A decade of experience in over 300 surgically treated spine patients with long-term oral anticoagulation: a propensity score matched cohort study.

PURPOSE: The aim of this study was to investigate the risks and outcomes of patients with long-term oral anticoagulation (OAC) undergoing spine surgery. METHODS: All patients on long-term OAC who underwent spine surgery between 01/2005 and 06/2015 were included. Data were prospectively collected within our in-house Spine Surgery registry and retrospectively supplemented with patient chart and administrative database information. A 1:1 propensity score-matched group of patients without OAC from the same time interval served as control. Primary outcomes were post-operative bleeding, wound complications and thromboembolic events up to 90 days post-surgery. Secondary outcomes included intraoperative blood loss, length of hospital stay, death and 3-month post-operative patient-rated outcomes. RESULTS: In comparison with the control group, patients with OAC (n = 332) had a 3.4-fold (95%CI 1.3-9.0) higher risk for post-operative bleeding, whereas the risks for wound complications and thromboembolic events were comparable between groups. The higher bleeding risk was driven by a higher rate of extraspinal haematomas (3.3% vs. 0.6%; p = 0.001), while there was no difference in epidural haematomas and haematoma evacuations. Risk factors for adverse events among patients with OAC were mechanical heart valves, posterior neck surgery, blood loss > 1000 mL, age, female sex, BMI > 30 kg/m2 and post-operative PTT levels. At 3-month follow-up, most patients reported favourable outcomes with no difference between groups. CONCLUSION: Although OAC patients have a higher risk for complications after spine surgery, the risk for major events is low and patients benefit similarly from surgery.

High incidence of diaphragmatic myopotential oversensing by a specific implantable cardioverter defibrillator.

INTRODUCTION: Diaphragmatic myopotential oversensing (dMPO) by implantable cardioverter defibrillators (ICDs) is thought to be a rare condition that can be misdiagnosed as lead failure and lead to unnecessary lead replacement. We observed several cases of dMPO in patients with Sorin/LivaNova ICDs (MicroPort Sci.). We sought to systematically assess the incidence of dMPO in patients with Sorin/LivaNova ICDs. METHODS AND RESULTS: A predefined number of 100 consecutive patients with Sorin/LivaNova ICDs were prospectively included in the device clinic of our center. Stored arrhythmia episodes were checked for spontaneous dMPO. In addition, we performed provocation maneuvers by Valsalva. At least one episode of spontaneous or provoked dMPO was seen in 12 (12%) of the 100 patients included in the study (86% males, median age: 66 years). Nine of 89 patients (10%) with true bipolar and 3 of 11 patients (27%) with integrated bipolar sensing configuration were affected. Spontaneous dMPO was observed in 7 of 58 patients (12%) with sensitivity programmed to 0.4 mV and in 2 of 42 patients (5%) with sensitivity programmed to 0.6 mV (not significant). In three patients, dMPO could be provoked with no spontaneous episodes recorded. In two nonpacemaker-dependent patients with a CRT-D, ventricular pacing was temporarily inhibited. No antitachycardia therapy was triggered by dMPO in any patient. CONCLUSIONS: DMPO is frequent in patients with Sorin/LivaNova ICDs, especially with sensitivity programmed to 0.4 mV. It also frequently occurs with true bipolar sensing configuration. DMPO should not be misinterpreted as lead failure to avoid unnecessary lead replacement.

Radiofrequency ablation lesion assessment using optical coherence tomography - a proof-of-concept study.

BACKGROUND: Radiofrequency catheter ablation (RFA) is an effective treatment for atrial fibrillation. However, ablation lesions are usually only assessed functionally. The immediate effect of RFA on the tissue is not directly visualized. Optical coherence tomography (OCT) is an imaging technique that uses light to capture high-resolution images with histology-like quality. Therefore, it might be used for high-precision imaging of ablation lesions. METHODS AND RESULTS: Radiofrequency ablation lesions (n = 25) were produced on the freshly excised left and right ventricular porcine endocardium. A Thermocool ST SF NAV ablation catheter (Biosense Webster Inc) and an EP-Shuttle ablation generator (Stockert GmbH) were used to produce ablation lesions with powers from 10 to 40 W (energies ranging from 100 Ws to 900 Ws). After ablation, the tissue was imaged with a swept source OCT system (at a wavelength of 1300 nm). Subsequently, the ablation lesions underwent the histological analysis. The ablation lesions could be visualized by OCT in all 17 samples with ablation powers ≥20 W, meanwhile, no lesion could be observed in the other eight samples with lower power (10 W). Lesion depths and lesion radiuses, as assessed by OCT, correlated well with those observed on the subsequent histological analysis (Spearman's r = 0.94, P < 0.001 and r = 0.84, P < 0.001). In addition, successful three-dimensional reconstructions of ablation lesions were performed. CONCLUSION: OCT can provide a visual high-resolution assessment of ablation lesions.

Cardiac electrophysiology catheters for electrophysiological assessments of the lower urinary tract-A proof of concept ex vivo study in viable ureters.

AIMS: To explore the feasibility of minimally invasive catheter-based electrophysiology studies in the urinary tract. This is a well-known method used in cardiology to investigate and treat arrhythmias. METHODS: We developed an experimental platform which allows electrophysiological recordings with cardiac catheters and conventional needle electrodes in ex vivo pig ureters. The action potential was triggered by a stimulating electrode. We considered 13 porcine ureters (freshly collected and harvested in organ bath), 7 of which were used to optimize the setup and define the stimulation parameters; we performed the recordings in the remaining six ureters. The electrical propagation of the generated action potential was tracked with multiple sensing electrodes, from which propagation directions, velocities, refractory periods, and pacing thresholds were extracted. RESULTS: We recorded propagating electrical activity in four ureters using needle electrodes and in two ureters using cardiac catheters. Propagation velocities for forward direction (from kidney to bladder) derived by the two methods were similar (15.1 ± 2.6 mm/s for cardiac catheters, 15.6 ± 2.3 mm/s for needle recordings). Pacing thresholds, activation patters, and refractory times were provided for the ureteric smooth muscle. Retrograde propagations and corresponding velocities were also observed and measured. CONCLUSIONS: This study is a proof-of-concept showing that electrical activity can be measured "from the inside" of urinary cavities using catheters and that obtained results are comparable with the more invasive needle recordings. Catheter-based electrophysiology may allow, in the clinical setting, for: i) a more differentiated understanding of urological disorders such as overactive bladder and ii) new therapeutic approaches (e.g., targeted tissue ablation).

Toward a novel semi-invasive activation mapping tool for the diagnosis of supraventricular arrhythmias from the esophagus.

AIMS: Supraventricular arrhythmia diagnosis using the surface electrocardiogram (sECG) is often cumbersome due to limited atrial signal quality. In some instances, use of esophageal electrocardiography (eECG) may facilitate the diagnosis. Here, we present a novel approach to reconstruct cardiac activation maps from eECG recordings. METHODS: eECGs and sECGs were recorded from 19 individuals using standard acquisition tools. From the recordings, algorithms were developed to estimate the esophageal ECG catheter's position and to reconstruct high-resolution mappings of the cardiac electric activity projected in the esophagus over time. RESULTS: Esophageal two-dimensional activation maps were created for five healthy individuals and 14 patients suffering from different arrhythmias. The maps are displayed as time-dependent contour plots, which not only show voltage over time as conventional ECGs, but also the location, direction, and projected propagation speed of the cardiac depolarization wavefront in the esophagus. Representative examples of sinus rhythm, atrial flutter, and ventricular pre-excitation are shown. CONCLUSION: The methodology presented in this report provides a high-resolution view of the cardiac electric field in the esophagus. It is the first step toward a three-dimensional mapping system, which shall be able to reconstruct a three-dimensional view of the cardiac activation from recordings within the esophagus.

Invasive electrophysiological testing to predict and guide permanent pacemaker implantation after transcatheter aortic valve implantation: A meta-analysis.

Background: Atrioventricular conduction abnormalities after transcatheter aortic valve implantation (TAVI) are common. The value of electrophysiological study (EPS) for risk stratification of high-grade atrioventricular block (HG-AVB) and guidance of permanent pacemaker (PPM) implantation is poorly defined. Objective: The purpose of this study was to identify EPS parameters associated with HG-AVB and determine the value of EPS-guided PPM implantation after TAVI. Methods: We performed a systematic review and meta-analysis of studies investigating the value of EPS parameters for risk stratification of TAVI-related HG-AVB and for guidance of PPM implantation among patients with equivocal PPM indications after TAVI. Results: Eighteen studies (1230 patients) were eligible. In 7 studies, EPS was performed only after TAVI, whereas in 11 studies EPS was performed both before and after TAVI. Overall PPM implantation rate for HG-AVB was 16%. AV conduction intervals prolonged after TAVI, with the AH and HV intervals showing the largest magnitude of changes. Pre-TAVI HV >70 ms and the absolute value of the post-TAVI HV interval were associated with subsequent HG-AVB and PPM implantation with odds ratios of 2.53 (95% confidence interval [CI] 1.11-5.81; P = .04) and 1.10 (95% CI 1.03-1.17; P = .02; per 1-ms increase), respectively. In 10 studies, PPM was also implanted due to abnormal EPS findings in patients with equivocal PPM indications post-TAVI (typically new left bundle branch block or transient HG-AVB). Among them, the rate of long-term PPM dependency was 57%. Conclusion: Selective EPS testing may assist in the risk stratification of post-TAVI HG-AVB and in the guidance of PPM implantation, especially in patients with equivocal PPM indications post-TAVI.

Estimating the sample size of sham-controlled randomized controlled trials using existing evidence.

Background: In randomized controlled trials (RCTs), the power is often 'reverse engineered' based on the number of participants that can realistically be achieved. An attractive alternative is planning a new trial conditional on the available evidence; a design of particular interest in RCTs that use a sham control arm (sham-RCTs). Methods: We explore the design of sham-RCTs, the role of sequential meta-analysis and  conditional planning in a systematic review of renal sympathetic denervation for patients with arterial hypertension. The main efficacy endpoint was mean change in 24-hour systolic blood pressure. We performed sequential meta-analysis to identify the time point where the null hypothesis would be rejected in a prospective scenario. Evidence-based conditional sample size calculations were performed based on fixed-effect meta-analysis. Results: In total, six sham-RCTs (981 participants) were identified. The first RCT was considerably larger (535 participants) than those subsequently published (median sample size of 80). All trial sample sizes were calculated assuming an unrealistically large intervention effect which resulted in low power when each study is considered as a stand-alone experiment. Sequential meta-analysis provided firm evidence against the null hypothesis with the synthesis of the first four trials (755 patients, cumulative mean difference -2.75 (95%CI -4.93 to -0.58) favoring the active intervention)). Conditional planning resulted in much larger sample sizes compared to those in the original trials, due to overoptimistic expected effects made by the investigators in individual trials, and potentially a time-effect association. Conclusions: Sequential meta-analysis of sham-RCTs can reach conclusive findings earlier and hence avoid exposing patients to sham-related risks. Conditional planning of new sham-RCTs poses important challenges as many surgical/minimally invasive procedures improve over time, the intervention effect is expected to increase in new studies and this violates the underlying assumptions. Unless this is accounted for, conditional planning will not improve the design of sham-RCTs.

Dexmedetomidine versus propofol for operator-directed nurse-administered procedural sedation during catheter ablation of atrial fibrillation: A randomized controlled study.

BACKGROUND: Operator-directed nurse-administered (ODNA) sedation with propofol (PRO) is the preferred sedation technique for catheter ablation of atrial fibrillation (AF) in many centers. OBJECTIVE: The purpose of this study was to investigate whether dexmedetomidine (DEX), an α2-adrenergic receptor agonist, is superior to propofol. METHODS: We randomized 160 consecutive patients undergoing first AF ablation to ODNA sedation by DEX (DEX group) vs PRO (PRO group), according to a standardized protocol. Patients were unaware of treatment allocation. The primary endpoint was a composite of inefficient sedation, termination/change of sedation protocol or procedure abortion, hypercapnia (transcutaneous CO2 >55 mm Hg), hypoxemia (SpO2 <90%) or intubation, prolonged hypotension (systolic blood pressure <80 mm Hg), and sustained bradycardia necessitating cardiac pacing. Secondary endpoints were the components of the primary endpoint and patient satisfaction with procedural sedation, as assessed by a standardized questionnaire given the day after ablation. RESULTS: The primary endpoint occurred in 15 DEX group and 25 PRO group patients (19% vs 31%; P = .068). Hypercapnia was significantly more frequent in PRO group patients (29% vs 10%; P = .003). There was no significant difference for the other components of the primary endpoint, and no procedure was aborted. Patient satisfaction was significantly better among PRO group patients (visual analogue scale 0-100; median 100 in PRO group vs median 93 in DEX group; P <.001). CONCLUSION: Efficacy of ODNA sedation with DEX was not different from that with PRO. Hypercapnia occurs less frequently with DEX, but patient satisfaction is better with PRO sedation. In selected patients, DEX may be used as an alternative to PRO for ODNA sedation during AF ablation.

Development and validation pathways of artificial intelligence tools evaluated in randomised clinical trials.

OBJECTIVE: Given the complexities of testing the translational capability of new artificial intelligence (AI) tools, we aimed to map the pathways of training/validation/testing in development process and external validation of AI tools evaluated in dedicated randomised controlled trials (AI-RCTs). METHODS: We searched for peer-reviewed protocols and completed AI-RCTs evaluating the clinical effectiveness of AI tools and identified development and validation studies of AI tools. We collected detailed information, and evaluated patterns of development and external validation of AI tools. RESULTS: We found 23 AI-RCTs evaluating the clinical impact of 18 unique AI tools (2009-2021). Standard-of-care interventions were used in the control arms in all but one AI-RCT. Investigators did not provide access to the software code of the AI tool in any of the studies. Considering the primary outcome, the results were in favour of the AI intervention in 82% of the completed AI-RCTs (14 out of 17). We identified significant variation in the patterns of development, external validation and clinical evaluation approaches among different AI tools. A published development study was found only for 10 of the 18 AI tools. Median time from the publication of a development study to the respective AI-RCT was 1.4 years (IQR 0.2-2.2). CONCLUSIONS: We found significant variation in the patterns of development and validation for AI tools before their evaluation in dedicated AI-RCTs. Published peer-reviewed protocols and completed AI-RCTs were also heterogeneous in design and reporting. Upcoming guidelines providing guidance for the development and clinical translation process aim to improve these aspects.

Discharge Location and Outcomes After Transcatheter Aortic Valve Implantation.

The relation between discharge location and outcomes after transcatheter aortic valve implantation (TAVI) is largely unknown. Thus, the objective of this study was to investigate the impact of discharge location on clinical outcomes after TAVI. Between August 2007 and December 2018, consecutive patients who underwent transfemoral TAVI at Bern University Hospital were grouped according to discharge location. Clinical adverse events were adjudicated according to VARC-2 end point definitions. Of 1,902 eligible patients, 520 (27.3%) were discharged home, 945 (49.7%) were discharged to a rehabilitation clinic and 437 (23.0%) were transferred to another institution. Compared with patients discharged to a rehabilitation facility or another institution, patients discharged home were younger (80.8 ± 6.5 vs 82.9 ± 5.4 and 82.8 ± 6.4 years), less likely female (37.3% vs 59.7% and 54.2%), and at lower risk according to STS-PROM (4.5 ± 3.0% vs 5.5 ± 3.8% and 6.6 ± 4.4%). At 1 year follow-up, patients discharged home had similar rates of all-cause mortality (HRadj 0.82; 95% CI 0.54 to 1.24), cerebrovascular events (HRadj 1.04; 95% CI 0.52 to 2.08) and bleeding complications (HRadj 0.93; 95% CI 0.61 to 1.41) compared with patients discharged to a rehabilitation facility. Patients discharged home or to rehabilitation were at lower risk for death (HRadj 0.37; 95% CI 0.24 to 0.56 and HRadj 0.44; 95% CI 0.32 to 0.60) and bleeding (HRadj 0.48; 95% CI 0.30 to 0.76 and HRadj 0.66; 95% CI 0.45 to 0.96) during the first year after hospital discharge compared with patients transferred to another institution. In conclusion, discharge location is associated with outcomes after TAVI with patients discharged home or to a rehabilitation facility having better clinical outcomes than patients transferred to another institution. Clinical Trial Registration: https://www.clinicaltrials.gov. NCT01368250.

Cardiovascular clinical trials in the era of a pandemic.

COVID-19 has reached pandemic levels in March 2020 and impacted public health with unpredictable consequences.1, 2 The conduct of clinical research in areas unrelated to COVID-19 has been disrupted and will be further affected. Researchers, trial participants and study personnel have to overcome challenges to sustain proper and safe conduct of clinical trials (i.e. logistical challenges, lower enrollment than expected, difficulties in follow-up and outcome assessment/adjudication, incomplete data collection, research funding prolongation).

Antidepressant treatment in patients following acute coronary syndromes: a systematic review and Bayesian meta-analysis.

AIMS: The aim of this study is to investigate the effect of antidepressant therapy on mortality and cardiovascular outcomes in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and performed a Bayesian random-effects meta-analysis of randomized controlled trials that investigated antidepressant pharmacotherapy in patients following ACS. The primary outcome was all-cause mortality. Secondary outcomes were repeat hospitalizations and recurrent myocardial infarctions (MIs). Ten randomized controlled trials with a total of 1935 patients qualified for inclusion. Selective serotonin reuptake inhibitors were investigated in six, bupropion in three, and mirtazapine in one trial. Placebo was used as control in eight trials. There was no difference in all-cause mortality [odds ratio (OR) 0.97, 95% credible interval (CrI) 0.66-1.42] and recurrent MI (OR 0.64, 95% CrI 0.40-1.02) between patients receiving antidepressants compared with controls, whereas antidepressant therapy was associated with less repeat hospitalizations (OR 0.62, 95% CrI 0.40-0.94). In patients with ACS and concomitant depression, antidepressants reduced the odds of recurrent MI compared with usual care/placebo (OR 0.45, 95% CrI 0.25-0.81). Extended funnel plots suggest robustness of the observations. CONCLUSIONS: Antidepressants in patients following ACS have no effect on mortality but reduce repeat hospitalizations; in patients with depression, there is a reduced risk of recurrent MI with antidepressant therapy.

Diagnostic and prognostic values of the QRS-T angle in patients with suspected acute decompensated heart failure.

AIMS: The aim of this study was to investigate the diagnostic and prognostic utility of the QRS-T angle, an electrocardiogram (ECG) marker quantifying depolarization-repolarization heterogeneity, in patients with suspected acute decompensated heart failure (ADHF). METHODS AND RESULTS: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of ADHF. The QRS-T angle was automatically derived from a standard 12-lead ECG recorded at presentation. The primary diagnostic endpoint was a final adjudicated diagnosis of ADHF. The primary prognostic endpoint was all-cause mortality during 2 years of follow-up. Among the 1915 patients enrolled, those with higher QRS-T angles were older, were more commonly male, and had a higher rate of co-morbidities such as arterial hypertension, coronary artery disease, or chronic kidney disease. ADHF was the final adjudicated diagnosis in 1140 (60%) patients. The QRS-T angle in patients with ADHF was significantly larger than in patients with non-cardiac causes of dyspnoea {median 110° [inter-quartile range (IQR) 46-156°] vs. median 33° [IQR 15-57°], P < 0.001}. The diagnostic accuracy of the QRS-T angle as quantified by the area under the receiver operating characteristic curve (AUC) was 0.75 [95% confidence interval (CI) 0.73-0.77, P < 0.001], which was inferior to N-terminal pro-B-type natriuretic peptide (AUC 0.93, 95% CI 0.92-0.94, P < 0.001), but similar to that of high-sensitivity troponin T (AUC 0.78, 95% CI 0.76-0.80, P = 0.09). The AUC of the QRS-T angle for discrimination between ADHF and non-cardiac dyspnoea remained similarly high in subgroups of patients known to be diagnostically challenging, including patients older than 75 years [0.71 (95% CI 0.67-0.74)], renal failure [0.79 (95% CI 0.71-0.87)], and atrial fibrillation at presentation [0.68 (95% CI 0.60-0.76)]. Mortality rates according to QRS-T angle tertiles were 4%, 6%, and 10% after 30 days (P < 0.001) and 24%, 31%, and 43% after 2 years (P < 0.001). After adjustment for clinical, laboratory, and ECG parameters, the QRS-T angle remained an independent predictor for 2 year mortality with a 4% increase in mortality for every 20° increase in QRS-T angle (P = 0.02). CONCLUSIONS: The QRS-T angle is a readily available and inexpensive marker that can assist in the discrimination between ADHF and non-cardiac causes of acute dyspnoea and may aid in the risk stratification of these patients.

Comparison of lead failure manifestation of Biotronik Linox with St. Jude Medical Riata and Medtronic Sprint Fidelis lead.

PURPOSE: To compare lead failure manifestation and lead performance of the Biotronik Linox/Sorin Vigila defibrillator lead (Linox group) with the St. Jude Medical Riata/Riata ST (Riata group) and Medtronic Sprint Fidelis defibrillator leads (Fidelis group). METHODS: We assessed the performance of all aforementioned leads implanted at our center and investigated the manifestation of lead failures. RESULTS: Of 93 Linox, 86 Riata, and 81 Fidelis leads implanted at our center, 11 (12%), 22 (26%), and 25 (31%) leads failed during a median follow-up of 46, 61, and 84 months, respectively. Inappropriate shocks were delivered in 64% (Linox), 5% (Riata), and 32% (Fidelis) of lead failures; a device alert was noted in none (Linox), 5% (Riata), and 52% (Fidelis); and lead failure was a coincidental finding in 36% (Linox), 91% (Riata), and 16% (Fidelis) of cases (p < 0.001). Non-physiological high rate signals were observed in 73% (Linox), 27% (Riata), and 80% (Fidelis) of lead failures (p = 0.001) and damaged lead integrity was found in 36% (Linox), 73% (Riata), and 24% (Fidelis) of cases (p = 0.064). Lead survival at 5 years was 88%, 92%, and 71% for Linox, Riata, and Fidelis group, respectively. CONCLUSIONS: The most frequent clinical manifestation of lead failure was inappropriate shocks for Linox, coincidental finding for Riata and device alert for Fidelis leads. Non-physiological high rate signals were frequently observed in Linox and Fidelis lead failures whereas in Riata lead failures, a damaged lead integrity was the predominant finding.

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact.

Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration.