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Aims Intraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement. Methods and results A prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia. Conclusion The present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

Background: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency AF ablations. Aim: We aimed to assess cryoballoon ablation-induced PV fibrosis via MRI and its correlation with AF recurrence. Methods and Results: This was a prospective study of consecutive patients with symptomatic AF who underwent pre- and post-ablation MRI to assess baseline and ablation-induced fibrosis, respectively. Post-ablation PV gaps were assessed by new semi-quantitative visual analysis assisted by computerized ADAS analysis. AF recurrence monitored via multiple ECGs and event monitoring at 6 and 12 months post ablation. Nineteen patients with 80 PVs were included, age 56 ± 11, with paroxysmal and persistent AF in 17/19 and 2/19 patients, respectively. Baseline MRI showed minimal LA fibrosis. All patients underwent successful cryoballoon PV electrical isolation. Post-ablation MRI revealed circumferential PV fibrosis among 63/80 (78.8%) PVs and partial fibrosis with major gaps among 17/80 (21.2%) PVs. AF recurred within one year in 5/9 (55.5%) patients with partial PV fibrosis, while no AF recurred among the 10 patients in whom all PVs had circumferential fibrosis (p < 0.01). Similarly, there were significantly more PVs without circumferential fibrosis (due to major gaps) among patients with AF recurrence as compared with patients without AF recurrence (42.9% vs. 13.5%; p < 0.01). Conclusion: Cryoballoon AF ablation results in circumferential PV fibrosis in the majority of PVs, as assessed by a new clinically relevant MRI-LGE analysis. Significant correlation was found between major PV gaps on post-ablation MRI and AF recurrence, suggesting that MRI might have the ability to predict AF recurrence.

Introduction D-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients. Nevertheless, data regarding D-dimer's prognostic impact among tertiary care intensive coronary care unit (ICCU) patients is scarce. Material and method All patients admitted to the ICCU between 1-12/2020 were prospectively included. Based on admission D-dimer level, patients were categorized into low and high D-dimer groups (< 500 ng/ml and ≥ 500 ng/ml) and also to age-adjusted D-dimer cutoff (500 ng/ml for ages ≤ 50 years old and age*10 for ages>50 years old). Results and discussion A total of 959 consecutive patients were included, including 296 (27.4%) and 663 (61.3%) patients with low and high D-Dimer levels, respectively. Patients with high D-dimer level were older compared with patients with low D-dimer level (age 70.4 ± 15 and 59 ± 13 years, p = 0.004) and had more comorbidities. The most common primary diagnosis on admission among the low D-dimer group was acute coronary syndrome (ACS) (74.3%), while in the high D-dimer group it was a combination of ACS (33.6%), cardiac structural interventions (26.7%) and various arrhythmias (21.1%). High D-dimer levels were associated with increased mortality rate, even after adjustment for age, gender, comorbidities and left ventricular ejection fraction (LVEF). High D-dimer levels were independently associated with increased overall 1-year mortality rate (HR = 5.8; 95% CI; 1.7-19.1; p = 0.004). Conclusion Elevated D-dimer levels on admission in ICCU patients is an independently poor prognostic factor for in-hospital morbidity and 1-year overall mortality rate following hospitalization.

Background: Heart failure (HF) patients with wide QRS often benefit from cardiac resynchronization therapy (CRT), although QRS narrowing does not always occur. The current study investigates the incidence and predictors for QRS narrowing following CRT and its long-term impact on clinical outcomes. Methods: Among individuals undergoing clinically indicated CRT, pre-and post-implantation electrocardiographs were meticulously analyzed for QRS duration change. All-cause mortality and the composite of mortality and HF hospitalizations were retrieved. Results: For 104 patients, mean age 67 years, 25% females, QRS narrowed within days by 20.2 ± 24.7 ms. In 55/104 (53%) QRS narrowed by ≥20 ms (“acute narrowing”). Female gender and baseline QRS predicted acute narrowing. Acute narrowing persisted for 1–6 weeks in 18/20 (90%) and 3–12 months in 21/31 (68%) of patients. During the average follow-up of 41 months, 29/104 (28%) died and 50/104 (48%) met the composite outcome. In a multivariable analysis including comorbidities and cardiac history, prolonged baseline PR interval (HR 1.015, CI 1.008–1.021, p < 0.001) and acute narrowing < 20 ms (HR 3.243, CI 1.593–6.603, p = 0.001) were significant and independent predictors for the composite outcome. Conclusions: Post-CRT acute QRS narrowing ≥ 20 ms is independently associated with favorable long-term outcomes and might be considered as a novel measure for procedural success.

A novel 3D mapping system (KODEX-EPD, EPD Solutions) enables catheter localization and real-time 3D cardiac mapping.To evaluate left atrium (LA) anatomical mapping accuracy created by the KODEX-EPD system during pulmonary vein isolation (PVI) compared with gold standard computed tomography (CT) images acquired from the same patients before the procedure.In 15 consecutive patients who underwent PVI, 3D mapping of the LA was created on the KODEX-EPD system using the Achieve catheter. Pulmonary vein (PV), posterior wall, and appendage anatomy and diameters, were compared to the CT 3D reconstruction measured on the CARTO 3 system. Measurements were done independently by two physicians in each method. Linear correlation and agreement between CT and EPD measurements were assessed by Spearman correlation and Bland-Altman plot.Mean LA mapping time was 7.7 ± 3.6 min. Very high interobserver correlation was found for both EPD and CT measurements (Spearman r = .9). High correlation (r = .75) was found between CT and EPD measurements. Bland-Altman plot method revealed that measurements assessed by EPD were slightly higher than those assessed by CT. Mean difference was 3.5 mm, p .01. In 2 (13.5%) patients each, disagreement regarding the presence of a left common PV and a right middle accessory vein anatomy was seen.The new KODEX-EPD mapping system allows quick and accurate mapping of the LA with high correlation to CT imaging. Some differences in left common and accessory right middle vein anatomy were seen.

BACKGROUND: Cardiac implantable electronic device (CIED) implantation rates as well as the clinical and procedural characteristics and outcomes in patients with known active coronavirus disease 2019 (COVID-19) are unknown. OBJECTIVE: The purpose of this study was to gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. METHODS: Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. RESULTS: The CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (P

Objectives: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterization and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients’ arrhythmic risk are still lacking, and are the aim of our study. Methods: We describe a single center cohort of hospitalized patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020 –30/5/2020. The study’s outcome was any documented arrhythmia during hospitalization, based on daily physical examination, routine ECG’s, periodic 24-hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. Results: Out of 390 COVID-19 patients included, 28 (7.2%) had documented arrhythmias during hospitalization, including: 23 atrial tachyarrhythmias, combined atrial fibrillation (AF) and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed significant correlation between disease severity and arrhythmia prevalence (p

OBJECTIVES: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterization and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients' arrhythmic risk are still lacking, and are the aim of our study. METHODS: We describe a single center cohort of hospitalized patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020 -30/5/2020. The study's outcome was any documented arrhythmia during hospitalization, based on daily physical examination, routine ECG's, periodic 24-hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. RESULTS: Out of 390 COVID-19 patients included, 28 (7.2%) had documented arrhythmias during hospitalization, including: 23 atrial tachyarrhythmias, combined atrial fibrillation (AF) and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed significant correlation between disease severity and arrhythmia prevalence (p

Advancement in the miniaturization of high-density power sources, electronic circuits, and communication technologies enabled the construction of miniaturized electronic devices, implanted directly in the heart. These include pacing devices to prevent low heart rates or terminate heart rhythm abnormalities (‘arrhythmias’), long-term rhythm monitoring devices for arrhythmia detection in unexplained syncope cases, and heart failure (HF) hemodynamic monitoring devices, enabling the real-time monitoring of cardiac pressures to detect and alert for early fluid overload. These devices were shown to prevent HF hospitalizations and improve HF patients’ life quality. Pacing devices include permanent pacemakers (PPM) that maintain normal heart rates, defibrillators that are capable of fast detection and the termination of life-threatening arrhythmias, and cardiac re-synchronization devices that improve cardiac function and the survival of HF patients. Traditionally, these devices are implanted via the venous system (‘endovascular’) using conductors (‘endovascular leads/electrodes’) that connect the subcutaneous device battery to the appropriate cardiac chamber. These leads are a potential source of multiple problems, including lead-failure and systemic infection resulting from the lifelong exposure of these leads to bacteria within the venous system. One of the important cardiac innovations in the last decade was the development of a leadless PPM functioning without venous leads, thus circumventing most endovascular PPM-related problems. Leadless PPM’s consist of a single device, including a miniaturized power source, electronic chips, and fixating mechanism, directly implanted into the cardiac muscle. Only rare device-related problems and almost no systemic infections occur with these devices. Current leadless PPM’s sense and pace only the ventricle. However, a novel leadless device that is capable of sensing both atrium and ventricle was recently FDA approved and miniaturized devices that are designed to synchronize right and left ventricles, using novel intra-body inner-device communication technologies, are under final experiments. This review will cover these novel implantable miniaturized cardiac devices and the basic algorithms and technologies that underlie their development. Advancement in the miniaturization of high-density power sources, electronic circuits, and communication technologies enabled the construction of miniaturized electronic devices, implanted directly in the heart. These include pacing devices to prevent low heart rates or terminate heart rhythm abnormalities (‘arrhythmias’), long-term rhythm monitoring devices for arrhythmia detection in unexplained syncope cases, and heart failure (HF) hemodynamic monitoring devices, enabling the real-time monitoring of cardiac pressures to detect and alert early fluid overload. These devices were shown to prevent HF hospitalizations and improve HF patients’ life quality. Pacing devices include permanent pacemakers (PPM) that maintain normal heart rates, defibrillators that are capable of fast detection and termination of life-threatening arrhythmias, and cardiac re-synchronization devices that improve cardiac function and survival of HF patients. Traditionally, these devices are implanted via the venous system (‘endovascular’) using conductors (‘endovascular leads/electrodes’) that connect the subcutaneous device battery to the appropriate cardiac chamber. These leads are a potential source of multiple problems, including lead-failure and systemic infection that result from the lifelong exposure of these leads to bacteria within the venous system. The development of a leadless PPM functioning without venous leads was one of the important cardiac innovations in the last decade, thus circumventing most endovascular PPM-related problems. Leadless PPM’s consist of a single device, including a miniaturized power source, electronic chips, and fixating mechanism, implanted directly into the cardiac muscle. Only rare device-related problems and almost no systemic infections occur with these devices. Current leadless PPM’s sense and pace only the ventricle. However, a novel leadless device that is capable of sensing both atrium and ventricle was recently FDA approved and miniaturized devices designed to synchronize right and left ventricles, using novel intra-body inner-device communication technologies, are under final experiments. This review will cover these novel implantable miniaturized cardiac devices and the basic algorithms and technologies that underlie their development.

Many tachy-brady syndrome (TBS) patients, are implanted a permanent pacemaker (PPM) to allow continuation of anti-arrhythmic drug (AAD) therapy to maintain sinus rhythm. Many of these PPM's are implanted as a preventive measure, in absence of symptomatic bradycardia. Our primary aim was to evaluate pacing use among these patients and find predictors for PPM use. Our secondary aim was to appreciate the portion of these patients who progress to permanent atrial fibrillation (AF).Retrospective study of TBS patients implanted a PPM as preventive measure, dividing cases into defined categories regarding highest percent atrial and ventricular pacing documented in PPM clinic visits during 3 year follow-up (F/U) period. Patients' baseline characteristics and AAD therapy were compared between cases with a major (90%) pacing use and cases with90% pacing use to find predictors for pacing use. Multivariable logistic regression was applied to identify independent variables associated with major pacing use.Our study included 119 TBS patients. Most (86.5%) TBS patients had a moderate (50%) pacing use and 58% had a major pacing use. Significant association was found between pre-implant severe sinus bradycardia (40 bpm), first degree atrioventricular block and amiodarone treatment to major pacing use on univariate analysis and severe sinus bradycardia was significantly associated with major pacing on multivariate analysis as well. Only minority (16.8%) of TBS patients progressed to permanent AF during the study F/U period.Our study reveals most TBS patients succeed to maintain sinus rhythm using an AAD with a significant pacing use, suggesting preventive PPM implantation might be advantageous in these cases. Pre-implant severe sinus bradycardia (40 bpm) is a possible predictor for major pacing use in this population.

Acute pulmonary congestion (APC) may occur within hours after electrical cardioversion of atrial fibrillation (AF). There is scarce data about its incidence, risk factors, and the outcome. In the present study, data of consecutive patients admitted for first electrical cardioversion for AF between 2007 and 2016 were retrospectively reviewed. APC within the 48 hours following cardioversion was defined as dyspnea and at least one of the following: drop in saturation to90%, administration of intravenous diuretic or an emergent chest X-ray with new pulmonary congestion. All-cause mortality was determined from the national registry. Total of 1,696 patients had first cardioversion for AF, of whom 66 (3.9%) had APC. In a multivariate logistic regression model independent predictors of APC included (OR [CI], p): older age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02 to 1.08, p = 0.001), rapid ventricular response (OR 1.98, 95% CI 1.17 to 3.34, 0.010), previous heart failure (OR 3.53, 95% CI 2.09 to 5.97, p0.001), Amiodarone loading (OR 2.38, 95% CI 1.18 to 4.79, p = 0.016) and diabetes mellitus (OR 1.77 95% CI 1.05 to 3.00, p = 0.033). There was no difference in cardioversion success rate (overall 94%). In-hospital mortality was 1.5% within the APC group and 0.5% without (p = 0.301). Patients with APC had higher rate of 6-month readmissions (28.8% vs 18.1% p0.028). Within a median follow-up of 2.9 years, APC following cardioversion was an independent predictor of overall mortality (hazard ratio 1.73, 95% CI (1.17 to 2.56) p = 0.006). In conclusion, APC occurs in 3.9% of hospitalized patients following electrical AF cardioversion. Risk factors include increased age, diabetes mellitus, heart failure, Amiodarone loading and rapid ventricular response. APC following cardioversion is associated with increased rates of readmissions and mortality.

Patients with life-threatening arrhythmias are often treated with cardiac implantable electronic devices (CIEDs), such as pacemakers and implantable cardioverter defibrillators (ICDs). Recent advancements in CIEDs have enabled advanced functionality and connectivity that make such devices (particularly ICDs) vulnerable to cyber-attacks. One of the most dangerous attacks on CIED ecosystems is a data manipulation attack from a compromised programmer device that sends malicious clinical programmings to the CIED. Such attacks can affect the CIED functioning and impact patient's survival and quality of life. In this paper, we propose Cardio-ML – an automated system for the detection of malicious clinical programmings that is based on machine learning algorithms and a novel missing values resemblance framework. Our system is designed to detect new variants of existing attacks and, more importantly, new unknown (zero-day) attacks, aimed at ICDs. We collected 1651 legitimate clinical programmings from 514 patients, over a four-year period, from programmer devices at two medical centers. Our collection also includes 28 core malicious functionalities created by cardiac electrophysiology experts that were later used to create different variants of malicious programmings. Cardio-ML was evaluated extensively in three comprehensive experiments and showed high detection capabilities in most attack scenarios. We achieved perfect classification results for detecting newly created variants of existing core malicious functionalities, with an AUC of 100%; for completely new unknown (zero-day) malicious clinical programmings, an AUC of 80% was obtained, which is 14% better than the state-of-the-art method. We were able to further improve our detection results by identifying the best combination of legitimate and zero-day malicious programmings in the dataset, achieving an AUC of 87%. CIED clinical programmings have many parameters without values for a large number of samples (programmings). To cope with the extreme amount of missing values in our dataset, we developed a novel missing values-based resemblance framework and evaluated it using three dataset-creation approaches: a standard expert-driven approach, our novel data-driven approach, and a combined approach incorporating both approaches. The results showed that our novel framework handles missing values in the data better than the expert-driven approach which yields an empty dataset. In particular, the combined approach showed a 40% improvement in data utilization compared to the data-driven approach.

Patients with left ventricular dysfunction (LVD) and prolonged QRS on surface electrocardiogram are at increased risk for heart failure and death and may benefit from resynchronization therapy. Patients with initial narrow QRS may prolong their QRS during the disease course. The occurrence of delayed QRS prolongation, its predictors and associated risk of heart failure hospitalizations (HFH) or death are currently unknown and the subject of this investigation.Patients with LVD, QRS 120 ms and available follow-up ECGs were retrospectively evaluated for persistent unprovoked QRS prolongation130 ms. Impact on mortality or HFH was assessed using Cox regression with QRS 130 ms as a time dependent covariate. Following 178 patients for 30 (10;59) median (IQR) months, 28 (16%) patients prolonged their QRS to130 ms, reaching a QRS duration of 154 ± 29 ms; LBBB pattern was diagnosed among 14 (50%) patients. Patients with delayed QRS prolongation were older (71.9 ± 11.8 vs 64.4 ± 15.1 years p = 0.014), had larger left ventricle and left atrial diameters (6.3 ± 0.9 vs 5.7 ± 0.9 cm p = 0.010; 4.9 ± 0.6 vs 4.5 ± 0.7 cm p = 0.006, respectively) and wider baseline QRS (104.8 ± 12.6 vs 91.4 ± 14.5 ms p 0.001) which was linearly associated with late QRS prolongation (p for trend0.0001). In a multivariable model, age, baseline QRS width and left atrial diameter were significantly associated with delayed QRS prolongation. QRS prolongation at follow-up was independently associated with risk of death or HFH (HR 7.426, 95% CI3.017-18.280, p 0.0001).QRS prolongation occurs in a significant proportion of patients with LVD and portends adverse outcome. Advanced age, prolonged QRS and larger left atria are potential predictors. Routine monitoring is justified and physicians may choose to plan ahead for resynchronization therapy in patients at risk for QRS prolongation.

Aim: Evaluate prevalence of heart failure (HF) medications and their association with ventricular arrhythmia (VA) and survival among patients implanted with primary prevention implantable cardiac defibrillator (ICD)/cardiac resynchronization therapy + defibrillator (CRTD) devices. Methods: Association of treatment and dose (% guideline recommended target) of beta-adrenergic receptor antagonist (BB), angiotensin-antagonists (AngA), and mineralocorticoid-antagonists (MRA), after ICD/CRTD implant with VA and mortality was retrospectively analyzed. Results: Study included 186 HF patients, 42.5% and 57.5% implanted with ICD and CRTD, respectively. During 3.8 (2.1, 6.7) years, 52 (28%) had VA and 77 (41.4%) died. Treatment (% of patients) included: BB (83%), AngA (87%), and MRA (59%). Median doses were 25(12.5, 50)% of target for all medications. BB treatment &gt, 25% target dose was associated with reduced VA incidence. In the multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was associated with reduced VA (hazard ratio (HR) 0.443 95% CI 0.222–0.885, p = 0.021). In the multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment, VA was associated with increased mortality (HR 2.672, 95% CI 1.429–4.999, p = 0.002) and AngA treatment was associated with reduced mortality (HR 0.515, 95% CI 0.285–0.929, p = 0.028). Conclusions: In this cohort of real-life HF patients discharged after ICD/CRTD implant, prevalence of guideline-based HF medications was high, albeit with low doses. Higher BB dose was associated with reduced VA, while AngA was associated with improved survival.

We describe a case of a teenager who presented with palpitations and abnormal low atrial rhythm. Celiac Disease (CD) serology, sent due to low ferritin, was positive and gastroscopy confirmed CD diagnosis. Both palpitations and abnormal rhythm resolved after gluten-free diet with normalization of CD serology.

A Novel Annotation Technique During Mapping to Facilitate the Termination of ATIntroduction The treatment of atrial tachycardia (AT) occurring after ablation for atrial fibrillation (AF) is challenging. The most common ablation strategy relies on entrainment, and electroanatomic activation mapping (EAM) using a conventional window of interest (WOI), centered on the easily detectable atrial signal on the coronary sinus catheter. We describe a novel EAM annotation technique that uses a WOI starting 40 milliseconds prior to the P wave in order to detect the reentrant AT exit site. This WOI timing is based on the similarity between scar-related reentrant AT and scar-related ventricular tachycardia. Methods Patients with AT after prior ablation for AF were included. The EAM of the AT was performed using the novel mapping annotation technique. The ablation was considered successful if the AT terminated during ablation at the site identified by this strategy. Results Twenty-eight patients with 36 ATs were included. The ATs were classified as follows: mitral annulus (13/36), roof (11/36), anterior/posterior/lateral left atrial wall (10/36), and RA (2/36). A complete EAM using the novel annotation technique was achieved in 34 of 36 AT's, encompassing 94 ± 6.5% of the cycle length. Low amplitude pre-P fractionated electrograms were found in 34 of 36 (94%) ATs and these occurred at a mean distance of 1.8 ± 1.2 mm from the “early-meets-late” line. Ablation at these areas resulted in termination of 34 of 36 ATs (94%). Conclusion The novel EAM annotation allows the accurate detection of the critical isthmus of post-AF ablation AT. Ablation of these isthmuses results in termination of the AT in the vast majority of patients.

Aims Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. Methods and results Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. Conclusion A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.

Background Radiation exposure in the electrophysiology lab is a major occupational hazard to the electrophysiologists. A catheter localization system (MediGuide Technology, St. Jude Medical Inc., St. Paul, MN, USA) allows the integration of electroanatomical mapping and x-ray imaging, and has been shown to be effective in reducing radiation exposure during several electrophysiological procedures. We intended to evaluate the feasibility of this catheter tracking system to guide transseptal (TS) access. Methods The feasibility of performing TS puncture with MediGuide (MDG) was assessed in a prospective observational study in 16 patients undergoing radiofrequency ablation for atrial fibrillation. These patients were compared to 16 matched patients undergoing similar procedures during the same time frame using conventional approach. There were no differences in mean age, gender distribution, and body mass index between the two groups. Total duration of fluoroscopic exposure during TS puncture was compared between the two groups. Results All patients underwent successful TS puncture. Fluoroscopy time for double TS puncture using the MDG system was significantly lower than the control group (0.48 ± 0.17 minutes vs. 5.9 ± 0.65 minutes; P < 0.0001). No major complications occurred during the procedures in either group. Conclusions TS puncture can be successfully performed using MDG, and results in significant reduction in radiation exposure.

Background Magnetic resonance imaging (MRI) has been considered contraindicated in patients with cardiac pacemakers (PPMs). Recently, Medtronic (MDT) MRI SureScan PPM (Medtronic Inc., Minneapolis, MN, USA) and leads were introduced into clinical practice in the United States of America. Objective To compare MDT CapSureFix 5086 MRI SureScan lead-associated perforation and dislodgement rates with MDT non-MRI SureScan active fixation leads. Methods We retrospectively analyzed the records of all patients implanted with MDT CapSureFix 5086 MRI SureScan leads as well as all patients implanted with MDT 4076 and 5076 leads at our institution from April 2011 to April 2014. Results Four of 72 patients implanted with MDT CapSureFix 5086 MRI SureScan leads (5.5%) had evidence of lead perforation, necessitating pericardiocentesis in three cases and lead revision in one case. Three of the four perforations were delayed perforations, presenting more than 3 weeks postimplant. Two patients implanted with MDT CapSureFix 5086 MRI SureScan leads (2.8%) had lead dislodgement. Of 420 patients implanted with MDT non-MRI SureScan leads, there were two perforations (0.47%) and four dislodgements (0.9%). There were significantly increased lead perforations associated with MDT CapSureFix 5086 MRI SureScan leads (P = 0.005) and a nonsignificant trend toward increased dislodgements (P = 0.18) when compared with MDT non-MRI SureScan leads. Conclusion In contradiction to prior studies, this retrospective study suggests an increased perforation rate with MDT CapSureFix 5086 MRI SureScan leads. Most perforations were delayed perforations, presenting more than 3 weeks postimplant. Higher volume prospective studies with longer follow-up are needed to confirm our findings.

The treatment of atrial tachycardia (AT) occurring after ablation for atrial fibrillation (AF) is challenging. The most common ablation strategy relies on entrainment, and electroanatomic activation mapping (EAM) using a conventional window of interest (WOI), centered on the easily detectable atrial signal on the coronary sinus catheter. We describe a novel EAM annotation technique that uses a WOI starting 40 milliseconds prior to the P wave in order to detect the reentrant AT exit site. This WOI timing is based on the similarity between scar-related reentrant AT and scar-related ventricular tachycardia.Patients with AT after prior ablation for AF were included. The EAM of the AT was performed using the novel mapping annotation technique. The ablation was considered successful if the AT terminated during ablation at the site identified by this strategy.Twenty-eight patients with 36 ATs were included. The ATs were classified as follows: mitral annulus (13/36), roof (11/36), anterior/posterior/lateral left atrial wall (10/36), and RA (2/36). A complete EAM using the novel annotation technique was achieved in 34 of 36 AT's, encompassing 94 ± 6.5% of the cycle length. Low amplitude pre-P fractionated electrograms were found in 34 of 36 (94%) ATs and these occurred at a mean distance of 1.8 ± 1.2 mm from the "early-meets-late" line. Ablation at these areas resulted in termination of 34 of 36 ATs (94%).The novel EAM annotation allows the accurate detection of the critical isthmus of post-AF ablation AT. Ablation of these isthmuses results in termination of the AT in the vast majority of patients.

Rationale: Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. Objective: To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). Methods and Results: We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes. Conclusions: Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.

We present a case of "inverted Tako-Tsubo" syndrome in a pre-menopausal woman with normal coronary arteries. Transient basal myocardial akinesia and ECG findings of healed myocardial infarction appeared shortly after emotional stress and resolved completely 4 days later.

The basal ganglia (BG) play a critical role in the pathogenesis and pathophysiology of Parkinson's disease (PD). Recent studies indicate that serotoninergic systems modulate BG activity and may be implicated in the pathophysiology and treatment of PD. The globus pallidus (GP), the rodent homologue of the primate GPe, is the main central nucleus of the basal ganglia, affecting the striatum, the subthalamic nucleus (STN), and BG output structures. We therefore studied the effect of serotonin (5-HT) and specific 5-HT agonists and antagonists on GP neurons from rat brain slices. Using intra- and extracellular recordings of GP neurons we found that serotonin increases the firing rate of GP neurons. Analyzing the effects of specific 5-HT agonists and antagonists on the firing rate of GP neurons showed that the increase in firing rate is due to the activation of 5-HT1B and 5-HT1A receptors. Intracellular recordings in both voltage- and current-clamp modes revealed that serotonin mediates its effect via pre- and postsynaptic mechanisms. The presynaptic effect is mediated by attenuation of γ-aminobutyric acid release, probably through activation of 5-HT1B receptors. Postsynaptically, serotonin activates a hyperpolarization-activated cation channel, probably via 5-HT1A receptors. Furthermore, serotonin decreases the fast synaptic depression characteristic of the striatal afferent input. The decreased serotonin concentrations in the BG nuclei in PD may contribute to depressed GP activity and enhance the emergence of BG pathological synchronous oscillations. We therefore suggest that future therapeutics of PD should be directed toward restoration of normal serotonin levels in BG nuclei.

Coronary involvement may appear in up to a third of patients with Takayasu's arteritis. This affliction may have a dominant impact on the clinical manifestations of the patient. Occlusion of the ostia of the left main coronary artery and of proximal segments of the coronary arteries is the most frequent finding of the coronary vasculature in patients with Takayasu's arteritis. Beyond the vasculitic process enhanced atherosclerosis has a significant and detrimental impact on the disease development. Revascularizations are often unsuccessful particularly when the inflammatory disease is not under satisfactory control. New techniques have been developed in order to use vessels that have not been damaged by the disease as grafts.

Radiation exposure in the electrophysiology lab is a major occupational hazard to the electrophysiologists. A catheter localization system (MediGuide Technology, St. Jude Medical Inc., St. Paul, MN, USA) allows the integration of electroanatomical mapping and x-ray imaging, and has been shown to be effective in reducing radiation exposure during several electrophysiological procedures. We intended to evaluate the feasibility of this catheter tracking system to guide transseptal (TS) access.The feasibility of performing TS puncture with MediGuide (MDG) was assessed in a prospective observational study in 16 patients undergoing radiofrequency ablation for atrial fibrillation. These patients were compared to 16 matched patients undergoing similar procedures during the same time frame using conventional approach. There were no differences in mean age, gender distribution, and body mass index between the two groups. Total duration of fluoroscopic exposure during TS puncture was compared between the two groups.All patients underwent successful TS puncture. Fluoroscopy time for double TS puncture using the MDG system was significantly lower than the control group (0.48 ± 0.17 minutes vs. 5.9 ± 0.65 minutes; P0.0001). No major complications occurred during the procedures in either group.TS puncture can be successfully performed using MDG, and results in significant reduction in radiation exposure.

The globus pallidus, one of the basal ganglia nuclei, plays a major role in both basal ganglia physiology and pathophysiology. The globus pallidus is innervated mainly by striatal spiny neurons and globus pallidus collaterals. These GABAergic synapses constitute 90% of the input to globus pallidus cells. Despite the dominance of this inhibitory GABAergic input, globus pallidus cells are spontaneously active and most of them increase their firing rate in a task related manner. To explain this apparent inconsistency, we studied the dynamic and spatial effects of GABAergic inputs to globus pallidus neurons. To this end, we used intra-cellular recording from globus pallidus neurons in rat brain slices, investigating the effect of bath and local GABA application, as well as the responses to electrical stimulation of the striatum. We showed that the properties of the responses to either local or global GABA applications are similar to the responses of globus pallidus cells to GABA release from nerve terminals. Since the stimulus-evoked responses have been shown to be inhibitory in nature, we concluded that GABAergic inputs to globus pallidus both at soma and dendrite level are inhibitory. Furthermore, we showed that GABA can promote globus pallidus synchronization by affecting the timing of globus pallidus spiking, and that the globus pallidus GABAergic synapse undergoes rapid frequency-dependent depression. This prominent synaptic depression can account for the ability of globus pallidus neurons to fire in the presence of a majority of inhibitory inputs and might indicate that globus pallidus neurons are tuned to detect frequency changes. Furthermore, globus pallidus synaptic depression rules out the possibility of activation of GABAeregic afferents as the main mechanisms of high-frequency deep brain stimulation, used for treatment of severe parkinsonian patients.

Background Exertional heat stroke (EHS) is one of the most serious conditions that occur when excess heat, generated by muscular exercise, exceeds the body’s heat-dissipation rate. The consequent elevated body core temperature causes damage to the body’s tissues, resulting in a characteristic multiorgan syndrome, which is occasionally fatal. Methods We analyzed the fatal EHS cases that occurred in the Israeli Defence Forces during the last decade according to Minard’s paradigm for evaluation of EHS predisposing factors, aiming to characterize the common features and unique circumstances leading to fatality. Results Accumulation of predisposing factors, particularly those concerning training regulations, coupled with inappropriate treatment at site, were found to be strong predictors of a grave prognosis. Analysis of the pathologic findings of the fatal EHS cases on autopsy revealed a possible association between the duration and length of exercise prior to EHS occurrence and the extent of pathologic findings. Conclusions Strict adherence to existing training regulations may prevent further heat stroke fatalities.

The prognosis of heat stroke in patients is directly related to the degree of hyperthermia and its duration. Therefore, the most important feature in the treatment of heat stroke is rapid cooling. Several cooling methods have been presented in the literature including immersion in water at different temperatures, evaporative cooling, ice pack application, pharmacological treatment and invasive techniques. This article describes the various cooling techniques in terms of efficacy, availability, adverse effects and mortality rate. Data suggest that cooling should be initiated immediately at time of collapse and should be based on feasible field measures including ice or tepid water (1-16 degrees C), which are readily available. In the emergency department, management should be matched to the patient's age and medical background and include immersion in ice water (1-5 degrees C) or evaporative cooling.

Magnetic resonance imaging (MRI) has been considered contraindicated in patients with cardiac pacemakers (PPMs). Recently, Medtronic (MDT) MRI SureScan PPM (Medtronic Inc., Minneapolis, MN, USA) and leads were introduced into clinical practice in the United States of America.To compare MDT CapSureFix 5086 MRI SureScan lead-associated perforation and dislodgement rates with MDT non-MRI SureScan active fixation leads.We retrospectively analyzed the records of all patients implanted with MDT CapSureFix 5086 MRI SureScan leads as well as all patients implanted with MDT 4076 and 5076 leads at our institution from April 2011 to April 2014.Four of 72 patients implanted with MDT CapSureFix 5086 MRI SureScan leads (5.5%) had evidence of lead perforation, necessitating pericardiocentesis in three cases and lead revision in one case. Three of the four perforations were delayed perforations, presenting more than 3 weeks postimplant. Two patients implanted with MDT CapSureFix 5086 MRI SureScan leads (2.8%) had lead dislodgement. Of 420 patients implanted with MDT non-MRI SureScan leads, there were two perforations (0.47%) and four dislodgements (0.9%). There were significantly increased lead perforations associated with MDT CapSureFix 5086 MRI SureScan leads (P = 0.005) and a nonsignificant trend toward increased dislodgements (P = 0.18) when compared with MDT non-MRI SureScan leads.In contradiction to prior studies, this retrospective study suggests an increased perforation rate with MDT CapSureFix 5086 MRI SureScan leads. Most perforations were delayed perforations, presenting more than 3 weeks postimplant. Higher volume prospective studies with longer follow-up are needed to confirm our findings.

On September 28, 2012, the US Food and Drug Administration approved the totally subcutaneous implantable cardioverter defibrillator (S-ICD) for the treatment of life-threatening ventricular tachyarrhythmias in patients who do not have symptomatic bradycardia, incessant ventricular tachycardia (VT), or spontaneous, frequently recurring VT that is reliably terminated with antitachycardia pacing (ATP). These devices hold the promise of life-saving defibrillation without some of the known problems of transvenous defibrillator systems (TV-ICD), including limited vascular access, transvenous lead durability, hazardous lead extractions, and risks of bloodstream infections. There are trade-offs with the S-ICD devices including reports of increased infections and the inability to deliver ATP. The subcutaneous position of the electrodes requires higher energy delivery with longer charge times. In addition, sophisticated signal processing is required for accurate arrhythmia detection and diagnosis. As we consider the appropriate patient population for S-ICD therapy, it is important to review the trade-offs of this system compared with traditional TV-ICD systems. Response by Poole and Gold on p 1251 Unlike transvenous ICDs that sense the local ventricular myocardial depolarization with an endocardial bipolar electrode, the S-ICD records a signal from 2 of its 3 subcutaneous electrodes. These are the distal sensing electrode located at the lead tip, a proximal sensing electrode located 14 cm proximal to the distal electrode, and the pulse generator itself. By their nature, the S-ICD signals are more susceptible to external and myopotential noise, as well as T-wave oversensing. Thus, sophisticated algorithms have been developed to filter noise from the true cardiac signals.1 Nevertheless, oversensing is responsible for the majority of inappropriate shocks in these systems as reported in a recent multicenter case–control study.2 The competing concern is that of undersensing true arrhythmias that can lead to delays in therapies. The best data available on S-ICD time to therapy come from …

Exertional heatstroke is a life-threatening event. It occurs mainly among the young healthy populations of athletes and soldiers. The severity of exertional heatstroke is directly correlated to the area under the temperature duration curve. Therefore, rapid cooling in the field has an enormous effect on prognosis. Four cases of exertional heatstroke are presented which differ in their outcome. We argue that there is a "window time period" within which simple and effective cooling techniques can determine prognosis.

The ability to achieve transmural, durable ablation lesions is a significant challenge of a pulmonary veins isolation (PVI) procedure resulting in their reconnection. We aim to assess the effect of utilization of a force-sense irrigated tip catheters in conjunction with a novel automated ablation

Heat stroke is a rare clinical phenomenon, characterized by systemic heat and cytokine-induced organ damage. Permanent neurological deficits rarely develop following heat strokes, and cerebellar dysfunction predominates among these rare cases. We report a case of severe heat stroke with recovery from severe multiorgan failure but with persistent neurological manifestations. These included a combination of resolving right-sided signs as well as persistent frontal subcortical dysfunction, with minimal, if any, cerebellar involvement. This combination and the absence of cerebellar involvement is an unusual neurological sequelae of heat stroke.

Background Mycoplasma pneumoniae is responsible for more than 20% of community acquired pneumonia cases, and capable of causing upper respiratory illness as well. Complications of M.pneumoniae infections include CNS involvement but other as pericarditis were also reported. The lack of feasible culture methods and under appreciation of the pathogens ability to cause invasive disease leads to reduced number of diagnosed M.pneumoniae related complications. In contrast to many other respiratory pathogens causing pneumonia, M. pneumoniae related severe pleural complications were almost never reported. Case presentation We report a previously healthy 57 years old woman presented with indolent massive right pleural effusion, leukocytosis and elevated ESR. Extensive microbiological evaluation didn't reveal any pathogen in the pus even before antibiotic treatment was started. Surprisingly, M.pneumoniae DNA was detected in the pus from the empyema using PCR designed to detect M.pneumoniae. A serological assay (Serodia-Myco II) using convalescent serum was indeterminate with a titer of 1:80. The patient responded well to a treatment that included right thoracotomy with pleural decortication and a combination of antibiotics and anti-inflammatory medications. Conclusion M.pneumoniae related empyema was never reported before in adult patients and was reported in only a few pediatric patients. In our patient there was no evidence to any common pathogens even before initiating antibiotic treatment. The only pathogen detected was M.pneumoniae. In this patient, serology was not helpful in establishing the diagnosis of M.pneumoniae related diseases, as was suggested before for older patients. We suggest that M.pneumoniae related empyema is probably under-diagnosed complication due to insensitivity of serology in older patients and under use of other diagnosis methods.

A major advance has occurred over recent decades in the treatment strategies for infective endocarditis (IE). A significant part of this progress is due to a clearer knowledge of IE insult patterns; especially those concerning valvular damage and resultant heart failure. Furthermore, the existence of IE unique vegetations ensuring a suitable platform for organism growth and partial antibiotic resistance, has led to an understanding of the limited capacity of antibiotics to treat IE. Accordingly, an increased emphasis on surgical intervention has emerged. Indeed, the last decades were characterized by increased attempts to explore the feasibility and efficacy of surgical approach in IE. The present review is a result of these attempts, summarizing the major indications for surgical intervention in IE, as was recently published by the American Heart Association. Generally, such intervention is warranted in IE complications including: hemodynamically significant valvular damage, paravalvular abscess, continuous infection despite optimal treatment, recurrent emboli and antibiotic-resistant organisms. Recognition of the prognostic influence of pre-treatment heart failure degree has led to the development of early surgical intervention, namely, surgical intervention during the active period of IE. Application of such early intervention has led to survival rates which are significantly higher than achieved by antibiotic treatment per se.

Cold weather injuries (CIs) in 242 incidences among Israeli soldiers, who were operating and training in a relatively warm country, were reviewed. Peripheral CIs accounted for 55% of all CIs, whereas hypothermia accounted for 45%. A significant relationship was found between peripheral CIs and continuous operations, characterized by prolonged static exposures to a relatively high environmental cold stress. A significant relationship was also found between hypothermia cases and training activities, characterized by relatively short exposures to a low environmental cold stress in the absence of adequate protective clothing for the cold. Static exposure to a cold environment while wearing wet clothing was found to be the leading cause of both CI types. Peripheral CI prevention requires the improvement of protective clothing for the cold, with special emphasis on protective gear for the extremities. Hypothermia prevention requires increased awareness of military regulations regarding cold weather behavior, especially the importance of changing wet clothing during static periods of the training program.