Changes in LA volume and diameter correlate with mechanisms of recurrence after paroxysmal AF ablation.

Papathanasiou et al point out that the two different methods of LA volume and diameter measurement in our recent publication could limit the significance of the correlations we reported with PV reconnection and non-PV foci as mechanisms of post AF ablation recurrence. While we acknowledge the lack of statistically significant correlations of smaller echo derived LA diameter with PV reconnection or of a larger angiographic LA volume with non-PV foci, the congruent confidence intervals of this correlation suggest a statistical trend. Non-uniform LA dimensional changes as an expression of structural remodelling may also be a possible explanation. Published data indicates that angiographic LA volumes consistently exhibit a positive bias compared to echocardiographic volumes but do provide intra-procedural measurements better correlating with gold standard techniques like CT or MRI. Finally we agree with Papathanasiou et al that dynamic changes in LA dimensions likely correlate with early and late mechanisms of recurrence and merit prospective studies

Predicting progression of aortic stenosis by measuring serum calcification propensity

BACKGROUND: The aim of this prospective, double‐blinded study in patients with aortic sclerosis was to determine whether a new calcification propensity measure in the serum could predict disease progression. METHODS: We included 129 consecutive patients with aortic sclerosis as assessed during a routine clinical echocardiographic exam. Clinical, echocardiographic, and serum laboratory parameters were collected, including a new blood test providing an overall measure of calcification propensity by monitoring the maturation time of calciprotein particles (T50 test). The echocardiographic exam was repeated after 1 year. Multiple regression analysis was performed to identify independent predictors of the annual increase of peak transvalvular Doppler velocity (∆vmax). Furthermore, the accuracy of the T50 test to detect patients with the most marked stenosis progression was assessed by receiver operating characteristic (ROC)‐analysis. RESULTS: Mean age was 75 ± 9 years, 79% were men. The T50 was 271 ± 58 min. Overall, there was no significant stenosis progression between baseline and follow‐up (∆vmax 3.8 ± 29.8 cm/s, p = ns). The T50 test was not found to be an independent linear predictor in multivariate testing. By ROC‐analysis, however, a T50‐value ≤ 242 min was able to significantly detect a ∆vmax above the 90th percentile (∆vmax ≥ 43 cm/s, AUC = 0.67, p = .04, Sensitivity = 69%, Specificity = 70%). CONCLUSIONS: The T50 test showed a modest but significant ability to identify a pronounced aortic stenosis progression in patients with aortic sclerosis. The test could not be established as an independent linear predictor of disease progression, possibly due to the low valvular disease burden and short follow‐up interval

Sigmoid isostiffness-lines: An in-vitro model for the assessment of aortic stenosis severity.

Introduction The aortic valve opening area (AVA), used to quantify aortic stenosis severity, depends on the transvalvular flow rate (Q). The currently accepted clinical echocardiographic method assumes a linear relation between AVA and Q. We studied whether a sigmoid model better describes this relation and determined "isostiffness-lines" across a wide flow spectrum, thus allowing building a nomogram for the non-invasive estimation of valve stiffness. Methods Both AVA and instantaneous Q (Qinst) were measured at 10 different mean cardiac outputs of porcine aortic valves mounted in a pulsatile flow loop. The valves' cusps were chemically stiffened to obtain three stiffness grades and the procedure was repeated for each grade. The relative stiffness was defined as the ratio between LV work at grade with the added stiffness and at native stiffness grade. corresponding to the selected of the highest 3 and 5 cardiac output values was predicted in K-fold cross-validation using sequentially a linear and a sigmoid model. The accuracy of each model was assessed with the Akaike information criterion (AIC). Results The sigmoid model predicted more accurately (AIC for prediction of AVA with of the 3 highest cardiac output values: -1,743 vs. -1,048; 5 highest cardiac output values: -1,471 vs. -878) than the linear model. Conclusion This study suggests that the relation between AVA and Q can be better described by a sigmoid than a linear model. This construction of "isostiffness-lines" may be a useful method for the assessment of aortic stenosis in clinical echocardiography

Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis.

BACKGROUND Rheumatic heart disease (RHD) accounts for the highest number of deaths from valvular heart disease globally. Yet, rheumatic aortic stenosis (AS) was excluded from landmark studies investigating the safety and efficacy of transcatheter aortic valve implantation (TAVI). We aimed to describe the clinical and anatomical characteristics of patients with rheumatic AS undergoing TAVI, and to compare procedural and clinical outcomes with patients undergoing TAVI for degenerative AS. METHODS In a prospective TAVI registry, patients with rheumatic AS were identified based on International Classification of Diseases version 10 codes and/or a documented history of acute rheumatic fever and/or the World Heart Federation criteria for echocardiographic diagnosis of RHD, and were propensity score-matched in a 1:4 ratio to patients with degenerative AS. RESULTS Among 2329 patients undergoing TAVI, 105 (4.5%) had rheumatic AS. Compared with patients with degenerative AS, patients with rheumatic AS were more commonly female, older, had higher surgical risk and more commonly suffered from multivalvular heart disease. In the unmatched cohort, both technical success (85.7% vs 85.9%, p=0.887) and 1-year cardiovascular mortality (10.0% vs 8.6%; HR 1.16, 95% CI 0.61 to 2.18, p=0.656) were comparable between patients with rheumatic and degenerative AS. In contrast, patients with rheumatic AS had lower rates of 30-day and 1-year cardiovascular mortality compared with matched patients with degenerative AS (1.9% vs 8.9%, adjusted HR (HRadj) 0.18, 95% CI 0.04 to 0.80, p=0.024; and 10.0% vs 20.3%, HRadj 0.44, 95% CI 0.24 to 0.84, p=0.012, respectively). CONCLUSION TAVI may be a safe and effective treatment strategy for selected elderly patients with rheumatic AS. TRIAL REGISTRATION NUMBER NCT01368250

Impact of conscious sedation and general anesthesia on periprocedural outcomes in Watchman left atrial appendage closure

Background: Transcatheter left atrial appendage closure (LAAC) is performed either in conscious sedation (CS) or general anesthesia (GA), and limited data exist regarding clinical outcomes for the two approaches. The aim of the study was to analyze the effect of CS versus GA on acute outcomes in a large patient cohort undergoing LAAC with a Watchman occluder.Methods: A cohort of 521 consecutive patients underwent LAAC with Watchman occluders at two centers (REGIOMED hospitals, Germany) between 2012 and 2018. One site performed 303 consecutive LAAC procedures in GA, and the other site performed 218 consecutive procedures in CS. The safety endpoint was a composite of major periprocedural complications and postoperative pneumonia. The efficacy endpoint was defined as device success.Results: After a 1:1 propensity score matching, 196 (CS) vs. 115 (GA) patients could be compared. In 5 (2.6%) cases CS was converted to GA. The primary safety endpoint (3.5% [CS] vs. 7.0% [GA], p = 0.18) and its components (major periprocedural complications: 2.5% vs. 3.5%, p = 0.73; postoperative pneumonia: 2.6% vs. 4.3%, p = 0.51) did not differ between the groups. Also, device success was comparable (96.9% vs. 93.9%, p = 0.24).Conclusions: In patients undergoing LAAC with the Watchman device, conscious sedation and general anesthesia showed comparable device success rates and safety outcomes. The type of anesthesia for LAAC may therefore be tailored to patient comorbidities, operator experience, and hospital logistics

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

Yield of Echocardiography in Ischemic Stroke and Patients With Transient Ischemic Attack With Established Indications for Long-Term Direct Oral Anticoagulant Therapy: A Cross-Sectional Diagnostic Cohort Study.

Background We aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event. Methods and Results This was a retrospective cohort study of consecutive patients with preceding established indications for long-term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management-relevant high-risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence-based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70-84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1-12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1-3) days. TTE identified 26 of 191 (14%) patients with 35 management-relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management-relevant pathologies. Most management-relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management-relevant high-risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], C-reactive protein, d-dimer, and troponin levels). Conclusions In patients with established indications for long-term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management-relevant high-risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients

Cardiovascular MRI Compared to Echocardiography to Identify Cardioaortic Sources of Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: To compare the diagnostic yield of echocardiography and cardiovascular MRI (CMR) to detect structural sources of embolism, in patients with ischemic stroke with a secondary analysis of non-stroke populations. Methods and Results: We searched MEDLINE/Embase (from 01.01.2000 to 24.04.2021) for studies including CMR to assess prespecified sources of embolism. Comparison included transthoracic and/or transesophageal echocardiography. Two authors independently screened studies, extracted data and assessed bias using the QUADAS-2 tool. Estimates of diagnostic yield were reported and pooled. Twenty-seven studies with 2,525 patients were included in a study-level analysis. Most studies had moderate to high risk of bias. Persistent foramen ovale, complex aortic plaques, left ventricular and left atrial thrombus were the most common pathologies. There was no difference in the yield of left ventricular thrombus detection between both modalities for stroke populations (4 studies), but an increased yield of CMR in non-stroke populations (28.1 vs. 16.0%, P < 0.001, 10 studies). The diagnostic yield in stroke patients for detection of persistent foramen ovale was lower in CMR compared to transoesophageal echocardiography (29.3 vs. 53.7%, P < 0.001, 5 studies). For both echocardiography and CMR the clinical impact of the management consequences derived from many of the diagnostic findings remained undetermined in the identified studies. Conclusions: Echocardiography and CMR seem to have similar diagnostic yield for most cardioaortic sources of embolism except persistent foramen ovale and left ventricular thrombus. Randomized controlled diagnostic trials are necessary to understand the impact on the management and potential clinical benefits of the assessment of structural cardioaortic stroke sources. Registration: PROSPERO: CRD42020158787

Development of a score for prediction of occult malignancy in stroke patients (occult-5 score).

BACKGROUND AND PURPOSE Malignancy associated acute ischemic stroke (AIS) requires specific diagnostic work-up, treatment and prevention to improve outcome. This study aimed to develop a biomarker-based score for prediction of occult malignancy in AIS patients. METHODS Single-center cross-sectional study including consecutive AIS patients treated between July 2017 and November 2018. Patients with active malignancy at presentation, or diagnosed within 1 year thereafter and patients free of malignancy, were included and malignancy associated biomarkers were assessed. LASSO analyses of logistic regression were performed to determine biomarkers predictive of active malignancy. Predictors were derived from a predictive model for active malignancy. A comparison between known and unknown (=occult) malignancies when the index stroke occurred was used to eliminate variables not associated with occult malignancy. A predictive score (OCCULT-5 score) for occult malignancy was developed based on the remaining variables. RESULTS From 1001 AIS patients, 61 (6%) presented an active malignancy. Thirty-nine (64%) were known and 22 (36%) occult. Five variables were included in the final OCCULT-5 score: age ≥ 77 years, embolic stroke of undetermined source, multi-territorial infarcts, D-dimer levels ≥ 820 µ/gL, and female sex. A score of ≥ 3 predicted an underlying occult malignancy with a sensitivity of 64%, specificity of 73%, positive likelihood ratio of 2.35 and a negative likelihood ratio of 0.50. CONCLUSIONS The OCCULT-5 score might be useful to identify patients with occult malignancy. It may thus contribute to a more effective and timely treatment and thus lead to a positive impact on overall outcome

Anxiety, concerns and COVID-19: Cross-country perspectives from families and individuals with neurodevelopmental conditions

BACKGROUND: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time. METHODS: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents. RESULTS: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children’s anxiety was best explained by child-related factors such as children’s concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents. CONCLUSIONS: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises