Deep sedation protocol during atrial fibrillation ablation using a novel variable-loop biphasic pulsed field ablation catheter.

BACKGROUND: Pulsed field ablation (PFA) is a novel, largely nonthermal ablative modality that, by virtue of its putative preferential action on myocardial tissue through the process of irreversible electroporation (IRE), may replace conventional thermal ablation for atrial fibrillation (AF). The recent inspIRE study confirmed safety and effectiveness of a fully integrated biphasic PFA system with a variable loop circular catheter for the treatment of paroxysmal AF. The majority of PFA procedures were performed using general anesthesia. However, due to the risks of general anesthesia we report the data regarding our sedation protocol used during inspIRE study. METHODS: A total of 29 patients (mean age 55±9 years; 72% male) were enrolled as part of this analysis within the inspIRE trial. The sedation protocol is reported in the manuscript. The Richmond Agitation-Sedation Scale (RASS), the Visual Analogue Scale (VAS) and the Patient State Index were collected during sedation. Each patient was monitored using the Masimo Sedline. At the end of ablation, the Likert Scale Questionnaire (LSQ) was used to assess the patients' satisfaction with intraoperative analgesia-sedation. RESULTS: No procedural complications were documented. Sufficient oxygen saturation was maintained in all patients during procedure. Non-invasive ventilation or tracheal intubation were not required for any patient. The RAAS score between -1 to -5 was obtained in 27 patients (93%) while the value 0 was obtained in 2 patients (7%). The VAS score between 0 to 2 was obtained in 24 patients (83%); the VAS score 3 in 3 patients (10%) and the VAS score 4 in 2 patients (7%). The PSI score <50 was achieved in 16 patients (55%) while the PSI between 50 and 70 was achieved in 9 patients (31%). Positive answers to LSQ were obtained in most patients. CONCLUSION: During PFA ablation procedures with the variable-loop circular catheter and its accompanying biphasic pulse, our deep sedation protocol is a valid alternative to general anesthesia.

Linear accelerator-based stereotactic arrhythmia radioablation for paroxysmal atrial fibrillation in elderly: a prospective phase II trial.

AIMS: Stereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients. METHODS AND RESULTS: Inclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001). CONCLUSION: The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04575662.

Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

BACKGROUND: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. METHODS: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). RESULTS: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). CONCLUSIONS: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

Use of mineral oil in IVF culture systems: physico-chemical aspects, management, and safety.

PURPOSE: The study aims to summarize current knowledge on the use of oil in embryo culture systems, with a focus on proper management of different types of oil and possible impact on culture systems. METHODS: PubMed was used to search the MEDLINE database for peer-reviewed English-language original articles and reviews concerning the use of oil in embryo culture systems. Searches were performed by adopting "embryo," "culture media," "oil," and "contaminants" as main terms. The most relevant publications were assessed and discussed critically. RESULTS: Oils used in IVF are complex mixtures of straight-chain hydrocarbons, cyclic and aromatic hydrocarbons, and unsaturated hydrocarbons, whose precise composition influences their chemical and physical properties. Possible presence of contaminants suggests their storage at 4 °C in the dark to prevent peroxidation. Washing, generally performed by manufacturers prior to commercialization, may remove trace chemical contaminants. Oils reduce evaporation from culture media at rates depending on their chemical physical properties, culture system parameters, and incubator atmosphere. Contaminants - mainly metal ion and plastic components derived from refinement processes and storage - can pass to the aqueous phase of culture systems and affect embryo development. CONCLUSIONS: Oils are essential components of culture systems. Their original quality and composition, storage, handling, and use can affect embryo development with significant efficiency and safety implications.

The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease.

Lysosomal storage diseases (LSDs) are inherited disorders caused by lysosomal deficiencies and characterized by dysfunction of the autophagy-lysosomal pathway (ALP) often associated with neurodegeneration. No cure is currently available to treat neuropathology in LSDs. By studying a mouse model of mucopolysaccharidosis (MPS) type IIIA, one of the most common and severe forms of LSDs, we found that multiple amyloid proteins including α-synuclein, prion protein (PrP), Tau, and amyloid ß progressively aggregate in the brain. The amyloid deposits mostly build up in neuronal cell bodies concomitantly with neurodegeneration. Treating MPS-IIIA mice with CLR01, a "molecular tweezer" that acts as a broad-spectrum inhibitor of amyloid protein self-assembly reduced lysosomal enlargement and re-activates autophagy flux. Restoration of the ALP was associated with reduced neuroinflammation and amelioration of memory deficits. Together, these data provide evidence that brain deposition of amyloid proteins plays a gain of neurotoxic function in a severe LSD by affecting the ALP and identify CLR01 as new potent drug candidate for MPS-IIIA and likely for other LSDs.

Stereotactic Ablative radiation therapy (SABR) for cardiac arrhythmia: A new therapeutic option?

AIM: Stereotactic ablative radiation therapy (SABR) is used in non-oncologic indications, recently even for cardiac arrhythmias. Thus, aim of this analysis is to review preclinical, early clinical evidences and future direction of the latter new treatment approach. METHOD: A collection of available data regarding SABR and cardiac arrhythmias was made, by Pubmed research and 2 independent researchers, including preclinical and clinical data. A review of ongoing trials was conducted on ClinicalTrials.gov. RESULTS: Preclinical research conducted in animal models showed that a safe and effective noninvasive treatment approach for cardiac arrhythmias could be represented by SABR with a median time of response around 2-3 months. The treatment dose plays a crucial role: the atrioventricular node would seem more radiosensitive than the other cardiac electric zones. Clinical data, such as published case series, case reports and early prospective studies, have already suggested the feasibility, efficacy and safety of SABR (25 Gy in one session) for refractory ventricular arrhythmias. CONCLUSION: Considering the ongoing trials of SABR and new technological improvements in radiotherapy (e.g. hybrid magnetic resonance) and in arrhythmias noninvasive mapping systems, the future analyses will improve the reliability of those preliminary results.

Electroanatomic guidance versus conventional fluoroscopy during transseptal puncture for atrial fibrillation ablation.

INTRODUCTION: Technological advancement in the setting of atrial fibrillation (AF) ablation has decreased radiation exposure and complications associated with the procedure. Yet, transseptal puncture (TSP) remains a challenging step that necessitates accurate guidance. We describe our experience performing TSP under electroanatomic (EA) guidance. METHODS AND RESULTS: The analysis included 145 consecutive EA-guided ablation procedures performed between June 2018 and April 2019 and 145 consecutive standard ablations performed before June 2018. EA guidance utilized the CARTO 3 three-dimensional mapping system to reconstruct anatomic and electrical characteristics of the right atrium and fossa ovalis. Patients with a history of previous cardiac surgery were excluded. For EA-guided procedures, the mean patient age was 60 ± 10 years, 75.2% were male, and 69.0% had paroxysmal AF. Similarly, the mean age for conventional procedures was 60 ± 11 years, 71.0% were male, and 71.7% had paroxysmal AF. The fossa ovalis was detected as a region of low voltage, <0.75 mV. EA guidance yielded shorter fluoroscopy times (EA vs. conventional, 3.6 ± 2.5 vs. 13.5 ± 10.5 min; p < .001) and a lower dose area product than conventional guidance (13 ± 11 Gy* cm2 vs. 28 ± 27 Gy* cm2 ; p < .001). The total procedure duration was similar between groups (146 ± 48 vs. 148 ± 54 min). There were no significant complications related to TSP. CONCLUSION: During AF ablation, TSP with EA guidance facilitated safe access to the left atrium while reducing radiation risk to both patients and operators.

Use of a multi-electrode radiofrequency balloon catheter to achieve pulmonary vein isolation in patients with paroxysmal atrial fibrillation: 12-Month outcomes of the RADIANCE study.

BACKGROUND: The RADIANCE first-in-man study evaluated acute (3-month) safety and design concept in terms of utility of a new multi-electrode radiofrequency (RF) balloon catheter (HELIOSTAR, Biosense Webster) to achieve pulmonary vein isolation (PVI). After study conclusion, a subset of patients was followed up to 12 months. METHODS: Patients with drug refractory paroxysmal atrial fibrillation were enrolled. Neurological assessment, cardiac and cerebral magnetic resonance imagings were performed pre and post procedure. Ablation was delivered at 15 Watts to each PV for 60 seconds (electrodes adjacent to the posterior wall limited to 20 seconds). Adenosine or isoproterenol was administered to confirm PVI. Esophageal endoscopy was performed 48 hours post procedure. Patients were clinically followed up for 12 months. RESULTS: Thirty-nine patients underwent catheter ablation from four centers. Mean age was 60.7 ± 10.0 years with 23 (57.5%) being male. Confirmation of PVI was performed in all PVs treated (152/152). Confirmation of isolation after one delivery was performed solely on 137 of 152 PVs of which 79.6% (109/137) achieved isolation with a single delivery of RF energy. Acute PV reconnection was seen in 4.6% (7/150) of PVs. Freedom from documented atrial arrhythmia at 12 months in those followed up was 86.4% (32/37). A total of 75.7% (28/37) of patients were free from atrial arrhythmia and off antiarrhythmic medications. CONCLUSION: The HELIOSTAR RF balloon catheter allows for rapid and safe PVI with majority of PVs only requiring one application.

Cardiopulmonary support in patients undergoing catheter ablation of poorly tolerated ventricular arrhythmias and electrical storm.

INTRODUCTION: Catheter ablation is an important treatment option for sustained ventricular arrhythmias (VA) that are refractory to pharmacological treatment; however, patients with fast VA or electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VA. METHODS: Nineteen patients (mean age, 62 ± 10 years; 84% male) were referred to our center for CA of ES between January 2017 and April 2018. ES was defined as the occurrence of ≥3 ventricular tachycardia or ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-hour period. ECMO support was implemented for all patients. RESULTS: CA of ES was completed in all patients. Activation mapping was performed for all VTs and substrate modification was performed by targeting sites identified by late/fragmented abnormal potentials. VTs were not inducible after ablation in 16 of 19 patients (84%). With regard to procedural complications, two patients underwent percutaneous angioplasty with stenting for a femoral artery dissection and one patient was treated for a dislodged ECMO arterial cannula and subsequent hemorrhagic shock. After a median follow-up of 10 months, three patients died from refractory heart failure and one patient died as a result of ES. Overall, the procedural success rate was 68% and the Kaplan-Meier mortality rate was 21%. CONCLUSIONS: ECMO support may be used for ablation procedures in patients with ES.

Conjugated linoleic acid prevents age-dependent neurodegeneration in a mouse model of neuropsychiatric lupus via the activation of an adaptive response.

Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of neuropsychiatric lupus, was previously associated with the improvement of nuclear factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However, little is known about the neuroprotective ability of a CLA mixture. This study investigated the age-dependent progression of oxidative stress and the hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2) in old/diseased MRL/lpr mice brains and examines the effect produced by dietary CLA supplementation. Disrupted redox homeostasis was evidenced in the blood, liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10-week-old MRL/lpr (Young) animals. This alteration was associated with significant hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte activation) in the brains of Old mice. Five-week daily supplementation with CLA (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the pathological hallmarks at a level comparable to Young mice or healthy controls (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model for the evaluation of the effectiveness of neuroprotective drugs. Notably, the preventive effect provided by CLA supplementation against age-associated neuronal damage and hyperactivation of compensatory mechanisms suggests that the activation of an adaptive response is at least in part accountable for its neuroprotective ability.

Safety and efficacy of pulmonary vein isolation using a surround flow catheter with contact force measurement capabilities: A multicenter registry.

INTRODUCTION: Pulmonary vein (PV) isolation is the cornerstone of catheter ablation in patients with atrial fibrillation (AF). Surround flow and contact force (CF) measurement capabilities might enhance procedure efficacy and safety. We report on the safety and midterm efficacy of a novel ablation catheter for PV isolation in patients with AF. METHODS AND RESULTS: Two hundred thirty-three consecutive patients (57 ± 11 years, 76% males, 51% with structural heart disease), referred for paroxysmal (157) or persistent (76) AF, underwent PV isolation by a surround flow catheter with CF measurement capability in four centers. Ablation was guided by electroanatomic mapping allowing radiofrequency (RF) energy delivery in the antral region aiming at PV isolation. Mean overall procedure time was 100 ± 42 minutes with a mean fluoroscopy time of 6 ± 5 minutes. Mean ablation time was 31±15 minutes; 99% of the targeted veins were isolated. The mean CF value during ablation was 13 ± 4 g. Intraprocedural early (30 minutes) PV reconnection occurred in 12% PVs, and all PVs were effectively reisolated. One pericardial effusion and five groin hematomas were reported. During a mean follow-up of 12 ± 6 months, 30 (12.9%) (10% paroxysmal AF vs. 18% persistent AF, P = 0.07) patients had an atrial arrhythmias recurrence. CONCLUSIONS: In this multicenter registry, RF ablation using a new surround flow catheter, with CF sensor, resulted as feasible, achieving a high rate of isolated PVs. Procedural and fluoroscopy times and success rates were comparable with other techniques with a low complication rate.

Presence of 'ghosts' and mortality after transvenous lead extraction.

AIMS: The number of cardiovascular implantable electronic devices has increased progressively, leading to an increased need for transvenous lead extraction (TLE) due to device infections. Previous studies described 'ghost' as a post-removal, new, tubular, mobile mass detected by echocardiography following the lead's intracardiac route in the right-sided heart chambers, associated with diagnosis of cardiac device-related infective endocarditis. We aimed to analyse the association between 'ghosts' assessed by transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) and mortality in patients undergoing TLE. METHODS AND RESULTS: We prospectively enrolled 217 patients (70 ± 13 years; 164 males) undergoing TLE for systemic infection (139), local device infection (67), and lead malfunction (11). All patients underwent TEE before and 48 h after TLE and ICE during TLE. Patients were allocated to two groups: either with (Group 1) or without (Group 2) post-procedural 'ghost'. Mid-term clinical follow-up was obtained in all patients (11 months, IQR 1-34 months). We identified 30 (14%) patients with 'ghost', after TLE. The significant predictors of 'ghost' were Charlson co-morbidity index (HR = 1.24, 95% CI 1.04-1.48, P = 0.03) and diagnosis of endocarditis assessed by ICE (HR = 1.82, 95% CI 1.01-3.29, P = 0.04). Mortality was higher in Group 1 than in Group 2 (28 vs. 5%; log-rank P < 0.001). Independent predictors of mid-term mortality were the presence of 'ghost' and systemic infection as the clinical presentation of device infection (HR = 3.47, 95% CI 1.18-10.18, P = 0.002; HR = 3.39, 95% CI 1.15-9.95, P = 0.001, respectively). CONCLUSION: The presence of 'ghost' could be an independent predictor of mortality after TLE, thus identifying a subgroup of patients who need closer clinical surveillance to promptly detect any complications.

Outcome of Patients Treated by Cardiac Resynchronization Therapy Using a Quadripolar Left Ventricular Lead.

BACKGROUND: Not all heart failure (HF) patients benefit from cardiac resynchronization therapy (CRT). We assessed whether choosing the site of left ventricular (LV) pacing by a quadripolar lead may improve response to CRT. METHODS AND RESULTS: We prospectively randomized 23 patients with HF (67±11 years; 21 males) to CRT with a quadripolar LV lead (group 1, with the LV pacing site chosen on the basis of QRS shortening using simultaneous biventricular pacing), and 20 patients (71±6 years; 16 males) to a bipolar LV lead (group 2, with devices programmed with a conventional tip-to-ring configuration). New York Heart Association (NYHA) class and LV ejection fraction (EF) by 2D echocardiography were assessed at baseline and after 3 months. The baseline EF was not different between the 2 groups (25±6% group 1 vs. 27±3% group 2; P=0.22), but after 3 months EF was higher in group 1 (35±13% group 1 vs. 31±4% group 2; P<0.001). A reduction in at least 1 NYHA class at 3 months was observed in 22 (96%) and 12 (60%) of group 1 and group 2 patients, respectively (P<0.05). CONCLUSIONS: CRT with a quadripolar LV lead was associated with an improvement of EF greater than that observed in patients receiving a bipolar LV lead. In devices with a quadripolar lead, CRT programming based on the best QRS shortening is reliable and effective. (Circ J 2016; 80: 613-618).

Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice.

PURPOSE: The beneficial effects of conjugated linoleic acid (CLA) mixture (cis9, trans11, c9; trans10, cis12, t10) against gliadin-induced toxicity in HLA-DQ8-transgenic mice (DQ8) have been associated with improved duodenal cytoprotective mechanisms [nuclear factor-E2-related factor-2, Nrf2; acylpeptide hydrolase (APEH)/proteasome]. The present study was aimed at investigating the ability of individual CLA isomers to improve the efficacy of these defensive mechanisms and to protect against duodenal injury caused by the combined administration of gliadin and indomethacin (GI). METHODS: Gluten-mediated enteropathy was induced in DQ8 mice by three intra-gastric administration of gliadin (20 mg kg(-1)/bw) and indomethacin (15 mg L(-1)) in drinking water for 10 days (GI). C9 or t10 CLA (520 mg kg(-1)/bw/day) were orally administered for 2 weeks. Pro-oxidant and toxic effects associated with GI treatment, anti-oxidant/detoxifying ability of c9 or t10-CLA and the protective effect induced by c9 pre-treatment (c9 + GI) were evaluated in DQ8 mice duodenum by combining enzymatic, immunoblotting, histological evaluation and quantitative real-time PCR assays. RESULTS: GI treatment produces the time-dependent decline of the considered detoxifying mechanisms thus leading to pro-apoptotic and pro-oxidant effects. APEH/proteasome pathway was not markedly affected by individual CLA isomers, but duodenal redox status and activity/mRNA levels of Nrf2-activated enzymes were significantly improved by c9 administration. c9 pre-treatment protects against GI-mediated accumulation of oxidative stress markers, and histological examination reveals the increase of goblet cells number in mouse duodenum but induces only a partial recovery of APEH/proteasome activity. CONCLUSIONS: The activation of and adaptive response by low doses of c9 supplementation prevents distinct signs of gliadin-induced enteropathy in DQ8 mice.

Neuroglial alterations in the zebrafish brain exposed to cadmium chloride.

Cadmium is an extremely toxic heavy metal that widely occurs in industrial workplaces with various hazardous effects on brain functions. The cytotoxic effects of cadmium chloride (CdCl2 ) on the neuroglial components of the zebrafish brain were analysed by detecting the glial fibrillary acidic protein (GFAP) expression and the mRNA levels of myelin genes mbp, mpz and plp1 in adult specimens exposed to cadmium for 2, 7 and 16 days. A significant decrease in the GFAP protein by Western blotting experiments was observed after 2 days of treatment, reaching 55% after 16 days. No change was observed in the mRNA levels. Using immunohistochemistry, a reduction in GFAP-positive structures was revealed with a progressive trend in all the brains at 2, 7 and 16 days of treatment. In particular, a considerable reduction in GFAP-positive fibres, with a different course, was observed in the ventricle areas and at the pial surface and in blood vessels after 16 days. Our experiments also showed a structural and chemical alteration of myelin and upregulation of mpz mRNA levels, the oligodendrocyte gene that is upregulated in experiments of neuronal injury, but not of plp1 and mbp mRNA levels, other myelin structural genes. These data confirm the toxic action of cadmium on the zebrafish brain. This action is time-dependent and involves the glial cells, key components of the protection and function of nerve cells, hence the basis for many neurological diseases. Copyright © 2016 John Wiley & Sons, Ltd.

The association between ICD interventions and mortality is independent of their modality: clinical implications.

BACKGROUND: Patients with severe structural heart disease have increased mortality after implantable cardioverter-defibrillator (ICD) shocks. Whether this is limited to ICD shock therapy only or extends also to no-shock therapies, such as antitachycardia pacing (ATP), is unclear. We investigated the impact of different ICD therapies on long-term mortality. METHODS: We enrolled 573 patients who underwent ICD implantation at our institution from 2004 to 2011. The population was divided into 3 groups: no device interventions (group 1), ATP interventions (group 2), and shock interventions (group 3). The endpoint was the all-cause mortality. RESULTS: Over a follow-up period of 48 months (range 1-110), 447 (78%) had no device interventions, 71 (12%) had ATP therapy only, and 55 (10%) had at least one shock intervention. All-cause mortality occurred in 94 patients in group 1 (21%), 23 patients (43%) in group 2, and 21 patients (38%) in group 3. At multivariable Cox regression analysis, ATP intervention (HR: 1.8; 95% CI 1.1-3; P < 0.001), shock intervention (HR: 1.39; 95% CI 1.09-1.77; P = 0.008), age (HR: 1.05; 95% CI 1.02-1.07; P < 0.001), and LVEF (HR: 0.95; 95% CI 0.93-0.98; P = 0.001) were predictors of all-cause mortality. No significant difference in mortality was found between group 2 and 3. CONCLUSION: Patients with ICDs who receive appropriate interventions are at increased risk of mortality. Such risk is not dependent on different types of ICD therapy, such as shocks or ATP. Our data suggest that sustained ventricular arrhythmias per se have a negative impact on prognosis rather than modality of ICD therapy.

Safety of transvenous lead extraction according to centre volume: a systematic review and meta-analysis.

BACKGROUND: Transvenous lead extraction (TLE) is a complex invasive procedure and the experience of the operator and the team is a major determinant of procedural outcomes. AIM: Because of very limited data available on minimum procedural volumes to enable training and ongoing competency for TLEs, we performed a meta-analysis aimed at assessing the outcomes of TLE in the centres with low, medium, and high volume of procedures. METHODS: Of the 280 papers initially retrieved until February 2013, 66 observational studies met inclusion criteria and were included in at least one stratified meta-analysis: 17 were prospective studies; 47 had a retrospective design; and 2 were defined 'experience studies'. We included only articles published after the introduction of laser technique (year 1999). We divided the studies in low, medium, and high volume centres utilizing either the European Heart Rhythm Association (EHRA) or Lexicon classification criteria. RESULTS: When meta-analyses were carried out separately for the studies with larger and smaller sample sizes, either using EHRA or Lexicon classification criteria, no clear differences emerged in the combined rate of major complications or intraoperative deaths. In contrast, both minor complications and mortality at 30 days decreased as centre volume increased. CONCLUSIONS: In our meta-analysis of observational studies, patients who have been treated in higher volume centres have a lower probability of minor complications and death at 30 days regardless of the infection rate, length of lead duration, type of device, and type of extraction.

Predictors of postoperative atrial fibrillation in patients with coronary artery disease undergoing cardiopulmonary bypass: a possible role for myocardial ischemia and atrial inflammation.

OBJECTIVE: To evaluate the preoperative presence of C-reactive protein (CRP) and troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing cardiopulmonary bypass (CPB) in order to better clarify the role of atrial inflammation and/or myocardial ischemia in the development of postoperative atrial fibrillation (POAF). DESIGN: Prospective, nonrandomized study. SETTING: University hospital. PARTICIPANTS: Thirty-eight consecutive ischemic patients admitted to the authors' hospital for CAD undergoing elective on-pump coronary artery bypass grafting (CABG). INTERVENTION: Elective on-pump CABG. MEASUREMENTS AND MAIN RESULTS: Peripheral blood samples were collected from all patients before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG telemetry. Biopsies from the right atrial appendage were obtained at the beginning of the CABG procedure in order to perform immunohistochemistry for CRP and reverse transcription polymerase chain reaction for CRP mRNA expression. Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31 patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not correlate with serum hs-CRP levels and with occurrence of POAF, but with the incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP levels, were identified as the only predictor of POAF occurrence (p = 0.016). CONCLUSIONS: In patients undergoing CABG, neither peripheral nor tissue preoperative CRP levels, but only postoperative hs-TnT levels, correlated with POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation.