Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy.

INTRODUCTION: Based on recent trials regarding the early time window, omitting intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in eligible patients seems unjustified. Whether this also concerns the extended time window, 4.5 to 9 h from last seen well, is yet unclear. PATIENTS AND METHODS: All consecutive patients treated with IVT, EVT, or IVT plus EVT in the extended time window at Helsinki University Hospital (HUS) between 1/2021 and 12/2022 were compared with matched controls treated in the early time window between 1/2016 and 12/2020. Regression analysis was applied on functional outcome at 90 days, evaluated on modified Rankin Scale (mRS), and on the occurrence of symptomatic intracerebral hemorrhage (sICH), adjusted for potential confounders. RESULTS: Altogether 134 patients and 134 matching controls were included. Functional outcomes did not significantly differ between the extended versus early time window. Among patients with IVT plus EVT, the adjusted odds ratio (aOR) for a favorable outcome shift on mRS was 1.15, 95% confidence interval (CI) 0.54-2.43. Although sICH occurred more frequently (2.2% versus 3.0%) in the extended time window, regression analysis did not show a significant difference, aOR 0.96, 95% CI 0.14-6.87. DISCUSSION AND CONCLUSION: We found no significant differences in the functional or safety outcomes between the extended versus early time window among patients with either IVT, EVT, or IVT plus EVT. There were no signals indicating, that IVT or EVT should be avoided in eligible patients in the extended time window which aligns with the current clinical treatment guidelines of HUS.

Association of admission plasma glucose level and cerebral computed tomographic perfusion deficit volumes.

INTRODUCTION: Hyperglycemia in acute ischemic stroke (AIS) is frequent and associated with worse outcome. Yet, strict glycemic control in AIS patients has failed to yield beneficial outcome. So far, the underlying pathophysiological mechanisms of admission hyperglycemia in AIS have remained not fully understood. We aimed to evaluate the yet equivocal association of hyperglycemia with computed tomographic perfusion (CTP) deficit volumes. PATIENTS AND METHODS: We included 832 consecutive AIS and transient ischemic attack (TIA) patients who underwent CTP as a part of screening for recanalization treatment (stroke code) between 3/2018 and 10/2020, from the prospective cohort of Helsinki Stroke Quality Registry. Associations of admission glucose level (AGL) and CTP deficit volumes, namely ischemic core, defined as relative cerebral blood flow <30%, and hypoperfusion lesions Time-to-maximum (Tmax) >6 s and Tmax >10s, as determined with RAPID® software, were analyzed with a linear regression model adjusted for age, sex, C-reactive protein, and time from symptom onset to imaging. RESULTS: AGL median was 6.8 mmol/L (interquartile range 5.9-8.0 mmol/L), and 222 (27%) patients were hyperglycemic (glucose >7.8 mmol/L) on admission. In non-diabetic patients (643 [77%]), AGL was significantly associated with volume of Tmax. >6 s (regression coefficient [RC] 4.8, 95% confidence interval [CI] 0.49-9.1), of Tmax >10s (RC 4.6, 95% CI 1.2-8.1), and of ischemic core (RC 2.6, 95% CI 0.64-4.6). No significant associations were shown in diabetic patients. CONCLUSION: Admission hyperglycemia appears to be associated with both larger volume of hypoperfusion lesions and of ischemic core in non-diabetic stroke code patients with AIS and TIA.

Comparative analysis of core and perfusion lesion volumes between commercially available computed tomography perfusion software.

Introduction: Computed tomography perfusion (CTP) imaging has become an important tool in evaluating acute recanalization treatment candidates. Large clinical trials have successfully used RAPID automated imaging analysis software for quantifying ischemic core and penumbra, yet other commercially available software vendors are also on the market. We evaluated the possible difference in ischemic core and perfusion lesion volumes and the agreement rate of target mismatch between OLEA, MIStar, and Syngo.Via versus RAPID software in acute recanalization treatment candidates. Patients and methods: All consecutive stroke-code patients with baseline CTP RAPID imaging at Helsinki University Hospital during 8/2018-9/2021 were included. Ischemic core was defined as cerebral blood flow <30% than the contralateral hemisphere and within the area of delay time (DT) >3s with MIStar. Perfusion lesion volume was defined as DT > 3 s (MIStar) and Tmax > 6 s with all other software. A perfusion mismatch ratio of ⩾1.8, a perfusion lesion volume of ⩾15 mL, and ischemic core <70 mL was defined as target mismatch. The mean pairwise differences of the core and perfusion lesion volumes between software were calculated using the Bland-Altman method and the agreement of target mismatch between software using the Pearson correlation. Results: A total of 1606 patients had RAPID perfusion maps, 1222 of which had MIStar, 596 patients had OLEA, and 349 patients had Syngo.Via perfusion maps available. Each software was compared with simultaneously analyzed RAPID software. MIStar showed the smallest core difference compared with RAPID (-2 mL, confidence interval (CI) from -26 to 22), followed by OLEA (2 mL, CI from -33 to 38). Perfusion lesion volume differed least with MIStar (4 mL, CI from -62 to 71) in comparison with RAPID, followed by Syngo.Via (6 mL, CI from -94 to 106). MIStar had the best agreement rate with target mismatch of RAPID followed by OLEA and Syngo.Via. Discussion and conclusion: Comparison of RAPID with three other automated imaging analysis software showed variance in ischemic core and perfusion lesion volumes and in target mismatch.

Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis.

Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF tends to be more severe than with other etiology of IS and patients with treated AF have reported to experience worse outcomes after endovascular treatment compared with patients without AF. As cardioembolism accounts for more than a fifth of ISs and the risk of future stroke can be mitigated with effective anticoagulation, which has been shown to be effective and safe in patients with paroxysmal or sustained AF, the screening of patients with cryptogenic IS (CIS) for AF is paramount. Embolic stroke of undetermined source (ESUS) is a subtype of CIS with a high likelihood of cardioembolism. The European Stroke Organization and European Society of Cardiology guidelines recommend at least 72 h of screening when AF is suspected. The longer the screening and the earlier the time point after acute IS, the more likely the AF paroxysm is found. Several methods are available for short-term screening of AF, including in-hospital monitoring and wearable electrocardiogram recorders for home monitoring. Implantable loop monitors provide an effective long-term method to screen patients with high risk of AF after IS and artificial intelligence and convolutional neural networks may enhance the efficacy of AF screening in the future. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists in both primary and secondary prevention of IS in AF patients. Recent data from the randomized controlled trials (RCT) also suggest that early initiation of DOAC treatment after acute IS is safe compared to later initiation. Anticoagulation treatment may still predispose for intracranial bleeding, particularly among patients with prior cerebrovascular events. Left atrial appendix closure offers an optional treatment choice for patients with prior intracranial hemorrhage and may offer an alternative to oral anticoagulation even for patients with IS, but these indications await validation in ongoing RCTs. There are still controversies related to the association of found AF paroxysms in CIS patients with prolonged screening, pertaining to the optimal duration of screening and screening strategies with prolonged monitoring techniques in patients with ESUS. In this review, we summarize the current knowledge of epidemiology, screening, and prognosis in AF patients with stroke.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0-3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models. RESULTS: Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features. CONCLUSION: Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

Is infarct core growth linear? Infarct volume estimation by computed tomography perfusion imaging.

OBJECTIVES: Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/- 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. MATERIALS AND METHODS: All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore ) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). RESULTS: Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p > .05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. CONCLUSIONS: Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.

Prognostic Value of 99mTc-HMDP Scintigraphy in Elderly Patients With Chronic Heart Failure.

BACKGROUND: This study evaluated the prevalence and prognostic significance of cardiac transthyretin amyloidosis (ATTR) diagnosed using 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy in an elderly heart failure population. METHODS: This retrospective study included 335 patients aged >70 years with heart failure and who underwent 99mTc-HMDP scintigraphy due to non-cardiac reasons in three imaging centres in Finland (Kymenlaakso Central Hospital, Jorvi Central Hospital, and Meilahti University Hospital). A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of ≥1.30 were considered positive for cardiac ATTR. The overall and cardiovascular mortality were obtained from the national statistical service (Statistics Finland). RESULTS: There were 234 deaths, of which 70 were classified as being due to cardiovascular causes during a median follow-up of 1 (1-3) year. Transthyretin amyloidosis was diagnosed in 22 patients (6.6%) using visual analysis and 17 patients using the H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs 80±5 yrs; p=0.002) and had higher N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels (1,451 [813-3,799] vs 6,192 [2,030-8,833] ng/L; p=0.02). Age, bone metastases, and glomerular filtration rate were independent predictors of overall mortality in multivariable analysis. Age, glomerular filtration rate, ≥grade 2 visual cardiac uptake, and H/CL ratio were independent predictors of cardiovascular mortality. CONCLUSIONS: Cardiac uptake suggestive of ATTR was found in 5% of elderly patients with chronic heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was independently associated with cardiovascular mortality.

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. METHODS: The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. RESULTS: There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. CONCLUSIONS: A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

Is the weekend effect true in acute stroke patients at tertiary stroke center?

BACKGROUND: There is contradicting evidence on the outcome of emergency patients treated during weekends versus weekdays. We studied if outcome of ischemic stroke patients receiving intravenous thrombolysis (IVT) differs according to the treatment time. METHODS: Our retrospective study included consecutive patients receiving IVT within 4.5 h of stroke onset between June 1995 and December 2018 at the Helsinki University Hospital. The patients were compared based on the treatment initiation either during weekdays (Monday to Friday) or weekend (Saturday and Sunday). The primary outcome was 3-month mortality and secondary outcomes comprised 3-month modified Rankin Scale (mRS) and incidence of symptomatic intracerebral hemorrhage (sICH). Additional analyses studied the effect of IVT treatment according to non-office hours, time of day, and season. RESULTS: Of the 3980 IVT-treated patients, 28.0% received treatment during weekends. Mortality was similar after weekend (10.0%) and weekday (10.6%) admissions in the multivariable regression analysis (OR 0.78; 95% CI 0.59-1.03). Neither 3-month mRS (OR 0.98; 95% CI 0.86-1.12), nor the occurrence of sICH (4.2% vs 4.6%; OR 0.87; 95% CI 0.60-1.26) differed between the groups. No outcome difference was observed between the office vs non-office hours or by the time of day. However, odds for worse outcome were higher during autumn (OR 1.19; 95% CI 1.04-1.35) and winter (OR 1.15; 95% CI 1.01-1.30). CONCLUSION: We did not discover any weekend effect for IVT-treated stroke patients. This confirms that with standardized procedures, an equal quality of care can be provided to patients requiring urgent treatment irrespective of time.

Comparison of automated infarct core volume measures between non-contrast computed tomography and perfusion imaging in acute stroke code patients evaluated for potential endovascular treatment.

INTRODUCTION: Patients with small core infarction and salvageable penumbra are likely to benefit from endovascular treatment (EVT). As computed tomography perfusion imaging (CTP) is not always available 24/7 for patient selection, many patients are transferred to stroke centers for CTP. We compared automatically measured infarct core volume (NCCTcore) from the non-contrast computed tomography (NCCT) with ischemic core volume (CTPcore) from CTP and the outcome of EVT to clarify if NCCTcore measurement alone is sufficient to identify patients that benefit from transfer to stroke centers for EVT. PATIENTS AND METHODS: We included all consecutive stroke-code patients imaged with both NCCT and CTP at Helsinki University Hospital during 9/2016-01/2018. NCCTcore and CTPcore volumes were automatically calculated from the acute NCCT images. Follow-up infarct volume (FIV) was measured from 24 h follow-up NCCT to evaluate efficacy of EVT. To study whether NCCTcore could be used to identify patients eligible to EVT, we sub-grouped patients based on NCCTcore volumes (>50 mL and ≥ 70 mL). RESULTS: Out of 1743 patients, baseline NCCTcore, CTPcore and follow-up NCCT was available for 288 patients. Median time from symptom onset to baseline imaging was 74 min (IQR 52-118), and time to follow-up imaging 24.15 h (22.25-26.33). Baseline NCCTcore was 20 mL (10-42), CTPcore 4 mL (0-16), and FIV 5 mL (1-49). Out of 288 patients, 23 had NCCTcore ≥ 70 mL and 26 had CTPcore ≥ 70 mL. NCCTcore and CTPcore performed similarly well in predicting large FIV (≥70 ml). CONCLUSION: NCCTcore is a promising tool to identify patients that are not eligible to EVT due to large ischemic cores at baseline imaging.