Reconnection patterns after CLOSE-guided 50 W high-power-short-duration circumferential pulmonary vein isolation and substrate modification-PV reconnection might no longer be an issue.

INTRODUCTION: Ablation of atrial fibrillation (AF) with high-power-short-duration (HPSD) radiofrequency (RF) technology is emerging as a new standard of care in many electrophysiology laboratories. While procedural short-term efficacy and efficiency is very promising, little is known about mid- to long-term effects of HPSD ablation for pulmonary vein isolation (PVI) and left atrial substrate modification. METHODS: In a single-center registry, 412 AF procedures were performed in 400 individual patients using a standardized CLOSE protocol-guided fixed 50 W HPSD ablation, aiming for an ablation index (AI) of 400 on the posterior and 550 on the anterior wall. Additional substrate-tailored lines were performed when required. RESULTS: After a mean clinical follow-up of 337 ± 134 days, 15 patients suffered from AF recurrence beyond the blinding period. Twelve gave consent to the indicated reablation. Here, 11 of 12 patients had chronic isolation of all four pulmonary veins (PV). In three of six patients, a reconnection of additional left atrial ablation lines was revealed. Ten out of 12 patients showed progressive fibrous atrial cardiomyopathy and required additional left atrial substrate modification or reisolation of left-atrial lines. During the follow-up no clinical case of atrioesophageal fistula was registered. No PV stenosis after initial HPSD PVI was documented. CONCLUSIONS: Patients requiring reablation of AF or other atrial tachycardia after a fixed 50 W HPSD circumferential PVI and substrate modification predominantly suffer from progressive fibrous atrial cardiomyopathy, while PV reconnection appears to be a rare cause of AF recurrence.

Esophageal safety in CLOSE-guided 50 W high-power-short-duration pulmonary vein isolation: The PREHEAT-PVI-registry.

INTRODUCTION: Pulmonary vein isolation (PVI) using high-power-short-duration (HPSD) radiofrequency ablation (RF) is emerging as the standard of care for treatment of atrial fibrillation (AF). While procedural short-term to midterm efficacy and efficiency are very promising, this registry aims to investigate esopahgeal safety using an optimized ablation approach. METHODS: In a single-center experience, 388 consecutive standardized first-time AF ablation were performed using a CLOSE-guided-fixed-50 W-circumferential PVI and substrate modification without intraprocedural esophageal temperature measurement. Three hundred patients underwent postprocedural esophageal endoscopy to diagnose and grade endoscopically detected esophageal lesions (EDEL) and were included in the analysis. RESULTS: EDEL were detected in 35 of 300 patients (11.6%), 25 of 35 were low-grade Kansas-city-classification (KCC) 1 lesions with fast healing tendencies. Six patients suffered KCC 2a lesions, 4 patients had KCC 2b lesions (1.3% of all patients). No esophageal perforation or fistula formation was observed. Patient baseline characteristics, especially patients age, gender, and body mass index did not influence EDEL incidence. Additional posterior box isolation did not increase the incidence of EDEL. In patients diagnosed with EDEL, mean catheter contact force during posterior wall ablation was higher (11.9 ± 1.8 vs. 14.7 ± 3 g, p < .001), mean RF duration was shorter (11.9 ± 1 vs. 10.7 ± 1.2 s, p < .001), while achieved ablation index was not different between groups (434 ± 4.9 vs. 433 ± 9.5, n.s.). CONCLUSION: Incidence of EDEL after CLOSE-guided-50 W-HPSD PVI is lower compared to historical cohorts using standard-power RF settings. Catheter contact force during posterior HPSD ablation should not exceed 15 g.

The short term influence of right ventricular pacing burden on echocardiographic and spiroergometric parameters in patients with preserved left ventricular ejection fraction.

BACKGROUND: The incidence of worsened clinical outcome due to high right ventricular (RV) pacing burden in patients with preserved left ventricular function remains controversial. OBJECTIVE: To investigate the impact of RV pacing on several echocardiographic and spiroergometric parameters. METHODS: In 60 pacemaker patients with preserved left ventricular ejection fraction (LVEF) serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally, in 48 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation. RESULTS: The patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP < 40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12-month pacemaker therapy no changes to left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), LVEF, E/A-ratio; E/E'-ratio and tricuspid annular plane systolic excursion (TAPSE) could be revealed, independently of the RV pacing burden. Additionally, after 24-month long term follow-up there were no differences in LVEF and TAPSE in both groups. Accordingly, no relevant changes of peak exercise capacity, ventilatory anaerobic threshold or maximal oxygen consumption could be demonstrated independently of the RV pacing. CONCLUSIONS: In pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence on several echocardiographic and spiroergometric surrogate parameters of pacemaker-induced cardiomyopathy after a follow-up of 12 to 24 month. Despite this, screening for pacemaker induced cardiomyopathy should be performed especially in the presence of new heart failure symptoms.

Short term outcome after left atrial appendage occlusion with the AMPLATZER Amulet and WATCHMAN device: results from the ORIGINAL registry (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure).

BACKGROUND: Various randomized multicenter studies have shown that percutaneous left atrial appendage closure (LAAC) is not inferior in stroke prevention compared to vitamin K antagonists (VKA) and can be performed safely and effectively. AIMS: The prospective multicenter ORIGINAL registry in the Free State of Saxony (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure) investigated the efficiency and safety of LAAC with Watchman or Amulet device in a real word setting. A special focus was put on the influence of LAAC frequency on periprocedural efficiency and safety. METHODS AND RESULTS: The total of 482 consecutive patients (Abbott Amulet N = 93 and Boston Scientific Watchman N = 389) were included in the periinterventional analyses. After 6 weeks, 353 patients completed the first follow-up including transoesophageal echocardiography (TEE) (73.2%). Successful LAAC could be performed in more than 94%. The complication rate does not significantly differ between device types (p = 0.92) according to Fischer test and comprised 2.2% in the Amulet and 2.3% in the Watchman group. The kind of device and the frequency of LAAC per study center had no influence on the success and complication rates. Device related thrombus could be revealed more frequently in the Watchman group (4.5%) than in the Amulet group (1.4%) but this difference is still not significant in Fisher test (p = 0.14). Same conclusion can be made about residual leakage 1.1% versus 0% [not significant in Fisher test (p = 0.26)]. Dual antiplatelet therapy followed the intervention in 64% and 22% of patients were discharged under a combination of an anticoagulant (VKA/DOAC/Heparin) and one antiplatelet agent. CONCLUSIONS: The ORIGINAL registry supports the thesis from large, randomized trials that LAAC can be performed with a very high procedural success rate in the everyday clinical routine irrespective of the used LAA device (Watchman or Amulet). The postprocedural antithrombotic strategy differs widely among the participating centers. Trial registration Name of the registry: "saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure", Trial registration number: DRKS00023803; Date of registration: 15/12/2020 'Retrospectively registered'; URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023803 .

Procedural efficacy and safety of standardized, ablation index guided fixed 50 W high-power short-duration pulmonary vein isolation and substrate modification using the CLOSE protocol.

INTRODUCTION: Ablation index (AI)-guided ablation according to the CLOSE protocol is very effective in terms of chronic pulmonary vein isolation (PVI). However, the optimal radiofrequency (RF) power remains controversial. Here, we thought to investigate the efficiency and safety of an AI-guided fixed circumferential 50 W high-power short-duration (HPSD) PVI using the CLOSE protocol. METHODS AND RESULTS: In a single-center trial, 40 patients underwent randomized PVI using AI-guided ablation without esophageal temperature monitoring. In 20 patients a CLOSE protocol guided fixed 50 W HPSD was followed irrespective of the anatomical localization. Twenty subjects were treated according to the CLOSE protocol with standard power settings (20 W posterior and 40 W roof and anterior wall). In addition, 80 consecutive patients were treated according to the HPSD protocol to gather additional safety data. All patients underwent postprocedural esophagogastroduodenoscopy to reveal esophageal lesions (EDELs). The mean total procedural time was 80.3 ± 22.5 in HPSD compared to control 109.1 ± 27.4 min (p < .001). The total RF-time was significantly lower in HPSD with 1379 ± 505 s versus control 2374 ± 619 s (p < .001). There were no differences in periprocedural complications. EDEL occurred in 13% in the HPSD and 10% in the control group. EDEL occurring in the 50 W HSDP patients were smaller, more superficial, and had a faster healing tendency. CONCLUSION: A fixed 50 W HPSD circumferential PVI relying on the AI and CLOSE protocol reduce the total procedure time and the total RF time, without increasing the complication rates. The incidence of EDELs was similar using 50 W at the posterior atrial wall.

Reduction of atrial fibrillation burden by pulmonary vein isolation leads to a decrease of CD11b expression on inflammatory cells.

Aims: It is hypothesized that inflammation could promote structural and electrical remodelling processes in atrial fibrillation (AF). Atrial infiltration of monocytes and granulocytes has been shown to be dependent on CD11b expression. The aim of this study was to investigate whether treatment of AF by pulmonary vein isolation (PVI) may lead to reduced inflammation, as indicated by a decrease of CD11b expression on monocytes and granulocytes. Methods and results: Flow-cytometric quantification analysis and determination of systemic inflammatory markers of peripheral blood were performed in 75 patients undergoing PVI 1 day before and 6 months after PVI. The extent of activation of monocytes and granulocytes was measured by quantifying the cell adhesion molecule CD11b. The mean expression of CD11b on monocytes (20.9 ± 2.5 vs. 10.2 ± 1.4; P < 0.001) and granulocytes (13.9 ± 1.6 vs. 6.8 ± 0.5; P < 0.001), as well as the relative count of CD11b-positive monocytes (P < 0.05) and CD11b-positive granulocytes (P < 0.01) were significantly reduced when comparing the identical patients before and 6 months after PVI. Systemic inflammatory parameters showed only a declining tendency after 6 months. Patients with unsuccessful PVI and ongoing AF on the day of follow-up showed no decrease in CD11b expression. Conclusions: A significant reduction of CD11b expression on monocytes and granulocytes, as a sign of reduced cellular inflammation, was achieved by treatment of AF using PVI. These data strongly support that AF is not only a consequence of but also a cause for inflammatory processes, which, in turn, may contribute to atrial remodelling.

Atheroprotective role of Caveolin-1 and eNOS in an innovative transplantation model is mainly mediated by local effects.

Endothelial dysfunction is crucial in the initiation of atherosclerosis, which is associated with a lack of nitric oxide. The endothelial NO synthase (eNOS) is responsible for constitutive synthesis of NO and inhibited by caveolin-1 (Cav1). In the current study, we examined the influence on intima formation through single and combined deletion of eNOS and Cav1 with a focus on differentiation of local and systemic effects. A sex-mismatch transplantation of denudated aortae from female C57BL/6n (WT), Cav1-/-, eNOS-/- and Cav1-/-/eNOS-/- (C/e--/--) mice in common carotid artery of male WT mice was performed. After six weeks on Western-type diet, the aortae were explanted and intimal lesions were quantified by determining the intima-media-ratio (IMR). Significantly larger plaques were observed in all knockout mice compared to WT. The highest IMR was detected in Cav1-/- arteries associated with an increased expression of α-smooth muscle actin (αSMA) and the proliferating cell nuclear antigen (PCNA). Both were reduced in aortae from C/e--/--. Galectin-3 (Gal3) immunostaining revealed only small infiltrations of macrophages. Systemic cell invasion was detected by Y chromosome fluorescence in situ hybridization (Y-FISH), which showed only small numbers of systemic cells and no differences between the genotypes. Loss of Cav1 increased vascular lesion by enhancing neointimal proliferation. The combined loss of Cav1 and eNOS, compared to Cav1-/-, lowered intima formation, suggesting an increasing effect of eNOS in the absence of Cav1 on vascular lesion. Furthermore, these effects seem to be mediated by local cells rather than by systemically invaded ones.

Association of platelet activation markers with recurrence of atrial fibrillation after pulmonary vein isolation.

Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.

Fluoroscopy integrated 3D mapping significantly reduces radiation exposure during ablation for a wide spectrum of cardiac arrhythmias.

AIMS: Despite the use of established 3D-mapping systems, invasive electrophysiological studies and catheter ablation require high radiation exposure of patients and medical staff. This study investigated whether electroanatomic catheter tracking in prerecorded X-ray images on top of an existing 3D-mapping system has any impact on radiation exposure. METHODS AND RESULTS: Two hundred and ninety-five consecutive patients were either ablated with the guidance of the traditional CARTO-3 system (c3) or with help of the CARTO-UNIVU system (cU): [typical atrial flutter (AFL) n = 58, drug refractory atrial fibrillation (AF) n = 81, ectopic atrial tachycardia (EAT) n = 37, accessory pathways (APs) n = 22, symptomatic, idiopathic premature ventricular complexes (PVCs) n = 56, ventricular tachycardias (VTs) n = 41]. The CARTO-UNIVU allowed a reduction in radiation exposure: fluoroscopy time: AFL c3: 8.6 ± 0.8 min vs. cU: 2.9 ± 0.3 min, P < 0.001; AF c3: 16.0 ± 1.3 min vs. cU: 6.4 ± 0.9 min, P < 0.001; EAT c3: 23.4 ± 3.1 min vs. cU: 9.7 ± 1.7 min, P < 0.001; AP c3: 7.1 ± 1.2 min vs. cU: 6.0 ± 1.5 min, P = 0.59; PVCs c3: 17.6 ± 2.3 min vs. cU: 15.2 ± 2.8 min, P = 0.52; VT c3: 31.4 ± 3.4 min vs. cU: 17.5 ± 2.4 min, P = 0.003. Corresponding to the fluoroscopy time the fluoroscopy dose was also reduced significantly. These advantages were not at the cost of increased procedure times, periprocedural complications, or decreased acute ablation success rates. CONCLUSION: In a wide spectrum of cardiac arrhythmias, and especially in AF and VT ablation, fluoroscopy integrated 3D mapping contributed to a dramatic reduction in radiation exposure without prolonging procedure times and compromising patient's safety. That effect, however, could not be maintained in patients with APs and PVCs.

Effects of the Peroxisome Proliferator-Activated Receptor-γ Agonist Pioglitazone on Peripheral Vessel Function and Clinical Parameters in Nondiabetic Patients: A Double-Center, Randomized Controlled Pilot Trial.

OBJECTIVE: Despite the advanced therapy with statins, antithrombotics, and antihypertensive agents, the medical treatment of atherosclerotic disease is less than optimal. Therefore, additional therapeutic antiatherosclerotic options are desirable. This pilot study was performed to assess the potential antiatherogenic effect of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in nondiabetic patients. METHODS: A total of 54 nondiabetic patients were observed in a prospective, double-blind, placebo-controlled study. Patients were randomized to pioglitazone or placebo. The following efficacy parameters were determined by serial analyses: artery pulse wave analysis and carotid-femoral pulse wave velocity (PWV), static and dynamic retinal vessel function, and the common carotid intima-media thickness (IMT). The main secondary endpoint was the change in different biochemical markers. RESULTS: After 9 months, no relevant differences could be determined in the two treatment groups in PWV (pioglitazone 14.3 ± 4.4 m/s vs. placebo 14.2 ± 4.2 m/s), retinal arterial diameter (pioglitazone 112.1 ± 23.3 µm vs. placebo 117.9 ± 21.5 µm) or IMT (pioglitazone 0.85 ± 0.30 mm vs. placebo 0.79 ± 0.15 mm). Additionally, there were no differences in the change in biochemical markers like cholesteryl ester transfer protein, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein or white blood cell count. CONCLUSIONS: Treatment with a peroxisome proliferator-activated receptor-γ agonist in nondiabetic patients did not improve the function of large and small peripheral vessels (PPP Trial, clinicaltrialsregister.eu: 2006-000186-11).

Effects of the PPARγ agonist pioglitazone on coronary atherosclerotic plaque composition and plaque progression in non-diabetic patients: a double-center, randomized controlled VH-IVUS pilot-trial.

Despite the advanced therapy with statins, antithrombotics and antihypertensive agents, the medical treatment of coronary artery disease is less than optimal. Therefore, additional therapeutic anti-atherosclerotic options are desirable. This VH-IVUS study (intravascular ultrasonography with virtual histology) was performed to assess the potential anti-atherogenic effect of the PPARγ agonist pioglitazone in non-diabetic patients. A total of 86 non-culprit atherosclerotic lesions in 54 patients with acute coronary syndrome were observed in a 9-month prospective, double-blind, and placebo-controlled IVUS study. Patients were randomized to receive either 30 mg pioglitazone (Pio) or placebo (Plac). As primary efficacy parameter, the change of relative plaque content of necrotic core was determined by serial VH-IVUS analyses. Main secondary endpoint was the change of total plaque volume. In contrast to placebo, in the pioglitazone-treated group, the relative plaque content of necrotic core decreased significantly (Pio -1.3 ± 6.9% vs. Plac +2.6 ± 6.5%, p < 0.01). In comparison to the placebo group, the plaques in pioglitazone-treated patients showed significantly greater reduction of the total plaque volume (Pio -16.1 ± 26.4 mm3 vs. Plac -1.8 ± 30.9 mm3, p = 0.02). Treatment with a PPARγ agonist in non-diabetic patients results in a coronary artery plaque stabilization on top of usual medical care.

Target temperature management of 33 degrees C exerts beneficial haemodynamic effects after out-of-hospital cardiac arrest.

BACKGROUND: Accumulating evidence indicates that target temperature management (TTM) is beneficial in patients resuscitated after cardiac arrest since it appears to improve neurological outcome. However, the optimal cooling method (surface vs. intravascular) has not yet been specified. Substantial heart disease is present in most of these patients and therefore haemodynamic effects of cooling need to be considered very carefully. We analysed the haemodynamic response to TTM in patients treated with surface versus intravascular cooling following out-of-hospital cardiac arrest. METHODS AND RESULTS: In this observational study 63 consecutive subjects presenting to the hospital after successful resuscitation following of out-of-hospital cardiac arrest received an intravascular (40 patients) or external cooling device (23 patients) to induce TTM. While with intravascular cooling the target temperature of 33 degrees C was reached after 159 minutes, the minimum temperature achieved with surface cooling was about 35 degrees C after 437 minutes. Haemodynamic parameters were recorded in a 4-hour rhythm for the first 12 hours after induction of hypothermia. Generally, TTM of 33 degrees C resulted in a higher systemic vascular resistance index (749 vs. 467 dyn*sec/cms/m2; P= 0.04) but also in a marked reduction of heart rate (67.70 vs. 100.00 bpm; P < 0.001), a higher mixed venous oxygen saturation (76 vs. 68%; P = 0.016), and a higher stroke volume index (45 vs. 33 mI/m2; P = 0.036). TTM additionally resulted in a higher cardiac power index (0.55 vs. 0.46 Watt/m2; P = 0.024). CONCLUSION: TTM of 33 degrees C compared to 35 degrees C exerts beneficial haemodynamic effects and might be viewed as an adjunct inotropic therapy avoiding the undesired side effects of vasoactive substances.

Safety and Efficiency of Cephalic Vein Puncture by Modified Seldinger Technique Compared to Subclavian Vein Puncture for Cardiac Implantable Electronic Devices.

INTRODUCTION: The establishment of venous access is one of the driving factors for complications during implantation of pacemakers and defibrillators (cardiac implantable electronic devices [CIED]). Recently, a novel approach of accessing the cephalic vein for CIED by cephalic vein puncture (CVP) using a modified Seldinger technique has been described, promising high success rates and simplified handling with steeper learning curves. In this single-center registry, we analyzed the safety and efficiency of CVP to SVP access after defining CVP as the primary access route in our center. METHODS: A total of 229 consecutive patients receiving a CIED were included in the registry. Sixty-one patients were implanted by primary or bail-out SVP; 168 patients received primary cephalic preparation and CVP was performed when possible, using a hydrophilic transradial sheath. RESULTS: Implantation of at least one lead via CVP was successful in 151 of 168 patients (90%), and implantation of all leads was possible in 122 of 168 patients (72.6%). Total implantation times and fluoroscopy times and doses did not differ between CVP and SVP implantations. Pneumothorax occurred in 0/122 patients implanted via CVP alone, but 8/107 (7.5%) patients received at least one lead via SVP. CONCLUSION: Our data confirms high success rates of the CVP for CIED implantation. Moreover, this method can be used without significantly prolonging the total procedure time or applying fluoroscopy dose compared to the highly efficient SVP while showing lower overall complication rates.

Semiclassical hybrid approach to condensed phase molecular dynamics: application to the I2Kr17 cluster.

We study the vibrational decoherence dynamics of an iodine molecule in a finite krypton cluster comprising the first solvation shell. A normal mode analysis allows us to successively increase the complexity of the description. For the ground state dynamics, comparison with experimental matrix results shows that already four degrees of freedom are sufficient to capture the main decoherence mechanism. For electronically excited iodine, we model the vibrational dynamics of initial Schrödinger cat-like states by the semiclassical hybrid dynamics [Grossmann, F. J. Chem. Phys. 2006, 125, 014111] and full quantum calculations, where available. Good agreement of the results is found for a reduced model with three degrees of freedom. We find non-Gaussian distortions of the bath density matrix, which is a necessary condition, if Schrödinger catlike states in the bath are to be identified. However, in contrast to the experiment [Segale, D.; et al. J. Chem. Phys. 2005, 122, 111104], we observe only incoherent superpositions of bath vibrational states.

Myeloid PHD2 deficiency accelerates neointima formation via Hif-1α.

The key players of the hypoxic response are the hypoxia-inducible factors (Hif), whose α-subunits are tightly regulated by Prolyl-4-hydroxylases (PHD), predominantly by PHD2. Monocytes/Macrophages are involved in atherosclerosis but also restenosis and were found at hypoxic and sites of the lesion. Little is known about the role of the myeloid PHD2 in atherosclerosis and neointima formation. The study aimed to investigate the consequences of a myeloid deficiency of PHD2 in the process of neointima formation using an arterial denudation model. LysM-cre mice were crossed with PHD2fl/fl, PHD2fl/fl/Hif1αfl/fl and PHD2fl/fl/Hif2αfl/fl to get myeloid specific knockout of PHD2 and the Hif-α subunits. Denudation of the femoral artery was performed and animals were fed a western type diet afterwards with analysis of neointima formation 5 and 35 days after denudation. Increased neointima formation in myeloid PHD2 knockouts was observed, which was blunted by double-knockout of PHD2 and Hif1α whereas double knockout of PHD2 and Hif-2α showed comparable lesions to the PHD2 knockouts. Macrophage infiltration was comparable to the neointima formation, suggesting a more inflammatory reaction, and was accompanied by increased intimal VEGF-A expression. Collagen-content inversely correlated to the extent of neointima formation suggesting a destabilization of the plaque. This effect might be triggered by macrophage polarization. Therefore, in vitro results showed a distinct expression pattern in differentially polarized macrophages with high expression of Hif-1α, VEGF and MMP-1 in proinflammatory M1 macrophages. In conclusion, the results show that myeloid Hif-1α is involved in neointima hyperplasia. Our in vivo and in vitro data reveal a central role for this transcription factor in driving plaque-vascularization accompanied by matrix-degradation leading to plaque destabilization.

Simple periprocedural precautions to reduce Doppler microembolic signals during AF ablation.

BACKGROUND: Doppler microembolic signals (MES) occur during atrial fibrillation ablation despite of permanent flushed transseptal sheaths, frequent controls of periprocedural coagulation status and the use of irrigated ablation catheters PURPOSE: To investigate the number and type of MES depending on the procedure time, prespecified procedure steps, the activated clotting time (ACT) during the ablation procedure and the catheter contact force. METHODS: In a prospective trial, 53 consecutive atrial fibrillation patients underwent pulmonary vein isolation by super-irrigated "point-by-point" ablation. All patients underwent a periinterventional, continuous transcranial Doppler examination (TCD) of the bilateral middle cerebral arteries during the complete ablation procedure. RESULTS: An average of 686±226 microembolic signals were detected by permanent transcranial Doppler. Thereby, 569±208 signals were differentiated as gaseous and 117±31 as solid MES. The number of MES with regard to defined procedure steps were as follows: gaseous: [transseptal puncture, 26 ± 28; sheath flushing, 24±12; catheter change, 21±11; angiography, 101±28; mapping, 9±9; ablation, 439±192; protamine administration, 0±0]; solid: [transseptal puncture, 8±8; sheath flushing, 9±5; catheter replacement, 6±6; angiography, not measurable; mapping, 2±5; ablation, 41±22; protamine administration, 0±0]. Significantly less MES occurred with shorter procedure time, higher ACT and the use of tissue contact force monitoring. CONCLUSION: The current study demonstrates that during atrial fibrillation ablation using irrigated, "point-by-point" RF ablation, masses of microembolic signals are detected in transcranial ultrasound especially in the period of RF current application. The number of MES depends on the total procedure time and the reached ACT during ablation. The use of contact force monitoring might reduce MES during RF ablation.

Comparison of uninterrupted direct oral anticoagulation with vitamin-K antagonists during AF-ablation in the clinical routine. A single center register.

BACKGROUND: Uninterrupted direct oral anticoagulation (DOAC) in AF-ablation is recommended, proven by randomized trials. The outcome and the periinterventional differences between DOACs and VKA in the real world clinical practice are discussed controversial. HYPOTHESIS: To investigate efficiency and safety of uninterrupted DOAC therapy compared to VKA during AF-Ablation in real world setting with a focus on periinterventional heparin dosage.

Myocardial strain analysis using cardiac magnetic resonance in patients with calpainopathy.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a genetically and clinically heterogeneous group of rare muscular dystrophies. Subtype 2A (LGMD2A) also known as "calpainopathy" is an inherited autosomal recessive gene defect. Cardiac dysfunction is common in several forms of LGMD. Cardiac involvement in LGMD2A, however, is not clear. The aim of this study was to perform cardiac magnetic resonance (CMR)-based strain analysis in LGMD2A patients, as this is a diagnostic parameter of subclinical cardiac involvement and a powerful independent predictor of mortality. We conducted the largest prospective cardiac magnetic resonance study to date, including 11 genetically verified LGMD2A patients and 11 age- and sex-matched control subjects and performed CMR-based strain analysis of the left and right ventricles. RESULTS: Left and right global longitudinal strain (GLS) were not significantly different between the two groups and within normal reference ranges (left ventricle: control - 21.8 (5.1) % vs. patients - 22.3 (3.2) %, p = 0.38; right ventricle: control - 26.3 (7.2) % vs. patients - 26.8 (5.8) %, p = 0.85). Also, global circumferential and radial strains did not significantly differ between the two groups (p = 0.95 and p = 0.86, respectively). LGMD2A patients did not show relevant amounts of late gadolinium enhancement (LGE) or malignant ventricular arrhythmias. CONCLUSIONS: No evidence of even subtle cardiac dysfunction is evident form CMR-based strain analysis in LGMD2A patients. Malignant ventricular arrhythmias were not detected. Thus, in case of non-pathological initial echocardiographic and electrocardiographic examination, a less frequent or even no cardiac follow-up may be acceptable in these patients. However, if there are signs and symptoms that suggest an underlying cardiac condition (e.g. palpitations, angina, shortness of breath), this approach needs to be individualized to account for the unknown.

Evaluation of Myocardial Strain Using Cardiac Magnetic Resonance in Patients with Wilson's Disease.

(1) Background: Wilson's disease (WD) is an inherited autosomal recessive disorder with the excessive deposition of copper into different organs, including the heart. Previous studies showed structural cardiac changes even in patients with no signs of heart failure. The aim of this study was to perform cardiac magnetic resonance-based strain analysis in WD patients, as it is a powerful independent predictor of mortality. (2) Methods: We conducted a prospective cardiac magnetic resonance study that included 61 patients and 61 age and sex-matched controls, and performed strain analysis of the left and right ventricle. (3) Results: Left ventricular global longitudinal strain (GLS) as a prognostic marker of increased mortality was not altered (control -22.8 (4.8) % vs. WD patients -21.8 (5.1) %, p = 0.124). However, 4 of the 61 patients had a markedly reduced GLS. Global circumferential strain did not significantly differ between the groups either (p = 0.534). WD patients had significantly reduced global radial strain (p = 0.002). Right ventricular GLS was also significantly reduced in WD patients (p = 0.01). (4) Conclusions: Strain analysis revealed functional impairment of the left and right ventricle in a small number of patients as a potential early sign of cardiac manifestation in asymptomatic WD patients.