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Jeannette A Goudzwaard,1 Eleonora Disegna,1 Marjo JAG de Ronde-Tillmans,2 Mattie J Lenzen,2 Peter PT de Jaegere,2 Francesco US Mattace-Raso11Section of Geriatric Medicine, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; 2Department of Interventional Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the NetherlandsBackground: Both aortic valve stenosis and aortic stiffness are moderators of arterio ventricular coupling and independent predictors of cardiovascular morbidity and mortality. Studies on the effect of transcatheter aortic valve implantation (TAVI) on aortic functional properties are limited. We performed a study to investigate the possible short-term changes in aortic stiffness and other aortic functional properties after TAVI in older patients.Methods: TAVI Care&Cure is an observational ongoing study including consecutive patients undergoing a TAVI procedure. Central and peripheral hemodynamic measurements were measured non invasively 1 day before (T-1) and 1 day after (T+1) TAVI using a validated oscillometric method using a brachial cuff (Mobil-O-Graph).Results: 40 patients were included. Mean aortic valve area at baseline was 0.76±0.24 cm2. Indices of severity of aortic valve stenosis improved significantly. Systolic blood pressure (SBP) dropped by 8.5%, from 130.3±22.9 mmHg to 119.5±15.8 mmHg (p=0.005). Diastolic blood pressure (DBP) dropped by 13.1% from 74.8±14.5 mmHg to 65.0±11.3 mmHg (p

Abstract. Background:. Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods:. Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University. Results:. 3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2–5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P

Abstract BackgroundAdolescent mental health is of utmost importance. E-mental health interventions, and serious games in particular, are appealing to adolescents and can have beneficial effects on their mental health. A serious game aimed at improving cognitive vulnerability (ie, beliefs or attitudes), which can predispose an individual to mental health problems, can contribute to the prevention of these problems in adolescents. ObjectiveThis study aimed to assess the feasibility of the prototype of a serious game called “Silver.” MethodsThe prototype of the serious game was developed using a user-centered participatory design. The prototype of Silver focused on 1 aspect of a serious game for improving cognitive vulnerability in adolescents, that is, the recognition and identification of cognitive distortions. Through the game, players were required to identify and classify the character’s thoughts as helpful or unhelpful. Upon successful advancement to the next level, the task becomes more challenging, as players must also identify specific types of cognitive distortions. A pre- and posttest uncontrolled design was used to evaluate the game, with a 1-week intervention phase in which participants were asked to play the game. Participants aged 12-16 years were recruited in schools. The outcomes of interest were the recognition of cognitive distortions and presence of participants’ cognitive distortions. The game was also evaluated on its effects, content, and usefulness. ResultsA total of 630 adolescents played Silver and completed the assessments. Adolescents were significantly better at recognizing cognitive distortions at the pretest (mean 13.09, SD 4.08) compared to the posttest (mean 13.82, SD 5.09; t629Pt629P ConclusionsFindings from this study suggest that a serious game may be an effective tool for improving cognitive vulnerability in adolescents. The development of such a serious game, based on the prototype, is recommended. It may be an important and innovative tool for the universal prevention of mental health problems in adolescents. Future research on the effects of the game is warranted.

BackgroundSuicide is a global public health problem. Digital interventions are considered a low-threshold treatment option for people with suicidal ideation or behaviors. Internet-based cognitive behavioral therapy (iCBT) targeting suicidal ideation has demonstrated effectiveness in reducing suicidal ideation. However, suicidal ideation often is related to additional mental health problems, which should be addressed for optimal care. Yet, the effects of iCBT on related symptoms, such as depression, anxiety, and hopelessness, remain unclear. ObjectiveWe aimed to analyze whether digital interventions targeting suicidal ideation had an effect on related mental health symptoms (depression, anxiety, and hopelessness). MethodsWe systematically searched CENTRAL, PsycInfo, Embase, and PubMed for randomized controlled trials that investigated guided or unguided iCBT for suicidal ideation or behaviors. Participants reporting baseline suicidal ideation were eligible. Individual participant data (IPD) were collected from eligible trials. We conducted a 1-stage IPD meta-analysis on the effects on depression, anxiety, and hopelessness—analyzed as 2 indices: symptom severity and treatment response. ResultsWe included IPD from 8 out of 9 eligible trials comprising 1980 participants with suicidal ideation. iCBT was associated with significant reductions in depression severity (b=−0.17; 95% CI −0.25 to −0.09; P

Background Recurrence of mitral regurgitation (MR) after surgical mitral valve repair (SMVR) varies and may require reoperation. Redo mitral valve surgery can be technically challenging and is associated with increased risk of mortality and morbidity. We aimed to assess the feasibility and safety of MitraClip as a treatment strategy after failed SMVR and identify procedure modifications to overcome technical challenges. Methods and Results This international multicenter observational retrospective study collected information for all patients from 16 high‐volume hospitals who were treated with MitraClip after failed SMVR from October 29, 2009, until August 1, 2017. Data were anonymously collected. Technical and device success were recorded per modified Mitral Valve Academic Research Consortium criteria. Overall, 104 consecutive patients were included. Median Society of Thoracic Surgeons score was 4.5% and median age was 73 years. At baseline, the majority of patients (82%) were in New York Heart Association class ≥III and MR was moderate or higher in 86% of patients. The cause of MR pre‐SMVR was degenerative in 50%, functional in 35%, mixed in 8%, and missing/unknown in 8% of patients. The median time between SMVR and MitraClip was 5.3 (1.9–9.7) years. Technical and device success were 90% and 89%, respectively. Additional/modified imaging was applied in 21% of cases. An MR reduction of ≥1 grade was achieved in 94% of patients and residual MR was moderate or less in 90% of patients. In‐hospital all‐cause mortality was 2%, and 86% of patients were in New York Heart Association class ≤II. Conclusions MitraClip is a safe and less invasive treatment option for patients with recurrent MR after failed SMVR. Additional/modified imaging may help overcome technical challenges during leaflet grasping.

Precision medicine has recently become widely advocated. It revolves around the individual patient, taking into account genetic, biomarker, phenotypic or psychosocial characteristics and uses biological, mechanical and/or personal variables to optimise individual therapy. In silico testing, such as the Virtual Physiological Human project, is being promoted to predict risk and to test treatments and medical devices. It combines artificial intelligence and computational modelling to select the best therapeutic option for the individual patient.

Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with

Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.

The number of transcatheter aortic valve implantation (TAVI) procedures is expected to increase significantly in the coming years. Improving efficiency will become essential for experienced operators performing large TAVI volumes, while new operators will require training and may benefit from accurate support. In this work, we present a fast deep learning method that can predict aortic annulus perimeter and area automatically from aortic annular plane images. We propose a method combining two deep convolutional neural networks followed by a postprocessing step. The models were trained with 355 patients using modern deep learning techniques, and the method was evaluated on another 118 patients. The method was validated against an interoperator variability study of the same 118 patients. The differences between the manually obtained aortic annulus measurements and the automatic predictions were similar to the differences between two independent observers (paired diff. of 3.3 ± 16.8 mm2 vs. 1.3 ± 21.1 mm2 for the area and a paired diff. of 0.6 ± 1.7 mm vs. 0.2 ± 2.5 mm for the perimeter). The area and perimeter were used to retrieve the suggested prosthesis sizes for the Edwards Sapien 3 and the Medtronic Evolut device retrospectively. The automatically obtained device size selections accorded well with the device sizes selected by operator 1. The total analysis time from aortic annular plane to prosthesis size was below one second. This study showed that automated TAVI device size selection using the proposed method is fast, accurate, and reproducible. Comparison with the interobserver variability has shown the reliability of the strategy, and embedding this tool based on deep learning in the preoperative planning routine has the potential to increase the efficiency while ensuring accuracy.

Background: Both aortic valve stenosis as aortic stiffness are moderators of arterio-ventricular coupling and independent predictors of cardiovascular morbidity and mortality. Studies on the effect of Transcatheter Aortic Valve Implantation (TAVI) on hemodynamic parameters are limited. We performed a pilot study to investigate possible short-term hemodynamic changes after TAVI in older patients. Methods: TAVI Care & Cure is an observational ongoing study including consecutive patients undergoing TAVI procedure. Central and peripheral hemodynamic measurements were measured non-invasively 1 day before (T0) and 1 day after (T1) TAVI using a validated oscillometric method using a brachial cuff (Mobil-O-Graph). Results: 40 patients were included. Mean aortic valve area at baseline was 0.73 ± 0.18 cm2. As expected indices of severity of the aortic valve stenosis improved. Systolic blood pressure (SBP) dropped by 8.5%, from 130.3 ± 22.9 mmHg to 119.5 ± 15.8 mmHg (p = 0.005). Diastolic blood pressure (DBP) dropped by 13.1 % from 74.8 ± 14.5 mmHg to 65.0 ± 11.3 mmHg (p < 0.001). The aPulse Wave Velocity (aPWV) decreased from 12.05 ± 1.99 m/s to 11.6 ± 1.56 m/s (p = 0.006)(Fig. 1). Patients with high aPWV at baseline showed a significantly larger reduction in SBP in comparison to patients with low aPWV: − 20.3 mmHg (−14,1%) vs – 3,1 mmHg (−2.6%), respectively (p = 0.033). The same trend was found for the DBP: −16.2 (−20.4%) v.s. −4.5 mmHg (−6.3%) for high vs. low aPWV at baseline (p=0.037). Conclusion: We found short term changes of blood pressure and aortic stiffness after TAVI. The amplitude of the changes was the largest in patients with elevated aortic stiffness at baseline.

Background: Aortic valve stenosis (AS) is common in the elderly and is associated with high morbidity and mortality, and leads to functional decline. The aim of this study was to investigate the possible relation between aortic stiffness, AS and frailty in older patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Methods: TAVI Care&Cure is an observational ongoing study including consecutive patients undergoing TAVI procedure at the Erasmus University Medical Center. Prior to TAVI echocardiography was performed and aortic stiffness was measured non-invasively by the Mobil-O-Graph. The frailty status was assessed including 5 domains. Primary outcome was to investigate the relationship between structural and functional cardiovascular parameters and frailty status. Linear regression was used. Results: A total of 212 patients were included for analysis. Mean age was 79,2 years (±7,8), 52,7% men, mean Aortic Valve Area (AVA) was 0,73 (± 0,3), mean Pulse Wave Velocity was 12,6 (±1,5). Frailty was found in 57,8%. Peripheral pulse pressure (p = 0.04) and central pulse pressure (p = 0.02) but not aortic stiffness were associated with AS severity. AVA was associated with frailty (p = 0.02) whereas measures of aortic stiffness were not. Conclusion: Aortic valve area but not measures of aortic stiffness is associated with frailty status in elderly patients with AS undergoing a TAVI procedure.

BackgroundCoronary artery perforation (CAP) is a potentially lethal complication of percutaneous coronary intervention. We report on the incidence, clinical characteristics, and management of iatrogenic coronary perforations based on an 11‐year single‐center experience. Methods and ResultsFrom February 9, 2005, through November 20, 2016, 150 CAP cases were identified from our percutaneous coronary intervention database of 21 212 procedures (0.71%). Mean age of CAP patients was 66±11 years, and 62.7% were male. Treated lesion type was B2/C in 94.6%, and 31.3% were chronic total occlusions. Nonworkhorse guidewires were applied in 74.3%. CAP types were Ellis type I in 2.9%, Ellis type II in 40.4%, Ellis type III in 54.8%, and Ellis type III cavity spilling in 1.9%. CAP treatment was conservative (including prolonged balloon inflation) in 73.3%. Covered stents, coiling, and fat embolization were used in 24.0%, 0.7%, and 2.0%, respectively. Pericardiocentesis for tamponade was required for 72 patients (48.0%), of whom 28 were initially unrecognized. Twelve patients (12.7%) required emergency cardiac surgery to alleviate tamponade. Periprocedural myocardial infarction occurred in 34.0%, and in‐hospital all‐cause mortality was 8.0%. All‐cause mortality accrued to 10.7% at 30 days and 17.8% at 1 year. ConclusionsCAP is a rare complication of percutaneous coronary intervention, but morbidity and mortality are considerable. Early recognition and adequate management are of paramount importance.

Background Right bundle branch block is an established predictor for new conduction disturbances and need for a permanent pacemaker (PPM) after transcatheter aortic valve replacement. The aim of the study was to evaluate the absolute rates of transcatheter aortic valve replacement related PPM implantations in patients with pre‐existent right bundle branch block and categorize for different transcatheter heart valves. Methods and Results We pooled data on 306 transcatheter aortic valve replacement patients from 4 high‐volume centers in Europe and selected those with right bundle branch block at baseline without a previously implanted PPM. Logistic regression was used to evaluate whether PPM rate differed among transcatheter heart valves after adjustment for confounders. Mean age was 83±7 years and 63% were male. Median Society of Thoracic Surgeons score was 6.3 (interquartile range, 4.1–10.2). The following transcatheter valve designs were used: Medtronic CoreValve (n=130; Medtronic, Minneapolis, MN); Edwards Sapien XT (ES‐XT; n=124) and Edwards Sapien 3 (ES‐3; n=32; Edwards Lifesciences, Irvine, CA); and Boston Scientific Lotus (n=20; Boston Scientific Corporation, Marlborough, MA). Overall permanent pacemaker implantation rate post‐transcatheter aortic valve replacement was 41%, and per valve design: 75% with Lotus, 46% with CoreValve, 32% with ES‐XT, and 34% with ES‐3. The indication for PPM implantation was total atrioventricular block in 98% of the cases. Lotus was associated with a higher PPM rate than all other valves. PPM rate did not differ between ES‐XT and ES‐3. Ventricular paced rhythm at 30‐day and 1‐year follow‐up was present in 81% at 89%, respectively. Conclusions Right bundle branch block at baseline is associated with a high incidence of PPM implantation for all transcatheter heart valves. PPM rate was highest for Lotus and lowest for ES‐XT and ES‐3. Pacemaker dependency remained high during follow‐up.

BACKGROUND:Suicide is a major public health issue and has large impact on the lives of many people. Innovative technologies such as smartphones could create new possibilities for suicide prevention, such as helping to overcome the barriers and stigma on help seeking in case of suicidal ideation. Due to their omnipresence, smartphone apps can offer suicide prevention tools very fast, they are easily-accessible, low-threshold and can help overcome some of the help-seeking barriers suicidal people experience. This article describes the development, testing and implementation of a mobile application for coping with suicidal crisis: BackUp. METHODS:Based on the analysis of literature and existing suicide prevention apps several tools were identified as relevant to include in a suicide prevention app. The selected tools (a safety planning tool, a hope box, a coping cards module, and a module to reach out) are evidence based in a face to face context, and could be easily transferred into a mobile app. The testing of existing apps and the literature also revealed important guidelines for the technical development of the application. RESULTS:BackUp was developed and tested by an expert panel (n = 9) and a panel of end users (n = 21). Both groups rated BackUp as valuable for suicide prevention. Suicidal ideation of the end user group was measured using the Beck Scale for Suicidal Ideation before and after testing BackUp, and showed a small but non-significant decrease. The majority of the testers used BackUp several times. All tools were evaluated as rather or very useable in times of suicidal crisis. CONCLUSION:BackUp was positively evaluated and indicates that self-help tools can have a positive impact on suicidal ideation. Apps in particular create opportunities in approaching people that are not reached by traditional interventions; on the other hand they can contribute to suicide prevention in addition to regular care. However, more research is needed on the impact and effect of suicide prevention apps.

PURPOSE:Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. METHODS:Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. RESULTS:Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5-30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). CONCLUSIONS:Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-associated adRP by the identification of 17 novel mutations.

Populations of bank voles (Clethrionomys glareolus) were monitored during a 4-year study in southern Belgium to assess the influence of agonistic behavior, reproductive status, mobility, and distribution of the rodents on the dynamics of Puumala virus (abbreviation: PUUV; genus: Hantavirus) infection. Concordance was high between data from serologic testing and results of viral RNA detection. Wounds resulting from biting or scratching were observed mainly in adult rodents. Hantavirus infection in adults was associated with wounds in the fall, i.e., at the end of the breeding season, but not in spring. In addition, sexually active animals were significantly more often wounded and positive for infection. Hantavirus infection was associated with higher mobility in juvenile and subadult males. Seroconversions observed 6 months apart also occurred more frequently in animals that had moved longer distances from their original capture point. During nonepidemic years, the distribution of infection was patchy, and positive foci were mainly located in dense ground vegetation.