive 25.2% (n=26)). New-onset atrial fibrillation was detected in 15.5% (n=16), two had thrombus in left atrial appendage (LAA) on cardiac CT. During a mean follow-up of 6.2 (±2.3) years, 14 (13.6%) died, and 29 (28.2%) experienced a composite endpoint of new stroke and/or death. In the multivariate Cox regression model CAD was an independent predictor of the composite endpoint of death or recurrent ischemic stroke (HR 2.70; 95% CI 1.13-6.21, p=0.024) adjusted for age, gender, smoking, new-onset atrial fibrillation, hypertension, and cardiac Troponin T. Conclusion: In patients with CS, CAD was highly prevalent and an independent predictor of recurrent stroke and mortality. While new-onset atrial fibrillation was observed in nearly every sixth patient, the incidence of LAA thrombus was very low, suggesting other mechanisms may contribute to stroke in these patients. Cardiovascular assessment is important in patients with CS to identify high-risk individuals to potentially reduce stroke recurrence and mortality.

Introduction: Patients who suffer from cryptogenic stroke (CS) are routinely screened for asymptomatic paroxysmal atrial fibrillation (AF) with implantable loop recorders (ILRs). The clinical risk factors associated with AF after CS are not fully defined, and it is a common perception that ILRs are not helpful in younger patients with CS. Research Questions/Objectives: To identify which clinical characteristics are associated with AF detection via ILR in patients who have suffered CS. To identify if there is an age cut-off, below which ILR implantation is likely to be futile in patients with CS. Methods: A retrospective cohort study was conducted on patients with CS who underwent ILR implantation at Thomas Jefferson University Hospital from 04/2019 to 04/2021. Patients were excluded from the analysis if there was &lt;6 months of ILR follow-up, delayed ILR placement (&gt;1 year after CS), or pre-existing (known) AF. Baseline demographics and clinical characteristics were collected (Table 1). Patients with and without AF detection within 1 year of CS were compared and multivariable logistic regression was applied to the univariate predictors that were significant (Table 2). Analyses were run in R Studio 4.4.2. Results: We identified a total of 282 patients with CS who received ILRs. Of these 282 patients, 218 formed the study group after applying exclusion criteria (age 63.45±10.58 years, 45% female). AF was detected within 1 year of CS in 47 patients (21.6%) with a mean time from CS to AF detection of 125.30± 94.64 days. In univariate analyses, AF was statistically significantly associated with older age, LAVI, CHA2DS2-VASc score, LVEF%, CKD stage, and presence of atrial runs (Table 1). After multivariable adjustment (Table 2), CKD stage 5 (OR 14.4, p=0.0168), atrial runs (OR 3.77, p=0.0079), and age (OR 1.11, p=0.0056) remained significantly associated with AF detection. However, there were 5 patients below the age of 60 who had AF detected. No significant differences were observed in sex, race, BMI, or other comorbidities. Conclusions: Stage 5 CKD, atrial runs, and age showed significant association with AF detection after cryptogenic stroke. Although age was statistically significant, the OR was low (1.11), and 5 patients below the age of 60 had AF detected. Renal failure and atrial runs were the strongest associates of AF detection after CS. We conclude that there should be no minimum age cut-off for ILR implantation in CS patients.

Introduction: Prolonged QT interval has been associated with first stroke of any type in the general population. Whether QT prolongation predicts recurrent stroke is unknown. Hypothesis: We hypothesized that QT prolongation would be associated with increased risk of recurrent stroke in individuals who recently suffered a cryptogenic stroke. Methods: The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial randomized individuals with cryptogenic stroke and atrial cardiopathy to apixaban versus aspirin to assess the prevention of recurrent strokes. We excluded participants with missing QT interval data and those who had ventricular conduction defects or pacemakers. The baseline electrocardiogram (ECG) was the first technically adequate ECG to be done after stroke onset. QT interval was corrected for heart rate (QTc) using a cohort-specific correction formula, as well as the Framingham, Hodges, Bazett, and Fridericia formulae. For each QTc variable, prolonged QTc was defined as &gt;450 ms in men or &gt;460 ms in women. Cox proportional hazards models were used to assess the association between QTc and recurrent stroke. Models were adjusted for randomization arm, age, sex, race, smoking, hypertension, diabetes, prior stroke, and N-terminal pro-B-type natriuretic peptide. Results: Among 881 participants, 139 (15.8%) had a prolonged cohort-specific QTc. Over a mean of 1.8 years, 62 recurrent strokes of any type occurred (crude rate 7.0%, annualized rate 3.9% per year). After multivariable adjustment, prolongation of cohort-specific QTc was associated with decreased risk of stroke (hazard ratio [95% confidence interval] = 0.72 [0.54-0.95] per standard deviation and 0.16 [0.04-0.64] for prolonged vs. normal QTc). These findings were consistent across all methods of QT correction ( Table) . Accounting for QRS duration, incident atrial fibrillation, and the competing risk of death did not change the results. Conclusions: In a population with recent cryptogenic stroke and atrial cardiopathy, QTc prolongation was associated with a lower risk of recurrent stroke. These findings contrast with the association observed between QTc prolongation and stroke in the general population, which may reflect selection bias or bias from ECGs obtained in the acute phase of stroke. If replicated, these findings suggest that repolarization markers like QTc may play different roles in stroke risk stratification for first versus recurrent stroke.

Background: The implantable loop recorder (ILR) is the most sensitive method for detecting atrial fibrillation (AF) following a cryptogenic stroke. However, to date, no study has demonstrated that it significantly reduces the rate of recurrent ischemic stroke. Objective: To assess the cumulative incidence of recurrent ischemic stroke in patients with a prior cryptogenic stroke who received an ILR, and to evaluate whether stroke recurrence is associated with device-detected AF. Methods: We conducted an observational study including consecutive patients with cryptogenic stroke who received an ILR in four academic centres in France. Prior to implantation, all patients underwent a standardized diagnostic workup, including cerebral CT angiography, brain MRI, carotid ultrasound, echocardiography, and at least 24 hours of ECG monitoring. Patients were followed from the date of ILR implantation until the first recurrence of stroke (primary endpoint), death from any cause (competing event), or end of follow-up (defined as ILR explant, last remote transmission, or final device interrogation). Device-detected AF and initiation of oral anticoagulation were analysed as time-dependent covariates in the univariate and multivariate analyses. Cause-specific Cox proportional Hazards model was used as the primary analysis. Results: We included 1,001 patients (median age 68 years [IQR 59–75]; 41% female; median CHA2DS2-VASc score 4 [IQR 3–5]). Over a median follow-up of 1.9 years, 67 recurrent ischemic strokes were recorded, yielding a cumulative incidence of 3.4% per year. ILR-detected AF occurred in 275 patients (27%). In univariate analysis, AF not treated with anticoagulation was associated with a significantly higher risk of recurrent stroke (HR 3.47, 95% CI 1.08–11.11, p=0.037), whereas AF with anticoagulation was not (HR 1.26, 95% CI 0.67–2.34, p=0.473). These associations remained consistent after multivariate adjustment for age, sex, peripheral artery disease, and renal function (HR 3.27, 95% CI 1.01–10.61, p=0.048 for untreated AF; HR 1.01, 95% CI 0.52–1.98, p=0.971 for anticoagulated AF). Conclusion: Among patients with cryptogenic stroke monitored with an ILR, recurrent ischemic stroke remains a significant concern. Device-detected AF is associated with a higher risk of recurrent stroke only when not treated with oral anticoagulation. These findings support early initiation of anticoagulation in patients with device-detected AF to reduce risk of stroke recurrence.

Background: Nearly one million individuals in the U.S. experience acute ischemic stroke (AIS) annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggest that up to 40% of AIS patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, evidence-based post-stroke evaluation and improved cardiology and neurology collaboration may help identify stroke etiology, reduce recurrent stroke risk, and improve outcomes. Hypothesis: Implementing an evidence-based post-stroke diagnostic evaluation that enhances cardiology and neurology collaboration will improve the identification of stroke etiology. Methods: In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of Stroke TM (GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics, and performance improvement feedback. Results compare 2022 (pre-initiative; baseline; N=4,981) to 2024 (initiative 2 nd year; follow-up; N=3,831). Results: Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (63.04% vs. 48.62%), while decreasing cryptogenic stroke rates (31.51% vs. 34.89%) and lack of a documented stroke etiology (5.46% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p&lt;0.0001). The use of evidence-based post-stroke diagnostic evaluation increased and was sustained in GTTHOS centers, including intracranial vascular and carotid imaging, echocardiography, short-term and extended (surface, implantable) cardiac monitoring (Table). Conclusion: In this novel AHA GTTHOS initiative in patients with AIS, which includes improved cardiology and neurology collaboration, rates of identified stroke etiology increased, while cryptogenic stroke and lack of a documented stroke etiology decreased. Furthermore, evidence-based post-stroke diagnostic evaluation, including imaging, echocardiography and short- and long-term surface and implantable cardiac monitoring, increased.

Background: Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare, benign cardiac anomaly involving non-encapsulated fat infiltration of the septum, typically sparing the fossa ovalis. Though often asymptomatic, LHIS may be associated with arrhythmias and, very rarely, embolic events. It can mimic myxomas on imaging and is seldom considered a direct cause of ischemic stroke. Research Questions: Can LHIS serve as a source of paradoxical embolism leading to ischemic stroke? Could structural changes from LHIS precipitate atrial fibrillation? Approach: An 82-year-old woman with hypertension, diabetes, and dementia presented with acute right gaze deviation, left hemineglect, and generalized weakness. CT perfusion confirmed a right middle cerebral artery (MCA) infarct, and she underwent mechanical thrombectomy. Workup included echocardiography, which revealed normal ejection fraction but a right atrial mass and a positive bubble study, indicating a patent foramen ovale (PFO). Transesophageal echocardiogram and cardiac CT angiography identified a 1×1 cm mass in the interatrial septum. Initially presumed to be a myxoma, the patient underwent mass excision, PFO closure, MAZE procedure, and left atrial appendage ligation following development of new-onset atrial fibrillation. Results: Histopathology confirmed lipomatous hypertrophy of the interatrial septum, not myxoma. The stroke was attributed to embolization of LHIS fragments through the PFO into systemic circulation, resulting in a right MCA infarction. Atrial fibrillation was likely precipitated by atrial distortion from the septal mass. The patient was discharged on metoprolol, diltiazem, and amiodarone in stable condition. Conclusion: This case highlights a rare cause of embolic stroke—LHIS—as both a source of paradoxical embolism and a trigger for atrial fibrillation. Accurate diagnosis requires histopathological confirmation, as imaging may misidentify LHIS as a myxoma. Clinicians should consider LHIS in cryptogenic stroke, especially in the presence of a PFO and interatrial masses.

Background: Patent foramen ovale (PFO) is a recognized contributor to embolic stroke, especially in hypercoagulable states (HCSs). However, patients with HCSs, including malignancy, were excluded from major PFO closure trials, creating a significant evidence gap. Objectives: This narrative review examines the role of PFO closure in secondary stroke prevention among patients with HCSs, including malignancy. We highlight key studies and current evidence in this understudied population. Methods: A systematic search of PubMed was conducted using pertinent MeSH terms. Due to limited data, a narrative synthesis of the literature was performed. Case Presentation and Narrative Review of Literature: A 43-year-old lady with a history of metastatic breast cancer and recent bilateral pulmonary emboli on anticoagulation (AC), presented with expressive aphasia. MRI brain confirmed a Broca-area infarct. Biopsy of an expansile pelvic mass yielded a diagnosis of ovarian mucinous cystadenocarcinoma. TEE demonstrated a PFO; an embolic stroke driven by hypercoagulability of malignancy was diagnosed. PFO closure was offered for secondary stroke prevention after risk-benefit discussion, as opposed to AC alone. While early trials (CLOSURE I, PC) showed no benefit of closure, subsequent studies (RESPECT, REDUCE, DEFENSE-PFO) favored it in selected patients, but notably, these trials excluded patients with HCSs and malignancy. The benefit of PFO closure in this population thus comes largely from observational data. Abrahamyan et al. found that PFO closure could be safely offered in patients with thrombophilia to prevent recurrent stroke. Liu et al., in their prospective study, noted that among patients with cryptogenic stroke and thrombophilia, PFO closure lowered the risk of recurrence. Similarly, a retrospective study from Greece found benefit from PFO closure in this population. Buber et al. found that among patients with HCSs and stroke, PFO closure offered a five-fold risk reduction from future CVA/TIA. The Society for Cardiovascular Angiography and Interventions (SCAI) guidelines recommend PFO closure in patients with thrombophilia for secondary stroke prevention (conditional recommendation- low certainty of evidence). Conclusions: Data on PFO closure for secondary stroke prevention in HCSs and malignancy are scant, necessitating individualized decision making. Current evidence supports PFO closure, but future studies are needed specifically in this vulnerable population.

Case Description: A 43-year-old female with a history of cryptogenic stroke and a large aneurysmal patent foramen ovale (PFO) underwent successful intra-cardiac echocardiography (ICE)-guided closure with a 30 mm GORE® CARDIOFORM Septal Occluder (Figure 1). Immediately post-procedure, she reported left-sided substernal chest pain. A STAT transthoracic echocardiogram (TTE) showed no pericardial effusion, no new wall motion abnormalities, and correct device positioning. She was discharged on aspirin and clopidogrel. The following day, she returned to the emergency department with persistent sharp, pleuritic, and positional chest pain, associated with dyspnea and unrelieved by acetaminophen or ibuprofen. Subsequent workup revealed leukocytosis, elevated inflammatory markers and troponin levels, diffuse concave ST-segment elevations on ECG (Figure 2), and a trace pericardial effusion on both computed tomography angiography (CTA) and TTE (Figure 3)—findings concerning for myopericarditis. She was treated with colchicine and ibuprofen, leading to rapid symptom improvement and discharge. Follow-up cardiac magnetic resonance imaging (MRI) three months later showed no residual inflammation. Discussion: Myopericarditis refers to concurrent inflammation of the pericardium and myocardium, most commonly caused by viral infections but occasionally triggered by cardiac interventions. Though rare, pericarditis and myocarditis have been reported following intracardiac device implantation, including PFO closure. One proposed mechanism involves a type IV hypersensitivity reaction to nickel, a component of nitinol used in many closure devices. The GORE® CARDIOFORM Septal Occluder, while containing nitinol, is encapsulated in expanded polytetrafluoroethylene (ePTFE), which may reduce direct nickel exposure compared to devices like the AMPLATZER™ PFO Occluder. However, no significant difference in the incidence of hypersensitivity reactions between devices has been established. Nickel skin testing has been suggested in select cases but is not validated for predicting systemic or device-related reactions. Even in patients with known nickel sensitivity, the clinical relevance remains uncertain, as the pre-test probability of device-related reaction is low, and no nickel-free alternatives currently exist. As such, the potential risk of hypersensitivity must be weighed against the proven benefit of PFO closure in reducing the risk of recurrent stroke in select patients.

Background: Paradoxical embolism through a patent foramen ovale (PFO) is a recognized cause of cryptogenic stroke and transient ischemic attacks (TIAs), especially in patients with intracardiac right-to-left shunting. Indwelling central venous catheters may lead to thrombus formation, but direct embolic events from catheter-associated thrombi interacting with a PFO are exceedingly rare and underrecognized. Case: A 39-year-old woman with a history of thalassemia, anemia, agoraphobia, anxiety, gastric bypass surgery, liver dysfunction, and multiple prior C-sections, a port-a-cath for recurrent blood transfusions presented with acute altered mental status, confusion, agitation, and restlessness. CT head showed subtle findings concerning for infarction in the right temporal and parietal lobes, although MRI brain was unremarkable. Her neurologic status returned to baseline. A transthoracic echocardiogram (TTE) with bubble study revealed right-to-left atrial shunting, raising suspicion for PFO. She was discharged with cardiology and neurology follow-up. At follow-up, she remained emotionally distressed and convinced she had suffered a stroke. Repeat TTE raised concern for an intracardiac mass. A transesophageal echocardiogram (TEE) revealed a port-a-catheter tip in the right atrium with a large, mobile thrombus attached to its distal end. A small PFO with intermittent right-to-left shunting was also identified. The thrombus moved like a pendulum, intermittently striking the interatrial septum at the PFO. It is likely that embolization of a portion of the thrombus through the PFO led to a TIA. Interventional Radiology administered catheter-directed tPA to facilitate clot dissolution. Discussion: This case highlights a rare but clinically significant mechanism of paradoxical embolism originating from a central venous catheter, diagnosed through high clinical suspicion and confirmatory imaging. Conclusion: In patients with neurologic symptoms and indwelling catheters, paradoxical embolism should be considered. TEE plays a vital role in detecting thrombi and intracardiac shunts. Early recognition and targeted therapy may prevent recurrence of embolic events.

Introduction: Patent foramen ovale (PFO) is present in ~25% of adults and is typically asymptomatic. Two indications for PFO closure include cryptogenic stroke and platypnea-orthodeoxia syndrome (POS), a rare condition marked by dyspnea and desaturation in the upright position due to posture-dependent right-to-left shunting. POS usually involves anatomic vulnerability, intrathoracic pressure (ITP) changes, and dynamic physiological triggers. We present a complex case illustrating this uncommon but life-threatening scenario. Case Vignette: A 66-year-old man with HIV non-adherent to antiretroviral therapy, emphysema, and a known small PFO presented with fever, hypoxia, leukopenia, and left lower lobe consolidation. Labs showed elevated procalcitonin, and he was treated for bacterial pneumonia based on CT findings. During hospitalization, when transitioning from bed to standing, he suffered sudden pulseless electrical activity (PEA) arrest. He was resuscitated and mechanically ventilated. He remained in the ICU for 10 days, requiring multiple extubations and reintubations for recurrent hypoxia. After each extubation, he showed marked positional desaturation (SpO 2 93% supine → 70% upright) despite radiographic improvement of consolidation. CT chest revealed no PE, but significant right lung hyperinflation, likely from barotrauma and air trapping compounded by underlying emphysema. Bubble contrast echo showed a large right-to-left shunt with immediate LA/LV opacification in one cardiac cycle. TEE confirmed an enlarged PFO with interval growth compared to prior imaging and a 1 cm anterior rim. Right heart catheterization showed no signs of Eisenmenger’s physiology, and patient underwent successful transcatheter closure with resolution of hypoxemia and successful extubation. Discussion: This case illustrates how a silent PFO can become clinically significant with multiple converging triggers. The patient’s non-compliant HIV status increased susceptibility to pulmonary infection. Combined with mechanical ventilation and right lung hyperinflation, there was increased right-sided intrathoracic pressure, worsening the right-to-left shunting and enlarging the PFO. These changes led to POS, likely causing the initial PEA arrest. Clinicians should suspect POS in cases of unexplained positional hypoxia or PEA arrest. Early recognition is key, as closure can be curative as illustrated in our challenging clinical case.

Introduction: The rates of pediatric ischemic stroke incidence have more than doubled over the past 3–4 decades; however, pediatric posterior circulation strokes are even more uncommon. These rising incidence rates have led to increasing awareness of pediatric strokes and the development of institutional guidelines regarding these patients to optimize outcomes when possible. Case Report: We describe a rare case of acute ischemic posterior circulation stroke in a 14-year-old previously healthy adolescent boy who presented with right-sided facial droop, dysarthria, and right-sided hemiplegia. An MRI of the brain demonstrated an acute infarct in the brainstem, and an echocardiogram demonstrated a patent foramen ovale (PFO). We also discuss how to localize brainstem lesions to a specific location within the brainstem and associated blood supply using symptomatology. Conclusions: All stroke patients require evaluation for possible etiologies of stroke and possible underlying risk factors. Nearly half of patients who suffer from cryptogenic stroke are found to have a PFO, and adult studies have shown that PFO closure is associated with reduced recurrent cryptogenic strokes, although pediatric-specific data is lacking. If a posterior stroke is suspected, specifically in the brainstem, then the Brainstem Rules of Four may be utilized to localize these lesions and identify blood supply using simplified knowledge of the brainstem anatomy.

Major uncertainty remains about the relationship between left ventricular (LV) systolic dysfunction, recurrent stroke, and the optimal antithrombotic therapy for secondary stroke prevention in patients with recent stroke and LV systolic dysfunction. We performed a post hoc analysis of data from the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke), a randomized trial comparing apixaban versus aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. Echocardiograms were sent from 185 enrolling sites in the United States and Canada for central review at the trial echocardiography laboratory. We defined LV systolic dysfunction as LV fractional shortening <25%, LV ejection fraction <50%, or any LV wall motion abnormality. The primary outcome of interest was recurrent ischemic stroke. First, we built Cox proportional hazard models to evaluate the association between LV systolic dysfunction and recurrent ischemic stroke risk adjusted for imbalanced covariates. Next, we used Cox proportional hazard models and interaction terms to compare the effect of apixaban versus aspirin on the outcome of interest in patients with and without LV systolic dysfunction. Among 964 patients with complete echocardiographic data of the 1015 patients enrolled in the trial, 165 (17.1%) had LV systolic dysfunction (mean age, 67 years; 43% female; mean follow-up, 1.7 years), and 799 (82.9%) had no LV systolic dysfunction (mean age, 68 years; 56% female; mean follow-up, 1.5 years). Recurrent ischemic stroke occurred more frequently in patients with LV systolic dysfunction (n=15, 9.1%) compared with those without LV systolic dysfunction (n=50, 6.3%), but LV systolic dysfunction was not significantly associated with recurrent stroke after adjustment for imbalanced covariates (hazard ratio, 1.3 [95% CI, 0.7-2.4]). Compared with aspirin, apixaban was associated with a significantly reduced risk of recurrent ischemic stroke in patients with LV systolic dysfunction (hazard ratio, 0.24 [95% CI, 0.07-0.87]) but not in those without LV systolic dysfunction (hazard ratio, 1.13 [95% CI, 0.65-1.96]; Pinteraction=0.028). In a secondary analysis of the ARCADIA trial data, apixaban was associated with a significantly lower risk of recurrent ischemic stroke than aspirin in patients with LV systolic dysfunction.

Patent foramen ovale (PFO) has been identified as a potential risk factor for cryptogenic stroke (CS). Although transesophageal echocardiography (TEE) is considered the gold standard for PFO detection, false-negative results remain a clinical concern, particularly in CS patients with high suspicion of PFO-related etiology. To evaluate the clinical utility of transcatheter PFO exploration (TPFOE) in CS patients with negative TEE findings but high suspicion of PFO-related etiology. Between January 2019 and May 2022, 30 CS patients with high suspicion of PFO-related etiology were enrolled. All showed grade III/IV RLS on contrast transthoracic echocardiography (cTTE) despite negative TEE. Each patient underwent TPFOE. Patients with confirmed PFO proceeded directly to immediate PFO closure, whereas negative cases received antiplatelet therapy alone. Follow‑up with transthoracic echocardiography (TTE), chest X‑ray, and electrocardiography (ECG) was performed at 12 h and at 1, 3, 6, and 12 months after the procedure. The study cohort comprised 14 males and 16 females, with a median age of 41.5 years (interquartile range: 34-48 years). TPFOE successfully identified PFO in 28 patients (93.3%), all of whom subsequently underwent successful interventional closure. Follow-up TTE confirmed ideal device position and morphology without residual shunting. The remaining two patients (6.7%) had negative exploration results, and they received antiplatelet therapy alone. No recurrent cerebrovascular events were reported in any patient during the follow-up period. TEE, though the gold standard for PFO diagnosis, carries a non‑negligible false‑negative rate. In CS patients with negative TEE but high suspicion of PFO-related etiology, TPFOE demonstrated potential as an adjunctive technique to increase PFO detection. Further studies are warranted to better define its diagnostic value for PFO in this patient population.

BackgroundPatients with acute ischemic stroke (AIS) and cancer are at exceptionally high risk for recurrent thromboembolism (RTE), which includes venous thromboembolism (VTE) and arterial thromboembolism (ATE). Yet contemporary data from Chinese patients remain scarce.MethodsIn this retrospective, observational study conducted at Tianjin First Central Hospital (June 2023-December 2024), consecutive adults with AIS and cancer were enrolled. The primary outcomes during 6 months follow-up were recurrent VTE།composite VTE (symptomatic and incidental VTE requiring treatment), recurrent stroke [cerebral infarction, transient ischemic attack (TIA), and systemic embolism (SE)], and bleeding (major bleeding and clinically significant non-major bleeding). Multivariable logistic regression was used to identify independent predictors of each endpoint.ResultsAmong 218 eligible patients, 49 (22.5%) had baseline VTE, of whom 45 (91.8%) were asymptomatic. Baseline VTE was independently predicted by cryptogenic stroke subtype (OR 2.70; 95% CI 1.101–6.621; P = 0.030) and D-dimer > 1.2 µg/mL (OR 3.619; 95% CI 1.505–8.703; P = 0.004). During follow-up, 25 patients (11.5%) experienced composite VTE, 71 patients (32.6%) experienced recurrent stroke, and 21 patients (9.6%) experienced bleeding. Multivariable analysis revealed that D-dimer > 1.2 µg/mL independently predicted recurrent VTE (OR 3.501; 95% CI 1.012–12.112; P = 0.048), whereas cancer metastasis portended recurrent stroke (OR 3.155; 95% CI 1.423–6.995; P = 0.005), and anticoagulant therapy was associated with an increased bleeding risk (OR 9.458; 95% CI 1.158–77.267; P = 0.036).ConclusionsIn this Chinese cohort of patients with acute ischemic stroke (AIS) and cancer, routine screening revealed venous thromboembolism (VTE) in roughly one-fifth of participants at baseline, most of whom were asymptomatic. Exploratory multivariable analyses indicated that cryptogenic stroke subtype and D-dimer > 1.2 µg/mL were associated with prevalent VTE, while D-dimer > 1.2 µg/mL also predicted recurrent VTE. These findings suggested that D-dimer guided VTE screening might be considered at the time of stroke presentation, even in the absence of symptoms. Cancer metastasis showed an association with recurrent stroke, whereas anticoagulant therapy was linked to a higher bleeding risk.

Cryptogenic stroke, named embolic stroke of undetermined source, refers to patients for whom the etiology of embolism remains unknown. Recently a new cardiac entity, the left-sided septal pouch (LSSP), has been identified as a possible source of thromboembolic events. In the current study, we aimed to perform a systematic review of the literature on this topic and to determine the association between the LSSP presence and occurrence of cryptogenic stroke using meta-analytical methodologies. A detailed search of electronic databases for studies that compared the presence of LSSP in subjects with cryptogenic stroke and non-stroke controls was performed. Data were extracted and pooled into a meta-analysis. We included eight studies in the meta-analysis, in which there were a total of 506 patients with cryptogenic stroke and 1600 patients in the control group. The pooled prevalence of LSSP among cryptogenic stroke patients was 31.6% (95% CI: 20.6–43.8). In the non-stroke control group the pooled prevalence of LSSP was 22.0% (95% CI: 15.0-29.8). The meta-analysis showed that there is a higher risk of cryptogenic stroke in patients with LSSP than in patients without LSSP (OR: 1.57, 95% CI: 1.23–2.01; p < 0.01). A subgroup meta-analysis of transesophageal echocardiography studies demonstrated the same association (OR: 1.59; 95% CI: 1.21–2.08; p < 0.01). In studies where the mean patient age was < 60 years, LSSP was associated with a higher risk of cryptogenic stroke (OR: 1.67; 95% CI: 1.22–2.29; p < 0.01). However, in studies where the mean patient age was > 60 years, the association was not statistically significant (OR: 1.58; 95% CI: 0.75–3.32).Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21285-y.