Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children. OBJECTIVE: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without ICD. METHODS: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic patients with CPVT with and without ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. RESULTS: The study included 235 patients, 73 with ICD (31.1%) and 162 without ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. CONCLUSION: SCD events occurred only in the no ICD group and in those not on optimal medical therapy. Patients with ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome.

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

Safety of Sports for Patients with Subcutaneous Implantable Cardioverter Defibrillator (SPORT S-ICD): study rationale and protocol.

Background: Recent studies suggest that participation in recreational and even competitive sports is generally safe for patients with implantable cardioverter-defibrillators (ICDs). However, these studies included only patients with implanted transvenous ICD (TV-ICD). Nowadays, subcutaneous ICD (S-ICD) is a safe and effective alternative and is increasingly implanted in younger ICD candidates. Data on the safety of sport participation for patients with implanted S-ICD systems is urgently needed. Objectives: The goal of the study is to quantify the risks (or determine the safety) of sports participation for athletes with an S-ICD, which will guide shared decision making for athletes requiring an ICD and/or wishing to return to sports after implantation. Methods: The SPORT S-ICD (Sports for Patients with Subcutaneous Implantable Cardioverter Defibrillator) study is an international, multicenter, prospective, noninterventional, observational study, designed specifically to collect data on the safety of sports participation among patients with implanted S-ICD systems who regularly engage in sports activities. Results: A total of 450 patients will undergo baseline assessment including baseline characteristics, indication for S-ICD implantation, arrhythmic history, S-ICD data and programming, and data regarding sports activities. LATITUDE Home Monitoring information will be regularly transferred to the study coordinator for analysis. Conclusion: The results of the study will aid in shaping clinical decision making, and if the tested hypothesis will be proven, it will allow the safe continuation of sports for patients with an implanted S-ICD.

Oral and fecal polio vaccine excretion following bOPV vaccination among Israeli infants.

INTRODUCTION: Inactivated polio virus (IPV) vaccinations are a mainstay of immunization schedules in developed countries, while oral polio vaccine (OPV) is administered in developing countries and is the main vaccine in outbreaks. Due to circulating wild poliovirus (WPV1) detection in Israel (2013), oral bivalent polio vaccination (bOPV) was administered to IPV primed children and incorporated into the vaccination regimen. OBJECTIVES: We aimed to determine the extent and timeframe of fecal and salivary polio vaccine virus (Sabin strains) shedding following bOPV vaccination among IPV primed children. METHODS: Fecal samples were collected from a convenience sample of infants and toddlers attending 11 Israeli daycare centers. Salivary samples were collected from infants and toddlers following bOPV vaccination. RESULTS: 398 fecal samples were collected from 251 children (ages: 6-32 months), 168 received bOPV vaccination 4-55 days prior to sample collection. Fecal excretion continued among 80 %, 50 %, and 20 %, 2, 3, and 7 weeks following vaccination. There were no significant differences in the rate and duration of positive samples among children immunized with 3 or 4 IPV doses. Boys were 2.3-fold more likely to excrete the virus (p = 0.006). Salivary shedding of Sabin strains occurred in 1/47 (2 %) and 1/49 (2 %) samples 4, and 6 days following vaccination respectively. CONCLUSIONS: Fecal detection of Sabin strains among IPV-primed children continues for 7 weeks; additional doses of IPV do not augment intestinal immunity; limited salivary shedding occurs for up to a week. This data can enhance understanding of intestinal immunity achieved by different vaccination schedules and guide recommendations for contact precautions of children following bOPV vaccination.

Regional Antibiotic Delivery for Implanted Cardiovascular Electronic Device Infections.

BACKGROUND: Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections. OBJECTIVES: The authors evaluated the efficacy of delivering continuous, in situ-targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction. METHODS: The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, 9 patients declined lead extraction because of prohibitive operative risk, and 6 patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction, but opted for CITA treatment, were compared with 81 patients with pocket infection and similar characteristics who underwent device/lead extraction as primary therapy. RESULTS: A total of 80 patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (n = 68 of 80) of patients, who remained free of infection (median follow-up 3 years [IQR: 1.0-6.8 years]). In the case-control study of CITA vs device/lead extraction, cure rates were higher after device/lead extraction than after CITA (96.2% [n = 78 of 81] vs 84.6% [n = 55 of 65]; P = 0.027). However, rates of serious complications were also higher after extraction (n = 12 [14.8%] vs n = 1 [1.5%]; P = 0.005). All-cause 1-month and 1-year mortality were similar for CITA and device/lead extraction (0.0% vs 3.7%; P = 0.25 and 12.3% vs 13.6%; P = 1.00, respectively). Extraction was avoided in 90.8% (n = 59 of 65) of extraction-eligible patients treated with CITA. CONCLUSIONS: CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction. (Salvage of Infected Cardiovascular Implantable Electronic Devices [CIED] by Localized High-Dose Antibiotics; NCT01770067).

Arrhythmogenic Effects of Cardiac Memory.

Cardiac memory is the term used to describe an interesting electrocardiographic phenomenon. Whenever a QRS complex is wide and abnormal, such as during ventricular pacing, the T waves will also be abnormal and will point to the opposite direction of the wide QRS. If the QRS then normalizes, such as after cessation of ventricular pacing, the T waves will normalize as well, but at a later stage. The period of cardiac memory is the phase between the sudden normalization of the QRS and the eventual and gradual return of the T waves to their baseline morphology. Cardiac memory is assumed to be an innocent electrocardiographic curiosity. However, during cardiac memory, reduction of repolarizing potassium currents increases left ventricular repolarization gradients. Therefore, when cardiac memory occurs in patients who already have a prolonged QT interval (for whatever reason), it can lead to a frank long QT syndrome with QT-related ventricular arrhythmias (torsades de pointes). These arrhythmogenic effects of cardiac memory are not generally appreciated and are reviewed here for the first time.

Association between tissue human neutrophil peptide 1-3 levels and cardiovascular phenotype: a prospective, longitudinal cohort study.

OBJECTIVE: Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1-3 (HNP1-3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1-3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes. METHODS: HNP1-3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1-3 levels. RESULTS: The risk of CAD was independently associated with age and HNP1-3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1-3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1-3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%). CONCLUSION: HNP1-3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1-3 levels may be suppressed using colchicine.

Does the use of polymer-free drug eluting stents improve clinical outcomes of patients undergoing percutaneous coronary interventions?

BACKGROUND: Implantation of drug eluting stents (DES) is the mainstay treatment for patients requiring percutaneous coronary intervention (PCI). The polymer coating of DES has been associated with inflammatory response, increased arterial injury and long-term in-stent restenosis and thrombosis. Polymer-free stents (PFS) were designed to overcome limitations of polymer-coated stents (PCS). Our aim was to compare clinical outcomes of patients undergoing PCI with PFS versus contemporary PCS. METHODS: This is a prospective, open-label registry study enrolling consecutive all-comers patients admitted to a single center and undergoing PCI using contemporary DES. Clinical outcomes were compared between patients treated with PFS and PCS. The primary endpoint was target lesion revascularization (TLR) at 12 months. Subgroup analyses were conducted for diabetic and nondiabetic patients. RESULTS: Overall, 1664 patients were included: 928 (55.8%) of which were treated with PFS and 736 (44.2%) with PCS for 2046 and 1462 lesions, respectively. At 12 months, TLR rates were not significantly different between the groups (1.7% vs. 2.3% for PFS and PCS, respectively, P = 0.48). The use of PFS did not improve clinical outcomes among diabetic patients in comparison with PCS. Target vessel revascularization and major adverse cardiac events rates were also similar between groups, regardless of diabetes status. CONCLUSION: Newer generation DES offer excellent results in diabetic and nondiabetic patients without significant differences in outcomes between PCS and PFS.

QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection.

Background: QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose: To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Materials and Methods: A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results: One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3-3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06-2.68, p = 0.027). Conclusion: Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

Outcomes of Patients Undergoing PCI of Ostial Coronary Lesions: A Single-Center Study.

INTRODUCTION: Ostial coronary lesions are a subset of proximal coronary lesions, which are relatively more difficult to treat and were associated with worse clinical outcomes in the early percutaneous coronary intervention (PCI) era. Data regarding the outcomes of ostial lesions' PCI in the contemporary era are lacking. METHODS: We conducted a single-center, all-comer, prospective registry study, enrolling patients undergoing PCI with the use of contemporary drug-eluting stents (DES) between July 2016 and February 2018. Included in the present analysis were only patients treated for proximal lesions. Clinical outcomes were compared between patients undergoing PCI of ostial versus proximal nonostial lesions. The primary endpoint was target vessel revascularization (TVR). Secondary endpoints included target lesion revascularization (TLR) and major cardiovascular adverse events (MACE) at 12 months. RESULTS: A total of 334 (84.7% male, 67.3 ± 10.7 years) patients were included, of which 91 patients were treated for ostial lesions and 243 were treated for proximal nonostial lesions. Baseline and procedural characteristics were similar between the two groups. At 12 months, TVR and TLR were numerically higher among patients undergoing PCI of ostial versus nonostial lesions without reaching statistical significance (5.5% vs. 3.3%; p = 0.35 and 4.4% vs. 2.5%; p = 0.47, respectively). The rate of MACE was similar between the two groups. CONCLUSION: In patients undergoing PCI with the use of contemporary DES, clinical outcomes were similar among patients treated for ostial compared to proximal nonostial lesions. Larger studies are required to further evaluate the performance of contemporary DES in this subset of lesions.

Forced Diuresis with Matched Isotonic Intravenous Hydration Prevents Renal Contrast Media Accumulation.

The accumulation of contrast media in the kidneys might lead to contrast-induced acute kidney injury. In this prospective, controlled observational study, we aimed to evaluate whether forced diuresis with matched isotonic intravenous hydration prevents the accumulation of contrast media in the kidneys of patients undergoing cardiac interventional procedures. We compared the intensity of contrast media accumulation as observed in nephrograms following these procedures, with and without peri-procedural controlled renal flushing. The study group consisted of 25 patients with impaired renal function treated with the RenalGuard system. The two control groups included 25 patients with normal kidney function and 8 patients with impaired renal function undergoing similar procedures with routine pre-procedural hydration, but without controlled renal flushing. Renal contrast media accumulation at the end of each procedure was scored by blinded cardiologists. The renal contrast accumulation score (CAS) in the study group was significantly lower, with a median score of 0 (IQR (0-0)) compared with 1.5 (IQR (1-2)) in the normal renal function control group and 1 (IQR (0.38-1.62)) in the impaired renal function control group (p < 0.001 and 0.003, respectively). In a multivariate analysis of CAS, RenalGuard treatment was independently associated with lower CAS compared to both control groups. In conclusion, RenalGuard use prevents renal contrast accumulation in patients with impaired renal function undergoing cardiac procedures with intra-arterial contrast media injection.

Reconstruction of the left atrium for atrial fibrillation ablation using the machine learning CARTO 3 m-FAM software.

PURPOSE: Atrial fibrillation (AF) ablation requires a precise reconstruction of the left atrium (LA) and pulmonary veins (PV). Model-based FAM (m-FAM) is a novel module recently developed for the CARTO system which applies machine learning techniques to LA reconstruction. We aimed to evaluate the feasibility and safety of a m-FAM-guided AF ablation as well as the accuracy of LA reconstruction using the cardiac computed tomography angiography (CTA) of the same patient LA as the gold standard, in 32 patients referred for AF ablation. METHODS: Consecutive patients undergoing AF ablation. The m-FAM reconstruction was performed with the ablation catheter (group 1) or a Pentaray and ablation catheters (group 2). The reconstruction accuracy was confirmed prior to the ablation by verification of pre-specified landmarks of the LA and PVs by an intracardiac echocardiogram (ICE) visualization and fluoroscopy. A cardiac CTA performed before the ablation was used as the gold standard of LA anatomy. For each patient, the m-FAM reconstruction was compared to his/her cardiac CTA. RESULTS: The m-FAM reconstruction was accurate in all patients regardless of the catheter used for mapping. Twelve percent re-acquisition of the LA landmarks was necessary to improve the accuracy. m-FAM time was shorter in group 2 while the M-Fam fluoroscopy time was similar. Pulmonary vein isolation was achieved in 100% of patients without major complications. The m-FAM reconstructions accurately resemble the cardiac CTA of the same patients. CONCLUSIONS: The m-FAM module allows for rapid and precise reconstruction of the LA and PV anatomy, which can be safely used to guide AF ablation.

QT interval dynamics in patients with ST-elevation MI.

Background: An association between excessively prolonged QT and ventricular arrhythmia in patients with ST-elevation myocardial infarction has been described; however, the QT dynamics, characterization, and long-term predictive value are not well known. Objective: To characterize QT interval dynamics in patients undergoing ST elevation myocardial infarction (STEMI) and determine its association with mortality. Methods: A retrospective analysis of 4,936 consecutive patients, hospitalized for STEMI between 01/2013-12/2021. Patients with less than three electrocardiograms (ECGs) during index hospitalization were excluded. Baseline demographics, cardiovascular history, clinical risk factors, treatment measures, laboratory results, and mortality data were retrieved from the hospital's electronic medical records. Results: We included 1,054 patients and 5,021 ECGs in our cohort with a median follow-up of 6 years [interquartile range (IQR) 4.3-7.4 years]. The QT was longer in women in comparison to men (428.6 ms ± 33.4 versus 419.8 ms ± 32.52, P-value = 0.001). QT prolongation was greater in females, elderly patients, and patients with STEMI caused by occlusion of the left anterior descending (LAD) coronary artery. We determined QT cutoff to be 445 ms. This value of QT divided our cohort upon arrival into a long QT group (217 patients, 26% of the cohort) and a "normal" QT group (835 patients, 74% of the cohort). The long QT group experienced an increase in combined short and long terms all-cause mortality. The QT upon arrival, on day 2 of hospitalization, and before discharge from the hospital, correlated with long-term mortality. Conclusion: QT duration is often prolonged during STEMI; this prolongation is associated with increased mortality and adverse events. Gender is an important mediator of QT dynamics.

Polymorphic Ventricular Tachycardia: Terminology, Mechanism, Diagnosis, and Emergency Therapy.

Polymorphic ventricular tachyarrhythmias are highly lethal arrhythmias. Several types of polymorphic ventricular tachycardia have similar electrocardiographic characteristics but have different modes of therapy. In fact, medications considered the treatment of choice for one form of polymorphic ventricular tachycardia, are contraindicated for the other. Yet confusion about terminology, and thus diagnosis and therapy, continues. We present an in-depth review of the different forms of polymorphic ventricular tachycardia and propose a practical step-by-step approach for distinguishing these malignant arrhythmias.