High-risk Cardioembolic Sources Research Articles

High-Risk Embolic Sources on Cardiac Computed Tomography in Patients With Acute Ischemic Stroke: A Case-Control Study.

Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS. We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020. Cases were patients with a final diagnosis of AIS. Controls were patients with a stroke mimic (SMi). We excluded patients with a transient ischemic attack. Diagnoses were established by an adjudication committee. Cardiac radiologists assessed the presence of structural high-risk sources of cardioembolism according to predefined criteria. We used the Firth penalized likelihood method to perform a logistic regression, adjusted for age, sex, and history of myocardial infarction to determine the association between high-risk embolic sources and AIS. For the primary analysis, we excluded patients with a history of atrial fibrillation. In a secondary analysis, patients with known atrial fibrillation were included. Of 774 patients, we excluded 167 patients due to no written informed consent or the diagnosis of transient ischemic attack. Of 607 patients, 107 patients had known atrial fibrillation and were excluded from the primary analysis. Of 500 included patients, 375 had AIS (75%, median age 70, 61% male) and 125 SMi (25%, median age 69, 42% male). A high-risk cardioembolic source was found on CT in 32/375 (8.5%) patients with AIS and 0/125 (0%) patients with SMi (adjusted odds ratio, 23.8 [95% CI, 3.3-3032.5]). Cardiac thrombi were the most commonly observed abnormality, present in 23 (6.1%) patients with AIS and 0 (0%) patients with SMi. A high-risk source of cardioembolism was detected on cardiac CT more frequently in patients with AIS than in patients with SMi. These data substantiate the clinical relevance of cardioembolic sources detected on acute cardiac CT in patients with ischemic stroke.

Abstract WP283: Association of High-Risk Cardioembolic Sources on Cardiac CT With Acute Ischemic Stroke: A Case-Control Study

Background: Cardiac CT is increasingly used to detect a source of cardioembolism in stroke patients. We assessed the association between sources of embolism on cardiac CT, which were predefined as high-risk, and acute ischemic stroke. Methods: We analyzed data from Mind the Heart, a prospective, single-center, observational cohort study, and included consecutive patients with a suspected stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Cases were patients with a final diagnosis of acute ischemic stroke (AIS), established by an adjudication committee. Controls were patients with stroke mimics (SMi). We excluded patients with a transient ischemic attack. Cardiovascular radiologists diagnosed structural high-risk sources of cardioembolism on cardiac CT according to predefined criteria. High-risk sources on cardiac CT were: cardiac thrombi, signs of endocarditis, recent myocardial infarction, prosthetic valve abnormalities, atrial myxomata and signs of rheumatic valvular disease. We used logistic regression, adjusting for age, sex, history of atrial fibrillation, and history of myocardial infarction. Results: Of 607 included patients, 452 had AIS (74%, median age 72, 59% male) and 155 had a SMi (26%, median age 70, 46% male). Diagnoses in the SMi group were: seizures (45/155, 29%) peripheral vestibulopathy (22/155, 14%), functional neurologic symptoms (16/155, 10%), benign headache disorder (8/155, 5%), intoxication (7/155, 5%), and other diagnoses (57/155, 37%). Cardiac CT detected a structural high-risk cardioembolic source in 52/452 AIS patients (12%) and in 5/155 SMi patients (3%, three patients with seizures, one with peripheral vestibulopathy and one with traumatic brain injury, aOR: 4.1, 95%CI 1.7-12.1). Cardiac thrombi were the most commonly observed high-risk sources of embolism and were detected in 38 (8%) AIS patients and in 2 (1%) SMi patients (aOR 7.0, 95%CI 2.1-43.9). Discussion and conclusion: A high-risk source of cardioembolism was detected on cardiac CT four times more often in patients with acute ischemic stroke than in patients with a stroke mimic. These data substantiate the clinical relevance of using acute CT to search for sources of cardioembolism in ischemic stroke patients.

Cardiac CT for intra-cardiac thrombus detection in embolic stroke of undetermined source (ESUS).

Embolic stroke of undetermined source (ESUS) is a common medical challenge regarding secondary prevention strategy. Cardiac imaging is the cornerstone of embolic stroke workup, in an effort to diagnose high risk cardio-embolic sources. Cardiac computed tomography angiography (CCTA) is an emerging imaging modality with high diagnostic performance for intra-cardiac thrombus detection. The yield of CCTA implementation in addition to standard care in ESUS workup is unknown. Thus, the aim of this study was to assess the utility of CCTA in detecting intra-cardiac thrombi in the routine ESUS workup. This is a retrospective observational analysis of ESUS cases managed in vascular neurology unit between 2019 and 2021. Within this ESUS registry, consecutive patients undergoing CCTA were included and carefully analyzed. During the study period 1066 Ischemic stroke (IS) cases were treated and evaluated. 266/1066 (25%) met ESUS criteria and 129/266 (48%) underwent CCTA. Intra-cardiac thrombus was detected by CCTA in 22/129 (17%; 95% CI, 11.5%-23.5%) patients: left ventricular thrombus (LVT) in 13 (10.1%) patients, left atrial appendage (LAA) thrombus in 8 (6.2%) patients, and left atrial (LA) thrombus in 1 (0.8%) patient. Only 5/22 (23%) of these thrombi were suspected, but could not be confirmed, in trans-thoracic echocardiogram (TTE). Among CCTA-undergoing patients, 27/129 (21%; 95% CI, 14%-28%) were found to have an indication (including pulmonary embolism) for commencing anticoagulation (AC) treatment, rather than anti-platelets. In favor of CCTA implementation, 22/266 (8.2%; 95% CI, 4.9%-11.5%) patients within the entire ESUS cohort were diagnosed with intra-cardiac thrombus, otherwise missed. CCTA improves the detection of intra-cardiac thrombi in addition to standard care in ESUS patients. The implementation of CCTA in routine ESUS workup can change secondary prevention strategy in a considerable proportion of patients.

Relationship between the Angle of the Posterior Inferior Cerebellar Artery and Cardioembolic Stroke

BackgroundIn patients with unilateral posterior inferior cerebellar artery (PICA) territory infarction, the absence of relevant vessel stenosis may make it difficult to determine the etiology of the infarction. The incidence of cardioembolic (CE) infarction and the factors associated with infarction in such patients remains largely unknown. We hypothesized that the PICA angle would affect the flow direction of embolic sources. Thus, we analyzed the association between high-risk CE sources and the PICA angle. MethodsPatients with an isolated unilateral PICA territory infarction without relevant vessel stenosis who were admitted between 2014 and 2017 were included from the Korea University Stroke Registry, which includes data from 3 university hospitals. We classified patients according to the presence of CE sources. For each case, we measured the angle between the vertebral artery (VA) and the proximal PICA. ResultsIn all, 71 patients met the final study entry criteria. Multivariable analysis showed that the PICA angle was independently associated with the risk of a CE source. The optimal cut-off value using Youden's index was 89°. We classified the PICA shape based on the optimal cut-off value. A CE source was identified in 83.3% of cases in which the PICA angle exceeded 89°. ConclusionsThe angle between the PICA and VA was an independent predictor of unilateral PICA stroke with high-risk CE sources without relevant artery stenosis, suggesting that an angle greater than 89° could be a new image marker for determining the stroke subtype.

Free fatty acid as a determinant of ischemic lesion volume in nonarterial-origin embolic stroke

GoalsThis study aimed to determine whether the plasma levels of free fatty acid (FFA) are associated with ischemic lesion characteristics in nonarterial-origin embolic stroke. Materials and methodsWe prospectively recruited 254 patients with acute cerebral infarction caused by cardioembolic stroke (CES, n=121) or with embolic stroke of undetermined source (ESUS, n=133). Plasma levels of FFA were measured during the acute stage (median of 2days after stroke onset). Acute ischemic lesions on diffusion-weighted imaging were measured in terms of size, composition, and pattern. Transthoracic echocardiography parameters were evaluated in all patients. FindingsPlasma levels of FAA were not different in CES and ESUS patients (mEq/L, 0.78±0.52 vs. 0.67±0.61, P=0.120). Echocardiography parameters, including left atrium volume index and E/e', were higher, and the ischemic lesion volume was larger in patients with CES than in those with ESUS. The ischemic lesion volume and the proportion of patients with mixed (small and large) and large cortical lesions increased with FFA quartile in both CES and ESUS groups. In a multivariable analysis, FFA level (coefficient, 5.249; standard error, 3.447; P=0.001), atrial fibrillation (coefficient, 7.673; standard error, 1.855; P<0.001), and fasting glucose (coefficient, 0.104; standard error, 0.023; P<0.001) were associated with ischemic lesion volume in nonarterial-origin embolic stroke. ConclusionElevated plasma FFA levels are associated with larger ischemic lesion volumes and a higher prevalence of large cortical infarcts in patients with nonarterial-origin embolic stroke regardless of the presence of a high-risk cardioembolic source.

Left ventricular wall motion abnormalities are associated with stroke recurrence.

To investigate the role of left ventricular wall motion abnormalities (LVWMA), unrelated to high-risk cardioembolic conditions, in stroke recurrence. This study included consecutive acute ischemic stroke patients. Transthoracic echocardiography was performed as a routine evaluation for stroke patients. The outcomes were the time to recurrent any stroke and ischemic stroke. Among 4,316 acute ischemic stroke patients, 430 had LVWMA without high-risk cardioembolic sources. The median observation periods of patients at risk of any stroke and ischemic stroke were 24.5 and 24.7 months. During the follow-up, any stroke and ischemic stroke recurrence were observed in 310 (7.2%) and 250 (5.8%) patients. LVWMA were associated with outcomes after adjustment for traditional cardiovascular risk factors, laboratory and imaging variables, and therapeutic interventions (hazard ratio [HR] 1.707, 95% confidence interval [CI] 1.262-2.310 for any stroke; HR 1.709, 95% CI 1.222-2.390 for ischemic stroke). Moreover, LVWMA could still be considered as independent risk factors after correction for covariates that were significantly associated with outcomes in univariable regression (HR 1.747, 95% CI 1.292-2.364 for any stroke; HR 1.704, 95% CI 1.219-2.382 for ischemic stroke). There were no significant interactions between LVWMA and outcomes between the subgroups except for the statin treatment subgroup. This study suggests that LVWMA, even when unassociated with high-risk cardioembolic sources, could be an independent predictor for stroke recurrence in patients with ischemic stroke.

Lenticulostriate Artery Involvement is Predictive of Poor Outcomes in Superficial Middle Cerebral Artery Territory Infarction.

PurposePatients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement.Materials and MethodsConsecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group.ResultsOf the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p<0.001) and larger infarct in the superficial MCA territory (40.8±62.6 cm3 vs. 10.8±21.8 cm3, p<0.001) than the SM group. A poor functional outcome (mRS >2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246) and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than the SM group. In multivariate analyses, LSA involvement was an independent predictor of poor functional outcomes and stroke mortality.ConclusionLSA territory involvement is predictive of poor long-term outcomes in patients with superficial MCA territory infarction.

Nonatheroscleotic Isolated Middle Cerebral Artery Disease May Be Early Manifestation of Moyamoya Disease.

Middle cerebral artery steno-occlusive disease (MCAD) is not an uncommon cause of ischemic stroke in young Asians. Aside from atherosclerosis, the pathogenesis of MCAD include various nonatherosclerotic vasculopathies, most of which are yet to be defined. This study investigated the pathogenesis of symptomatic isolated MCAD in young Asian patients using high-resolution magnetic resonance imaging (HR-MRI) and mutation analysis of RNF213. Patients aged <60 years with stroke or transient ischemic attack caused by MCAD were prospectively enrolled. Patients with a confirmed diagnosis of moyamoya disease, dissection, and vasculitis; with significant steno-occlusion in cerebral arteries other than the MCA; or with high-risk cardioembolic source were excluded. Using high-resolution MRI, patients were classified into an atherosclerosis group and a nonatherosclerosis group. Eighty-one patients were enrolled, 45 (56.6%) in the atherosclerosis and 36 (44.4%) in the nonatherosclerosis group. The nonatherosclerosis group was significantly younger (P=0.013), had a smaller number of vascular risk factors (P=0.001), showed a lower homocysteine level (P<0.001), thinner intima-media thickness (P=0.006), and had more frequent heterozygotes at RNF213 (P=0.045) than the atherosclerosis group. Diffusion-weighted image lesion pattern showed no significant differences in assumed stroke mechanisms between the 2 groups. Nonatherosclerotic pathogenesis are common in young Asians with symptomatic isolated MCAD. Clinical findings, high-resolution MRI features, and results of RNF213 mutation analysis suggest that moyamoya disease is responsible etiologically for a significant portion of nonatherosclerotic lesions. Symptomatic isolated MCAD may be an early manifestation of moyamoya disease in young Asian adults.

Infarct Pattern and Clinical Outcome in Acute Ischemic Stroke Following Middle Cerebral Artery Occlusion

Background: Cerebral arterial occlusion develops via two distinct mechanisms: thrombosis and embolism. Discrimination between thrombosis and embolism is an important aspect needed for further determining the etiology of stroke in a patient. This study evaluated infarct patterns and outcomes in acute stroke patients with relevant artery occlusions, focusing on features specific to each occlusion mechanism. Methods: Acute ischemic stroke patients who were consecutively registered in a tertiary hospital between 2002 and 2010 with infarctions in the middle cerebral artery territory and a corresponding M1 occlusion confirmed by magnetic resonance angiography, computed tomography angiography, or conventional angiography were enrolled. Patients with a high-risk cardioembolic source, clear recanalization, concurrent infarct in an arterial territory other than the occlusion site, or no prior occlusion in a previous imaging within 1 month were assigned to the embolic occlusion group, and the remaining patients were assigned to the thrombotic occlusion group. The infarct pattern was categorized into seven groups: scattered, territorial, lenticulostriatal, scattered-territorial, scattered-lenticulostriatal, territorial-lenticulostriatal, and scattered-territorial-lenticulostriatal. Data of stroke recurrence and mortality were collected through electronic medical record and the National Vital Statistics System. Results: Of 114 patients, 54 (47.4%) were classified as having an embolic occlusion. When infarct patterns were compared between the groups, any-scattered infarct pattern was more common in the thrombotic occlusion group (71.2% vs. 40.7%, p = 0.002), and any-territorial infarct pattern was more prevalent in the embolic occlusion group (55.6% vs. 28.8%, p = 0.005). In addition, scattered-without-territorial pattern was higher in the thrombotic occlusion group (OR: 0.25; CI: 0.11-0.57; p = 0.001). Any-territorial infarct pattern was also related to initial stroke severity (NIHSS on admission, OR: 400.98; CI: 2.94-54,741.32; p = 0.017) and poor functional outcome (modified Rankin Scale score ≥4) at discharge (OR: 14.40; CI: 1.37-152.00; p = 0.027) independent of other parameters. However, no association was found between stroke recurrence, mortality and occlusion mechanism. Conclusion: This study shows that specific infarct patterns are related to cerebral arterial occlusion mechanisms and are correlated with functional outcome. Otherwise, the results of our study indicates that infarct patterns on DWI might be a clue for determining ischemic stroke etiology on patients with major cerebral artery occlusion.

Feasibility and Clinical Utility of Transesophageal Echocardiography in the Acute Phase of Cerebral Ischemia

We evaluated the feasibility and clinical utility of transesophageal echocardiography (TEE) in the early management of ischemic stroke. TEE was performed in consecutive patients with acute cerebral ischemia within 48 hours of symptoms onset. The data were analyzed by age (<55 vs ≥55 years), and the baseline stroke etiology was classified (determined vs undetermined). TEE was feasible in 660 (61%) of 1,080 patients. Left atrial abnormalities and complicated aortic plaques prevailed in older patients (p <0.05), irrespective of the stroke etiology. A patent foramen ovale prevailed in younger patients (p <0.05) but even in older patients was present in 13% of the determined and 31% of the undetermined stroke subgroups. Overall, high-risk and potentially high-risk cardioembolic sources were detected in 47% of the patients, and stroke etiology was consequently reviewed: 40% of the baseline undetermined strokes were reclassified as cardioembolic, and 29% of lacunar, 42% of large artery, and 30% of other determined-cause strokes were reclassified as concurrent etiology. Subsequently, according to the current guidelines, 12% of patients were reassigned from antiplatelet to anticoagulant therapy and 17% of patients were treated with high-dose statins; overall, secondary prevention treatment was modified in 26% of patients. In conclusion, TEE was feasible in about 2/3 of the patients investigated within 48 hours of the index event, contributed to stroke classification in 1/3 of cases, and guided secondary prevention therapy in 1/4 of patients. Therefore, TEE is useful for defining patients' risk profile for stroke recurrence.

Safety and outcome after thrombolytic treatment in ischemic stroke patients with high-risk cardioembolic sources and prior subtherapeutic warfarin use

Background Hemorrhage is a major complication of thrombolytic treatment. Concerns have been raised about the risk of hemorrhage in patients having received warfarin. Therefore, different indications for thrombolytic treatment are in use for stroke patients on warfarin. However, it remains uncertain whether the prior warfarin use actually increases their risk of bleeding in patients treated with thrombolysis. Methods This study included 179 consecutive patients who had high-risk cardioembolic sources and received thrombolytic treatment. Patients were treated with intravenous thrombolytic agents, or underwent intraarterial thrombolysis if their international normalized ratio (INR) was ≤ 1.7. We compared the frequency of bleeding complications between patients with prior warfarin use and those without. We also investigated whether there were differences in functional outcome and recanalization rates between them. Results A prior warfarin use was present in 28 patients (15.6%). Although INR levels were higher in the prior warfarin group, the frequency of bleeding complications was not different between patients who received prior warfarin and those who did not. No differences were observed in patients with or without prior warfarin use, for successful recanalization rate (Thrombolysis in Myocardial Infarction grade 2 or 3), mortality, or modified Rankin score (≤ 2) at 3 months. Conclusions Thrombolytic therapy for patients who previously received warfarin and had an INR ≤ 1.7 did not affect bleeding risk, clinical outcome, or recanalization rate. Our data suggest that patients with a history of prior warfarin use may be safely treated with thrombolytic agents when their INR levels are low.

Angioplasty and stenting of symptomatic and asymptomatic vertebral artery stenosis: to treat or not to treat

Comprehensive indications for treatment of symptomatic vertebral stenosis remain unavailable. Even less is known about endovascular treatment of asymptomatic cases. We treated symptomatic and asymptomatic vertebral ostium stenosis with angioplasty and stenting and investigated the long term outcome. Consecutive patients with two different indications were included. Group 1 (G1) had symptomatic >50% stenosis. Group 2 (G2) had asymptomatic >50% stenosis and severe lesions of anterior circulation and were expected to benefit from additional cerebral blood supply. Twenty nine vertebral origin stenoses in 28 patients (75% men, mean age 64 +/- 9 years) were treated. There were 16 G1 and 13 G2 cases. Technical success rate was 100%. Immediate neurological complications rate was 3.4% (one G1 patient with vertebral TIA due to release of emboli). Two further strokes were seen during follow up (32 +/- 24 months): vertebrobasilar stroke in a G2 patient with permeable stent in V1 segment, new ipsilateral V3 occlusion and high-risk cardioembolic source, and carotid stroke in a G1 patient who had had ipsilateral carotid stenting. There were no deaths of any cause. Asymptomatic restenosis was observed in one out of 19 patients from both groups who underwent a follow up angiography. Angioplasty and stenting appears to be technically feasible and safe in asymptomatic and symptomatic vertebral stenosis. More studies are needed in order to clarify its role in primary and secondary prevention of vertebrobasilar stroke. High risk anterior circulation lesions should be taken into account as a possible indication in patients with asymptomatic vertebral stenosis.

High prevalence of unrecognized cerebral infarcts in first-ever stroke patients with cardioembolic sources

With magnetic resonance imaging (MRI) analysis, we investigated the prevalence, clinical significance, and factors related to the presence of unrecognized cerebral infarcts in patients with first-ever ischaemic stroke. We consecutively included patients who were admitted with first-ever stroke. Unrecognized cerebral infarct was defined as an ischaemic infarction or primary intracerebral hemorrhage on MRI irrelevant to the index stroke, without acute lesions on diffusion-weighted image. Of the total 203 patients, 78 (39.4%) patients were observed as having unrecognized cerebral infarct. Patients with high-risk cardioembolic sources (e.g., atrial fibrillation) more frequently had unrecognized stroke than those without (P = 0.008, 21/36 [58.3%] vs. 57/167 [34.1%]). On univariate analysis, male sex (P = 0.027) and cardioembolic source (P = 0.008) were associated with the presence of unrecognized cerebral infarcts. After adjustment for gender, age and risk factors, the presence of cardioembolic sources independently increased the risk of unrecognized cerebral infarct (P = 0.002, odds ratio 3.56, 95% confidence interval 1.58-8.02). Regarding clinical outcome at 3 months, the presence of unrecognized cerebral infarct was not associated with the poor clinical outcome. In our study, the presence of cardioembolic sources was an independent risk factor for the unrecognized cerebral infarct in patients with first-ever stroke.

The role of warfarin and aspirin in secondary prevention of stroke.

Antithrombotic therapy plays a central role in secondary prevention after ischemic stroke and transient ischemic attack. The choice among warfarin, aspirin, and other antiplatelet agents, however, depends on the cause of stroke and other individual patient characteristics. The use of warfarin anticoagulation in patients with atrial fibrillation and ischemic stroke has demonstrated robust reductions in risk of recurrent events, comparable with those achieved in primary prevention. Warfarin may also be recommended for patients with other high-risk cardioembolic sources of stroke. The role of warfarin in noncardioembolic ischemic stroke is more controversial. The Warfarin Aspirin Recurrent Stroke Study found no evidence of superiority of warfarin over aspirin in stroke patients overall, nor in any major stroke subtype, including those patients with patent foramen ovale. In post-hoc analyses, there was some evidence of benefit with warfarin in patients with cryptogenic stroke without hypertension. Risks of major bleeding did not differ significantly between warfarin and aspirin groups. For most patients with noncardioembolic strokes, therefore, antiplatelet therapy is the preferred option, although clinician experience still dictates practice in individual situations. Newer antiplatelet agents, and the combination of novel agents with aspirin, are also finding a role in stroke prevention as clinical trial data become available.