24-hour Imaging Research Articles

Improved Door-to-Needle Time After Implementation of Tenecteplase as the Preferred Thrombolytic for Acute Ischemic Stroke at a Large Community Teaching Hospital Emergency Department

Background: Acute ischemic stroke is a leading cause of death and long-term disability. To improve patient outcomes, timely restoration of blood flow to the ischemic brain tissue is vital. One reperfusion strategy includes the administration of thrombolytics. Historically, alteplase has been the thrombolytic of choice for acute ischemic stroke; however, given recent safety and efficacy data, tenecteplase has gained popularity due to its optimal pharmacokinetic profile. Objectives: This study compares outcomes between adult patients with acute ischemic stroke who received tenecteplase as the preferred thrombolytic versus alteplase. Methods: This was a single center, retrospective cohort study that included adult patients who received intravenous thrombolytic therapy, either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg, for acute ischemic stroke from May 2021 to December 2023. The primary outcome was door-to-needle time. Secondary safety outcomes included the incidence of symptomatic intracerebral hemorrhage (ICH), any ICH on 24-hour follow-up imaging, major extracranial bleeding, and angioedema. Secondary efficacy outcomes included discharge with a favorable neurological outcome, discharge disposition, ICU length of stay, and overall length of stay. Secondary stroke metric times evaluated include door-to-computed tomography (CT) time, CT-to-needle time, neurologist notification-to-needle time, and thrombolytic decision-to-needle time. Results: Fifty patients were included in the alteplase group and 50 patients were included in the tenecteplase group. The primary outcome, door-to-needle time, was significantly shorter in the tenecteplase group (36 vs 30 minutes, P = .006). There were no statistically significant differences found in the secondary safety and efficacy outcomes. Patients who received tenecteplase experienced significantly faster CT-to-needle times (17 vs 11 minutes, P = .006), neurologist notification-to-needle times (32 vs 25 minutes, P = .001), and thrombolytic decision-to-needle times (9 vs 5 minutes, P < .001). Conclusions: In this retrospective, observational study, there was a statistically significant decrease in door-to-needle time with tenecteplase compared to alteplase. No significant differences in secondary safety and efficacy outcomes were observed.

Comparison of Perfusion Imaging Definitions of the No-Reflow Phenomenon after Thrombectomy-What Is the Best Perfusion Imaging Definition?

We performed an external validation of 4 existing published definitions of no-reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c-3) angiographic reperfusion who underwent 24-hour perfusion imaging from 2 international randomized controlled trials (EXTEND-IA TNK part-1 and 2) and a multicenter prospective observational study. Receiver-operating-characteristic and Bayesian-information-criterion (BIC) analyses were performed with the outcome variable being dependent-or-dead at 90-days (modified Rankin Score [mRS] ≥3). Of 131 patients analyzed, the prevalence of no-reflow significantly varied between definitions (0.8-22.1%; p < 0.001). There was poor agreement between definitions (kappa 5/6 comparisons <0.212). Among patients with no-reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (p = 0.006), cerebral blood volume (CBV) (p < 0.001), and mean-transit-time (MTT) (p = 0.005). No-reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of >15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = -8.105) and demonstrated an association between no-reflow and clinical outcome among patients with eTICI3 reperfusion. Existing imaging definitions of no-reflow varied significantly in prevalence and post-treatment perfusion imaging profile, potentially explaining the variable prevalence of no-reflow reported in literature. The definition of >15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with <Thrombolysis in Cerebral Infarction 3 reperfusion after thrombectomy. The model's performance was evaluated with discrimination, calibration accuracy, and clinical decision curves. We included 371 patients (38% with PPD). The externally validated model had good discrimination (C-statistic 0.81, 95% CI 0.77-0.86) and adequate calibration (intercept 0.25, 95% CI 0.21-0.29 and slope 0.98, 95% CI 0.90-1.12). Across a wide range of probability thresholds (i.e., depending on the physicians' preferences on how the model should be used), the model shows net benefit on clinical decision curves, informing physicians on the likelihood of PPD. If a physician's attitude toward false-positive and false-negative ratings is equal, the model would reduce 13 in 100 unnecessary interventions by correctly predicting complete delayed reperfusion, without missing a patient with PPD. The externally validated model had adequate predictive accuracy and discrimination. Depending on the acceptable threshold probability, the model accurately predicts persistent incomplete reperfusion and may advise physicians whether additional reperfusion attempts should be performed.

Association between CT Perfusion Parameters and Hemorrhagic Transformation after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Prevalence of "Ghost Infarct Core" after Endovascular Thrombectomy.

Baseline CTP sometimes overestimates the size of the infarct core ("ghost core" phenomenon). We investigated how often CTP overestimates infarct core compared with 24-hour imaging, and aimed to characterize the patient subgroup in whom a ghost core is most likely to occur. Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergoing endovascular treatment were randomized to intravenous nerinetide or placebo. Patients with available baseline CTP and 24-hour follow-up imaging were included in the analysis. Ghost infarct core was defined as CTP core volume minus 24-hour infarct volume > 10 mL). Clinical characteristics of patients with versus without ghost core were compared. Associations of ghost core and clinical characteristics were assessed by using multivariable logistic regression. A total of 421 of 1105 patients (38.1%) were included in the analysis. Forty-seven (11.2%) had a ghost core > 10 mL, with a median ghost infarct volume of 13.4 mL (interquartile range 7.6-26.8). Young patient age, complete recanalization, short last known well to CT times, and possibly male sex were associated with ghost infarct core. CTP ghost core occurred in ∼1 of 10 patients, indicating that CTP frequently overestimates the infarct core size at baseline, particularly in young patients with complete recanalization and short ischemia duration.

Impact of genotype on clinical course in biventricular arrhythmogenic cardiomyopathy

Aim. To analyze the correlation between genotype and phenotype in patients with biventricular arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods. The clinical phenotype of 9 unrelated probands (89 % men, median age 35 [34; 37]) with biventricular ARVC were observed. The clinical and instrumental examination included a 12-lead ECG, 24-hour Holter ECG monitoring, transthoracic echocardiography and cardiac magnetic resonance imaging with late gadolinium enhancement. Biventricular variant of ARVC was diagnosed according to the 2020 Padua criteria for both right and left ventricles involvement. High-throughput sequencing was utilized to search for mutations in genes linked to the onset of cardiomyopathies and other inherited rhythm disorders. Statistical analysis procedures were performed using the STATISTICA-12 program.Results. In all patients with biventricular ARVC, according to late gadolinium enchansment magnetic resonance imaging, left ventricular involvement of varying degrees was detected, characterized by fibrous or fibrofatty infiltration of the myocardium, as well as regional or global systolic dysfunction. Genotyping in 9 patients with biventricular ARVC revealed 10 variants of the nucleotide sequence of III-V classes of pathogenicity according to the criteria of ACMG (2015) in 4 genes associated with ARVC (PKP2, DSP, DSC2, DSG2). Of these, 7 variants belonged to classes IV and V (PKP2 - 4 mutations, DSP - 2 mutations, DSG2 - 1 mutation); 3 nucleotide substitutions were variants with uncertain significance (VUS, class III) - 2 in DSC2 gene and 1 in DSP gene. A combination of nucleotide variants in two genes (DSP and DSC2) was detected in 1 patient. The findings highlight that mutations in DSP gene were associated with more severe systolic dysfunction and left ventricle dilation compared to carriers of mutations in PKP2 gene. In patients with variants of class III pathogenicity in DSC2 gene the most adverse clinical course of the disease was observed with the early onset of the first sustained ventricular tachycardia and the development of severe dysfunction and dilation of both ventricles requiring heart transplantation in comparison with carriers of mutations in other genes.Conclusion. The results obtained in a cohort of patients with biventricular ARVC demonstrate a specific correlation between genotype and clinical course and disease severity as well.

Cortical and Subcortical Brain Atrophy Assessment Using Simple Measures on NCCT Compared with MRI in Acute Stroke.

Brain atrophy is an important surrogate for brain reserve, the capacity of the brain to cope with acquired injuries such as acute stroke. It is unclear how well atrophy measurements on MR imaging can be reproduced using NCCT imaging. We aimed to compare pragmatic atrophy measures on NCCT with MR imaging in patients with acute ischemic stroke. This is a post hoc analysis, including baseline NCCT and 24-hour follow-up MR imaging data from the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Cortical atrophy was measured using the global cortical atrophy scale, and subcortical atrophy was measured using the intercaudate distance-to-inner-table width (CC/IT) ratio. Agreement and correlation between these measures on NCCT and MR imaging were calculated using the Gwet agreement coefficient 1 and Pearson correlation coefficients, respectively. Among 1105 participants in the ESCAPE-NA1 trial, interpretable NCCT and 24-hour MR imaging were available in 558 (50.5%) patients (mean age, 67.2 [SD, 13.7] years; 282 women). Cortical atrophy assessments performed on NCCT underestimated atrophy severity compared with MR imaging (eg, patients with global cortical atrophy of ≥1 assessed on NCCT = 133/558 [23.8%] and on MR imaging = 247/558 [44.3%]; a 20.5% difference). Overall, cortical (ie, global cortical atrophy) atrophy assessments on NCCT had substantial or better agreement with MR imaging (Gwet agreement coefficient 1 of > 0.784; P < .001). Subcortical atrophy measures (CC/IT ratio) showed strong correlations between NCCT and MR imaging (Pearson correlation = 0.746, P < .001). Brain atrophy can be evaluated using simple measures in emergently acquired NCCT. Subcortical atrophy assessments on NCCT show strong correlations with MR imaging. Although cortical atrophy assessments on NCCT are strongly correlated with MR imaging ratings, there is a general underestimation of atrophy severity on NCCT.

Low Levels of Low-Density Lipoprotein Cholesterol Increase the Risk of Post-Thrombectomy Delayed Parenchymal Hematoma.

Low levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to increase the risk of hemorrhagic transformation (HT) following acute ischemic stroke. However, the literature on the relationship between LDL-C levels and post-thrombectomy HT is sparse. The aim of our study is to investigate the association between LDL-C and delayed parenchymal hematoma (PH) that was not seen on immediate post-thrombectomy dual-energy computed tomography (DECT). A retrospective analysis was conducted on all patients with anterior circulation large vessel occlusion who underwent thrombectomy at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients received DECT immediately post-thrombectomy and magnetic resonance imaging or CT at 24 hours. The presence of immediate hemorrhage was assessed by DECT, while delayed PH was assessed by 24-hour imaging. Multivariable analysis was performed to identify predictors of delayed PH. Patients with hemorrhage on immediate post-thrombectomy DECT were excluded to select only those with delayed PH. Of 159 patients without hemorrhage on immediate post-thrombectomy DECT, 18 (11%) developed delayed PH on 24-hour imaging. In multivariable analysis, LDL-C (odds ratio [OR], 0.76; P=0.038; 95% confidence interval [CI], 0.59-0.99; per 10 mg/dL increase) independently predicted delayed PH. High-density lipoprotein cholesterol, triglyceride, and statin use were not associated. After adjusting for potential confounders, LDL-C ≤50 mg/dL was associated with an increased risk of delayed PH (OR, 5.38; P=0.004; 95% CI, 1.70-17.04), while LDL-C >100 mg/dL was protective (OR, 0.26; P=0.041; 95% CI, 0.07-0.96). LDL-C ≤50 mg/dL independently predicted delayed PH following thrombectomy and LDL-C >100 mg/dL was protective, irrespective of statin. Thus, patients with low LDL-C levels may warrant vigilant monitoring and necessary interventions, such as blood pressure control or anticoagulation management, following thrombectomy even in the absence of hemorrhage on immediate post-thrombectomy DECT.

The clinical utility of dual-energy CT in post-thrombectomy care: Part 2, the predictive value of contrast density and volume for delayed hemorrhagic transformation

ObjectivesDual-energy CT allows differentiation between blood and iodinated contrast. This study aims to determine the predictive value of contrast density and volume on post-thrombectomy dual-energy CT for delayed hemorrhagic transformation and its impact on 90-day outcomes. Materials and MethodsA retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients underwent dual-energy CT immediately post-thrombectomy and MRI or CT 24 hours afterward. The presence of hemorrhage and contrast staining was evaluated by dual-energy CT. Delayed hemorrhagic transformation was determined by 24-hour imaging and classified into petechial hemorrhage or parenchymal hematoma using ECASS III criteria. Univariable and multivariable analyses were performed to determine predictors and outcomes of delayed hemorrhagic transformation. ResultsOf 97 patients with contrast staining and without hemorrhage on dual-energy CT, 30 and 18 patients developed delayed petechial hemorrhage and delayed parenchymal hematoma, respectively. On multivariable analysis, delayed petechial hemorrhage was predicted by anticoagulant use (OR,3.53;p=0.021;95%CI,1.19-10.48) and maximum contrast density (OR,1.21;p=0.004;95%CI,1.06-1.37;per 10 HU increase), while delayed parenchymal hematoma was predicted by contrast volume (OR,1.37;p=0.023;95%CI,1.04-1.82;per 10 mL increase) and low-density lipoprotein (OR,0.97;p=0.043;95%CI,0.94-1.00;per 1 mg/dL increase). After adjusting for potential confounders, delayed parenchymal hematoma was associated with worse functional outcomes (OR,0.07;p=0.013;95%CI,0.01-0.58) and mortality (OR,7.83;p=0.008;95%CI,1.66-37.07), while delayed petechial hemorrhage was associated with neither. ConclusionContrast volume predicted delayed parenchymal hematoma, which was associated with worse functional outcomes and mortality. Contrast volume can serve as a useful predictor of delayed parenchymal hematoma following thrombectomy and may have implications for patient management.

Targeting Exportin 1 as treatment for cutaneous squamous cell carcinoma.

e21564 Background: Cutaneous squamous cell carcinomas (cSCC) are among the most frequent solid cancers in humans and in the U.S., cSCC cases are increasing. Molecular mechanisms transitioning premalignant lesions to cancer are not well characterized. As a result, targeted therapies need to be identified to treat these lesions. Preliminary data shows that Exportin 1 (XPO1) is one of the major proteins regulating nuclear export of proteins, helping to maintain cellular homeostasis. Previous work showed that Exportin 1 modulates the nuclear:cytoplasmic ratio of signaling proteins in skin cancer; resulting in an anti-apoptotic effect by adjusting the nuclear-cytoplasmic balance of pro-survival proteins such as CDC25A and Survivin. XPO1 expression is upregulated in many cancers, thereby affecting the nuclear:cytoplasmic ratio of many pro-survival proteins and enhancing tumorigenesis. This research project was designed to investigate the effects of XPO1 inhibition on cSCC survival. Selinexor is FDA cleared for treatment of multiple myeloma patients. Selinexor is a selective inhibitor of XPO1 regulated nuclear transport causing target molecules to remain within the cell leading to decreased cancer cell growth and decreased cancer cell survival. We hypothesize that inhibiting XPO1 with Selinexor or by CRISPRi genetic knockdown of XPO1 in cSCC cells will reduce proliferation and increase apoptosis in cSCC cells. Methods: Human cSCC cell lines SCC13 and SRB12 were seeded in 96-well plates at 8,000 cells/well density and 3,000 cells/well, respectively. Cells were treated with varying concentrations of Selinexor (0.005mM – 5mM) or DMSO as vehicle control. At 24-hour intervals, cell imaging and Neutral red staining assays were conducted to determine the IC50 concentration for Selinexor in cSCC cell lines. SCC13 cells stably expressing dCas9-KRAB and a doxycycline-inducible XPO1 guide RNA were used for CRISPRi experiments. Cells were treated with doxycycline daily and apoptosis was assayed by Caspase Glo 3/7 daily for four days. CRIPSRi enabled a doxycycline inducible XPO1 knock down on SCC13 cells allowing us to disrupt the cellular transporter protein XPO1. Results: Selinexor treatment of SRB12 cells resulted in an IC50 of 1.174 μM and 0.071 μM for SCC13. In contrast, normal human keratinocyte cell lines had higher IC50 values of 2.18 μM for HaCaT and 5.29 μM for KerCT cells. Apoptosis significantly increased after 72 and 96 hours of XPO1 knock down in SCC13 cells measured by Caspase Glo. Conclusions: These results document how XPO1 inhibition reduces proliferation and is toxic to both normal keratinocytes and cSCC cells. Additionally, cSCC cells had lower IC50 values for Selinexor, suggesting cSCC may be more sensitive to XPO1 inhibition compared to normal keratinocytes. Further, targeting XPO1 also increases apoptosis in these cells. This data supports the hypothesis that targeting XPO1 may be effective in treating cSCC.

Diffusion-Weighted Imaging Lesion Reversal in Older Patients With Stroke Treated With Mechanical Thrombectomy.

Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients <80 versus ≥80 years old, (1) the effect of successful recanalization on DWIR and (2) the impact of DWIR on functional outcome. We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected. Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6-35) in patients ≥80, and 19% (interquartile range, 10-34) in patients <80 (P=0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 (P=0.004) and <80 (P=0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% (P>0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 (P=0.003) and <80 (P=0.013) patients; the effect of DWIR% on outcome was not influenced by the age group (P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion.

Analysis of the left ventricular involvement in patients with a biventricular phenotype of arrhythmogenic ardiomyopathy: a case series description

Aim. To assess the prevalence of the left ventricle involvement and the features of the biventricular phenotype of arrhythmogenic cardiomyopathy in patients with pathogenic mutations in the PKP2 and DSP genes.Material and methods. Three unrelated probands underwent a comprehensive molecular-genetic, clinical and instrumental examination, which included a 12-lead ECG, 24-hour ECG monitoring, transthoracic echocardiography, and cardiac magnetic resonance imaging with late gadolinium enhancement.Results. The results of our clinical observations showed that in three studied patients with arrhythmogenic cardiomyopathy left ventricle involvement of various degree was found. The left ventricle damage was characterized by fibrous or fibro-fatty infiltration of the myocardium, as well as regional or global systolic dysfunction of different severity. The patients had pathogenic mutations c.1912C &gt; T (p.Gln638*, rs397517012, rs397517012); c.1237C &gt; T (p.Arg413*, rs372827156) in the PKP2 gene and a new probably pathogenic variant in the form of a c.3494delA deletion in the DSP gene. It was found that the mutation in the DSP gene was associated with a more pronounced systolic dysfunction and a greater percentage of fibrous replacement of the left ventricular myocardium compared with carriers of mutations in the PKP2 gene. All patients had life-threatening ventricular arrhythmias with the need for implantation of a cardioverter-defibrillator.Conclusion. Our clinical observations have shown that in patients with biventricular arrhythmogenic cardiomyopathy, the detection of a mutation in the DSP gene is associated with a more pronounced systolic dysfunction and a higher percentage of fibrous replacement of the left ventricle myocardium compared with carriers of mutations in the PKP2 gene.

Demonstrating 24-hour continuous vertical monitoring of atmospheric optical turbulence.

We report what is believed to be the first example of fully continuous, 24-hour vertical monitoring of atmospheric optical turbulence. This is achieved using a novel instrument, the 24-hour Shack-Hartmann Image Motion Monitor (24hSHIMM). Optical turbulence is a fundamental limitation for applications such as free-space optical communications, where it limits the achievable bandwidth, and ground-based optical astronomy, restricting the observational precision. Knowledge of the turbulence enables us to select the best sites, design optical instrumentation and optimise the operation of ground-based optical systems. The 24hSHIMM estimates the vertical optical turbulence coherence length, time, angle and Rytov variance from the measurement of a four-layer vertical turbulence profile and a wind speed profile retrieved from meteorological forecasts. To illustrate our advance we show the values of these parameters recorded during a 36-hour, continuous demonstration of the instrument. Due to its portability and ability to work in stronger turbulence, the 24hSHIMM can also operate in urban locations, providing the field with a truly continuous, versatile turbulence monitor for all but the most demanding of applications.

Abstract TMP3: Prediction Model For Medical Rescue Treatment Strategies In Patients With Incomplete Reperfusion

Background: After successful reperfusion is achieved (extended Thrombolysis in Cerebral Infarction (eTICI) ≥2b50), decision on pursuing additional treatment strategies in order to achieve complete reperfusion (eTICI=2c/3), is multifactorial and depends on patient’s clinical and imaging characteristics. We have developed and validated a clinical decision tool to provide individualized predictions on achieving delayed reperfusion based on individual patient data. Methods: Single-center registry analysis for all consecutive patients admitted between 02/2015 - 12/2020. Primary variable of interest was perfusion imaging outcome in patients with incomplete reperfusion (eTICI 2a-2c), evaluated on the 24-hour follow-up imaging. This variable was dichotomized into delayed reperfusion, in case of non-observable perfusion deficit, and persistent perfusion deficit, in case of perfusion deficit captured on the final angiography imaging. Final model variable selection was performed via bootstrapped (n=200) stepwise backwards regression. Model was split into a training and testing set (80:20 ratio), with 10-fold cross validation resampling. Results: 372 patients (50.8% female, mean age 74) were included, with 228 (61.2%) of them having delayed reperfusion. Final model identified seven variables of importance including: age, sex, atrial fibrillation, Intervention-to-Follow-Up time, maneuver count, eTICI and collateral status. Model’s discriminative ability for predicting delayed reperfusion was adequate (AUC 0.83, 95% CI 0.74 -0.92), with an overall adjusted calibration (Brier score 0.17, 95% CI 0.15-0.18). Conclusions: Current model presents a tool that may aid clinical decision-making process in selection of patients for pursuing additional treatment strategies after incomplete reperfusion has been achieved. This is an important next step towards personalized treatment of stroke patients undergoing mechanical thrombectomy.

Editors' Note: Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow).

Pooling data from the EXTEND-IA, EXTEND-IA TNK, and EXTEND IA-TNK part 2 clinical trials, Dr. Ng et al. found that persistent hypoperfusion (“no-reflow”) on follow-up perfusion imaging after successful recanalization was common and associated with poor clinical outcomes. One in 4 patients had perfusion imaging evidence of “no-reflow” at 24 hours, and this radiographic finding accounted for 60% of the final infarct volume and was associated with a 4-fold higher odds of being functionally dependent or dead by day 90. Dr. Schiphorst et al. sought to validate these findings using their data set but found the prevalence of “no-reflow” occurred in half as many patients. They also emphasize that the relationship of no-reflow and clinical outcome is uncertain. Nonetheless, inherent methodologic differences in these studies, specifically selection bias for 24-hour perfusion imaging may account for the variability in findings. The systematic use of perfusion imaging in 99% of included patients from the pooled analysis by Ng et al. and larger sample size make for a convincing argument that postreperfusion hypoperfusion is not only common, but a useful prognostic factor. Pooling data from the EXTEND-IA, EXTEND-IA TNK, and EXTEND IA-TNK part 2 clinical trials, Dr. Ng et al. found that persistent hypoperfusion (“no-reflow”) on follow-up perfusion imaging after successful recanalization was common and associated with poor clinical outcomes. One in 4 patients had perfusion imaging evidence of “no-reflow” at 24 hours, and this radiographic finding accounted for 60% of the final infarct volume and was associated with a 4-fold higher odds of being functionally dependent or dead by day 90. Dr. Schiphorst et al. sought to validate these findings using their data set but found the prevalence of “no-reflow” occurred in half as many patients. They also emphasize that the relationship of no-reflow and clinical outcome is uncertain. Nonetheless, inherent methodologic differences in these studies, specifically selection bias for 24-hour perfusion imaging may account for the variability in findings. The systematic use of perfusion imaging in 99% of included patients from the pooled analysis by Ng et al. and larger sample size make for a convincing argument that postreperfusion hypoperfusion is not only common, but a useful prognostic factor.

Predictors of ventricular arrhythmias in arrhythmic mitral valve syndrome – a study using implantable loop recorders

Abstract Background Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias, but the incidence and methods for risk stratification of ventricular arrhythmias are not well known. Purpose In this prospective study, we aimed to describe the incidence of ventricular arrhythmias by use of continuous rhythm monitoring and propose risk stratification in patients with arrhythmic mitral valve syndrome. Methods We included consecutive patients with arrhythmic mitral valve prolapse, defined as mitral valve prolapse and/or mitral annulus disjunction (MAD) with arrhythmic symptoms or documented complex premature ventricular complexes (PVC). We implanted loop recorders (ILR) in patients with arrhythmic mitral valve syndrome with no previous severe ventricular arrhythmias and all were followed by remote monitoring. We monitored for non-sustained ventricular tachycardias (NSVT) and severe ventricular arrhythmia, defined as aborted cardiac arrest, sustained ventricular tachycardia and NSVT with syncope/presyncope. At baseline, patients underwent echocardiography, 24-hour Holter monitoring, stress ECG and cardiac magnetic resonance imaging. Results We included 60 patients (73% female, 49 years [interquartile range [IQR] 37–60]). At baseline, median PVC burden was 232 per 24-hours (IQR 33–1329), and 8 (13%) patients had NSVT by Holter monitoring or stress ECG. During 3.0±0.5 years of follow-up, severe ventricular arrhythmia occurred in 7 (12%) patients (1 aborted cardiac arrest, 6 NSVT with syncope/pre-syncope). Annual incidence rate of severe events was 4% per person-year (95% confidence interval [CI] 2–9)). Predictors of severe ventricular arrhythmia were frequent PVCs (6683 PVCs per 24h [IQR 612–10861] vs. 154 PVCs per 24h [IQR 25–562], p=0.01), more NSVTs by ILR (4 NSVTs [IQR 2–7] vs. 0 NSVTs [0–1], p&amp;lt;0.001), greater left ventricular diameter (57±6 mm vs. 51±6 mm, p=0.01) and greater posterolateral MAD distance (9 mm [IQR 8–12] vs. 4 mm [IQR 0–6], p=0.02). Adjustment for age and sex did not change significant risk markers (all p&amp;lt;0.02). During follow-up 102 NSVTs were recorded in 24 (40%) patients. In multivariate Poisson regression adjusting for age, mitral regurgitation grade and bileaflet prolapse, predictors of high NSVT burden were frequent PVCs (incidence rate ratio [IRR] 1.14 [95% CI 1.04–1.27], p=0.01), PVCs from inferior left ventricle (IRR 5.19 [95% CI 2.80–9.63], p&amp;lt;0.001) and late gadolinium enhancement (IRR 3.16 [95% CI 1.68–5.97], p&amp;lt;0.001). Conclusion Yearly incidence of first severe ventricular arrhythmia was 4% in patients with arrhythmic mitral valve syndrome, emphasizing the high risk of life-threatening events in these patients. Frequent PVCs, NSVTs, greater left ventricular diameter and greater posterolateral MAD distance were predictors of first severe ventricular arrhythmia and should be used in risk stratification. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by a public grant from the Norwegian Research Council (#288438 and #309762), Precision Health Center for optimized cardiac care (ProCardio).

Increased blood pressure variability during general anaesthesia is associated with worse outcomes after mechanical thrombectomy: a prospective observational cohort study

ObjectivesOptimal periprocedural blood pressure (BP) management during mechanical thrombectomy (MT) for acute ischaemic stroke is still controversial. The aim of this study was to investigate the association between intraprocedural BP...

Pretherapeutic functional connectivity of tractography-based targeting of the ventral intermediate nucleus for predicting tremor response in patients with Parkinson's disease after thalamotomy with MRI-guided focused ultrasound.

Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson's disease (PD). PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%-94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = -0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.

Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow).

The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.