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Funding Acknowledgements Type of funding sources: None. Background Left atrial appendage electrical isolation (LAA) is an important adjunctive ablation strategy in patients with nonparoxysmal atrial fibrillation. If impaired mechanical function following isolation is observed, long-term oral anticoagulation (OAC) or, as an alternative, LAA occlusion are required. Although focal electrical potentials from the LAA do not result in normalization of appendage mechanical function, they may potentially be a source of arrhythmogenic triggers. Those focal areas might be challenging to ablate after LAA occlusion device implantation. Purpose We sought to report the incidence of focal electrical potentials in patients with a previously isolated LAA and transesophageal echocardiography (TEE) evidence of severely impaired LAA mechanical function undergoing endocardial LAA occlusion. Methods In 124 patients undergoing LAA occlusion following LAA isolation, a circular mapping catheter (CMC) was used before occlusion to document any residual LAA electrical activity. Results At preprocedural TEE, the median LAA contraction velocity was 0.13 m/s (IQR: 0.05-0.19) and was significantly impaired in all patients. Of the 124 patients (mean age: 69±8 years; 71.7% males), 61 (49.2%) did not display any evidence of residual LAA electrical activity. In the remaining 63 (50.8%) patients, residual electrical potentials resulting in LAA reconnection were recorded on the CMC positioned into the appendage. On average, 4.9±1.7 radiofrequency energy applications (45W, mean duration of each RFA: 14.2±3.4s) were required to re-achieve complete isolation. Subsequent appendage occlusion was successful in all patients. No leaks ≥5mm and 3 (2.4%) 3-4mm-leaks were documented at 45day-TEE. Conclusions Focal electrical activity from the LAA was documented in approximately half of our patients. Although focal electrical potentials do not result in normalization of LAA mechanical function, they may potentially act as arrhythmogenic triggers. Since it may be challenging after device implantation, assessment and ablation of those areas should be considered before occlusion device deployment.

Funding Acknowledgements Type of funding sources: None. Background Left atrial appendage (LAA) electrical isolation (ei) may be achieved via radiofrequency (RF) energy applications at the level of the appendage ostium targeting the sites of earliest activation recorded by a mapping catheter. Notably, RF has long been used in vascular, orthopedic, and aesthetic surgery to promote thermal-induced collagen matrix contraction, fibrosis, and tissue retraction. LAA anatomical changes associated to RF-induced tissue retraction have never been reported. Purpose To quantify the anatomical changes of the LAA ostium following RF-based LAAei. Methods Thirty-four consecutive patients requiring AF ablation with LAAei underwent transesophageal echocardiography (TEE) within 7 days before (baseline TEE) and apx 6 months after (follow-up TEE) ablation. The diameter of LAA orifice and landing zone were measured at 4 different views (0°, 45°, 90°, 135°). Measurements were performed by two independent reviewers blinded to the patient’s identity. Results Among 43 AF patients (67±6yrs, 72.1% males), the LAA morphology was classified as chicken wing in 19 (44.2%) patients, windsock in 12 (27.9%), cactus in 8 (18.6%), and cauliflower in 4 (9.3%). At baseline TEE, the mean maximum and mean minimum ostial diameters were 25±4mm and 22±4mm, respectively. The mean maximum and mean minimum diameters of the landing zone were 26±4mm and 23±3mm, respectively. On average, LAAei was achieved after 17±6 minutes of RF at a power of 45W. Follow-up TEE was performed 294±136 days after LAAei. The median LAA contraction velocity was 0.1 m/s (IQR: 0.02-0.18) and was significantly impaired in all patients. At follow-up TEE, the mean maximum and mean minimum ostial diameters were 19±4mm and 17±3mm, respectively. The mean maximum and mean minimum diameters of the landing zone were 20±4mm and 18±4mm, respectively. The mean relative reduction of the ostium and the landing zone was -24.4% and -22.5%, respectively. Box-Whisker plots of the maximum and minimum ostial diameters before and after LAAei are reported in Fig.1. Conclusion RF led to a >20% reduction of the diameters of the ostium and the landing zone. These changes may have important implications for a successful percutaneous occlusion procedure and justify a staged approach of isolation and occlusion.

Funding Acknowledgements Type of funding sources: None. Background Left atrial appendage (LAA) imaging is critical during percutaneous occlusion procedures. 3D-intracardiac echocardiography (ICE) features direct visualization of LAA from multiple cross-sectional planes at a time. Purpose To report procedural success of 3D-ICE-guided LAA occlusion and the correlation between pre-procedural transesophageal echocardiography (TEE) and intraprocedural 3D-ICE for LAA sizing. Methods Among 274 patients undergoing LAAO, periprocedural ICE guidance was achieved via a commercially available 2D-ICE catheter (220 patients) or a novel 3D-ICE one (54 patients; Fig.1). Primary endpoint was a composite of procedural success and LAA sealing at follow-up TEE. Secondary endpoint was a composite of periprocedural device recapture/resizing plus presence of leaks≥3mm at follow-up TEE. Results 3D-ICE measurements of maximum landing zone correlated highly with preprocedural TEE reference values [Pearson’s: 0.94; p The agreement between 3D-ICE-based device selection and final device size was 96.3% versus 79.1% with 2D-ICE (p=0.005). The incidence of the primary endpoint was 98.1% with 3D-ICE and 97.3% with 2D-ICE (p=0.99). 2D-ICE patients had a trend towards a higher incidence of periprocedural device recapture/redeployment (31.5% vs 44.5%; p=0.09). The secondary endpoint occurred in 31.5% of 3D-ICE patients versus 45.9% of 2D-ICE ones (p=0.065). Conclusions ICE-guided LAAO showed a very high success, with no major adverse events. A very high level of agreement for LAA sizing was found between pre-procedural TEE and periprocedural 3D-ICE. 3D-ICE performed significantly better than 2D-ICE for device size selection and may provide better guidance during device deployment.

Objective To describe the process of initiation of semaglutide for complex management of type 2 diabetes mellitus (T2DM) in a patient after liver transplantation. Setting Family medicine clinic. Practice Description A family medicine clinic comprising six physicians with an ambulatory care pharmacist. The pharmacist has direct interaction with patients and providers within the clinic assisting in the management of chronic disease states under a collaborative practice agreement. Practice Innovation A 63-year-old White male with a history of liver transplantation in the context of T2DM, treated with basal-bolus insulin therapy, was referred by his family medicine provider to the ambulatory care pharmacist for diabetes management because of a hemoglobin A1c (HbA1c) level greater than 10%. Semaglutide was initiated and titrated to improve blood glucose control in combination with basal-bolus insulin adjustments taking disease states, cost, and health literacy into consideration. Results The addition of semaglutide, over an eight-month period, assisted with glycemic control to an HbA1c of less than 7%. Conclusion Semaglutide, in addition to basal-bolus insulin therapy, allowed for overall improved glycemic control; however, further studies are needed to evaluate efficacy because of the complexity of diabetes management in this patient population. Throughout the course of treatment of patients with T2DM and organ transplantation, dual monitoring of antidiabetic therapy and antirejection medications is essential to reduce the risk of organ rejection.

In this study, the authors investigated the ablation success of scar homogenization with combined (epicardial + endocardial) vs endocardial-only approach for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up.Best ablation approach to achieve long-term success rate in VT patients with ICM is not known yet.Consecutive ICM patients undergoing VT ablation at our center were classified into group 1: endocardial + epicardial scar homogenization and group 2: endocardial scar homogenization. Patients with previous open heart surgery were excluded. Epicardial ablation was performed despite being noninducible after endocardial ablation in all group 1 patients. All patients underwent bipolar substrate mapping with standard scar settings defined as normal tissue1.5 mV and severe scar 0.5 mV. Noninducibility of monomorphic VT was the procedural endpoint in both groups. Patients were followed up every 4 months for 5 years with implantable device interrogations.A total of 361 patients (group 1: n = 70 and group 2: n = 291) were included in the study. At 5 years, 81.4% (n = 57/70) patients from group 1 and 66.3% (n = 193/291) from group 2 were arrhythmia-free (P = 0.01) Of those patients, 26 of 57 (45.6%) and 172 of 193 (89.1%) from group 1 and group 2 respectively were on anti-arrhythmic drugs (AAD) (log-rank P0.001). After adjusting for age, sex, and obstructive sleep apnea, endo-epicardial scar homogenization was associated with a significant reduction in arrhythmia-recurrence (HR: 0.48; 95% CI: 0.27-0.86; P = 0.02).In this series of patients with ICM and VT, epicardial substrate was detected in all group 1 patients despite being noninducible after endocardial ablation. Moreover, combined endo-epicardial scar homogenization was associated with a significantly higher success rate at 5 years of follow-up and a substantially lower need for antiarrhythmic drugs after the procedure compared with the endocardial ablation alone.

AimsThis study aimed to examine the clinical benefits of targeted ablation of all Premature ventricular complex (PVC) morphologies vs. predominant PVC only.Methods and resultsA total of 171 consecutive patients with reduced left ventricular ejection fraction (LVEF) and ≥2 PVC morphology with high burden (>10%/day) undergoing their first ablation procedure were included in the analysis. At the initial procedure, prevalent PVC alone was ablated in the majority. However, at the redo, all PVC morphologies were targeted for ablation. : At the first procedure, 152 (89%) patients received ablation of the dominant PVC only. In the remaining 19 (11%) patients, all PVC morphologies were ablated. At two years, high PVC burden was detected in 89 (52%) patients. Repeat procedure was performed in 78 of 89, where all PVC morphologies were ablated. At 5 years after the repeat procedure, 71 (91%) had PVC burden of ConclusionIn this observational series, ablation of all PVC morphologies was associated with significantly lower PVC burden and improvement of LVEF at long-term follow-up, compared with ablation of the dominant morphology only.

Atrial fibrillation (AF) and premature ventricular complexes (PVC) are common arrhythmias. We aimed to investigate AF prevalence in patients with PVC and its impact on PVC ablation outcomes.Consecutive patients undergoing PVC ablation at a single institution between 2016 and 2019 were included and prospectively followed for 2 years. Patients with severe valvular heart disease, hyperthyroidism, malignancy, alcohol use disorder and advanced renal/hepatic diseases were excluded. Twelve-lead electrocardiograms were used to diagnose AF and assess PVC morphology. All PVCs were targeted for ablation using 4-mm irrigated-tip catheters at standardized radiofrequency power guided by 3-D mapping and intracardiac echocardiography. Patients were followed with remote monitoring, device interrogations and office visits every 6 months for 2 years. Detection of any PVCs in follow-up was considered as recurrence.A total of 394 patients underwent PVC ablation and 96 (24%) had concurrent AF. Patients with PVC and AF were significantly older (68.2 ± 10.8 vs. 58.3 ± 15.8 years, p .001), had lower LV ejection fraction (43.3 ± 13.3% vs. 49.6 ± 12.4%, p .001), higher CHAAF was documented in 1/4 of patients undergoing PVC ablation and was associated with lower procedural success at long-term follow-up. This was likely attributed to older age, worse LV function and higher prevalence of multiple PVC morphologies in patients with concurrent AF.

Background: Data on atrial fibrillation (AF) ablation and outcomes are limited in patients with congenital heart disease (CHD). We aimed to investigate the characteristics of patients with CHD presenting for AF ablation and their outcomes. Methods: A multicenter, retrospective analysis was performed of patients with CHD undergoing AF ablation between 2004 and 2020 at 13 participating centers. The severity of CHD was classified using 2014 Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society guidelines. Clinical data were collected. One-year complete procedural success was defined as freedom from atrial tachycardia or AF in the absence of antiarrhythmic drugs or including previously failed antiarrhythmic drugs (partial success). Results: Of 240 patients, 127 (53.4%) had persistent AF, 62.5% were male, and mean age was 55.2±13.3 years. CHD complexity categories included 147 (61.3%) simple, 68 (28.3%) intermediate, and 25 (10.4%) severe. The most common CHD type was atrial septal defect (n=78). More complex CHD conditions included transposition of the great arteries (n=14), anomalous pulmonary veins (n=13), tetralogy of Fallot (n=8), cor triatriatum (n=7), single ventricle physiology (n=2), among others. The majority (71.3%) of patients had trialed at least one antiarrhythmic drug. Forty-six patients (22.1%) had reduced systemic ventricular ejection fraction Conclusions: AF ablation in CHD was safe and resulted in AF control in a majority of patients, regardless of complexity. Future work should address the most appropriate ablation targets in this challenging population.

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Background Left atrial appendage (LAA) electrical isolation (ei) may be achieved via radiofrequency (RF) energy applications at the level of the appendage ostium targeting the sites of earliest activation recorded by a mapping catheter. Notably, RF has long been used in vascular, orthopedic, and aesthetic surgery to promote thermal–induced collagen matrix contraction, fibrosis, and tissue retraction. LAA anatomical changes associated to RF–induced tissue retraction have never been reported. Objective To quantify the anatomical changes of the LAA ostium following RF–based LAAei. Methods Thirty–four consecutive patients requiring AF ablation with LAAei underwent transesophageal echocardiography (TEE) within 7 days before (baseline TEE) and >6 months after (follow–up TEE) ablation. The diameter of LAA orifice and landing zone were measured at 4 different views (0°, 45°, 90°, 135°). Measurements were performed by two independent reviewers blinded to the patient’s identity. Results Among 34 AF patients (68±7yrs, 73.5% males), the LAA morphology was classified as chicken wing in 15 (44%) patients, windsock in 10 (29%), cactus in 6 (18%), and cauliflower in 3 (9%). At baseline TEE, the mean maximum and mean minimum ostial diameters were 25±4mm and 22±4mm, respectively. The mean maximum and mean minimum diameters of the landing zone were 26±4mm and 23±3mm, respectively. On average, LAAei was achieved after 16±7 minutes of RF at a power of 45–47W. Follow–up TEE was performed 257±148 days after LAAei. The median LAA contraction velocity was 0.1 m/s (IQR: 0.04–0.18) and was significantly impaired in all patients. At follow–up TEE, the mean maximum and mean minimum ostial diameters were 19±4mm and 17±3mm, respectively. The mean maximum and mean minimum diameters of the landing zone were 20±4mm and 18±4mm, respectively. The mean relative reduction of the ostium and the landing zone were –24.4% and –22.5%, respectively. Box–Whisker plots of the maximum and minimum ostial diameters before and after LAAei are reported in Fig. 1. Conclusion RF led to a > 20% reduction of the diameters of the ostium and the landing zone. These changes may have important implications for a successful percutaneous occlusion procedure and justify a staged approach of isolation and occlusion.

Background Stroke prophylaxis in very high risk (CHA2DS2–VASc ≥ 5) patients with atrial fibrillation (AF) is one of the major challenges faced by physicians. Specifically, initiating direct oral anticoagulants (DOACs) in these patients poses a therapeutic conundrum due to the concomitant high risk of bleeding. Left atrial appendage occlusion (LAAO) might be a potential alternative for thromboembolic (TE) prevention; however, there are no studies comparing these two strategies in very high–risk patients. Objective To evaluate the efficacy of LAAO versus DOACs in AF patients at very high TE risk. Methods Data were extracted from two prospective databases including 1053 Watchman and 1328 DOAC patients. Watchman patients with a CHA2DS2–VASc ≥ 5 accounted for 26.3% (n = 277). In order to attenuate the imbalance in covariates, a 1:1 propensity score matching technique was used (co–variates: age, sex, CHA2DS2–VASc and HAS–BLED scores). This method resulted in 554 matched patients (277 patients per group; mean age: 79±7y; 57.4% F; CHA2DS2–VASc: 5.8±0.9). The primary endpoint was a composite of cardiovascular (CV) death, TE events (Stroke/TIA/peripheral embolism) and clinically significant bleeding. The annual TE and major bleeding risks were estimated based on the CHA2DS2–VASc score and compared with the annualized observed risk. Results After a mean follow–up of 26±7 months, total events were 55 (9.4 event rates per 100 patient–years) in LAAO group vs. 78 (14.9 event rates per 100 patient–years) in DOAC group. DOACs had a significantly higher risk of the primary endpoint (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.08 to 1.56; p = 0.03). TE events (HR: 1.15; 95% CI: 0.84 to 1.57; p = 0.63) and CV death (HR: 1.13; 95% CI: 0.84 to 1.54; p = 0.63) did not differ between groups. Major bleeding events were significantly lower in LAAO patients (HR: 0.75; 95% CI: 0.51 to 0.82; p = 0.04). The unadjusted estimated risk of TE events was 12.3% with LAAO and 12.4% with DOACs. The annualized incidence of TE was 3.2% with LAAO and 4.1% with DOACs, which led to a risk reduction of 74% and 67%, respectively. Conclusion In a large cohort of AF patients at very high TE risk (CHA2DS2–VASc ≥ 5), LAAO showed similar stroke prevention but a significantly lower risk of major bleeding than DOACs during a > 2year follow–up.

Background Whether residual peri–device leaks after left atrial appendage occlusion (LAAO) portend a higher risk of thromboembolism (TE), it is still a matter of debate. Objectives We report the TE risk in patients with incomplete LAA closure before and after leak closure with endovascular coils. Methods One hundred twenty–four Watchman patients with a significant (≥3mm) leak (mean age: 74 ± 9 years; 66.9% males; CHA2DS2–VASc: 4.4 ± 1.7; HAS–BLED: 3.1 ± 1) underwent LAA leak coiling. The expected annual TE risk was estimated based on the patients’ CHA2DS2–VASc and compared with the annualized incidence observed before and after coiling (Fig.1B). Results The time between LAAO and leak coiling was 8±6 months [83 patients–year (PY)]; before leak closure, 6 (4.8%) patients had a TE event (annualized rate: 7.2%). Coil deployment was successful in all cases [median n. of coils deployed: 5 (IQR: 2–10)]. Procedure time was 79 ± 40 min; the mean volume of iodinated contrast medium used was 80 ± 43mL. The overall complication rate was 2.4% (1 pericardial tamponade, 2 pericardial effusion). Follow–up TEE after 61±14 days revealed complete LAA sealing or a negligible leak in 117 cases (94.4%); the remaining 7 patients had a moderate leak. During 14±6 months post–coiling (145 PY), 1 (0.8%) patient suffered from stroke. The incidence of TE events was significantly lower after leak closure than before coiling (0.8% vs 4.8%; log–rank p = 0.02; Fig.1A). The annualized TE rates were 7.2% before and 0.7% after leak closure (Fig. 1A). According to the expected rate estimated from the patients’ CHA2DS2–VASc (9.8%), LAAO with and without significant leaks yielded to a risk reduction of 26.5% and 92.9% (Fig. 1B). Conclusions Transcatheter leak occlusion via endovascular coils was safe. LAA closure led to a significant reduction in TE events.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

This study evaluated the association of the post-ablation scar with stroke risk in patients undergoing atrial fibrillation (AF) ablation.Late gadolinium enhancement-cardiac magnetic resonance studies have reported a direct association between pre-ablation left atrial scar and thromboembolic events in patients with AF.Consecutive patients with AF were classified into 2 groups based on the type of ablation performed at the first procedure. Group 1 involved limited ablation (isolation of pulmonary veins, left atrial posterior wall, and superior vena cava); and group 2 involved extensive ablation (limited ablation + ablation of nonpulmonary vein triggers from all sites except left atrial appendage). During the repeat procedure, post-ablation scar (region with bipolar voltage amplitude 0.5 mV) was identified by using 3-dimensional voltage mapping.A total of 6,297 patients were included: group 1, n = 1,713; group 2, n = 4,584. Group 2 patients were significantly older and had more nonparoxysmal AF. Nineteen (0.3%) thromboembolic events were reported after the first ablation procedure: 9 (1.02%) in group 1 and 10 (0.61%) in group 2 (p = 0.26). At the time of the event, all 19 patients were experiencing arrhythmia. Median time to stroke was 14 (interquartile range: 9 to 20) months in group 1 and 14.5 (interquartile range: 8 to 18) months in group 2. Post-ablation scar data were derived from 2,414 patients undergoing repeat ablation. Mean scar area was detected as 67.1 ± 4.6% in group 2 and 34.9 ± 8.8% in group 1 at the redo procedure (p 0.001).Differently from the cardiac magnetic resonance-detected pre-ablation scar, scar resulting from extensive ablation was not associated with increased risk of stroke compared with that from the limited ablation.

This study investigated the use of direct visualization to enhance minimally invasive epicardial procedures. A commercially available miniature camera was placed in a prototype subxiphoid introducer needle and bench top, in vitro and in vivo tests of system performance were made during simulated and actual attempts at pericardial access and cardio-endoscopy. This system had an unshielded field of view of 100° and a resolution of 220 × 224 pixels. When a sleeve used to maintain depth of field was slid past the distal tip of the camera probe, the field of view would decrease by ≈15° per millimetre of sleeve extension, but without loss of image quality. While tests during in vivo subxiphoid access in a porcine model revealed that the pericardial membrane was difficult to localize, the results also showed excellent resolution of the coronary arteries on the epicardial surface. These findings and potential improvements are discussed in detail.

SummaryObjective(s)Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures.MethodsFour-year old wethers (n = 6/group) underwent sham operation, cranial pole release (CPR), mid-body transection (MBT) or total MX of the medial meniscus. Joints were assessed for gross pathology (cartilage erosion and osteophytes), histomorphometry, two histopathology scoring methods (modified Mankin-type and Pritzker score), and immunohistology for ADAMTS- and MMP-cleaved neoepitopes, at 12 weeks post-op. Ground reaction forces (GRFs) were determined by force plate in a subset (n = 4/group) at baseline, 2.5, 8, and 12 weeks post-op.ResultsGross pathology scores of operated groups differed significantly from sham animals (P 12 weeks) in MBT animals.ConclusionThe well-validated ovine MX model and the simpler meniscal destabilisation procedures resulted in broadly similar joint pathology and lameness. Meniscal CPR or MBT, as easier and more clinically relevant procedures, may represent preferred models for the induction of OA and evaluation of potential disease-modifying therapies.

Advanced optical systems of telescopes and scientific instrumentation require high accuracy mounting and joining of components. Applications for deep UV, under high energetic radiation, for vacuum operation, or assemblies subjected to environmental loads (e.g. humidity and temperature) require a replacement of organic adhesives or optical cement by a more robust bonding agent. Soldering allows the bonding of different materials with an inorganic filler material. We present the optimization of the laser-based Solderjet Bumping for the mounting of optical components and the parameters of the bonding process for fused silica and LAK9G15 (radiation resistant glass) with thermally matched metal mounts. The investigation covers the experimental determination and optimization of solder wetting to the respective base materials and the bond strengths achieved.

Solder joining using metallic solder alloys is an alternative to adhesive bonding. Laser-based soldering processes are especially well suited for the joining of optical components made of fragile and brittle materials such as glasses, ceramics and optical crystals. This is due to a localized and minimized input of thermal energy. Solderjet bumping technology has been used to assemble a lens mount breadboard taking as input specifications the requirements found for the optical beam expander for the European Space Agency (ESA) EarthCare Mission. The silica lens and a titanium barrel have been designed and assembled with this technology in order to withstand the stringent mission demands; handling high mechanical and thermal loads without losing its optical performances. Finally a high-precision opto-mechanical lens mount has been assembled with a minimal localized stress (

The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5-L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800-1,300 A) compared to cortical bone (300-600 A). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by an endochondral ossification-like process. The decrease in disc proteoglycan content and size suggests that calcification may precede or predispose to disc degeneration in ageing sheep.

Introduction: Focal impulse and rotor modulation (FIRM)-guided ablation targets localized sources that are thought to sustain AF. In previous reports, it has been shown that FIRM is effective in terminating or organizing AF. We sought to evaluate the acute success of FIRM in patients with persistent and LSP AF undergoing ablation in our centers. Methods: This was a multicenter prospective observational study. FIRM was performed alone or before conventional ablation. Rotors were ablated as confirmed by their absence during remapping and acute success was defined as AF termination, organization or slowing 10%. Results: 57 patients were enrolled (mean age 63 ± 10; 7% LSP). Rotors-only ablation was performed in 56% of patients, and preceded conventional ablation in 44%. There were no major periprocedural adverse events. No focal impulses were found, while rotors were present in all patients (3.9 ± 1.2 per patient; 66% in the LA). In the RA, the majority of rotors were in the lateral wall (53%) and in the septum (30%). In the LA, most of the rotors were in proximity of the pulmonary veins (48%), with the second most common locations being around the mitral annulus or in the septum (17% and 13% respectively). Mean procedural time for FIRM only procedures was 226 ± 52 minutes vs a median of 210 (168-240) minutes for FIRM + conventional ablation procedures (p = NS). Overall acute success was achieved in 35% of patients (3% AF termination, 16% AF organization, 16% AF slowing) with a mean RF time to complete FIRM ablation of 30 ± 15 minutes; no difference in acute success was found when comparing persistent to LSP patients (28% vs 50%; p = NS). Conventional ablation following FIRM did not significantly increase the rate of acute success (1 additional patient converted to sinus rhythm during pulmonary vein isolation). Conclusion: Rotors were present in all patients undergoing ablation for non-paroxysmal AF, most commonly the right atrial lateral wall, septum or around the pulmonary veins. Their ablation was not effective in obtaining AF organization/termination during the procedure.

Introduction: We sought to investigate the characteristics and outcomes of patients who underwent RF ablation of PM ventricular arrhythmias (VA) in our center. Results: 26 patients were included, median age was 66 years (16 to 85), 46% female, all with normal LVEF. PM VAs were PVCs in 68% patients, and PVC + VT in 32%. Site of origin was the LV infero-septal PM in 73%, LV antero-lateral PM in 15% and right ventricular RV septal PM in 12%. 46% of patients showed other VAs in addition to the one originating from the PMs; in 33% of these patients, additional VAs were 2 or more. These VAs were mostly PVCs (92%), localized in the LVOT (64% - 56 % in the basal LV and 44% in the aortic cusps) and the septal RVOT (36%). The only additional VT was fascicular. All the PMs and mappable additional VAs were ablated with RF energy through an irrigated catheter and the aid of ICE; a remote magnetic navigation system (RMS) was used in half of the procedures. In one case, PVC suppression required additional epicardial ablation. Major complications occurred in 2 patients (8%): 1 pericardial effusion (the patient underwent ablation of a crista terminalis premature atrial complex in the same procedure) and 1 pseudoaneurysm. Acute success (PM VA suppression/non-inducibility) was achieved in 96% of patients (the patient with pericardial effusion could be anticoagulated further and the procedure was stopped). After a median follow-up period of 8 (4-14) months, long-term success (no PM VT recurrence or PVC burden reduced by 80% off antiarrhythmic drugs) was 92% after a single procedure, 96% after repeat procedures. When considering additional VAs, the only recurrence was a parahisian RVOT PVC. No difference in acute or overall long-term success was observed when comparing RMS-guided vs standard procedures (respectively 92% vs 100 % and 100% vs 92%; P = NS). Conclusion: PM VAs are most commonly PVCs originating from the LV infero-septal PM and are frequently (48%) associated with an additional ventricular focus (LVOT > RVOT >> fascicular VT). RF ablation is safe and effective in eliminating or significantly reduce the burden of PM VAs, as well the extra-PM foci that are commonly encountered in this population. RMS guided ablation is not inferior to standard ablation in this subset of patients.

A novel laser-based soldering technique – Solderjet Bumping – using liquid solder droplets in a flux-free process with only localized heating is presented. We demonstrate an all inorganic, adhesive free bonding of optical components and support structures suitable for optical assemblies and instruments under harsh environmental conditions. Low strain bonding suitable for a following high-precision adjustment turning process is presented, addressing components and subsystems for objectives for high power and short wavelengths. The discussed case study shows large aperture transmissive optics (diameter approx. 74 mm and 50 mm) made of fused silica and LAK9G15, a radiation resistant glass, bonded to thermally matched metallic mounts. The process chain of Solderjet Bumping – cleaning, solderable metallization, handling, bonding and inspection – is discussed. This multi-material approach requires numerical modelling for dimensioning according to thermal and mechanical loads. The findings of numerical modelling, process parametrization and environmental testing (thermal and vibrational loads) are presented. Stress and strain introduced into optical components as well as deformation of optical surfaces can significantly deteriorate the wave front of passing light and therefore reduce system performance significantly. The optical performance with respect to stress/strain and surface deformation during bonding and environmental testing were evaluated using noncontact and nondestructive optical techniques: polarimetry and interferometry, respectively. Stress induced surface deformation of less than 100 nm and changes in optical path difference below 5 nm were achieved. Bond strengths of about 55 MPa are reported using tin-silver-copper soft solder alloy.

Solder-joining using metallic solder alloys is an alternative to adhesive bonding. Laser-based soldering processes are especially well suited for the joining of optical components made of fragile and brittle materials such as glasses, ceramics and optical crystals due to a localized and minimized input of thermal energy. The Solderjet Bumping technique is used to assemble a miniaturized laser resonator in order to obtain higher robustness, wider thermal conductivity performance, higher vacuum and radiation compatibility, and better heat and long term stability compared with identical glued devices. The resulting assembled compact and robust green diode-pumped solid-state laser is part of the future Raman Laser Spectrometer designed for the Exomars European Space Agency (ESA) space mission 2018.

We present Solderjet Bumping, a laser-based soldering process, as an all inorganic joining technique for optical materials and mechanical support structures. The adhesive-free bonding process enables the low-stress assembly of fragile and sensitive components for advanced optical systems. Our process addresses high demanding applications, e.g. under high energetic radiation (short wavelengths of 280 nm and below and/or high intensities), for vacuum operation, and for harsh environmental conditions. Laser-based soldering allows the low stress assembly of aligned sub-cells as key components for high quality optical systems. The evaluation of the optical path difference in fused silica and the radiation resistant LAK9G15 glass components after soldering and environmental testing shows the potential of the technique.

Introduction: Earlier studies have demonstrated that some AF patients develop spontaneous atrial scarring that leads to genesis and perpetuation of the arrhythmia. However, it is still unclear why it happens in some and not in others. Therefore, we hypothesized that the atrial scar phenotype is associated with certain specific genetic variants and examined the relationship between AF-related single-nucleotide polymorphisms (SNP) and left atrial scar. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS identified by GWAS study were performed from the collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. The Hardy-Weinberg equilibrium was assessed using Chi-square analyses. Multivariable logistic model was utilized to identify predictors of LA scar after adjusting for age, gender, LA size, hypertension and diabetes mellitus and odds ratio (OR) and 95% confidence intervals were computed. Results: Of all 16 SNPs, rs3807989 showed a strong inverse association with LA scar at univariate analysis (0.54 [0.348-0.89] p= 0.014) in the overall population. After adjustment for covariates, the association became highly significant indicating a 50% reduction in scar risk (OR 0.50 (0.30-0.83) p=0.007). When stratified by type of AF, rs3807989 genotype predicted a substantially stronger 69% risk-reduction in the non-PAF population (OR 0.31 (0.15-0.62) p=0.0009). Conclusion: The SNP, rs3807989 on chromosome 7p31, was demonstrated to be associated with reduced risk of left atrial scar formation in AF patients. This genetic variant is located in close proximity to the caveolin-1 gene which is known to have an anti-fibrotic role by inhibiting transforming growth factor-β1, a key mediator in the fibrosis process. Therefore, it can be postulated that by some unknown mechanism the candidate chromosomal variant potentially upregulates caveolin-1 function resulting in attenuation of fibrosis and scar formation.

Introduction: Catheter ablation of cavo-tricuspid isthmus (CTI) is considered to be the most effective therapy for eliminating target arrhythmia in lone atrial flutter (AFL). However, many patients subsequently develop AF after CTI ablation. Therefore, prophylactic pulmonary vein antrum isolation (PVAI) along with CTI ablation could be considered as an alternate option in these patients. We aimed to compare long-term incidence of post-ablation atrial fibrillation following CTI alone or CTI plus PVAI in patients presenting with isolated AFL and no history of atrial fibrillation. Methods: This multi-center prospective randomized study enrolled 216 patients undergoing catheter ablation for isolated typical atrial flutter. Patients were randomized to CTI alone (group 1, n=108, 61.2±9.7 year, 75% male, LVEF 59±10%) or combined ablation CTI+PVAI (group 2, n=108, 62.4±9.3 year, 73% male, LVEF 57±11%). Insertible Loop Recorder (ILR) was implanted in 21 and 19 patients from group 1 and 2 respectively, on the day of the ablation procedure. Remaining patients were monitored for recurrence with event recorders, ECG, 7-day Holter and cardiology evaluation. All patients were followed up for 18±6 months for recurrence. Results: Compared to group 1, group 2 had significantly longer average procedural duration (75.9±33 min vs. 161±48 min [p Conclusion: Prophylactic PVAI in lone atrial flutter caused marked reduction in new-onset AF in patients ≥ 55 years whereas younger patients (

Autogenous saphenous vein graft wrapping of the tibial nerve has been described as an effective treatment option for failed tarsal tunnel decompression. Various theories have been proposed to explain how this method works, with little histologic evidence to date. A pathologic investigation of a sectioned nerve that had been previously wrapped provides some insight into these proposals.

Auf Vorhofebene wurden zwei aktiv fixierte steroidfreisetzende Schraubelektroden (CapSureFix 4068, Medtronic, n = 17; Accufix II DEC 033-812, Telectronics, n = 16) und auf Ventrikelebene zwei aktiv fixierte Schraub- (Cap SureFix 4068, Medtronic, n = 11; Accufix II DEC 033-212, Telectronics, n = 20) und eine passiv fixierte Ankerelektrode (Encor DEC 033-448, Telectronics, n = 18) miteinander verglichen. Die Messungen erfolgten intraoperativ (= akut), nach 7 ± 3 Tagen (= subakut) sowie im Langzeitverlauf nach 3 und 6 Monaten. Im Vorhof zeigten sich akut keine Unterschiede der Reizschwellen (Accufix II DEC: 0,76 ± 0,23 V - CapSureFix: 0,75 ± 0,16 V). Im weiteren Verlauf kam es in beiden Gruppen zu einem statistisch nicht signifikanten Reizschwellenanstieg (Accufix II DEC: subakut 0,99 ± 0,45 V; 3 Monate 0,79 ± 0,43 V; 6 Monate: 0,84 ± 0,45 V - CapSureFix: subakut 0,76 ± 0,18 V; 3 Monate 0,87 ± 0,31 V; 6 Monate 0,88 ± 0,32 V). Auffallig waren die akut signifikant niedrigeren Reizschwellen im Bereich des rechten Herzohrs im Vergleich zur rechtslateralen Wand, wobei im chronischen Verlauf diese Unterschiede nicht langer nachweisbar waren (Herzohr n = 20 akut, 0,69 ± 0,11 V; rechtslaterale Wand n = 13 akut 0,85 ± 0,25 V). Im Ventrikel waren intraoperativ zwischen der Encor-DEC-Elektrode (0,56 ± 0,15 V) und der Accufix-II-DEC-Elektrode (0,53 ± 0,13 V) keine Unterschiede; die CapSureFix-Elektrode wies signifikant hohere Werte auf (0,8 ± 0,16 V). Subakut kam es bei allen drei Elektroden zu einem Reizschwellenanstieg, der bei der CapSureFix-Elektrode im Gegensatz zu den anderen beiden Sonden erst nach 3 Monaten statistische Signifikanz erlangte. Bei der Accufix-II-DEC-Elektrode zeigte sich im Gegensatz zu den eher ansteigenden Werten der Encor-DEC-Elektrode ein tendenzieller nichtsignifikanter Ruckgang nach 3 und 6 Monaten (Encor DEC: subakut 0,71 ± 0,22 V; 3 Monate 0,77 ± 0,23 V; 6 Monate 0,8 ± 0,28 V. - Accufix II DEC: subakut 0,86 ± 0,44 V; 3 Monate 0,8 ± 0,25 V; 6 Monate 0,74 ± 0,21 V. - CapSureFix: subakut 0,92 ± 0,17 V; 3 Monate 1,14 ± 0,46 V; 6 Monate 1,12 ± 0,32 V). Die Werte der CapSureFix-Elektrode lagen zu allen Meszeitpunkten signifikant hoher als die der anderen beiden Elektroden, die untereinander keinen Unterschied zeigten. In bezug auf das Sensingverhalten ergaben sich intraoperativ auf Vorhof- und Ventrikelebene keine Unterschiede zwischen den einzelnen Elektroden. Bei allen Elektroden kam es subakut zum signifikanten Schwellenabfall, welcher chronisch nicht weiter zunahm (Vorhof: CapSureFix akut 4,08 ± 1,34 mV, subakut 3,09 ± 0,88 mV, 3 Monate 2,91 ± 1,02 mV, 6 Monate 3,0 ± 1,22 mV; Accufix II DEC akut 4,34 ± 1,49 mV, subakut 2,86 ± 1,18 mV, 3 Monate 3,07 ± 1,04 mV, 6 Monate 2,91 ± 1,16 mV - Ventrikel: CapSureFix akut 11,55 ± 4,5 mV, subakut 9,99 ± 3,51 mV, 3 Monate 9,36 ± 3,23 mV, 6 Monate 9,13 ± 3,4 mV; Accufix II DEC akut 10,66 ± 3,0 mV, subakut 7,49 ± 4,04 mV, 3 Monate 7,25 ± 3,64 mV, 6 Monate 7,52 ± 4,1 mV; Encor DEC akut 11,65 ± 3,9 mV; subakut 9,04 ± 3,29 mV, 3 Monate 8,69 ± 3,83 mV, 6 Monate 8,78 ± 3,32 mV). Bezuglich der Sondenwiderstande zeigte sich auf Vorhofebene bei der Accufix-II-DEC-Elektrode eine signifikant niedrigere Impedanz als bei der CapSureFix-Elektrode, wobei im chronischen Verlauf beide keine signifikanten Unterschiede mehr aufwiesen. Auf Ventrikelebene zeigte die Accufix-II-DEC-Elektrode ebenfalls die signifikant niedrigste Impedanz, wobei es bei beiden aktiv fixierten Sonden subakut zu einem signifikanten Impedanzabfall kam, welcher bei den chronischen Messungen jedoch wieder ausgeglichen war. Die passive Encor-DEC-Elektrode hatte uber den gesamten Beobachtungszeitraum von allen drei Sonden die hochsten Impedanzen ohne signifikante Abweichungen zu den verschiedenen Mespunkten. Zusammenfassend zeigt sich, das durch das Dexamethasondepot bei beiden aktiv fixierten Vorhofelektroden ein subakuter und chronischer Reizschwellenanstieg effektiv verhindert werden kann und hiermit durchgehend eine energiesparende Programmierung bei gutem Sensingverhalten ermoglicht wird. Der auf Ventrikelebene bei allen drei Elektroden zu verzeichnende Reizschwellenanstieg fuhrt bei der CapSureFix-Elektrode zu signifikant hoheren chronischen Reizschwellen, wohingegen zwischen der passiv fixierten Encor-DEC-Elektrode und der aktiv fixierten Accufix-II-DEC-Elektrode keine signifikanten Unterschiede bestehen. Hervorzuheben ist die Ankerelektrode aufgrund der hochsten Impedanz mit hieraus resultierendem niedrigerem Stromflus bei gleich gutem Sensingverhalten ohne erhohte ventrikulare Dislokationsrate. Eine Impulsamplitude von 2,5 Volt kann bei nahezu allen Patienten programmiert werden.

Objectives: Autopsy rates continue to decline in the United States despite the demonstrated value of this procedure in many different settings. We sought to review clinical pathologic discordance information generated by autopsies on an internal medicine service in the urban United States and to determine whether resident services appear to influence autopsy rates. Methods: We reviewed consecutive deaths and autopsies on an inpatient internal medicine service during a 30-month period at a 400-bed community hospital in Baltimore, MD. Results: There were 622 deaths and 65 autopsies (10.3%). Resident teaching status correlated with a higher rate of autopsies performed (P = 0.048). Clinical pathologic discordance was common, with a major discordance rate of 39%. Major discordance was indicated by only one of nine autopsies performed on patients with human immunodeficiency virus. Conclusions: The autopsy was a valuable educational and quality improvement tool on the urban internal medicine service. Residency influences may be a major factor in continuing this exercise. In our study, although the numbers were small, patients with human immunodeficiency virus had a very low discordance rate.

Osteoarthritis (OA) is a highly prevalent joint disease. Its slow progressive nature and the correlation between pathological changes and clinical symptoms mean that OA is often well advanced by the time of diagnosis. In the absence of any specific pharmacological treatments, there is a pressing need to develop robust biomarkers for OA. We have adopted a nuclear magnetic resonance (NMR)-based metabolomic strategy to identify molecular responses to surgically induced OA in an animal model. Sheep underwent one of three types of surgical procedure (sham (control), meniscal destabilization, MD or anterior cruciate ligament transaction, ACLT), and for every animal a serum sample was collected both pre- and postoperatively, thus, affording two types of "control" data for comparison. 1D 1H NMR spectra were acquired from each sample at 800 MHz and the digitized spectral data were analyzed using principal components analysis and partial least-squares regression discriminant analysis. Our approach, combined with the study design, allowed us to separate the metabolic responses to surgical intervention from those associated with OA. We were able to identify dimethyl sulfone (DMSO2) as being increased in MD after 4 weeks, while ACLT-induced OA exhibited increased 3-methylhistidine and decreased branched chain amino acids (BCAAs). The findings are discussed in the context of interpretation of metabolomic results in studies of human disease, and the selection of appropriate "control" data sets.

Bronchoalveolar lavage (BAL) has gained widespread use as a tool for investigating human lung diseases. In certain cases, it can be useful to obtain BAL material in a serial manner. There is convincing evidence from experimental and clinical studies that BAL can cause influx of neutrophils into the bronchoalveolar space. However, conflicting data have been reported on whether this side effect of BAL also affects previously nonlavaged lung areas. In addition, there is little information available on whether multiple repetitive BAL procedures cause damage to lung tissue. To reexamine the short-term effects of serial BAL procedures, the left lung of 10 cynomolgus monkeys was lavaged with five 20-ml aliquots of saline four times at 24-h intervals (Group A). 72 h after the initial BAL, the right lung was lavaged as a control. The percentage of neutrophils increased significantly (p0.05), with the greatest effect seen at 48 h (30.7 +/- 5.8 versus 0.8 +/- 0.3%, mean +/- SEM). No significant changes were observed in the control BAL of the right lung at 72 h. A multidisciplinary approach was used to assess the long-term effects of multiple BAL procedures. BAL was performed 14 times over 26 mo at 2-mo intervals (Group B, n = 5). The right lung was lavaged as a control 25 mo after the initial BAL. In addition to standard cellular BAL parameters, the concentrations of fibronectin, procollagen III amino-terminal peptide-related antigen, total phospholipids, and lactate dehydrogenase activity were measured.(ABSTRACT TRUNCATED AT 250 WORDS)