Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia

Disease severity in hospitalized COVID-19 patients: comparing routine surveillance with cohort data from the LEOSS study in 2020 in Germany

Introduction Studies investigating risk factors for severe COVID-19 often lack information on the representativeness of the study population. Here, we investigate factors associated with severe COVID-19 and compare the representativeness of the dataset to the general population. Methods We used data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) of hospitalized COVID-19 patients diagnosed in 2020 in Germany to identify associated factors for severe COVID-19, defined as progressing to a critical disease stage or death. To assess the representativeness, we compared the LEOSS cohort to cases of hospitalized patients in the German statutory notification data of the same time period. Descriptive methods and Poisson regression models were used. Results Overall, 6672 hospitalized patients from LEOSS and 132,943 hospitalized cases from the German statutory notification data were included. In LEOSS, patients above 76 years were less likely represented (34.3% vs. 44.1%). Moreover, mortality was lower (14.3% vs. 21.5%) especially among age groups above 66 years. Factors associated with a severe COVID-19 disease course in LEOSS included increasing age, male sex (adjusted risk ratio (aRR) 1.69, 95% confidence interval (CI) 1.53–1.86), prior stem cell transplantation (aRR 2.27, 95% CI 1.53–3.38), and an elevated C-reactive protein at day of diagnosis (aRR 2.30, 95% CI 2.03–2.62). Conclusion We identified a broad range of factors associated with severe COVID-19 progression. However, the results may be less applicable for persons above 66 years since they experienced lower mortality in the LEOSS dataset compared to the statutory notification data.Peer Reviewe

Long‐Term Outcome and Quality of Life in Patients With Stroke Presenting With Extensive Early Infarction

Background The benefit of mechanical thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for short‐term outcomes is debatable and long‐term outcomes remain unknown. This retrospective, monocentric cohort study aimed to assess the association between reperfusion grade and the long‐term functional outcome measured with modified Rankin scale as well as the long‐term health‐related quality of life recorded at the last follow‐up in patients according to baseline ASPECTS (0–5 versus 6–10). Methods Deceased patients were identified from the Swiss population register and follow‐up telephone interviews were conducted with all surviving patients with stroke treated with mechanical thrombectomy between January 1, 2010, and December 31, 2018. Favorable outcome was defined as modified Rankin scale 0 to 3; health‐related quality of life was assessed using the 3‐level version of the EuroQol 5‐dimensional questionnaire. The EuroQol 5‐dimension utility index was calculated for statistical analyses. The reperfusion grade was core laboratory adjudicated using the expanded treatment in cerebral ischemia score. Adjusted odds ratios for the association between the reperfusion grade assessed by expanded treatment in cerebral ischemia and outcomes were calculated from multivariable logistic regression. Results Of the 1114 patients with available long‐term follow‐up records (median follow‐up, 3.67 years), 997 were included in the final analysis. Respectively, patients with low ASPECTS more often had complaints regarding mobility (67.1% versus 42.1%, P<0.001), self‐care (53.4% versus 31.2%, P<0.001), and usual activities (65.8% versus 41.4%, P<0.001) than patients with high ASPECTS, whereas reported pain/discomfort (65.7% versus 69.9%, P=0.49) and anxiety/depression (71.2% versus 78.9%, P=0.17) did not differ. In patients with low ASPECTS, increasing reperfusion grade was associated with a higher likelihood of long‐term favorable functional outcome (adjusted odds ratio, 1.43; 95% CI, 1.09–1.88 [P=0.01]) and health‐related quality of life (adjusted linear correlation coefficient, 0.05; 95% CI, 0.02–0.08) despite early extensive infarction. Conclusion Despite low baseline ASPECTS, a higher reperfusion grade results in better functional outcomes and may improve health‐related quality of life in the long term

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable

Prediction of delayed reperfusion in patients with incomplete reperfusion following thrombectomy.

BACKGROUND The clinical course of patients with incomplete reperfusion after thrombectomy, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2a-2c, is heterogeneous. Patients showing delayed reperfusion (DR) have good clinical outcomes, almost comparable to patients with ad-hoc TICI3 reperfusion. We aimed to develop and internally validate a model that predicts DR occurrence in order to inform physicians about the likelihood of a benign natural disease progression. PATIENTS AND METHODS Single-center registry analysis including all consecutive, study-eligible patients admitted between 02/2015 and 12/2021. Preliminary variable selection for the prediction of DR was performed using bootstrapped stepwise backward logistic regression. Interval validation was performed with bootstrapping and the final model was developed using a random forests classification algorithm. Model performance metrics are reported with discrimination, calibration, and clinical decision curves. Primary outcome was concordance statistics as a measure of goodness of fit for the occurrence of DR. RESULTS A total of 477 patients (48.8% female, mean age 74 years) were included, of whom 279 (58.5%) showed DR on 24 follow-up. The model's discriminative ability for predicting DR was adequate (C-statistics 0.79 [95% CI: 0.72-0.85]). Variables with strongest association with DR were: atrial fibrillation (aOR 2.06 [95% CI: 1.23-3.49]), Intervention-To-Follow-Up time (aOR 1.06 [95% CI: 1.03-1.10]), eTICI score (aOR 3.49 [95% CI: 2.64-4.73]), and collateral status (aOR 1.33 [95% CI: 1.06-1.68]). At a risk threshold of R = 30%, use of the prediction model could potentially reduce the number of additional attempts in one out of four patients who will have spontaneous DR, without missing any patients who do not show spontaneous DR on follow-up. CONCLUSIONS The model presented here shows fair predictive accuracy for estimating chances of DR after incomplete thrombectomy. This may inform treating physicians on the chances of a favorable natural disease progression if no further reperfusion attempts are made

Association of Intravenous Thrombolysis with Delayed Reperfusion After Incomplete Mechanical Thrombectomy.

PURPOSE Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT. METHODS Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed. RESULTS In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively). CONCLUSION A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies

Absence of Susceptibility Vessel Sign in Patients With Malignancy-Related Acute Ischemic Stroke Treated With Mechanical Thrombectomy.

Background and Purpose Clots rich in platelets and fibrin retrieved from patients with acute ischemic stroke (AIS) have been shown to be independently associated with the absence of the susceptibility vessel sign (SVS) on MRI and active malignancy. This study analyzed the association of SVS and the presence of active malignancy in patients with AIS who underwent mechanical thrombectomy (MT). Methods This single-center, retrospective, and cross-sectional study included consecutive patients with AIS with admission MRI treated with MT between January 2010 and December 2018. SVS status was evaluated on susceptibility-weighted imaging. Adjusted odds ratios (aORs) were calculated to determine the association between absent SVS and the presence of active or occult malignancy. The performance of predictive models incorporating and excluding SVS status was compared using areas under the receiver operating characteristics curve (auROC). Results Of 577 patients with AIS with assessable SVS status, 40 (6.9%) had a documented active malignancy and 72 (12.5%) showed no SVS. The absence of SVS was associated with active malignancy (aOR 4.85, 95% CI 1.94-12.11) or occult malignancy (aOR 11.42, 95% CI 2.36-55.20). The auROC of predictive models, including demographics and common malignancy biomarkers, was higher but not significant (0.85 vs. 0.81, p = 0.07) when SVS status was included. Conclusion Absence of SVS on admission MRI of patients with AIS undergoing MT is associated with malignancy, regardless of whether known or occult. Therefore, the SVS might be helpful in detecting paraneoplastic coagulation disorders and occult malignancy in patients with AIS