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Objective : Autonomic dysregulation in preterm infants requires continuous monitoring of vital signs such as heart rate over days to months. Unfortunately, common surface electrodes are prone to electrocardiography (ECG) signal artifacts and cause serious skin irritations during long-term use. In contrast, esophageal ECG is known to be very sensitive due to the proximity of electrodes and heart and insensitive to external influences. This study addresses if multichannel esophageal ECG qualifies for heart rate monitoring in preterm infants. Methods : We recorded esophageal leads with a multi-electrode gastric feeding tube in a clinical study with 13 neonates and compared the heartbeat detection performance with standard surface leads. A computationally simple and versatile ECG wave detection algorithm was used. Results : Multichannel esophageal ECG manifested heartbeat sensitivity and positive predictive value greater than 98.5% and significant less false negative ( FN ) ECG waves as compared to surface ECG due to site-typical electrode motion artifacts. False positive bradycardia as indicated with more than 13 consecutive FN ECG waves was equally expectable in esophageal and surface channels. No adverse events were reported for the multi-electrode gastric feeding tube. Conclusion : Heart rate monitoring of preterm infants with multiple esophageal electrodes is considered as feasible and reliable. Less signal artifacts will improve the detection of bradycardia, which is crucial for immediate interventions, and reduce alarm fatigue. Significance : Due to the possibility to integrate the multichannel ECG into a gastric feeding tube and meanwhile omit harmful skin electrodes, the presented system has great potential to facilitate future intensive care of preterm infants.

Supplemental Digital Content is available in the text., Background and Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Aims Leadless cardiac pacemaker (PM) implantation differs from conventional PM implantation. While the procedure has been considered safe, recent real-world data raised concerns about the learning curve of new operators and their implantation quality. The goal of this study was to investigate the influence of the first operator’s experience on leadless PM implantation quality and procedural efficiency. Methods and results We performed a bicentric analysis of all Micra TPS™ implantations in two large tertiary referral hospitals. We assessed both leadless PM implantation quality based on the absence of complications (requiring intervention or prolonged hospitalization), good electrical performance (pacing threshold ≤ 1.5 V/0.24 ms, R-wave amplitude > 5 mV), and acceptable fluoroscopy duration ( Conclusion The operator’s learning curve is a critical factor for leadless PM implantation quality and procedural efficiency.

Background Loss of biventricular stimulation can result in nonresponse to cardiac resynchronization therapy (CRT). Problems associated with the left ventricular (LV) lead and LV sensing can be challenging to detect and their incidence is unclear. The purpose of this study was to investigate mechanisms of loss of biventricular pacing due to LV lead- and LV sensing-associated problems. Methods In this bicentric study, CRT patients were surveilled using a novel remote monitoring algorithm from Biotronik (Germany) that registers LV electrograms (EGMs) during intermittent loss of resynchronization. The episodes were analyzed to assess the mechanisms of resynchronization interruptions. Results We analyzed 582 EGMs from 61 patients. During a median follow-up of 6 months, 59% of the patients had such episodes. The majority of the episodes (61%) were related to inappropriate inhibition of LV pacing, mostly due to upper rate lock-in caused by LV sensing (58%). In contrast, 8% of episodes showed intermittent loss of LV capture, which was identified thanks to LV sensing. The remaining 31% of episodes were due to physiological reasons for resynchronization interruptions (eg, supraventricular tachycardia [18%], premature beats [8%], and others [5%]). Patients with CRT interruption episodes had lower resynchronization rates (median: 98.5% vs 100%, P = .044). Conclusions Inadequate programming (active LV sensing with T-wave protection) is the main cause of impaired resynchronization in devices with LV sensing. In general, we recommend the deactivation of the LV T-wave protection function.

Background Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. Methods We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. Results Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (−2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and −3.51 (−7.05 to −1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. Conclusions Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring.

Accurate evaluations of stent encrustation patterns, such as volume distribution, from different patient groups are valuable for clinical management and the development of better stents. This study compared stent encrustation patterns from stone and kidney transplant patients. Twenty-three double-J ureteral stents were collected at a single center from patients with stone disease or underwent kidney transplantation. Encrustations on stent samples were quantified by means of micro‑computed tomography and semantic segmentation using Convolutional Neural Network models. Luminal encrustation volume per stent unit was derived to represent encrustation level, which did not differ between patient groups in the first six weeks. However, stone patients showed higher encrustation levels over prolonged indwelling times (p = 0.036). Along the stent shaft body, the stone group showed higher encrustation levels near the ureteropelvic junction compared to the ureterovesical junction (p = 0.013), whereas the transplant group showed no such difference. Possible explanations were discussed regarding vesicoureteral refluxes. In both patient groups, stent pigtails were more susceptible to encrustations, and no difference between renal and bladder pigtail was identified. Our results suggest that excessively long stents with superfluous pigtails should be avoided.

Background: The prevalence of atrial fibrillation (AF) is high in older patients. The present study aimed to estimate the age and sex specific prevalence of clinical and screen-detected atrial fibrillation (AF) in hospitalized patients. Methods: The STAR-FIB cohort study was a prospective cohort study recruiting participants from a large source population of hospitalized patients aged 65–84 years. The estimated size of the source population was 26,035 (95% CI 25,918–26,152), and 795 consenting patients without clinical AF were included in the cohort study after stratification by sex and age (49.2% females, mean age 74.7 years). Patients in the cohort study underwent three seven-day Holter ECGs in intervals of two months to screen for AF. Results: In the source population, the estimated prevalence of clinical AF was 22.2% (95% CI 18.4–26.1), 23.8% for males (95% CI 20.9–26.6) and 19.8% for females (95% CI 17.3–22.4, p for difference between sexes, 0.004). There was a linear trend for an increase in the prevalence of clinical AF with increasing age, overall and in both sexes. In the cohort study, AF was newly diagnosed in 38 patients, for an estimated prevalence of screen-detected AF of 4.9% overall (95% CI 3.3–6.6), 5.5% in males (95% CI 3.2–7.8) and 4.0% in females (95% CI 2.0–6.0, p for difference between sexes, 0.041). The estimated prevalence of screen-detected AF in the source population was 3.8% overall, 4.2% in males and 3.2% in females. Conclusion: In a large hospital-based patient population aged 65–84 years, the prevalence of clinical AF and of screen-detected AF was 22.2% and 3.8%, respectively, and significantly higher in males than females.

STUDY QUESTION Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(s) There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT 02511626.

Aims Catheter ablation for atrial fibrillation (AF) is increasingly performed. Both clinical risk factors as well as the AF phenotype have been shown to influence ablation outcomes. The inter-relationship of the two however is incompletely understood. Methods In a retrospective analysis of a prospective registry of patients undergoing a first pulmonary vein isolation, the association of 8 predefined clinical risk factors (age >70 years, female gender, hypertension, BMI >30 kg/m2, coronary artery disease, heart failure, chronic kidney disease (CKD; eGFR Results Overall, 715 patients were enrolled (median age 63 years, 27% females, 69% paroxysmal AF). The prevalence of obesity, hypertension, heart failure and CKD was significantly higher in persistent AF, while female gender was more prevalent in paroxysmal AF. After 2 years of follow-up, overall freedom from recurrence was 46%, and was higher in paroxysmal AF compared to persistent AF (54.1% vs. 29.1%, p Conclusion Clinical risk factors predict outcome after pulmonary vein isolation in patients with paroxysmal, but not persistent AF. This is likely due to a strong association of those risk factors with the occurrence of persistent AF. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

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.

Background Optimal treatment strategy in patients with mild ischemic stroke remains uncertain. While functional dependency or death has been reported in up to one-third of non-thrombolyzed mild ischemic stroke patients, intravenous thrombolysis is currently not recommended in this patient group. Emerging evidence suggests two risk factors—rapid early improvement and large vessel occlusion—as main associates of unfavorable outcome in mild ischemic stroke patients not undergoing intravenous thrombolysis. Aims To analyze natural course as well as safety and three-month outcome of intravenous thrombolysis in mild ischemic stroke without rapid early improvement or large vessel occlusion. Methods Mild ischemic stroke was defined by a National Institute of Health Stroke Scale score ≤6. We used the modified Rankin Scale (mRS) to compare three-month functional outcome in 370 consecutive mild ischemic stroke patients without early rapid improvement and without large vessel occlusion, who either underwent intravenous thrombolysis (n = 108) or received best medical treatment (n = 262). Results Favorable outcome (mRS ≤ 1) was common in both groups (intravenous thrombolysis: 91%; no intravenous thrombolysis: 90%). Although intravenous thrombolysis use was independently associated with a higher risk of asymptomatic hemorrhagic transformation (OR = 4.62, p = 0.002), intravenous thrombolysis appeared as an independent predictor of mRS = 0 at three months (OR = 3.33, p Conclusions Mild ischemic stroke patients without rapidly improving symptoms and without large vessel occlusion have a high chance of favorable three-month outcome, irrespective of treatment type. Patients receiving intravenous thrombolysis, however, more often achieved complete remission of symptoms, which particularly in mild ischemic stroke may constitute a meaningful endpoint.

Contemporary cardiac implantable electronic devices such as pacemakers or event recorders are powered by primary batteries. Device replacement due to battery depletion may cause complications and is costly. The goal of energy harvesting devices is to power the implant with energy from intracorporeal power sources such as vibrations and blood flow. By replacing primary batteries with energy harvesters, reinterventions can be avoided and the size of the total device might be reduced. This paper introduces a device with a lever, which is deflected by the blood stream within the right ventricular outflow tract (RVOT), an attractive site for cardiac pacing. The resulting torque is converted to electrical energy by an electromagnetic mechanism. The blood flow harvester weighs 6.4 g and has a volume of 2 cm3, making the harvester small enough for catheter implantation. It was tested in an experimental setup mimicking flow conditions in the RVOT. The blood flow harvester generated a mean power of 14.39 ± 8.38 μW at 60 bpm (1 Hz) and up to 82.64 ± 17.14 μW at 200 bpm (3.33 Hz) during bench experiments at 1 m/s peak flow velocity. Therefore, it presents a viable alternative to power batteryless and leadless cardiac pacemakers.

Funding Acknowledgements Type of funding sources: None. Background A pace & ablate strategy may be performed in cases of severe refractory atrial arrhythmias. Purpose We aimed to assess gender related differences in patient selection and clinical outcomes after pace & ablate. Methods In a retrospective multicenter study, patients undergoing AV-junction-ablation between 2011 and 2019 were studied. Gender-related differences in terms of baseline characteristics, device-related complications, heart failure (HF) hospitalisations and death were assessed. Results Overall, 513 patients underwent AV-junction-ablation (median age 75 years, 50% males). At baseline, male patients were younger (72 vs. 78 years, p Conclusion A Pace & Ablate strategy is safe and results in improvement of EHRA class and LVEF in a substantial number of patients. We found significant gender differences in patient selection for pace & ablate. Female patients had a more favorable clinical course after AV-junction-ablation, which was independent of age, EF and type of stimulation. Abstract Figure. Comb. endpoint of death or heart failure

INTRODUCTION Chemical ablation by retrograde infusion of ethanol into the vein of Marshall (VOM-EI) can facilitate the achievement of mitral isthmus block. This study sought to describe the efficacy and safety of this technique. METHODS AND RESULTS Twenty-two consecutive patients (14 males, median age 71 years) with attempted VOM-EI for mitral isthmus ablation were included in the study. VOM-EI was successfully performed with a median of 4���ml of 96% ethanol in 19 patients (86%) and the mitral isthmus was successfully blocked in all (100%). Touch up endocardial and/or epicardial ablation after VOM-EI was necessary for 12 patients (63%). Perimitral flutter was present in 12 patients (63%) during VOM-EI and terminated or slowed by VOM-EI in 4 and 3 patients, respectively. The low-voltage area of the mitral isthmus region increased from 3.1���cm2 (interquartile range [IQR] 0-7.9) before to 13.2���cm2 (IQR: 8.2-15.0) after VOM-EI and correlated significantly with the volume of ethanol injected (p���=���.03). Median high-sensitive cardiac troponin-T increased significantly from 330���ng/L (IQR: 221-516) the evening of the procedure to 598���ng/L (IQR: 382-769; p���=���.02) the following morning. A small pericardial effusion occurred in three patients (16%), mild pericarditis in one (5%), and uneventful VOM dissection in two (11%). After a median follow-up of 3.5 months (IQR: 3.0-11.0), 10 of 18 patients (56%) with VOM-EI and available follow-up had arrhythmia recurrence. Repeat ablation was performed in five patients (50%) and peri-mitral flutter diagnosed in three (60%). CONCLUSION VOM-EI is feasible, safe, and effective to achieve acute mitral isthmus block.

Purpose The pre-clinical testing of cardiovascular implants gains increasing attention due to the complexity of novel implants and new medical device regulations. It often relies on large animal experiments that are afflicted with ethical and methodical challenges. Thus, a method for simulating physiological heart motions is desired but lacking so far. Methods We developed a robotic platform that allows simulating the trajectory of any point of the heart (one at a time) in six degrees of freedom. It uses heart motion trajectories acquired from cardiac magnetic resonance imaging or accelero-meter data. The rotations of the six motors are calculated based on the input trajectory. A closed-loop controller drives the platform and a graphical user interface monitors the functioning and accuracy of the robot using encoder data. Results The robotic platform can mimic physiological heart motions from large animals and humans. It offers a spherical work envelope with a radius of 29 mm, maximum acceleration of 20 m/s2 and maximum deflection of ±19° along all axes. The absolute mean positioning error in x-, y- and z-direction is 0.21 ±0.06, 0.31 ±0.11 and 0.17 ±0.12 mm, respectively. The absolute mean orientation error around x-, y- and z-axis (roll, pitch and yaw) is 0.24 ±0.18°, 0.23 ±0.13° and 0.18 ±0.18°, respectively. Conclusion The novel robotic approach allows reproducing heart motions with high accuracy and repeatability. This may benefit the device development process and allows re-using previously acquired heart motion data repeatedly, thus avoiding animal trials.

AIMS OF THE STUDY Anticoagulation of patients with screen-detected atrial fibrillation may prevent ischaemic strokes. The STAR-FIB study programme aims to determine the age- and sex-specific prevalence of silent atrial fibrillation and to develop a clinical prediction model to identify patients at risk of undiagnosed atrial fibrillation in a hospitalised patient population. METHODS The STAR-FIB study programme includes a prospective cohort study and a case-control study of hospitalised patients aged 65–84 years, evenly distributed for both age and sex. We recruited 795 patients without atrial fibrillation for the cohort study (49.2% females; median age 74.8 years). All patients had three serial 7-day Holter ECGs to screen for silent atrial fibrillation. The primary endpoint will be any episode of atrial fibrillation or atrial flutter of ≥30 seconds duration. The age- and sex-specific prevalence of newly diagnosed atrial fibrillation will be estimated. For the case-control study, 120 patients with paroxysmal atrial fibrillation were recruited as cases (41.7% females; median age 74.6 years); controls will be randomly selected from the cohort study in a 2:1 ratio. All participants in the cohort study and all cases were prospectively evaluated including clinical, laboratory, echocardiographic and electrical parameters. A clinical prediction model for undiagnosed atrial fibrillation will be derived in the case-control study and externally validated in the cohort study. CONCLUSIONS The STAR-FIB study programme will estimate the age- and sex-specific prevalence of silent atrial fibrillation in a hospitalised patient population, and develop and validate a clinical prediction model to identify patients at risk of silent atrial fibrillation.

BACKGROUND The implantation of left ventricular (LV) leads for cardiac resynchronization therapy (CRT) and the management of lead-related complications can be challenging. The introduction of the quadripolar IS-4 LV lead may have facilitated the implantation procedure and may have reduced lead-related complications. Data of long-term follow-up (FU) comparing the IS-4 lead with the IS-1 LV lead are rare and conflicting. PURPOSE Comparison of lead-related complications and all-cause mortality between CRT patients who received an IS-4 or an IS-1 LV lead in the long-term FU. METHODS Adults with an indication for a CRT-Defibrillator or CRT-Pacemaker, a successful endovascular IS-4 or IS-1 LV lead implantation, and a minimal FU of three years were included in this retrospective study. The combined primary endpoint was freedom from lead-related complications defined as (i) occurrence of persisting high pacing threshold (>2.75V/0.4ms), (ii) unresolved phrenic nerve stimulation, (iii) LV lead dislodgement/disruption, (iv) the necessity of re-interventions affecting the LV lead, and (v) LV lead deactivation/explantation. Secondary endpoints were all singular complications and all-cause mortality. RESULTS Eligible for the study were 133 patients (IS-4 n = 66; IS-1 n = 67) with a mean FU of 4.03 ± 1.93 years. Baseline characteristics of both patient groups did not differ significantly. Freedom from lead-related complications was higher in patients with an IS-4 lead as compared to an IS-1 lead (Figure 1; 87.9% vs. 65.7%; p = 0.002). The secondary outcomes showed a higher rate of LV lead dislodgement/disruption (4.5% vs. 17.9%; p = 0.015) in the IS-1 patient group and more patients suffered from unresolved phrenic nerve stimulation with an IS-1 lead (3.0% vs. 13.4%; p = 0.029). LV lead deactivation/explantation during FU and LV lead-related re-interventions were fewer in case of an IS-4 lead (4.5% vs 22.4%; p = 0.003; 6.1% vs. 17.9%; p = 0.036, respectively). The rate of persisting high pacing thresholds and all-cause mortality did not differ (4.5% vs. 9.0%; p = 0.492; 22.7% vs 25.4%; p = 0.721, respectively). CONCLUSION The quadripolar IS-4 LV lead showed in this retrospective study a better long-term performance than the bipolar IS-1 lead. Abstract Figure 1

Objective Case series with different clinical presentations indicating central nervous system (CNS) involvement in coronavirus disease 2019 (COVID-19) have been published. Comprehensive work-ups including clinical characteristics, laboratory, electroencephalography (EEG), neuroimaging and cerebrospinal fluid (CSF) findings are needed to understand the mechanisms.DesignWe evaluated 32 consecutive patients with severe SARS-CoV-2 infection treated at a tertiary care centre from March 09 to April 03, 2020 for concomitant severe central nervous system (CNS) symptoms occurring during their critical disease state. Those with CNS disorders were examined in detail regarding clinical characteristics and undergoing additional examinations, e.g. computed tomography (CT), magnetic resonance imaging (MRI), (EEG), (CSF) analysis and autopsy if they had died.ResultsOf 32 critically ill patients with COVID-19 eight (18%) had severe CNS involvement (mean [SD] age, 67.6 [6.8] years; seven men; two patients died). All eight patients had cardiovascular risk factors, most frequently arterial hypertension. Two patients presented with lacunar ischemic stroke and one with status epilepticus in the early phase. As most common presentation, six patients presented with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in three of them with additional subarachnoid haemorrhage and in another two with additional small ischemic lesions. In three patients intracranial vessel wall sequence MRI was performed, for the first time to our knowledge. All cases showed contrast-enhancement of vessel walls in large and middle-sized cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. CSF analysis showed normal cells counts and chemistry. RT-PCRs for SARS-CoV-2 in CSF were all negative, and no intrathecal SARS-CoV-2 specific IgG synthesis was detectable.ConclusionsCNS disorders are common in patients with severe COVID-19. Different mechanisms might be involved. Besides unspecific encephalopathy and encephalitic syndromes, large vessel strokes might occur early after disease onset. In a later phase, microbleeds and microinfarctions indicate potential CNS small vessel disease. MRI vessel wall contrast enhancement suggests cerebral vascular wall pathologies with an inflammatory component. CNS disorders associated with COVID-19 may lead to long-term disabilities aggravating socio-economic damage. The mechanisms have to be investigated urgently in order to develop preventive and therapeutic neuroprotective strategies.

Subdermal solar harvesting has the potential to obviate the need for the periodic battery replacements as required in patients with cardiac pacemakers. The achievable power output of the subdermal solar module depends on implantation depth, optical skin properties and to an important part on solar cell characteristics. Monte Carlo simulations of light distribution in human skin were used to estimate the power output of subdermal solar cells under midday sunlight exposure in geographical mid-latitudes as a function of implantation depth and solar panel size. For the darkest skin type, the daily energy demand of a modern cardiac pacemaker (0.864 J at a power demand of 10 μ W ) can be provided by a 2 cm 2 solar cell implanted subdermally at a depth of 3 mm when exposed to just 11 min of midday, clear sky irradiance. Our study reveals that solar harvesting with relatively small solar cells if optimized for the spectral subdermal fluence has the potential to power cardiac pacemakers in all skin types within reasonable irradiation exposure times. Solar energy harvesting is very promising to power electronic implants.

BACKGROUND Subcutaneous implantable cardioverter-defibrillator (S-ICD) implantations are rapidly expanding. However, the subcutaneous detection and interpretation of cardiac signals in S-ICDs is much more challenging than by conventional devices. There is a complete paradigm shift in cardiac signal sensing with subcutaneous signal detection, leading in some cases to oversensing with restricted programming options.OBJECTIVES The aim of this single-center study was to quantify and describe cases where recurring oversensing made the extraction of the device necessary.METHODS Consecutive patients (n = 108) implanted with an S-ICD in our tertiary referral hospital were considered for analysis. Clinical and remote monitoring data were analyzed.RESULTS The S-ICD had to be explanted in 6 of 108 implanted patients (5.6%) because of refractory oversensing issues: myopotential oversensing, P- or T-wave oversensing, rate-dependent left bundle branch block aberrancy during exercise with R-wave double counting, and R-wave amplitude decrease after ventricular tachycardia ablation leading to noise detection. Seventeen of 108 patients experienced oversensing (15.7%): 9 patients had at least 1 inappropriate charge without a shock (8.3%), 3 patients had at least 1 inappropriate shock (2.8%), and 5 patients had both episodes (4.6%).CONCLUSION So far, cardiologists have had to deal with transvenous ICD lead fractures, but signal oversensing without correcting programming option could be the equivalent weakness of S-ICDs, despite an adequate screening.

Background Pacing leads are the Achilles heel of pacemakers. Most manufacturers report a 3-year survival rate of >99% of their leads. We observed several failures of the Beflex/Vega leads (MicroPort, Shanghai, China; formerly Sorin/LivaNova). Objective The purpose of this study was to investigate failure rates of Beflex/Vega leads. Methods We analyzed the performance of Beflex/Vega leads implanted at our tertiary referral center. All-cause lead failures (any issues requiring reinterventions such as lead dislocations, cardiac perforations, and electrical abnormalities) were identified during follow-up. The Beflex/Vega lead was compared with a reference lead (CapSureFix Novus 5076, Medtronic, Minneapolis, MN) implanted within the same period and by the same operators. Results A total of 585 leads were analyzed (382 Beflex/Vega and 203 CapSureFix Novus 5076 leads). Cumulative failure rate estimates were 5.2%, 6.3%, and 12.4% after 1, 2, and 3 years for the Beflex/Vega lead. This was worse compared to the reference lead (1.5%, 1.5%, 3.7% after 1, 2, and 3 years; P = .001). Early failure manifestations up to 3 months occurred at a similar rate (Beflex/Vega vs CapSureFix Novus 5076 lead: 1.3% vs 0.5% for dislocations; 1.3% vs 1.0% for perforations). During follow-up, electrical abnormalities such as noise oversensing (P = .013) and increased pacing thresholds (P = .003) became more frequent in the Beflex/Vega group. Electrical abnormalities were the most common failure manifestation 3 years after implantation in this group (9.4% vs 2.2% for the CapSureFix Novus 5076). Conclusion The failure rate of the Beflex/Vega lead of >10% after 3 years was higher than that of a competitor lead. This gives rise to concern since >135,000 such leads are active worldwide.

Visual Abstract, Highlights • The new leadless pacemakers overcome important limitations of conventional devices but only provide single-chamber pacing capability. • The presented concept involves 2 leadless pacemakers that communicate wirelessly with each other and thus enable synchronized leadless dual-chamber pacing. • A novel technology is presented for pacemaker communication, using the myocardium and blood as the transmission medium. Optimal communication parameters were assessed in vivo and in vitro, and various features having an influence on signal transmission have been identified. • A leadless dual-chamber pacemaker prototype was developed and successfully tested in vivo. • The presented technique has shown to be a promising and energy-efficient wireless communication method for leadless dual-chamber pacemakers., Summary Contemporary leadless pacemakers only feature single-chamber pacing capability. This study presents a prototype of a leadless dual-chamber pacemaker. Highly energy-efficient intrabody communication was implemented for wireless pacemaker synchronization. Optimal communication parameters were obtained by in vivo and ex vivo measurements in the heart and blood. The prototype successfully performed dual-chamber pacing in vivo. The presented wireless communication method may in the future also enable leadless cardiac resynchronization therapy.

OBJECTIVE Unexplained cardiac arrest (UCA) is often the first manifestation of an inherited arrhythmogenic disease. Genetic testing in UCA is challenging due to the complexities of variant interpretation in the absence of supporting cardiac phenotype. We aimed to investigate if a KCNQ1 variant [p.(Pro64_Pro70del)], previously reported as pathogenic, contributes to the long-QT syndrome phenotype, co-segregates with disease or affects KCNQ1 function in vitro. METHODS DNA was extracted from peripheral blood of a 22-year-old male after resuscitation from UCA. Targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 190 clinically relevant cardiac genes with minor allele frequency A in PKP2 (p.Arg811Ser), classified as likely benign. Two asymptomatic family members with no evident phenotype hosted the KCNQ1 variant. Functional studies showed that the wild-type and mutant channels have no significant differences in current levels, conductance-voltage relationships, as well as activation and deactivation kinetics, in the absence and presence of the auxiliary subunit KCNE1. CONCLUSIONS Based on our data and previous reports, available evidence is insufficient to consider the variant KCNQ1:c.190_210del as pathogenic. Our findings call for cautious interpretation of genetic tests in UCA in the absence of a clinical phenotype.

Aims To explore the use of time-frequency analysis as an analytical tool to automatically detect pattern changes in bladder pressure recordings of patients with overactive bladder (OAB). To provide quantitative data on the bladder's non-voiding activity which could improve the current diagnosis and potentially the treatment of OAB. Methods We developed an algorithm, based on time-frequency analysis, to analyze bladder pressure during the filling phase of urodynamic studies. The algorithm was used to generate a bladder overactivity index (BOI) for a quantitative estimation of the average bladder non-voiding-activity. We tested the algorithm with one control group and two groups of patients with OAB symptoms: one group with detrusor overactivity (DO), assessed by an experienced urologist (OAB-with-DO group), and another group for which detrusor overactivity was not diagnosed (OAB-without-DO group). Results The algorithm identified diagnostically significant data on the bladder non-voiding activity in a specified frequency range. BOI was significantly higher for both OAB groups compared to the control group: the median value of BOI was twice as big in OAB-without-DO and more than four times higher in OAB-with-DO compared to control group. Moreover the algorithm was successfully tested to detect episodes of detrusor overactivity. Conclusions We have shown that a simple algorithm, based on time-frequency analysis of bladder pressure, may be a promising tool in the clinical setting. The algorithm can provide quantitative data on non-voiding bladder activity in patients and quantify the changes according to phenotype. Moreover the algorithm can detect DO, showing potential for triggering conditional bladder stimulation.

A new pseudo asynchronous level crossing analogue-to-digital converter ( adc ) architecture targeted for low-power, implantable, long-term biomedical sensing applications is presented. In contrast to most of the existing asynchronous level crossing adc designs, the proposed design has no digital-to-analogue converter ( dac ) and no continuous time comparators. Instead, the proposed architecture uses an analogue memory cell and dynamic comparators. The architecture retains the signal activity dependent sampling operation by generating events only when the input signal is changing. The architecture offers the advantages of smaller chip area, energy saving and fewer analogue system components. Beside lower energy consumption the use of dynamic comparators results in a more robust performance in noise conditions. Moreover, dynamic comparators make interfacing the asynchronous level crossing system to synchronous processing blocks simpler. The proposed adc was implemented in $0.35\,{\mu }{\text{m}}$ complementary metal-oxide-semiconductor ( cmos ) technology, the hardware occupies a chip area of $0.0372\,\mathrm{mm}^2$ and operates from a supply voltage of $1.8\,{\text{V}}$ to $2.4\,{\text{V}}$ . The adc 's power consumption is as low as $0.6\,{\mu }\mathrm{W}$ with signal bandwidth from $0.05\,{\text{Hz}}$ to $1\,{\text{kHz}}$ and achieves an equivalent number of bits ( enob ) of up to 8 bits.

Introduction Pacing leads remain the weak link of current pacemaker systems. Various differences in design and material exist among companies. Lead performance is mainly assessed via post-marketing studies of the manufacturing companies. Reliable independent reports are rare. We aimed to study the early and long-term performance of the Microport (formerly Sorin/Livanova) Beflex and Vega leads at our centre, for which a lead survival >99% at 3 years has been reported by the company. Method In this single centre, retrospective study we analysed the performance of all right ventricular Microport pacemaker leads implanted at our centre between January 2014 and January 2018. Only first pacemaker implants were considered. Lead failure was defined as any lead issue requiring reintervention during follow-up (dislocation, perforation, electrical abnormalities such as lead noise or excessively high thresholds). Results A total of 271 Microport right ventricular pacing leads were implanted (233 Beflex and 38 Vega leads). Mean patient age was 76±13.1 years (66% men). Dual chamber pacemakers were implanted in 162 patients (60%) and single chamber in 109 (40%). Mean threshold at implant was 0.6V/0.5ms (range 0.3–1.2V), mean R wave 13.2 mV (range 1.5–30mV) and mean impedance 816 Ohm (range 469–1639 Ohm). Patients without available follow-up information were excluded (N=18, 6.6%). The remaining 253 patients (93.4%) were analysed. Median follow-up was 1.26 years, IQR [25%=0.91 and 75%=2.24]. We observed a total of 25 lead failures (10%). Lead dislocation occurred in 2 cases (0.8%), lead perforation in 5 cases (2%), electrical abnormalities in 6 cases (2.4%) and excessively high threshold in 12 cases (4.8%; mean voltage 4V, range 2–7.5V; mean pulse width 0.75ms, range 0.35–1ms). Yearly incidence of lead failure per 100 leads was 6.1% (95%-CI [4.09–8.98] with a failure rate of 12.74% at 3 year in Kaplan-Meier analysis (Figure). Figure 1 Conclusion We found an unexpectedly high rate of lead failure of the Microport Beflex and Vega pacing leads at our centre. The two main reasons for premature lead failure were excessively high thresholds as well as electrical abnormalities during follow-up. Comparison of lead performance with other centres and against other leads are needed to further assess the magnitude of the problem.

Introduction Patients with complete transposition of the great arteries (d-TGA) and atrial switch face a high lifetime risk of arrhythmias. Interventions in these patients are challenging because of their particular anatomy. Reports on ablation procedures in this patient population are scarce and missing for Switzerland. Method We retrospectively analyzed all ablation procedures performed in the above-mentioned population at a Swiss tertiary care center. Results Among 73 d-TGA pts. (71% male; N=37 Senning; N=36 Mustard) followed at our center, 17 ablations were performed in 11 pts. (15%; one ablation in 8 pts., two in 2 pts. and five in 1 patient). Median age at first ablation was 34 years (range 15–49 years). A total of 17 different intra-atrial reentry tachycardias (IART) and 3 AVNRT were targeted. Of the IART, 10 were cavotricuspid isthmus (CTI)-dependent and 7 were not. In two procedures (12%) only the systemic venous (SV) baffle was accessed for ablation. In 15 procedures (88%), ablation was performed within the pulmonary venous (PV) baffle. Access to the PV baffle was retrograde via the aorta in 6 cases (35%), via a baffle leak in 3 (18%) and via baffle puncture in 6 (35%). All procedures with retrograde approach to the PV baffle or with SV baffle only ablation were performed up to January 2012 and all remaining procedures afterwards. The 3 pts. requiring repeat procedures had retrograde or SV baffle approaches initially, and one additional ablation via baffle puncture was successful. The CTI was targeted in 10 pts. (91%) and ablation was finally successful in all with bidirectional block demonstrated in 8 pts. The coronary sinus was found to drain into the SV baffle in 5 pts. (46%) and useful for assessment of CTI block. The seven CTI-independent IART were scar-related micro-reentries. Ablation of all 3 AVNRTs was successful after one procedure without recurrence. Slow pathway ablation was performed in the SV baffle in two and in the PV baffle in one case (Figure). After a median follow-up of 7 months (range 2–186 months) 9 pts. are without recurrence and in 2 pts. rare self-limited arrhythmias still occur. No procedural complications occurred. Conclusion Arrhythmias in patients with complete d-TGA and atrial switch are mainly CTI-dependent IART or scar-related micro-reentries, and a few patients also have AVNRT. Ablation of these arrhythmias is safe and successful if PV baffle access is achieved via a baffle leak or baffle puncture.

What are the specific characteristics of sexual activity in women with endometriosis compared with women without endometriosis?Multicentre case control study. Participants were recruited from university hospitals, district hospitals and doctor's offices in Germany, Switzerland and Austria. A total of 565 women with endometriosis were pair-matched to 565 control women by age and ethnic background. Diagnosis of endometriosis was confirmed by histology, and disease stage was classified according to American Society for Reproductive Medicine criteria. Data on sexuality were collected using selected questions from the Brief Index of Sexual Function and the Sexual History Form.Altogether, 69.1% of women with endometriosis and 77.8% of control women engaged in sexual activity during the month before the study period (P0.001). Overall, 42.3% of endometriosis-affected women and 30.5% of the control women desired a higher frequency of sexual activity (P0.001). Petting, foreplay and vaginal sexual intercourse were reported to be practised less often by women with endometriosis. Frequencies for masturbation, reciprocal masturbation, oral and anal sex were similar in both groups. Dyspareunia was negatively associated with sexual activity (OR 2.42, 95% CI 1.26 to 4.63), whereas chronic pain showed no association with sexual activity (OR 1.35, 95% CI 0.93, 1.96).Women with endometriosis have lower frequencies of petting, foreplay and vaginal sexual intercourse than control women; this difference has to be attributed, at least in part, to dyspareunia. Potentially pain-free sexual options are used to a limited degree. As endometriosis-affected women desire higher levels of sexual activity, sexual counselling should be included in medical support.

PURPOSE To enhance the utility of motion detection with nuclear magnetic resonance (NMR) markers by removing the need for sequence-dependent calibration. METHODS Two sets of NMR markers are used for simultaneous observation of magnetic field dynamics during imaging procedures. A set of stationary markers at known positions in the laboratory frame serves to determine the field evolution in that frame. Concurrent recording from a set of head-mounted markers then permits calculating their lab-frame positions and derived rigid-body motion parameters. The precision and accuracy of this approach are evaluated relative to current calibration-based solutions. Use for prospective motion correction is then demonstrated in high-resolution imaging of long scan duration. RESULTS Motion detection with real-time field tracking overcomes the need for explicit calibration without compromising precision, which is assessed at 10 to 30 µm. Relative to full conventional calibration, it is found to offer superior robustness against thermal drift. Relative to more economical modes of calibration, it achieves substantially higher accuracy. Prospective motion correction based on real-time field tracking resulted in consistently high image quality even when head motion exceeded the image resolution by one order of magnitude. CONCLUSION Real-time field tracking enables motion detection with NMR markers without calibration overhead and thus overcomes a key obstacle toward routine use. In addition, it renders this mode of motion tracking more robust against system imperfections.

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

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.

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

Introduction Some cardiac resynchronization therapy (CRT) device manufacturers (Biotronik, Germany; Boston Scientific, United States) have implemented left ventricular (LV) sensing functionality to prevent pacing into the vulnerable phase. Physicians are only partially aware of programming pitfalls related to LV sensing and general programming advice is lacking. Methods and results We provide an illustrative case-series-based review of the variety of potential problems with LV sensing. LV sensing may inappropriately impair CRT delivery due to LV-sensing issues or improper device programming. This can cause beat-wise loss of resynchronization but also ongoing desynchronization. On the other hand, LV sensing provides additional diagnostic information, which may reveal intermittent problems of the LV lead such as capture loss. We summarize the available evidence to provide manufacturer-specific recommendations on device programming and troubleshooting for daily clinical practice. Conclusion CRT devices with LV sensing may suffer from impaired resynchronization due to programming pitfalls. If LV sensing is active (nominal setting in Biotronik and Boston Scientific devices), careful lookout for related problems and resynchronization percentage is required. Optimization is mandatory and even deactivation of LV sensing may have to be considered.

ObjectivesEndometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life.Design, setting and participantsIn the context of a multicentre case–control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors’ practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work–life and career choices of study participants.Main outcome measuresAssociations between endometriosis/disease symptoms and limitations in career development as well as ability to work.ResultsWomen with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p2=0.072, p2=0.087, pConclusionsEndometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended.Trial registration numberNCT02511626; Pre-results.

PURPOSE Targets for substrate-based catheter ablation of scar-related ventricular tachycardia (VT) include sites with fractionated and late potentials (LPs). We hypothesized that in patients with cardiac resynchronization therapy (CRT), the pacing mode may influence the timing of abnormal electrograms (EGMs) relative to the surface QRS complex. METHODS We assessed bipolar EGM characteristics in left ventricular low bipolar voltage areas (

Introduction Atrial Fibrillation (AF) stabilization depends on remodelling processes affecting the electrophysiological, metabolic, and structural properties of the atrial muscle. Objective Develop an AF Sheep model to study the electrophysiogical, structural and bioenergetic remodelling of the cardiac tissue. Methods An algorithm controlled pacemaker stimulating repeatedly the right atria at 10 Hz during 30 sec followed by 5 sec of sinus rhythm (SR) detection was used to induce AF. Its development was monitored by telemetry. Electrophysiological remodelling was studied in vivo by contact mapping and ex vivo by optical mapping. Structural remodelling was studied at the organ level using computed tomography (μCT) and at the mitochondrial level by electronic microscopy. Bioenergetic remodelling was evaluated on isolated mitochondria. AF sheep were kept 75 days before being studied. Results AF induction rate was 80%. AF developed and stabilized after 25 and 48 days, respectively. Animals remained less than 0.02 ± 0.03% in SR once AF was installed. In vivo contact mapping revealed a decreased voltage in AF atria compared to Sham. The highest AF frequencies were localised in the pulmonary veins. When compared to Sham, AF induced: (1) a 50% decrease of the atrial effective refractory periods; (2) a left atrial decrease in action potential duration; (3) an increase in atrial volumes; (4) Fat infiltration; (5) a decrease in mitochondrial cristae density; (6) a decrease in ATP synthesis rate; (7) an increased oxidation of the mitochondrial NAD(P)H pool; (9) an increased mitochondrial H2O2 emission, independently of the respiratory substrates used to fuel the electron transport chain. Conclusions The AF Sheep model developed is characterized by occurrence of remodelling processes at different levels. Further studies will establish the time course of development of remodelling processes in order to improve AF therapeutics strategies by targeting atrial remodelling.

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency

Objective: A new generation of leadless cardiac pacemakers effectively overcomes the main limitations of conventional devices, but only offer single-chamber pacing, although dual-chamber or multisite pacing is highly desirable for most patients. The combination of several leadless pacemakers could facilitate a leadless multisite pacemaker but requires an energy-efficient wireless communication for device synchronization. This study investigates the characteristics of conductive intracardiac communication between leadless pacemakers to provide a basis for future designs of leadless multisite pacemaker systems. Methods: Signal propagation and impedance behavior of blood and heart tissue were examined by in vitro and in vivo measurements on domestic pig hearts and by finite-element simulations in the frequency range of 1 kHz to 1 MHz. Results: A better signal transmission was obtained for frequencies higher than 10 kHz. The influence of a variety of practical parameters on signal transmission could be identified. A larger distance between pacemakers increases signal attenuation. A better signal transmission is obtained through larger inter-electrode distances and a larger electrode surface area. Furthermore, the influence of pacemaker encapsulation and relative device orientation was assessed. Conclusion: This study suggests that conductive intracardiac communication is well suited to be incorporated in leadless pacemakers. It potentially offers very low power consumption using low communication frequencies. Significance: The presented technique enables highly desired leadless multisite pacing in near future.

Background Contemporary leadless pacemakers (PMs) only feature single-chamber ventricular pacing. However, the majority of patients require dual-chamber pacing or cardiac resynchronization therapy (CRT). Several leadless PMs implanted in the same heart would make that possible if they were able to synchronize their activity in an efficient, safe, and reliable way. Thus, a dedicated ultra-low-power wireless communication method for PM synchronization is required. Objective The purpose of this study was to develop a leadless CRT system and to evaluate its function in vivo. Methods Device synchronization was implemented using conductive intracardiac communication (CIC). Communication frequencies were optimized for intracardiac device–device communication. Energy consumption, safety, and reliability of the leadless PM system were tested in animal experiments. Results We successfully performed CRT pacing with 3 independent devices synchronizing their action using CIC. No arrhythmias were induced by the novel communication technique. Ninety-eight percent of all communication impulses were transmitted successfully. The optimal communication frequency was around 1 MHz, with a corresponding transmitted power of only 0.3 μW at a heart rate of 60 bpm. Conclusion Leadless PMs are able to synchronize their action using CIC and may overcome the key limitation of contemporary leadless PMs.

A 59-year-old male patient without the history of heart disease was referred for coronary angiography due to typical chest pain and signs of myocardial ischemia during exercise stress test. On admission, the patient was in sinus rhythm. After successful PCI, the patient was enrolled in a study to investigate esophageal long-term electrocardiography (eECG) comprising simultaneous rhythm monitoring with surface and esophageal leads during 16 h. The surface ECG (sECG) was recorded using a two-channel Holter ECG recorder with a sampling frequency of 1,024 Hz allowing continuous rhythm monitoring for 7 days (Lifecard CF, Spacelabs Healthcare, USA). The eECG was recorded using an esophageal ECG electrode (Esosoft 6S, FIAB, Italy) connected to a dedicated two-channel eECG recorder—a proprietary development—with a sampling frequency of 512 Hz. We registered two bipolar channels (interelectrode spacings of 60 and 15 mm). The eECG was well tolerated; the patient reported only a slight pharyngeal foreign body feeling without any impact on his common daily activities such as eating, talking and sleeping. The sECG was analyzed using an automatic beat classifier system (Pathfinder, Spacelabs Healthcare, USA). The software correctly detected five atrial premature beats (APB’s) but no other atrial arrhythmias. In the eECG, we unmasked another 40 APB’s, as well as 178 episodes with atrial ectopic rhythm [mean duration ± SD 25 ± 31 beats (Fig. 1)]. This report illustrates the limited sensitivity of surface long-term ECG for atrial rhythm disorders. For the sECG, software-based automatic classification of atrial arrhythmias is accomplished by calculating the ratio of the R–Rinterval to be classified and the preceding R–R-interval(s). This quotient is then compared to a coupling interval threshold, e.g., the Pathfinder software uses by default 66 % of the preceding R–R-interval duration. The number of detected atrial arrhythmias strongly depends on this threshold: atrial ectopic beats are only identifiable if they are premature enough as compared to this threshold. The sECG uses R–R-intervals as surrogate markers of the true atrial activity, while morphologic features of atrial signals are not considered. The lack of a direct classifier for atrial arrhythmias is a major limitation of sECG monitoring in cases without evident change in R–R cycle duration. Moreover, reliable detection of atrial arrhythmias is of increasing importance for risk stratification, because it has been shown that excessive supraventricular ectopic activity [1] as well as atrial premature beats [2–4] are associated with an increased risk of stroke and atrial fibrillation. Esophageal electrocardiography may provide an elegant way out by offering excellent atrial signals that additionally allow waveform analysis for the direct and reliable classification of atrial rhythm. Lead movements due to eating or respiration can confound esophageal electrocardiography. We exclude that the morphologic changes are caused by such artifacts for the ClinicalTrials.gov Identifier: NCT01436344.

Detection of arrhythmic atrial beats in surface ECGs can be challenging when they are masked by the R or T wave, or do not affect the RR-interval. Here, we present a solution using a high-resolution esophageal long-term ECG that offers a detailed view on the atrial electrical activity. The recorded ECG shows atrial ectopic beats with long coupling intervals, which can only be successfully classified using additional morphology criteria. Esophageal high-resolution ECGs provide this information, whereas surface long-term ECGs show poor atrial signal quality. This new method is a promising tool for the long-term rhythm monitoring with software-based automatic classification of atrial beats.

The hyperpolarization-activated cyclic nucleotide-gated (HCN) cation (Na+/K+) currents (If/Ih) are generated by 4 members of the channel family (HCN1–4).1 These currents contribute to the pacemaker function2 in heart and brain.3 The HCN4 current is known to play a crucial role in the automaticity of the sinus node through the generation of a slow diastolic depolarization during the phase 4 of the cardiac action potential.4 Thus, it is a crucial channel for appropriate pacemaker activity and conduction system function because it facilitates rapid repolarization. Interestingly, HCN4 has been shown to be expressed in essentially the entire heart tissue.5 Mutations in HCN4 have been associated mainly with sick sinus syndrome phenotype6; however, in recent years, a broad spectrum of phenotypes has been reported, including sinus bradycardia,7 inappropriate sinus tachycardia,8 early-onset atrial fibrillation,9,10 atrio-ventricular block,11,12 idiopathic ventricular tachycardia,13 left ventricular noncompaction (LVNC),14–17 dilation of the aorta, and mood and anxiety disorders.19 In the present study, we report a case with sick sinus syndrome, LVNC, mood and anxiety disorders, and ventricular fibrillation (VF) hosting 2 novel HCN4 -pore mutations. The index patient was a 36-year-old man, who presented initially with mood and anxiety disorders characterized by important depressive episodes. Previous clinical records revealed a slightly impaired left ventricular function, paroxysmal atrial fibrillation, frequent premature ventricular complexes, and nonsustained tachycardia originating from the right ventricle. Therapy with β-blocker was initiated but discontinued shortly because of profound sinus bradycardia, which did not resume after washout. A cardiac magnetic resonance imaging excluded a right ventricular cardiomyopathy. The left ventricle showed an uncommon hypertrabeculation; however, the criteria for an LVNC were not fulfilled at that time. Eight years later, the patient was hospitalized because of heart failure and …

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).

Zusammenfassung. Herzschrittmacher sind die therapeutischen Grundpfeiler bradykarder Herzrhythmusstörungen. Moderne Schrittmacher sind zuverlässig und bieten eine Vielzahl an Möglichkeiten zur patientenspezifischen Therapie. Schrittmacherwechsel aufgrund von Batterieerschöpfung sind allerdings häufig (~25 % aller Implantationen) und können Komplikationen nach sich ziehen. Batterielose Herzschrittmacher wären wünschenswert um die Anzahl der Schrittmacherwechsel zu minimieren. Ein solches Gerät müsste seine Energie im Körper selbst mittels eines speziellen Generators gewinnen. Dieser Generator könnte beispielsweise aus subkutan implantierten Solarzellen bestehen, welche die kleine Menge Licht, die in unseren Körper eindringt, in elektrische Energie umwandeln. Alternativ könnte der Blutfluss mittels kleiner intravaskulärer Turbinen als Energiequelle genutzt werden. Ein dritter Ansatz verfolgt die direkte Umwandlung eines Teils der mechanischen Energie der Ventrikelkontraktion in elektrische Energie, wozu ein spezielles mechanisches Uhrwerk auf das Myokard aufgebracht wird. Alle diese Ansätze wurden in ersten in vivo Studien erfolgreich getestet. Speziell erfolgsversprechend für die Zukunft scheinen miniaturisierte Generatoren, welche katheterbasiert intraventrikulär implantiert werden können und somit gleichzeitig erlauben, auf Schrittmacherelektroden zu verzichten – eine andere Achillesferse gegenwärtiger Schrittmacher.

Purpose Gradient imperfections remain a challenge in MRI, especially for sequences relying on long imaging readouts. This work aims to explore image reconstruction based on k-space trajectories predicted by an impulse response model of the gradient system. Theory and Methods Gradient characterization was performed twice with 3 years interval on a commercial 3 Tesla (T) system. The measured gradient impulse response functions were used to predict actual k-space trajectories for single-shot echo-planar imaging (EPI), spiral and variable-speed EPI sequences. Image reconstruction based on the predicted trajectories was performed for phantom and in vivo data. Resulting images were compared with reconstructions based on concurrent field monitoring, separate trajectory measurements, and nominal trajectories. Results Image reconstruction using model-based trajectories yielded high-quality images, comparable to using separate trajectory measurements. Compared with using nominal trajectories, it strongly reduced ghosting, blurring, and geometric distortion. Equivalent image quality was obtained with the recent characterization and that performed 3 years prior. Conclusion Model-based trajectory prediction enables high-quality image reconstruction for technically challenging sequences such as single-shot EPI and spiral imaging. It thus holds great promise for fast structural imaging and advanced neuroimaging techniques, including functional MRI, diffusion tensor imaging, and arterial spin labeling. The method can be based on a one-time system characterization as demonstrated by successful use of 3-year-old calibration data. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.