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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Current guidelines advocate for the use of prophylactic implantable cardioverter defibrillators (ICDs) for all patients with symptomatic heart failure (HF) with low ejection fraction (EF). As many patients will never use their device and some are prone to device-related complications, scoring systems for delineating subgroups with differential ICD survival benefits are crucial to maximize ICD benefit and mitigate complications. This review summarizes the main scores, including MADIT trial-based Risk Stratification Score (MRSS) and Seattle Heart Failure Model (SHFM), which are based on randomized trials with a control group (HF medication only) and validated on large cohorts of 'real-world' HF patients. Recent studies using cardiac MRI (CMR) to predict ventricular arrhythmia (VA) are mentioned as well. The review shows that most scores could not delineate sustained VA incidence, but rather mortality without prior appropriate ICD therapies. Multiple scores could identify high-risk subgroups with extremely high probability of early mortality after ICD implant. On the other hand, low-risk subgroups were defined, in whom a high ratio of appropriate ICD therapy versus death without prior appropriate ICD therapy was found, suggesting significant ICD survival benefit. Moreover, MRSS and SHFM proved actual ICD survival benefit in low- and medium-risk subgroups when compared with control patients, and no benefit in high-risk subgroups, consisting of 16-20% of all ICD candidates. CMR reliably identified areas of myocardial scar and 'channels', significantly associated with VA. We conclude that as for today, multiple scoring models could delineate patient subgroups that would benefit differently from prophylactic ICD. Due to their modest-moderate predictability, these scores are still not ready to be implemented into clinical guidelines, but could aid decision regarding prophylactic ICD in borderline cases, as elderly patients and those with multiple co-morbidities. CMR is a promising technique which might help delineate patients with a low- versus high-risk for future VA, beyond EF alone. Lastly, genetic analysis could identify specific mutations in a non-negligible percent of patients, and a few of these mutations were found to predict an increased arrhythmic risk.

Aims: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB., Methods and Results: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up., Conclusion: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Management of acute myocarditis (AM) patients experiencing ventricular arrhythmia (VA) during acute illness is controversial, especially regarding early implantable cardioverter-defibrillator (ICD) implantation., Objectives: The purpose of this study was to evaluate the prevalence of and find predictors for long-term sustained VA recurrence and overall mortality among AM patients with VA., Methods: This was a multicenter retrospective analysis of AM patients (verified by cardiac magnetic resonance imaging or myocardial biopsy) with documented VA during the acute illness ("initial VA"). Patients with history of myocardial infarction, heart failure, or VA were excluded. The study endpoint was a composite of sustained VA and overall mortality during follow-up., Results: The study included 69 AM patients with initial VA: sustained monomorphic ventricular tachycardia (MMVT) (n = 25), sustained polymorphic ventricular tachycardia (VT)/ventricular fibrillation (n = 13), and nonsustained VT (n = 31). Age was 44 ± 13 years, and 23 of 69 (33.3%) were women. During median follow-up of 5.5 years, 27 of 69 (39%) patients reached the composite endpoint including sustained VA (n = 24) and death (n = 11). Initial MMVT, predischarge left ventricular dysfunction (left ventricular ejection fraction <50%), and anteroseptal delayed enhancement on cardiac magnetic resonance imaging were significantly associated with the composite endpoint. On multivariable analysis, initial MMVT (HR: 5.17; 95% CI: 1.81-14.6; P = 0.001) and predischarge LV dysfunction (HR: 4.57; 95% CI: 1.83-11.5; P = 0.005) were independently associated with the composite endpoint. Using these 2 predictors, we could delineate subgroups with low (∼4%), medium (∼42%), and high (∼82%) 10-year incidence of composite endpoint., Conclusions: AM patients presenting with VA have high incidence of sustained VA recurrence and mortality posthospitalization. Initial MMVT and predischarge LV dysfunction are independently associated with VA recurrence and mortality. Implantable cardioverter-defibrillator implantation may be considered in such high-risk patients., Competing Interests: Funding Support and Author Disclosures This study was supported by Shaare Zedek Medical Center scientific grant number 18004723 including 20,000 Israeli Shekel (∼5000$), which was mainly used to pay for statistical analysis. The authors have reported that they have no relationships relevant to the contents of tis paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Background: Primary ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) are potentially lethal complications in patients suffering from acute myocardial infarction (MI). In contrast with the profound data regarding the incidence and prognostic value of ventricular arrhythmias in ST elevation myocardial infarction (STEMI) patients, data regarding contemporary non-ST elevation myocardial infarction (NSTEMI) patients with ventricular arrhythmias is scarce. The aim of the current study was to investigate the incidence of VF/VT complicating NSTEMI among patients admitted to an intensive coronary care unit (ICCU). Methods: Prospective, single-center study of patients diagnosed with NSTEMI admitted to ICCU between June 2019 and December 2022. Data including demographics, presenting symptoms, comorbid conditions, and physical examination, as well as laboratory and imaging data, were analyzed. Patients were continuously monitored for arrhythmias during their admission. The study endpoint was the development of VF/sustained VT during admission. Results: A total of 732 patients were admitted to ICCU with a diagnosis of NSTEMI. Of them, six (0.8%) patients developed VF/VT during their admission. Nevertheless, three were excluded after they were misdiagnosed with NSTEMI instead of posterior ST elevation myocardial infarction (STEMI). Hence, only three (0.4%) NSTEMI patients had VF/VT during admission. None of the patients died during 1-year follow-up. Conclusions: VF/VT in NSTEMI patients treated according to contemporary guidelines including early invasive strategy is rare, suggesting these patients may not need routine monitoring and ICCU setup.

Introduction: Point-of-care ultrasound has become a universal practice, employed by physicians across various disciplines, contributing to diagnostic processes and decision-making., Aim: To assess the association of reduced (<50%) left-ventricular ejection fraction (LVEF) based on prospective point-of-care ultrasound operated by medical students using an artificial intelligence (AI) tool and 1-year primary composite outcome, including mortality and readmission for cardiovascular-related causes., Methods: Eight trained medical students used a hand-held ultrasound device (HUD) equipped with an AI-based tool for automatic evaluation of the LVEF of non-selected patients hospitalized in a cardiology department from March 2019 through March 2020., Results: The study included 82 patients (72 males aged 58.5 ± 16.8 years), of whom 34 (41.5%) were diagnosed with AI-based reduced LVEF. The rates of the composite outcome were higher among patients with reduced systolic function compared to those with preserved LVEF (41.2% vs. 16.7%, p = 0.014). Adjusting for pertinent variables, reduced LVEF independently predicted the composite outcome (HR 2.717, 95% CI 1.083-6.817, p = 0.033). As compared to those with LVEF ≥ 50%, patients with reduced LVEF had a longer length of stay and higher rates of the secondary composite outcome, including in-hospital death, advanced ventilatory support, shock, and acute decompensated heart failure., Conclusion: AI-based assessment of reduced systolic function in the hands of medical students, independently predicted 1-year mortality and cardiovascular-related readmission and was associated with unfavorable in-hospital outcomes. AI utilization by novice users may be an important tool for risk stratification for hospitalized patients.

Background: Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators., Methods: The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA., Results: The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3 years after enrollment., Conclusions: There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current guidelines advocate prophylactic implantable cardioverter-defibrillator (ICD) for all patients with symptomatic heart failure (HF) with low left ventricular ejection fraction. Because many patients will never use their device, a score delineating subgroups with differential ICD benefit is crucial. We aimed to evaluate the MADIT-II-based Risk Stratification Score (MRSS) feasibility to delineate the ICD survival benefit in a nationwide registry of patients with HF with prophylactic ICDs. Accordingly, all Israeli patients with HF with prophylactic ICD/cardiac resynchronization therapy defibrillators were categorized into MRSS-based risk subgroups. The study end points included overall mortality, sustained ventricular arrhythmia (VA), and a competing risk of VA (potential preventable arrhythmic death, where ICD could benefit survival) versus nonarrhythmic death. Potential ICD survival benefit was estimated by the area between these cumulative incidence curves. In 2,177 patients with HF implanted prophylactic device, 189 patients (8.7%) had VA and 316 (14.5%) died during a median follow-up of 2.9 years. The MRSS risk subgroups were significantly associated with overall mortality (p <0.001) and weakly with VA (p = 0.3). The competing risk analysis of VA versus nonarrhythmic death revealed a significantly shorter duration (p <0.001) and smaller magnitude of ICD survival benefit with increased risk subgroups, yielding an estimated 76, 60, 38, and 0 life days gained from prophylactic ICD implant during a 5-year follow-up for the MRSS low-, intermediate-, high-, and very high-risk subgroups, respectively (p for trend <0.05). In conclusion, MRSS use in a nationwide registry of patients with ischemic and nonischemic cardiomyopathy, revealed subgroups with differing ICD survival benefit, suggesting it could help evaluate prophylactic ICD survival benefit., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Aims: The aims of this study is to characterize the transvenous lead extraction (TLE) population with active (A) compared with passive fixation (PFix) leads and to compare the safety, efficacy, and ease of extracting active fixation (AFix) compared with PFix right atrial (RA) and right ventricular (RV) leads., Methods and Results: The European Lead Extraction ConTRolled Registry (ELECTRa) was analysed. Patients were divided into three groups; those with only AFix, only PFix, and combined Fix leads. Three outcomes were defined. Difficult extraction, complete radiological, and clinical success. Multivariate model was used to analyse the independent effect of Fix mechanism on these outcomes. The study included 2815 patients, 1456 (51.7%) with only AFix leads, 982 (34.9%) with only PFix leads, and 377 (13.4%) with combined Fix leads. Patients with AFix leads were younger with shorter lead dwelling time. Infection was the leading cause for TLE among the combined Fix group with lowest rates among AFix group. No difference in complications rates was noted between patients with only AFix vs. PFix leads. Overall, there were 1689 RA (1046 AFix and 643 PFix) and 2617 RV leads (1441 AFix and 1176 PFix). Multivariate model demonstrated that PFix is independently associated with more difficult extraction for both RA and RV leads, lower radiological success in the RA but has no effect on clinical success., Conclusion: Mechanism of Fix impact the ease of TLE of RA and RV leads and rates of complete radiological success in the RA but not clinical success. These findings should be considered during implantation and TLE procedures., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: A novel 3D mapping system (KODEX-EPD, EPD Solutions) enables catheter localization and real-time 3D cardiac mapping., Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

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.

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 <.001). Most devices were implanted due to high-degree/complete atrioventricular block (112 [67.5%]) or sick sinus syndrome (31 [18.7%]). Of the 166 patients in the study survey, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a fatal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs 66 years; P <.001) with a nonsignificant higher complication rate (16.5% vs 7.7%; P = .2) was observed in Europe vs North America, whereas higher rates of critically ill patients (33.3% vs 3.3%; P <.001) and mortality (26.9% vs 5%; P = .002) were observed in North America vs Europe., Conclusion: CIED procedure rates during known active COVID-19 disease varied greatly, from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take these risks into consideration before proceeding with CIED implantation in active COVID-19 patients., (Copyright © 2021 Heart Rhythm Society. All rights reserved.)

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.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 >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.

Objectives: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterisation 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-centre cohort of hospitalised patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020 and 30/5/2020. The study's outcome was any documented arrhythmia during hospitalisation, 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 hospitalisation, 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 a significant correlation between disease severity and arrhythmia prevalence (P < .001) with a low arrhythmic prevalence amongst mild disease patients (2%). Multivariate analysis revealed background heart failure (CHF) and disease severity are independently associated with overall arrhythmia while age, CHF, disease severity, and arrhythmic symptoms are associated with tachyarrhythmias. A novel decision tree using age, disease severity, CHF, and troponin levels was created to stratify patients into high and low risk for developing arrhythmia., Conclusions: Dominant arrhythmia amongst COVID-19 patients is AF. Arrhythmia prevalence is associated with age, disease severity, CHF, and troponin levels. A novel simple Classification tree, based on these parameters, can discriminate between high and low arrhythmic risk patients., (© 2021 John Wiley & Sons Ltd.)

Aims: 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)., Methods: 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 with <90% pacing use to find predictors for pacing use. Multivariable logistic regression was applied to identify independent variables associated with major pacing use., Results: 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., Conclusion: 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., (© 2020 John Wiley & Sons Ltd.)

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.

Aims: 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., Methods & Results: Patients with LVD, QRS < 120 ms and available follow-up ECGs were retrospectively evaluated for persistent unprovoked QRS prolongation >130 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 to >130 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 trend<0.0001). 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)., Conclusion: 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., (Copyright © 2019. Published by Elsevier B.V.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction: 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., (© 2016 Wiley Periodicals, Inc.)

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.

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 gamma-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.