A Neuronal Network-Based Score Predicting Survival in Patients Undergoing Aortic Valve Intervention: The ABC-AS Score.

Background: Despite being the most commonly performed valvular intervention, risk prediction for aortic valve replacement in patients with severe aortic stenosis by currently used risk scores remains challenging. The study aim was to develop a biomarker-based risk score by means of a neuronal network. Methods: In this multicenter study, 3595 patients were divided into test and validation cohorts (70% to 30%) by random allocation. Input variables to develop the ABC-AS score were age, the cardiac biomarker high-sensitivity troponin T, and a patient history of cardiac decompensation. The validation cohort was used to verify the scores' value and for comparison with the Society of Thoracic Surgery Predictive Risk of Operative Mortality score. Results: Receiver operating curves demonstrated an improvement in prediction by using the ABC-AS score compared to the Society of Thoracic Surgery Predictive Risk of Operative Mortality (STS prom) score. Although the difference in predicting cardiovascular mortality was most notable at 30-day follow-up (area under the curve of 0.922 versus 0.678), ABC-AS also performed better in overall follow-up (0.839 versus 0.699). Furthermore, univariate analysis of ABC-AS tertiles yielded highly significant differences for all-cause (p < 0.0001) and cardiovascular mortality (p < 0.0001). Head-to-head comparison between both risk scores in a multivariable cox regression model underlined the potential of the ABC-AS score (HR per z-unit 2.633 (95% CI 2.156-3.216), p < 0.0001), while the STS prom score failed to reach statistical significance (p = 0.226). Conclusions: The newly developed ABC-AS score is an improved risk stratification tool to predict cardiovascular outcomes for patients undergoing aortic valve intervention.

Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement.

Introduction: Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. Methods: A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. Results: The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). Conclusions: HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible.

Takotsubo syndrome before and during the COVID-19 pandemic in Austria: a retrospective cohort study (TOSCA-19).

AIMS: This study aims to investigate the prevalence of Takotsubo syndrome (TTS) as a percentage of the total number of acute coronary syndrome (ACS), including non-STE-elevation myocardial infarction and ST-elevation myocardial infarction, as well as the short-term outcome of TTS patients before and during the COVID-19 pandemic. METHODS AND RESULTS: We compared patients from two different periods: (i) Period 1 (before the COVID-19 pandemic): 1 March to 30 December 2019, and (ii) Period 2 (during the COVID-19 pandemic): 1 March to 30 December 2020. The retrospective database was created from the archives of the participating hospitals or electronic hospital systems by trained medical personnel. The subjects' medical history, cardiovascular risk factors, laboratory values, echocardiography findings, and an in-hospital outcome were variables of interest. Furthermore, propensity score matching analysis was performed to evaluate the short-term prognosis in TTS and ACS patients. Altogether six Austrian centres-(i) 3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring, Vienna, Austria; (ii) 5th Medical Department of Cardiology, Clinic Favoriten, Vienna, Austria; (iii) 2nd Medical Department, Hanusch Hospital, Vienna, Austria; (iv) University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Austria; (v) Department of Cardiology, University Hospital Graz, Graz, Austria; (vi) Department of Cardiology and Intensive Medicine, Kepler University Clinic, Linz, Austria-participated in the study. During period 1, 87 (3.5%) patients out of 2482 ACS patients had TTS in all participating centres. During period 2, 71 (2.7%) patients out of 2572 ACS patients had TTS in all participating centres. Accordingly, the prevalence of TTS remained stable irrespective of potential psychologic stress during the COVID pandemic. Furthermore, the baseline characteristics of TTS patients did not change during the COVID-19 pandemic. The prevalence of in-hospital complications [cardiogenic shock (4.6% vs. 4.3%, P = 0.925), ventricle thrombus (1.1% vs. 1.4%, P = 0.885) and in-hospital bleeding (3.4% vs. 1.4%, P = 0.417)] remained stable. The all-cause in-hospital mortality of TTS patients did not change during the COVID-19 pandemic [χ2 (2) = 0.058, P = 0.810]. Moreover, a propensity score matching analysis of all-cause in-hospital mortality between matched TTS and ACS patients showed higher in-hospital mortality in ACS patients during COVID-19 pandemic (P = 0.043). CONCLUSIONS: Despite the well-known increased psychologic stress during the COVID-19 pandemic, the prevalence of TTS during the COVID-19 pandemic and the short-term clinical outcome in Austria remained unimpacted.

Development of a PNGase Rc Column for Online Deglycosylation of Complex Glycoproteins during HDX-MS.

Protein glycosylation is one of the most common PTMs and many cell surface receptors, extracellular proteins, and biopharmaceuticals are glycosylated. However, HDX-MS analysis of such important glycoproteins has so far been limited by difficulties in determining the HDX of the protein segments that contain glycans. We have developed a column containing immobilized PNGase Rc (from Rudaea cellulosilytica) that can readily be implemented into a conventional HDX-MS setup to allow improved analysis of glycoproteins. We show that HDX-MS with the PNGase Rc column enables efficient online removal of N-linked glycans and the determination of the HDX of glycosylated regions in several complex glycoproteins. Additionally, we use the PNGase Rc column to perform a comprehensive HDX-MS mapping of the binding epitope of a mAb to c-Met, a complex glycoprotein drug target. Importantly, the column retains high activity in the presence of common quench-buffer additives like TCEP and urea and performed consistent across 114 days of extensive use. Overall, our work shows that HDX-MS with the integrated PNGase Rc column can enable fast and efficient online deglycosylation at harsh quench conditions to provide comprehensive analysis of complex glycoproteins.

NT-pro-BNP as a Predictor for Recurrence of Atrial Fibrillation after Primary Cryoballoon Pulmonary Vein Isolation.

NT-pro-BNP is produced in the cardiac atria and ventricles in response to increased wall stress. It may be a marker of both AF disease progression and co-morbidities that affect success after pulmonary vein isolation (PVI). This single-center retrospective study analyzed the association between pre-procedural NT-pro-BNP serum levels and the long-term outcome after a first-ever PVI in cryo-technique. Patients were followed by searching the hospital information system and conducting structured telephone interviews. Treatment failure was defined as any relapse of atrial fibrillation (AF) occurring 90 days after the index PVI at the earliest. Kaplan−Meier survival curves and Cox proportional hazards models were computed to assess the impact of NT-pro-BNP on AF recurrence. Following 374 patients over a median of 3.8 years (range: 0.25−9.4 years), baseline NT-pro-BNP was associated with the combined endpoint in univariate analysis (HR 1.04 per 100 pg/mL increase, 95% CI: 1.02−1.07, p < 0.001). Results were virtually unchanged in the multivariate model or if the data were log-transformed. Intraprocedural left atrial pressure correlated positively with log NT-pro-BNP. NT-pro-BNP was associated with AF relapse during a long-term follow-up after first-ever cryo-PVI in our cohort of patients with predominantly normal left ventricular function. This lab parameter is easy to obtain and has significant potential to guide treatment decisions.

Byzantine Empire Economic Growth: Did Past Climate Change Play a Role?

Different chronicles of the Byzantine Empire's history have noted various economic data gleaned from historical documents and accounts of the Empire's existence. I provide conjectures on approximate real GDP per capita for the Empire over its existence from AD 300 to 1453. I use these to investigate whether climate forcing variables are associated with real GDP per capita fluctuations. Some hypotheses on factors that would have affected Byzantine economic performance are tested using climate/environmental factors in time series regression. The results support and confirm some findings on how the Byzantine economy may have been affected by periods of regional climate change. Supplementary Information: The online version contains supplementary material available at 10.1007/s10745-022-00343-3.

Neutrophile-Lymphocyte Ratio and Outcome in Takotsubo Syndrome.

Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of independent predictors on long-term survival was evaluated. Results: A total of 338 patients (median age 72 years, 86.9% female) from six centers were included. Severe in-hospital complications occurred in 14.5% of patients. In multivariable analysis, high neutrophile-lymphocyte-ratio (NLR; OR 1.04 [95% CI 1.02−1.07], p = 0.009) and low LVEF (OR 0.92 [0.90−0.95] per %, p < 0.001) were significant predictors of severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were significantly associated with reduced 5-year survival. Conclusions: Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short- and long-term outcome after TTS.

PNGase H + variant from Rudaea cellulosilytica with improved deglycosylation efficiency for rapid analysis of eukaryotic N-glycans and hydrogen deuterium exchange mass spectrometry analysis of glycoproteins.

The analysis of glycoproteins and the comparison of protein N-glycosylation from different eukaryotic origins require unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N-glycosylation currently depends extensively on bacterial peptide-N4-(N-acetyl-ß-glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine-linked oligosaccharides (N-glycans) from glycoproteins. So far, only limited PNGase candidates are available for N-glycans analysis, and particularly the analysis of plant and invertebrate N-glycans is hampered by the lack of suitable PNGases. Furthermore, liquid chromatography-mass spectrometry (LC-MS) workflows, such as hydrogen deuterium exchange mass spectrometry (HDX-MS), require a highly efficient enzymatic release of N-glycans at low pH values to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N-glycanase (PNGase H+ ) originating from the soil bacterium Rudaea cellulosilytica (Rc), which has significantly improved enzymatic properties compared to previously described PNGase H+ variants. Active and soluble recombinant PNGase Rc was expressed at a higher protein level (3.8-fold) and with higher specific activity (~56% increase) compared to the currently used PNGase H+ variant from Dyella japonicum (Dj). Recombinant PNGase Rc was able to deglycosylate the glycoproteins horseradish peroxidase and bovine lactoferrin significantly faster than PNGase Dj (10 min vs. 6 h). The versatility of PNGase Rc was demonstrated by releasing N-glycans from a diverse array of samples such as peach fruit, king trumpet mushroom, mouse serum, and the soil nematode Caenorhabditis elegans. The presence of only two disulfide bonds shown in the AlphaFold protein model (so far all other superacidic PNGases possess more disulfide bonds) could be corroborated by intact mass- and peptide mapping analysis and provides a possible explanation for the improved recombinant expression yield of PNGase Rc.

A Home Care Regimen With Oral-B iO Toothbrush and Targeted Clean Brush Head to Reduce Peri-Implant Mucositis.

OBJECTIVE: This practice-based case series evaluated the effects of the Oral-B® iO™ oscillatingrotating (O-R) electric toothbrush with the novel Targeted Clean™ brush head as part of a home care regimen on the health of the tissues surrounding implant-borne fixed restorations. METHODS: Eight generally healthy, nonsmoking patients withj peri-implant mucositis in at least one implant site and moderate-to-high plaque levels who had not had a professional cleaning in 3 months and were not currently using an O-R toothbrush were recruited from the author's practice. Fixed implant restorations on these eight patients were evaluated for plaque and gingival inflammation (erythema, swelling, and bleeding on probing [BOP]). In collaboration with the dental hygiene team, the patients were introduced to specific protocols for implant maintenance utilizing the Oral-B iO O-R brush and the Targeted Clean brush head. After 6 weeks, the patients were re-evaluated. Clinical findings with photographs and probing as well as the impact of the intervention on each patient's motivation and compliance in maintaining oral hygiene at home were recorded. RESULTS: After 6 weeks, implant sites with baseline peri-implant mucositis demonstrated no BOP or other signs of infl ammation and reduced plaque scores. The patients' home care compliance and motivation to maintain effective oral hygiene around their implants saw a substantial improvement. CONCLUSIONS: The Oral-B iO O-R electric toothbrush with the novel Targeted Clean brush head, used as part of a home care regimen, markedly reduced peri-implant mucositis around fixed implant restorations among all eight patients in this case series. Key factors were the patient owning their disease pattern and the doctor/hygienist collaboration and use of education protocols to help improve the patients' home care compliance and motivation.

Impact of Contact Force-Sensing Catheters on Fluoroscopy Time in Interventional Electrophysiology: A European Survey.

This multicenter European survey systematically evaluated the impact of using contact force-sensing catheters (CFSCs) on fluoroscopy and procedure time in interventional electrophysiology. Data from 25 participating centers were collected and analyzed, also considering important confounders. With the use of CFSCs, fluoroscopy time was reduced for right- and left-sided atrial ablations (median −6.4 to −9.6 min, p < 0.001 for both groups), whereas no such effect could be found for ventricular ablations. Moreover, the use of CFSCs was associated with an increase in procedure time for right-sided atrial and ventricular ablations (median +26.0 and +44.0 min, respectively, p < 0.001 for both groups), but not for left-sided atrial ablations. These findings were confirmed independent of career level and operator volume, except for very highly experienced electrophysiologists, in whom the effect was blunted. In the subset of pulmonary vein isolations (PVIs), CFSCs were shown to reduce both fluoroscopy and procedure time. In conclusion, the use of CFSCs was associated with a reduced fluoroscopy time for atrial ablations and an increased procedure time for right atrial and ventricular ablations. These effects were virtually independent of the operator experience and caseload. When considering only PVIs as an important subset, CFSCs were shown to reduce both fluoroscopy and procedure time.

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.

Pore dynamics and asymmetric cargo loading in an encapsulin nanocompartment.

Encapsulins are protein nanocompartments that house various cargo enzymes, including a family of decameric ferritin-like proteins. Here, we study a recombinant Haliangium ochraceum encapsulin:encapsulated ferritin complex using cryo-electron microscopy and hydrogen/deuterium exchange mass spectrometry to gain insight into the structural relationship between the encapsulin shell and its protein cargo. An asymmetric single-particle reconstruction reveals four encapsulated ferritin decamers in a tetrahedral arrangement within the encapsulin nanocompartment. This leads to a symmetry mismatch between the protein cargo and the icosahedral encapsulin shell. The encapsulated ferritin decamers are offset from the interior face of the encapsulin shell. Using hydrogen/deuterium exchange mass spectrometry, we observed the dynamic behavior of the major fivefold pore in the encapsulin shell and show the pore opening via the movement of the encapsulin A-domain. These data will accelerate efforts to engineer the encapsulation of heterologous cargo proteins and to alter the permeability of the encapsulin shell via pore modifications.

Delayed Total Atrioventricular Block After Transcatheter Aortic Valve Replacement Assessed by Implantable Loop Recorders.

OBJECTIVES: The aims of this study were to evaluate the rate and time course of delayed total atrioventricular block (DT-AVB) after transcatheter aortic valve replacement (TAVR) using continuous electrocardiographic monitoring by implantable loop recorders and to identify potential predictors. BACKGROUND: DT-AVB has been defined as onset more than 2 days after TAVR or after hospital discharge and is reported in 10% to 15% of patients at 30-day follow-up. To date, there is no standardized diagnostic and therapeutic algorithm to manage TAVR patients at risk for DT-AVB. METHODS: Consecutive patients undergoing TAVR and simultaneous electrophysiologic testing without persistent or recurrent total atrioventricular block within 48 hours after the procedure underwent loop recorder implantation for full disclosure of atrioventricular conduction during 12-month follow-up. RESULTS: DT-AVB occurred in 7 of 59 patients (11.9%), with onset between 2 days and 3 months after the procedure. Both prolongation of the PQ interval between baseline and day 2 after TAVR (OR: 1.04; 95% CI: 1.01-1.09); P = 0.032) and prolongation of the HV interval during the procedure (OR: 1.07; 95% CI: 1.02-1.14; P = 0.015) significantly predicted the onset of DT-AVB. CONCLUSIONS: TAVR was associated with a considerable rate of DT-AVB of nearly 12% in this series. Prolongation of the PQ interval between baseline and day 2 and intraprocedural prolongation of the HV interval were significant predictors of DT-AVB.

Troponin interference with special regard to macrocomplex formation.

Biomarkers, such as troponin-T and troponin-I, are regarded as the gold standard laboratory parameter for diagnosing many cardiological diseases. These parameters have been approved for clinical use. Many cardiological guidelines recommend the analysis of troponins in the majority of cardiological disease diagnoses and to also gain prognostic information. Nonetheless, many medical circumstances could cause false troponin elevations. In this article, we focus on troponin artifacts, particularly macro-immune complex formation, as important interference factors. Therefore, we performed a literature search from 2006 to 06/2021.

Predictors of true-severe classical low-flow low-gradient aortic stenosis at resting echocardiography.

BACKGROUND: Classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) is subclassified into a true-severe (TS) and a pseudo-severe (PS) subform using low-dose dobutamine stress echocardiography (DSE). In clinical practice a resting peak jet velocity (Vmax) >3.5 m/s or a mean transvalvular gradient (MPG) >35 mmHg suggests the presence of TS classical LF/LG AS, but there is no data to support this. The aim of this study was therefore to investigate whether a resting Vmax >3.5 m/s or MPG >35 mmHg reliably predicted diagnosis of TS classical LF/LG AS. METHODS: One hundred (100) consecutive patients with classical LF/LG AS were prospectively recruited. All patients underwent DSE for subcategorization. The impact of Vmax and MPG for the presence of the TS subform were analyzed. RESULTS: TS classical LF/LG AS was diagnosed in 72 patients. Resting Vmax and resting MPG predicted true-severity with an ROC-AUC of 0.737 (95%CI: 0.635-0.838; p < 0.001) and 0.725 (95%CI: 0.615-0.834; p < 0.001), respectively. The optimal positive predictive values (PPV) for the diagnosis of TS classical LF/LG AS were obtained with a resting Vmax >3.5 m/s or resting MPG >35 mmHg. In a multivariate logistic regression analysis, Vmax >3.5 m/s was independently associated with a 5.33-fold odds-ratio of TS classical LF/LG AS (OR 5.33; 95%CI: 1.34-21.18, p = 0.018). CONCLUSIONS: TS classical LF/LG AS can be reliably predicted by a resting Vmax >3.5 m/s or a resting MPG >35 mmHg. Further imaging for subclassification is not needed in this situation.

Cardiac Computed Tomography-Derived Left Atrial Volume Index as a Predictor of Long-Term Success of Cryo-Ablation in Patients With Atrial Fibrillation.

Patients with symptomatic, drug-refractory atrial fibrillation (AF) are frequently treated with catheter ablation. Cryo-ablation has been established as an alternative to radiofrequency ablation but long-term outcome data are still limited. This study aimed at elucidating the influence of the left atrial volume index (LAVI), derived from cardiac computed tomography (cCT) data, on the long-term outcome of ablation-naïve AF patients, after their first cryo-ablation. 415 patients (n = 290 [69.90%] male, 60.00 [IQR: 53.00 to 68.00] years old) who underwent a cCT and subsequent cryo-ablation index procedure were included in this single centre retrospective data analysis. A composite end point was defined (AF on electrocardiogram and/or electric cardioversion and/or re-do). Patients were closely followed for a year and then contacted for long-term follow-up after a median of 53.00 months (IQR: 34.50 to 73.00). Statistical analyses of the outcome and predictors of AF recurrence were conducted. In 224 patients (53.98%) no evidence of AF recurrence could be found. LAVI differed significantly between the positive and adverse (AF recurrence) outcome group (49.96 vs 56.07 ml/m2, p < 0.001). Cox regression analyses revealed cCT LAVI (HR: 1.022, 95% CI: 1.013 to 1.031, p < 0.001), BMI (HR: 1.044, 95% CI: 1.005 to 1.084, p < 0.05) and the type of AF (HR: 1.838 for nonparoxysmal AF, 95% CI: 1.214 to 2.781, p < 0.01) to be effective predictors of AF recurrence. A prognostic cCT LAVI cut-off value of 51.99 ml/m2 was calculated and must be validated in future prospective studies. In conclusion, LAVI is an accurate, yet underutilized predictor of AF recurrence after pulmonary vein isolation with cryo-energy and scores for calculating AF recurrence or progression risks might underemphasize the importance of CT-derived LAVI as a predictive factor.

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood. OBJECTIVE: The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing. METHODS: AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3). RESULTS: Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = -0.03, P = .762; and ρ = 0.15, P = .130, respectively). CONCLUSION: Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

Self-assessment of medical students and young physicians in training : Self-confidence of clinical competencies and working or learning environment.

BACKGROUND: In 2015 medical training regulations have been restructured for postgraduate medical training in Austria resulting in a significant shortening of the training period. Furthermore, a restriction of working hours for physicians to 48 h per week was implemented affecting the framework of postgraduate medical training. The aim of this study was to obtain a self-assessment of students and young physicians in Austria regarding their self-confidence in clinical skills and their working and learning environment. METHODS: In this study 6th year medical students, physicians in their basic training (common trunk), physicians in family medicine training, and residents in their first 18 months of training were asked to participate in a survey. Self-reported data were collected for five different prespecified domains (communication, motor skills, knowledge, documentation, and emergency). RESULTS: In all domains, self-confidence increased significantly during medical training. Analysis further revealed better results of residents compared with all other groups in all domains, whereas physicians in family medicine training only rated themselves better in the documentation domain (p = 0.010); however, the interest in family medicine was low, even among physicians in family medicine training. The workload significantly increased during medical education, with the highest stress levels for physicians in family medicine training and residents (p = 0.001). CONCLUSIONS: Self-confidence of young physicians but also their stress levels increased during the medical training. Further studies are needed to answer the question why the interest in family medicine was so unexpectedly low in this cohort.

Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT).

D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = - 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.