Cryptogenic Ischemic Stroke Research Articles

Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study.

Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure. A Danish nationwide cohort study was conducted. During 2008-2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5-10] in the PFO closure cohort, 3.1% (95% CI: 2.0-4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8-1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3-4.0) within the first 3 months and 0.7 (95% CI: 0.3-1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21-125) within the first 3 months and 2.5 (95% CI: 1.2-5.0) thereafter. Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.

Rigorous and long-term cardiac monitoring strategy in cryptogenic stroke or TIA patients in a tertiary care centre results in a two-fold increase in AF detection

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Special Research Fund (Bijzonder Onderzoeksfonds, BOF) Hasselt University. This study is part of Limburg Clinical Research Center, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Background Atrial fibrillation (AF) is a major cause of ischaemic stroke. Oral anticoagulation is recommended in stroke survivors with AF to prevent recurrence. Prolonged ECG monitoring using insertable cardiac monitors (ICMs) has been shown to increase the detection rate of AF compared to standard 24-hour ECG monitoring in cryptogenic stroke patients. However, prolonged ambulatory ECG monitoring is underutilized, likely contributing to an underdiagnosis of AF and missed anticoagulation treatment opportunities for secondary stroke prevention. Purpose This study aims to evaluate how our evolving cardiac monitoring strategy affected AF detection rates one year after cryptogenic ischaemic stroke or transient ischaemic attack (TIA) in a tertiary care centre. Methods We retrospectively identified all consecutive cryptogenic stroke or TIA patients admitted to our centre between 1/01/2017 – 1/01/2022. Patients with a pacemaker or implantable cardioverter-defibrillator were excluded from the analysis. Data were collected from the electronic medical record. Available cardiac monitoring modalities included 24-hour Holter monitoring, 7-day Holter monitoring, and insertable cardiac monitors (ICM). After October 2020 (i.e., period 2), the latter became part of our routine diagnostic workup for AF detection in case extended (7-day) Holter monitoring was negative. Results All 691 cryptogenic stroke or TIA patients admitted to our hospital during the inclusion period were considered. These were elderly patients (69.7 ± 13.2 years) with a CHA2DS2-VASc score of 3 [2 - 5]. Figure 1 shows evolving trends in the use of the different cardiac monitoring tools before and after October 2020. In particular, the use of 7-day Holter monitoring and long-term continuous monitoring with ICM increased after implementing our new diagnostic protocol compared to 24-hour Holter monitoring (p<.001). ICMs were inserted 95 [66 – 145] days after index stroke or TIA. The new diagnostic protocol detected more AF one year after the index stroke or TIA (3.7% vs. 10.1%, p<.001, Figure 2). In 95.6% of patients with AF detected within one year, oral anticoagulation was initiated. Future research should determine whether adopting a strategy of routine ICM following cryptogenic stroke and, thus, more appropriate anticoagulant therapy may improve clinical outcome in these patients. Conclusions The increased use of prolonged cardiac monitoring in cryptogenic stroke or TIA patients resulted in a two-fold increase in AF detection one year after stroke. Therefore, our results underscore the need to implement guideline-recommended prolonged rhythm monitoring using ICMs in addition to short-term ECG monitoring to ensure adequate secondary stroke prevention.

P58 SCREENING FOR SUBCLINICAL ATRIAL FIBRILLATION AFTER EMBOLIC STROKE OF UNDETERMINED SOURCE: A SINGLE CENTRE EXPERIENCE

Abstract Introduction Embolic stroke of undetermined source (ESUS) describes a stroke for which no cause has been found, which implicates embolism as a cause of stroke. There are several mechanisms of cryptogenic ischemic stroke including a covert structural cardiac lesion, paroxysmal atrial fibrillation (AF), hypercoagulable state or undiagnosed malignancy. As ESUS is associated with a significant stroke recurrence, a clear risk prediction and management is of utmost importance to improve prognosis. In ESUS, the options for further investigation include long–term cardiac monitoring, transesophageal echocardiography, investigation for occult malignancy or arterial hypercoagulability. Implantable cardiac monitors offer the capability to maximize the chances to detect AF and should be considered after non–invasive monitoring in patients with previous stroke at higher probability of having AF. Current guidelines do not suggest a specified approach (ie, blood, echocardiographic, ECG or brain imaging biomarkers) to screen AF in ESUS patients. Methods We enrolled consecutive patients with ESUS admitted to our Stroke Unit from January 2021 to October 2022. Results In the study period, 509 patients with acute ischemic stroke were admitted in our Stroke Unit. ESUS was diagnosed in 10.6% of patients (54/509). Only 12 of these patients underwent loop recorder implantation (mean age 76.5 y, 75% male), according to clinician judgment. AF was detected in 16.6% of these patients (2/12). Conclusions AF is one of the causes of ESUS; a recognition of AF in these patients is important, because its treatment can modify the risk of recurrence. A tailored diagnostic pathway, including clinical and echocardiographic parameters, is advisable to improve the recognition of this arrhythmia in ESUS patients.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults

Background In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. Patients and Methods In this substudy of the international multicenter case–control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18–49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. Results 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20–12.42), in participants without antihypertensives (4.86; 1.07–22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47–36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37–17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. Conclusions Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution. Key Messages Nocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale. It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Platypnoea orthodeoxia syndrome and its association with cryptogenic ischaemic stroke.

Platypnoea orthodeoxia syndrome is a rare condition, which can be present in patients with patent foramen ovale (PFO). In this case, a 72-year-old lady presented to the emergency department with a cryptogenic stroke associated with right thalamic infarct. While in hospital, it was noticed that the patient had desaturations in the upright position, and these improved in the recumbent position, consistent with platypnoea orthodeoxia syndrome. The patient was found to have a PFO, which was then closed, and her saturations returned to normal. This case highlights the importance of patients who present with cryptogenic stroke and features of platypnoea orthodeoxia syndrome need to be considered for underlying PFO or other septal defect.

Does left atrial appendage morphology and dimension differ amongst etiological stroke subtypes in patients without known atrial fibrillation? Results from the left atrial appendage morphology and dimension assessment by TEE in patients with stroke without known atrial fibrillation (LAMDA-STROKE) study

ContextComplex left atrial appendage (LAA) morphology is increasingly associated with cryptogenic ischemic stroke as compared to cardioembolic stroke due to atrial fibrillation (AF). However, data on such an association in patients with other etiological stroke subtypes in the absence of AF is limited. AimThe study aimed to assess the LAA morphology, dimension and other echocardiographic parameters by transesophageal echocardiography (TEE) in patients with embolic stroke of undetermined source (ESUS) and compare it with other etiological stroke subtypes without known AF. MethodsThis was a single-Centre, observational study involving comparison of echocardiographic parameters including LAA morphology and dimension in ESUS patients (group A; n = 30) with other etiological stroke subtypes i.e., TOAST (Trial of Org 10172 in Acute Stroke Treatment) class I-IV without AF (group B; n = 30). ResultsComplex LAA morphology was predominant in group A (18 patients in group A versus 5 patients in group B, p-Value = 0.001). Mean LAA orifice diameter (15.3 + 3.5 mm in group A versus 17 + 2.0 mm in group B, p-Value = 0.027) and LAA depth were significantly lower in group A (28.4 + 6.6 mm in group A versus 31.7 + 4.3 mm in group B, p-Value = 0.026). Out of these three parameters only complex LAA morphology was found to be independently associated with ESUS [OR = 6.003, 95% CI {1.225–29.417}, p = 0.027]. ConclusionComplex LAA morphology is a predominant feature in ischemic stroke patients with ESUS and may contribute to an increased risk of stroke in these patients.

Abstract Number ‐ 243: The Non‐stenosing Carotid Artery Plaque in Embolic Stroke of Undetermined Source: A Retrospective Study

Introduction Atherosclerotic cervical internal carotid artery disease is one of the major causes of ischemic stroke and transient ischemic attacks. The risk of stroke from mild to moderate stenoses (i.e., < 50% stenosis) might be underestimated, and further investigation is mandated to describe the association between high‐risk plaque features and ESUS. Methods This was a retrospective observational study. Using the stroke registry of our hospital’s system between June 20th 2016 and June 20th 2021. We reviewed data for patients diagnosed with ESUS according to previously published definition criteria. Using computed tomography angiography (CTA), we analyzed laterality of high‐risk plaque features in relation to the stroke side, and then we identified the incidence of recurrent stroke events. Results Out of 1779 patients with cryptogenic ischemic stroke, only 152 met the inclusion criteria for ESUS. We Compared high‐risk plaque features ipsilateral to stroke side as to contralaterally. There were significantly more ulcerations defined as >1 mm depression (19.08% vs 5.26%, p< .0001), plaque thickness >3 mm (19.08% vs 7.24%, p = 0.001), and plaque length >1cm (13.16% vs 5.92%, p = 0.0218).Also, there was a significant difference in stenosis of ipsilateral to stroke when compared contralaterally, especially for stenoses of 10–30% and 31–49% (17.76% vs 10.53% and 5.26% vs 2.63%, respectively. p = 0.0327). There was also a significant difference in plaque component; both components (soft and calcified) and only soft plaque (42.76% vs 23.68% and 17.76% vs 9.21%, respectively. p< .0001) were more prevalent ipsilaterally. In total, 17patients were found to have a recurrent stroke event, 8 patients had an ipsilateral stroke to the index event, 7 had a bilateral and 2 had a contralateral event. Conclusions ESUS is more commonly found ipsilateral to high‐risk plaque features. Qualitative assessment of plaque features using CTA could be easily implemented in clinical practice. The small number of our sample is definitely a limitation. Further large and multicenter studies aiming to form precise prediction models and scoring systems are needed to help guide treatment with carotid artery stenting or carotid endarterectomy versus maximizing medical therapy.

Аortic arch atheroma as a source of arterio-arterial embolism and ischemic stroke

Introduction. Currently, despite the introduction of modern diagnostic algorithms in 20-40 % of patients with ischemic stroke, it is not possible to establish its cause. Potential causes of acute cerebral ischemia in patients with cryptogenic ischemic stroke include paroxysmal atrial fibrillation, patent foramen ovale, atrial cardiomyopathy, carotid network, aortic arch atheroma, and cancer-associated thrombophilia.Target: to systematize data on methods for diagnosing and preventing aortic arch atheroma.Material and methods. The literature search was carried out in electronic search systems Scopus, eLibrary, PubMed using the key words: ischemic stroke, cryptogenic stroke, aortic arch atheroma, pathogenesis of ischemic stroke.Results. At present, despite such a detailed study of therapeutic strategies for the prevention of recurrent thrombotic events in patients with aortic arch atheroma, none of the drugs has proven its advantage. Although the NAVIGATE ESUS and RESPECT ESUS trials did not show the superiority of oral anticoagulants over antiplatelet agents in preventing recurrent ischemic strokes in patients with cryptogenic stroke, it was found that cryptogenic ischemic stroke is heterogeneous, which requires a differentiated approach to secondary prevention.Conclusion. Аortic atheroma can be the cause of embolic syndrome and cryptogenic stroke. The main methods for diagnosing aortic atheroma are transesophageal echocardiography and computed tomographic angiography. The therapeutic strategy for the treatment of aortic atheroma is lipid-lowering, antithrombotic therapy in combination with blockers of the renin-angiotensin-aldosterone system.

Abstract WMP70: Young Adults With Cryptogenic Ischemic Stroke Have Longer Corrected QT Intervals Than Healthy Controls

Introduction: In cryptogenic ischemic stroke, no definite etiology is found and high-risk cardiac sources of embolism are excluded. However, it has been hypothesized that many cryptogenic strokes could be cardioembolic especially in younger patients. We assessed whether resting ECG could reveal cardiac differences in young patients with cryptogenic ischemic stroke, as compared to healthy controls. Methods: We recruited prospectively 477 patients with cryptogenic ischemic stroke at age 18-49 and 455 controls at 19 European tertiary centers. We obtained vast clinical data and resting 12-lead ECG (at subacute phase from patients). From the ECGs we measured heart rate, presence of conduction blocks, QRS transition zone in precordial leads, presence of abnormal T-wave inversions, presence of ST depression and corrected QT-interval (QTc). We constructed multivariate models for each ECG parameter, adjusting for demographic and clinical data, using binomial logistic regression. Results: Median age for both patients and controls was 41 years, with 54.0% of patients and 54.6% of controls being men. Compared to controls, patients had higher prevalence of hypertension (38.8% vs. 30.0%, P=0.005) and obesity (38.8% vs. 30.1%, P=0.005), were more frequently heavy drinkers (14.6% vs. 7.6%, P<0.001), and were more likely to smoke (34.1% vs. 17.5%, P<0.001). Patients with cryptogenic ischemic stroke had longer QTc interval than controls (median QTc 416ms vs. 409ms, P<0.001). After adjustments, longer QTc interval was associated with stroke (odds ratio 1.12 per 10ms increase, P<0.001). There were no statistically significant differences in other ECG-abnormalities between patients and controls. Conclusion: Young patients with cryptogenic ischemic stroke have a longer corrected QT interval than healthy controls. The reason for this novel finding is unclear, and could reflect both underlying cardiogenic and neurogenic reasons.

Abstract TP160: The Non-stenosing Carotid Artery Plaque In Embolic Stroke Of Undetermined Source: A Retrospective Study

Introduction: Atherosclerotic cervical ICA disease is one of the major causes of ischemic stroke. The risk of stroke from mild to moderate stenoses (i.e., <50% stenosis) might be underestimated. Further investigation is mandated to describe the association between high-risk plaque features and ESUS. Methods: This was a retrospective observational study. Using the stroke registry of our hospital's system between June 20th 2016 and June 20th 2021, we reviewed data for patients diagnosed with ESUS according to previously published definition criteria. Using CTA, we analyzed laterality of high-risk plaque features in relation to the stroke side, and then we identified the incidence of recurrent stroke events. Results: Out of 1779 patients with cryptogenic ischemic stroke, only 152 met the inclusion criteria for ESUS. We Compared high-risk plaque features ipsilateral to stroke side as to contralaterally. There were significantly more ulcerations defined as >1 mm depression (19.08% vs 5.26%, p<.0001), plaque thickness >3 mm (19.08% vs 7.24%, p=0.001), and plaque length >1cm (13.16% vs 5.92%, p=0.0218). Also, there was a significant difference in stenosis of ipsilateral to stroke when compared contralaterally, especially for stenoses of 10-30% and 31-49% (17.76% vs 10.53% and 5.26% vs 2.63%, respectively. p=0.0327). There was also a significant difference in plaque component; both components (soft and calcified) and only soft plaque (42.76% vs 23.68% and 17.76% vs 9.21%, respectively. p<.0001) were more prevalent ipsilaterally. In total, 17 patients were found to have a recurrent stroke event, 8 patients had an ipsilateral stroke to the index event, 7 had a bilateral and 2 had a contralateral event. Conclusion: ESUS is more commonly found ipsilateral to high-risk plaque features. The small number of our sample is definitely a limitation. Further large and multicenter studies aiming to form precise prediction models and scoring systems are needed to help guide treatment.

The Role of Advanced Echocardiographic Parameters of the Left Atrial Function in the Incidence of Cryptogenic Ischemic Stroke: A Review.

Stroke is one of the primary causes of morbidity and mortality worldwide, including a large proportion of cryptogenic strokes. Long-term electrocardiographic monitoring is beneficial in prospective studies for detecting atrial fibrillation in patients with cryptogenic stroke. This review aimed to evaluate the advanced echocardiographic parameters and their roles in assessing left atrial (LA) function in the incidence of cryptogenic and ischemic strokes. Main resources, including PubMed, Scopus, and ISI Web of Science databases, were evaluated for articles published in English from 2010 until May 2021. LA echocardiographic parameters such as LA strain and strain rate, isovolumetric relaxation time (IVRT), the mean left atrial volume index (LAVI), LA reservoir volume, systole strain rate (SSR) of left atrial appendage, and lack of LA function response to maximal exercise as measured by the LA ejection fraction during rest and exercise could be considered for assessing the risk of cryptogenic strokes and ischemic strokes. The results indicated that increased LA volumes and reduced LA strain rate were correlated with cryptogenic stroke. Advanced parameters of LA function, measured by speckle tracking echocardiography, such as strain and strain rate values in different parts of the cardiac cycle, in addition to standard measures of LA function such as LA ejection fraction and LAVI, will define an excellent understanding regarding LA myopathy and risk assessment of cryptogenic stroke, independent of considering conventional cardiovascular risk factors.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Phenotyping of embolic cryptogenic stroke based on ultrasound diagnosis and determination of serum concentration NT-proBNP

Determining the potential mechanisms underlying cryptogenic ischemic stroke is essential to guide diagnostic discovery and personalize secondary prevention.Purpose is to study the phenotypes of embolic stroke of undetermined source (ESUS) based on ultrasound diagnosis and determination of the serum concentration of pro-natriuretic N-terminal peptide B-type (N-Terminal Pro-brain Natriuretic Peptide, NT-proBNP).Materials and methods. 141 patients with ESUS were examined. In addition to the standard examination aimed at fi nding the cause of stroke, the functional characteristics of the left atrium were assessed using the emptying fraction (left atrial emptying fraction, LAEF) and the functional index (left atrial function index, LAFI), and the concentration of NT-proBNP in blood serum was also measured.Results. The most common potential sources of embolism were atherosclerotic plaques in the stroke-associated carotid artery with stenosis in 30–49% (31.9% of patients) and atrial cardiopathy with a decrease in LAEF < 51.8% (24.8% of patients). An analysis of combinations of potential sources showed that 46.1% of patients had a negative phenotype, 21.3% of patients had a cardiac phenotype, 19.1% of patients had an atherosclerotic phenotype, and 13.5% of the examined patients had a mixed phenotype. Patients with a cardio-atherosclerotic phenotype diff ered from patients with a negative phenotype by higher disability on the Rankin scale at discharge from the hospital.Conclusion. The main potential embolic sources in patients with ESUS are non-stenosing carotid atherosclerosis and atrial cardiopathy with decreased LAEF. Cardiac and atherosclerotic phenotypes are determined in a quarter of patients, a mixed phenotype is found in every seventh patient, while in almost half of the patients no sources of embolism are found.

A scoping review protocol on diagnostic strategies to detect occult malignancies in individuals with ischemic stroke.

Emerging data show an increased risk of ischemic stroke in patients with a new diagnosis of cancer. As the risk of stroke begins to increase 150 days before cancer is diagnosed, stroke may be the first clinical manifestation of undiagnosed cancer. About 6% of patients with cryptogenic ischemic stroke (unknown etiology after diagnostic evaluations) are diagnosed with cancer within one year. However, the optimal cancer screening strategy in this population is not known. We aim to conduct a scoping review of screening strategies for occult cancer in individuals with ischemic stroke. Electronic databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and Scopus will be systematically searched to identify articles that report on screening strategies for occult cancer in individuals with ischemic stroke. At least two investigators will independently perform two-stage study selection consisting of title/abstract screening and full-text review, followed by data extraction. Thereafter, a thematic analysis will be conducted to provide an overview of what diagnostic tests/strategies have been used, and their clinical utility in terms of positive and negative predictive value (when available). We anticipate that the findings of this scoping review will identify strategies used to detect occult cancer in individuals with ischemic stroke and summarize their clinical utility (if reported). Addressing this knowledge gap will help guide the development of future clinical trials on occult cancer screening patients with ischemic stroke.

Prognostic value of unrecognized myocardial infarction and silent ischemia detected by stress CMR in asymptomatic patients with prior cryptogenic ischemic stroke

Prognostic value of unrecognized myocardial infarction and silent ischemia detected by stress CMR in asymptomatic patients with prior cryptogenic ischemic stroke

Effect of atrial septal dilation tumor and patent foramen rotundus on cryptogenic ischemic stroke in young and middle-aged patients.

To investigate the effect of atrial septal aneurysm (ASA) and patent foramen ovale (PFO) on cryptogenic ischemic stroke in young and middle-aged patients. A case-control study was conducted to select 96 young and middle-aged patients with cryptogenic ischemic stroke in the Department of Neurology of our hospital from January 2015 to January 2020 (observation group). A total of 192 patients with non-ischemic stroke were selected as the control group. The clinicadata and transthoracic echocardiography (cTTE) results were compared between the two groups. The ASA depth and tumor wall thickness in the observation group were 15.50 (12.40, 19.80) mm and 3.90 (2.80,4.50) mm, respectively, which were significantly higher than those in the control group (P < 0.05). Logistic regression analysis showed that PFO, and PFO combined with ASA were the influencing factors of cryptogenic ischemic stroke in middle-aged and young people OR = 1.923 and 1.384, P < 0.05). Atrial septal aneurysm combined with PFO and PFO are independent influencing factors factor for the occurrence of cryptogenic ischemic stroke in young and middle-aged people, which is worthy of further study.

Transoesophageal echocardiography findings in young patients with cryptogenic ischemic stroke

Abstract Background and purpose The cause of ischemic stroke (IS) remains often unclear in young patients. Relevant structural heart abnormities with known embolic potential may represent cause of IS also in young population. The use of transoesophageal echocardiography (TEE) allows reliable detection of most relevant structural pathologies. The aim was to assess frequency and spectrum of relevant cardiac abnormities in young IS patients. Subjects and methods The study set consisted of young acute IS patients &amp;lt;50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study, registered on ClinicalTrials.gov NCT01541163). In all patients, the brain ischemia was confirmed on CT or MRI. Admission ECG, serum specific cardiac markers, TEE, 24-hour and 3-week ECG-Holter were performed in all patients. Results Out of 1284 patients enrolled in the HISTORY study, 135 (73 males, mean age 40.2±8.1 years) were &amp;lt;40 years. In total, the relevant TEE abnormities were present in 47 (35%) of these patients. Patent foramen ovale (PFO) with evident left to right shunt was detected in 38 (28%) patients, with significant right to left shunt in 25 (19%) patients, and other atrial septal defect with clinically significant bidirectional flow in 4 (3%) patients. Significant valvular heart disease was present in 2 (1%) patients (1 bicuspid aortic valve with moderate aortic regurgitation, 1 chronic severe mitral regurgitation), and 4 (3%) patients severe left ventricular systolic dysfunction (left ventricular ejection fraction ≤35%) due to idiopathic dilated cardiomyopathy. Left atrial myxoma was detected in one patient. Conclusion The relevant structural abnormities with embolic potential were detected using TEE in 35% of young IS patients. Routine use of TEE to elucidate the causes of stroke, has a role especially in young patients who present with cryptogenic stroke and no cardiovascular risk factors, as well as in the setting of a PFO associated with a deep venous thrombosis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): IGA LF UP, MH CZ - DRO

Cryptogenic stroke and extrasystolic arrythmia: is there any correlation?

Abstract Up to 45% of all ischemic strokes (IS) are cryptogenic. Purpose To reveal the possible reasons of cryptogenic IS. Methods We analyzed the cases of computer tomography verified IS in patients admitted the hospital during the period of 3 years. All these 268 patients had unidentified source of IS. We analyzed hemostasiograms, lipids levels, performed echocardiography, Doppler ultrasound of brachiocephalic arteries, 24-hours ECG monitoring and common carotid arteries sphygmography (SG). Results None of the patients had atrial fibrillation, hemodynamically significant stenoses of brachiocephalic arteries or hematological pathology associated with hypercoagulation. 234 (87.3%) patients had atherosclerotic plaques in carotid area bifurcation (in 36 (13.4%) – intima-media thickness was 1.1 mm, in 74 (27.6%)– stenosis &amp;lt;40%, in 124 (46.3%) had 40–69% stenosis in diameter). The internal carotid stenosis in diameter is calculated by ECST, NASCET and St. Mary's ratio criteria. To detect the type of the plaques we used Gray-Weale–Nicolaides ultrasound classification. In 39 (14.5%) was type I: uniformly echolucent plaque; in 88 (32.8%) type II: predominately echolucent plaque; in 71 (26.5%) type III: predominantly echogenic plaque, none had type IV: uniformly echogenic plaque or type V: heavy calcification. In 24-hours ECG monitoring and SG we revealed that most of the patients – 244 (91.0%) had extrasystolic arrhythmia which ventricular contraction of extrasystole appeared in the early phase of cardiocycle – before the transmitral blood flow peak. In 1st post-extrasystolic wave after such extrasystole we detected the growth of linear blood flow speed in carotid bifurcation (2.5 m/sec) and kinetic arteries parameters of SG (2.6 times). Conclusion The appearance of IS is higher in patients with extrasystolic arrhythmia appearing in the cardiocycle before the transmitral blood flow peak. In cryptogenic stroke, the reason of it can be the atherosclerotic plaque defragmentation with further embolism, caused by the additional mechanical trauma of increased hemodynamical and kinetic parameters of pulse wave of the 1st post-extrasystolic contraction. Funding Acknowledgement Type of funding sources: None.

Incremental prognostic value of stress CMR for cardiovascular risk stratification after a cryptogenic ischemic stroke

Abstract Background One-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest of CAD screening in patients with cryptogenic stroke is still debated. Purpose The aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke. Methods Between 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia. Results Of 542 patients (55.2% male, mean age 71.4±8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18% and 17% of patients, respectively. Using Kaplan-Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE (hazard ratio, HR: 8.43 [95% CI: 5.11–13.9]; HR: 7.87 [95% CI: 4.80–12.9]; respectively, p&amp;lt;0.001). In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE (HR: 8.08 [95% CI: 4.21–15.5]; HR: 6.65 [95% CI: 3.49–12.7]; respectively, p&amp;lt;0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.428; IDI=0.048). Conclusions In patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors. Funding Acknowledgement Type of funding sources: None.

Transcranial Doppler Screening for Patent Foramen Ovale Closure in Cryptogenic Strokes in Young: A Single Center Experience from South India.

Cryptogenic strokes are common in young adults. Patent foramen ovale (PFO) is an important cause of cryptogenic ischemic strokes. Transcranial Doppler (TCD) with bubble contrast is a noninvasive bedside tool in screening for PFO and other right to left shunt (R-L shunt). Percutaneous PFO closure in selected patients with a high risk for paradoxical emboli is beneficial. Data on PFO in young cryptogenic strokes from India are limited. To determine the utility of screening for R-L shunt using TCD in young patients with cryptogenic strokes and to identify clinical predictors of an R-L shunt. This was a hospital-based prospective study conducted between January 2013 and December 2019 in a tertiary hospital in South India. All consecutive patients with ischemic stroke and ages between 18 and 45 years were included. TCD with bubble contrast study was performed on all patients. Those who were TCD bubble contrast study positive and had features of an embolic stroke of undetermined source (ESUS) underwent transesophageal echocardiography (TEE) to confirm a PFO and to look for its high-risk features. Selected ESUS patients with PFO and associated high-risk features as identified on TEE underwent percutaneous PFO device closure. All patients were followed up in the stroke and cardiology clinics. During the study period, 6,197 patients with ischemic strokes were screened for eligibility of which 304 (4.9%) were between the age of 18 and 45 years. Of these, 300 patients with ischemic stroke in young underwent the TCD bubble contrast study. R-L shunt was found in 121 (40.3%) patients. Based on an extensive etiological evaluation, 72 patients were identified to have an ESUS and underwent TEE for confirming PFO. Of these, 65 patients had PFO, four were negative, and three were found to have extracardiac shunts. Based on clinical findings, imaging features, and high-risk features on TEE, 29 patients underwent PFO closure. Activity at the time of stroke onset equivalent to a Valsalva maneuver (p ≤ 0.01), isolated cortical infarction (p = 0.027), and posterior circulation involvement (p = 0.0135) were significantly associated with the presence of an R-L shunt. The patients who had a higher modified anatomical-functional risk of paradoxical embolism (AF-RoPE) score, a high-grade shunt on the TCD bubble contrast study had a longer length of the tunnel and had the presence of an interatrial septal aneurysm (p = 0.012) were referred for PFO device closure. R-L shunt is common in cryptogenic ischemic strokes in young. TCD with bubble contrast study is a noninvasive and feasible bedside tool to detect them. Applying the ESUS criteria in these cryptogenic strokes with a positive TCD bubble contrast study can be then used for selecting patients for more invasive tests like TEE. High-risk PFOs picked up with TEE can be then considered for PFO closure for secondary stroke prevention. The history of Valsalva maneuver-like activity (such as lifting heavy weights or straining) at the time of stroke onset can be a clinical predictor for the presence of an R-L shunt. In addition to isolated cortical infarction, the presence of posterior circulation infarct in ESUS can predict the presence of an R-L shunt.