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The article discusses the chemical composition of human saliva and examines the presence of sodium, potassium, and calcium in saliva. The chemical makeup of saliva is compared with the chemical makeup of serum. Details about the secretion rate of sodium, potassium, and calcium in saliva are also provided and compared with a previous study which examined the secretion rate of ash, total solids, and chlorides.

The article focuses on research into the chemical composition of mixed human saliva. It states that saliva was gathered through mastication of paraffin. It states that subjects who produced low levels of saliva had higher total nitrogen and phosphate and low levels of chloride. It mentions that subjects who produced high levels of saliva had high levels of chloride and low levels of phosphates.

Background: Subcutaneous implantable cardioverter-defibrillator (S-ICD) implantations are rapidly expanding. However, the subcutaneous detection and interpretation of cardiac signals in S-ICDs is much more challenging than by conventional devices. There is a complete paradigm shift in cardiac signal sensing with subcutaneous signal detection, leading in some cases to oversensing with restricted programming options., Objectives: The aim of this single-center study was to quantify and describe cases where recurring oversensing made the extraction of the device necessary., Methods: Consecutive patients (n = 108) implanted with an S-ICD in our tertiary referral hospital were considered for analysis. Clinical and remote monitoring data were analyzed., Results: The S-ICD had to be explanted in 6 of 108 implanted patients (5.6%) because of refractory oversensing issues: myopotential oversensing, P- or T-wave oversensing, rate-dependent left bundle branch block aberrancy during exercise with R-wave double counting, and R-wave amplitude decrease after ventricular tachycardia ablation leading to noise detection. Seventeen of 108 patients experienced oversensing (15.7%): 9 patients had at least 1 inappropriate charge without a shock (8.3%), 3 patients had at least 1 inappropriate shock (2.8%), and 5 patients had both episodes (4.6%)., Conclusion: So far, cardiologists have had to deal with transvenous ICD lead fractures, but signal oversensing without correcting programming option could be the equivalent weakness of S-ICDs, despite an adequate screening., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Various strategies for ablation of ventricular tachycardia (VT) have been described, but their impact on ventricular fibrillation (VF) is largely unknown. The aim of our study was to assess the effect of substrate-based VT ablation targeting local abnormal ventricular activity (LAVA) on recurrent VF events in patients with structural heart disease., Methods: A retrospective 2-center study was performed on patients with structural heart disease and both VT and VF, with incident VT ablation procedures targeting LAVAs. Generalized estimating equations with a Poisson loglinear model were used to assess the impact of catheter ablation on VF episodes. The change in VF events before and after catheter ablation was compared with matched controls without ablation., Results: From a total of 686 patients with an incident VT ablation procedure targeting LAVAs, 21 patients (age, 57±14 years; left ventricular ejection fraction, 30±10%) had both VT and VF and met inclusion criteria. A total of 80 VF events were recorded in the implantable cardioverter-defibrillator logs the 6 months preceding ablation. Complete and partial LAVA elimination was achieved in 11 (52%) and 10 (48%) patients, respectively. Catheter ablation was associated with a highly significant reduction in VF recurrences ( P <0.0001), which were limited to 3 (14%) patients at 6 months. The total number of VF events thereby decreased from 80 to 3, from a median of 1.0 (range, 1-29) to 0.0 (range, 0-1) in the 6 months before and after ablation, respectively. The reduction in VF events was significantly greater in patients with catheter ablation compared with 21 matched controls during 6-month periods following and preceding a baseline assessment (Poisson β-coefficient, 1.39; P =0.0003)., Conclusions: Substrate-guided VT ablation targeting LAVAs may be associated with a significant reduction in recurrent VF, suggesting that VT and VF share overlapping arrhythmogenic substrates in patients with structural heart disease.

Objectives: A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD)., Background: The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system's ability to accurately define the tachycardia circuit., Methods: Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed., Results: Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence., Conclusions: We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra-high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We present a new, easily applicable approach for the guidance of cryoballoon (CB) pulmonary vein isolation (PVI) procedures that use the combination of a 3D-mapping system image integration module and computed tomographic (CT)-derived anatomy. The aim of this retrospective, nonrandomized study was to investigate: (a) an alternative use for an established radiofrequency image integration module for cryo procedures; (b) a guidance technology for cryo PVI based on integrated CT anatomy; and (c) its clinical impact., Methods and Results: CT left atrium-angiography was performed in 50 consecutive patients before a CB PVI procedure, and a 3D reconstruction of the cardiac anatomy was segmented. A total of 25 patients were treated using conventional fluoroscopy; 25 patients were treated using the 3D image integration technique. In the image integration group, the CARTO3 UNIVU (Biosense Webster) module was used for image integration of 3D anatomy and fluoroscopic imaging. Transseptal puncture and cryo PVI were guided by 3D-overlay imaging. Procedures were feasible without complications in all patients and cryo PVI procedures were successfully guided using the image integration technique. The intraprocedural time needed to perform image integration was 37 ± 10 seconds. Fluoroscopy time was 31.7 ± 11.7 minutes in the conventional group and 20.1 ± 7.9 minutes in the image integration group (P < .001), procedure time was 116.3 ± 29.0 minutes in the conventional group vs 101.2 ± 20.9 minutes in the 3D group (P = .04)., Conclusion: 3D-overlay guidance of CB PVI is feasible, safe, and applicable in real time with minimal effort. It may significantly reduce radiation exposure by introducing 3D information, known from electroanatomic mapping systems, into cryo PVI procedures., (© 2019 Wiley Periodicals, Inc.)

Electrocardiographic imaging is a mapping technique aiming to noninvasively characterize cardiac electrical activity using signals collected from the torso to reconstruct epicardial potentials. Its efficacy has been demonstrated clinically, from mapping premature ventricular complexes and accessory pathways to of complex arrhythmias. Electrocardiographic imaging uses a standardized workflow. Signals should be checked manually to avoid automatic processing errors. Reentry is confirmed in the presence of local activation covering the arrhythmia cycle length. Focal breakthroughs demonstrate a QS pattern associated with centrifugal activation. Electrocardiographic imaging offers a unique opportunity to better understand the mechanism of cardiac arrhythmias and guide ablation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Atrial tachycardias (ATs) are often seen in the context of atrial fibrillation (AF) ablation., Objectives: To evaluate the role of the Marshall bundle (MB) network in left atrial (LA) ATs using high-density 3-dimensional mapping., Methods: A total of 199 ATs were mapped in 140 patients (112 male, mean age: 61.8 years); 133 (66.8%) were macroreentrant and 66 (33.2%) were scar-related reentry circuits. MB-dependent ATs were suggested by activation mapping analysis and confirmed with entrainment along the circuit., Results: The MB network participated in 60 (30.2%) reentrant ATs: 31 perimitral ATs (PMATs) and 29 localized reentry circuits. Of 60 MB-related ATs, 49 (81.6%) terminated with radiofrequency (RF) ablation: 44 (73.3%) at the MB-LA junction and 5 (8.3%) at the MB-coronary sinus (CS) junction, while 9 (15%) terminated after 2.5-5 cc of ethanol infusion inside the vein of Marshall (VOM). Of the 31 PMATs, 17 (54.8%) terminated at the MB-LA junction, 5 (16.1%) at the MB-CS junction, and 7 (22.6%) with ethanol infusion. Of the 29 localized reentry circuits using the MB, 27 (93.1%) terminated at the MB-LA junction, none at the MB-CS junction, and 2 (6.9%) after ethanol infusion. Recurrences were mostly observed after RF ablation (18 of 37 patients, 49%) compared to ethanol infusion (1 of 9 patients, 11%) (P = .06)., Conclusions: MB reentrant ATs accounted for up to 30.2% of the left ATs after AF ablation. Ablation of the MB-LA or CS-MB connections or ethanol infusion inside the VOM is required to treat these arrhythmias., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Ablation of complex atrial tachycardias (ATs) is difficult., Objective: The purpose of this study was to elucidate a mechanism underlying the behavior of ATs during ablation and to create an algorithm to predict it., Methods: An algorithm predicting termination/conversion of AT and the second AT circuit associated with the ablation site was developed from 52 index reentrant AT high-resolution activation maps in 45 patients (retrospective phase). First, the wavefront collision site was identified. Then, the N or N-1 beat was defined for each collision associated with the ablation site. When the AT involved wavefront collision solely between N-1/N-1 (N/N) beats, the AT would terminate during ablation. Conversely, when the AT included wavefront collision between N/N-1 beats, the index AT would convert to a second AT. The algorithm was then prospectively tested in 172 patients with 194 ATs (127 anatomic macroreentrant ATs [AMATs], 44 non-AMATs, 23 multiple-loop ATs)., Results: Accuracy in predicting AT termination/conversion and the second AT circuit was 95.9% overall, 96.1% in AMATs, 95.5% in non-AMATs, and 95.7% in multiple-loop ATs. Median (25th-75th percentile) absolute variation between predicted and actually observed cycle length of the second AT was 6 (4-9) ms. Prediction failure occurred in 8 ATs; either the second AT used an unmapped chamber or structure in the index map (n = 7) or a line of block was misinterpreted as very slow conduction in the index map (n = 1)., Conclusion: A simple mechanism underlies the behavior of ATs during ablation, even in complex ATs. With a simple algorithm using high-resolution mapping, AT termination/conversion and the second AT circuit and cycle length may be predicted from the index activation map., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between the local electrograms (EGMs) and wall thickness (WT) heterogeneity within infarct scars has not been thoroughly described. The relationship between WT and voltages and substrates for ventricular tachycardia (VT) was examined., Methods: In 12 consecutive patients with myocardial infarction and VT, WT, defined by a multidetector computed tomography, and voltage were compared. In multicomponent EGMs, amplitudes of both far- and near-field components were manually measured, and the performance of the three-dimensional-mapping system automatic voltage measurement was assessed., Results: Of 15 748 points acquired, 2677 points within 5 mm of the endocardial surface were analyzed. In total, 909 (34.0%) multicomponent EGMs were identified; 785 (86.4%) and 883 (97.1%) were distributed in the WT less than 4 and 5 mm, respectively. Far-field EGM voltages increased linearly from 0.14 mV (0.08-0.28 mV) in the WT: 0 to 1 mm to 0.70 mV (0.43-2.62 mV) in the WT: 4 to 5 mm (ρ = 0.430; P < 0.001), and a significant difference was demonstrated between any two WT-groups (P ≤ 0.001). In contrast, near-field EGM voltages varied from 0.27 mV (0.11-0.44 mV) in the WT: 0 to 1 mm to 0.29 mV (0.17-0.53 mV) in the WT: 4 to 5 mm with a poorer correlation (ρ = 0.062, P = 0.04). The proportion of points where the system automatically measured the voltage on near-field EGMs increased from less than 10% in areas of WT: 4 to 5 mm to 50% in areas less than 2 mm. Of 21 VTs observed, seven hemodynamically stable VTs were mapped and terminated in WT: 1 to 4 mm area., Conclusions: Although far-field voltages gradually increase with the WT, near-field does not. The three-dimensional-mapping system preferentially annotates the near-field components in thinner areas (center of the scar) and the far-field component in thicker areas when building a voltage map. Critical sites of VT are distributed in WT: 1 to 4 mm areas., (© 2018 Wiley Periodicals, Inc.)

Objectives: This study sought to evaluate the relation between bipolar electrode spacing and far- and near-field electrograms., Background: The detailed effects of bipolar spacing on electrograms (EGMs) is not well described., Methods: With a HD-Grid catheter, EGMs from different bipole pairs could be created in each acquisition. This study analyzed the effect of bipolar spacing on EGMs in 7 infarcted sheep. A segment was defined as a 2-mm center-to-center bipole. In total, 4,768 segments (2,020 healthy, 1,542 scar, and 1,206 in border areas, as defined by magnetic resonance imaging [MRI]) were covered with an electrode pair of spacing of 2 mm (Bi-2), 4 mm (Bi-4), and 8 mm (Bi-8)., Results: A total of 3,591 segments in Bi-2 were free from local abnormal ventricular activities (LAVAs); 1,630 segments were within the MRI-defined scar and/or border area. Among them, 172 (10.6%) segments in Bi-4 and 219 (13.4%) segments in Bi-8 showed LAVAs. In contrast, LAVAs were identified in 1,177 segments in Bi-2; 1,118 segments were within the MRI-defined scar and/or border area. Among them, LAVAs were missed in 161 (14.4%) segments in Bi-4 and in 409 (36.6%) segments in Bi-8. In segments with LAVAs, median far-field voltage increased from 0.09 mV (25th to 75th percentile: 0.06 to 0.14 mV) in Bi-2, to 0.16 mV (25th to 75th percentile: 0.10 to 0.24 mV) in Bi-4, and to 0.28 mV (25th to 75th percentile: 0.20 to 0.42 mV) in Bi-8 (p < 0.0001). Median near-field voltage increased from 0.14 mV (25th to 75th percentile: 0.08 to 0.25 mV) in Bi-2, to 0.21 mV (25th to 75th percentile: 0.12 to 0.35 mV) in Bi-4, and to 0.32 mV (25th to 75th percentile: 0.17 to 0.48 mV) in Bi-8 (p < 0.0001). The median near-/far-field voltage ratio decreased from 1.67 in Bi-2, to 1.43 in Bi-4, and 1.23 in Bi-8 (p < 0.0001)., Conclusions: Closer spacing better discriminates surviving tissue from dead scar area. Although far-field voltage systematically increases with spacing, near-field voltages were more variable, depending on local surviving muscular bundles. Near-field EGMs are more easily observed with smaller spacing, largely due to the reduction of the far-field effect., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Successful mapping and ablation of ventricular tachycardias remains a challenging clinical task. Whereas conventional entrainment and activation mapping was for many years the gold standard to identify reentrant circuits in ischaemic ventricular tachycardia ablation procedures, substrate mapping has become the cornerstone of ventricular tachycardia ablation. In the last decade, technology has dramatically improved. In parallel to high-density automated mapping, cardiac imaging and image integration tools are increasingly used to assess the structural ventricular tachycardia substrate. The aim of this review is to describe the technologies underlying these new mapping systems and to discuss their possible role in providing new insights into identification and visualization of reentrant tachycardia mechanisms., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The direct effect of bipolar orientation on electrograms (EGMs) remains unknown., Objective: The purpose of this study was to examine the variation of EGMs with diagonally orthogonal bipoles., Methods: The HD-32 Grid catheter (Abbott, Minneapolis, MN) can assess the effect of bipolar orientation while keeping the interelectrode distance and center unchanged. Seven sheep with anterior myocardial infarction were analyzed using diagonally orthogonal electrode pairs across splines by comparing local EGMs from each pair of opposing electrodes {eg. A1-B3 (southeast direction [SE]) vs A3-B1 (northeast direction [NE])}., Results: A total of 4084 EGMs (1 in each direction) were analyzed for 2042 sites (544 in the infarcted area, 488 in the border area, and 1010 in the normal area). The higher and lower voltages measured using each pair of opposing electrodes significantly differed (1.10 mV [0.43-2.56 mV] vs 0.69 mV [0.28-1.58 mV]; P < .0001), and the median variation was 0.28 mV (0.11-0.80 mV) (31.7% [16.0%-48.9%]). The voltage variation was maximized to 48.7% (37.7%-61.6%) (P < .0001) on sites where the activation wavefront was perpendicular to the one bipolar direction and parallel to the other. A total of 594 of 719 (82.6%) sites with the voltage <0.5 mV and 539 of 699 (77.1%) sites with the voltage >1.5 mV in NE stayed in the same voltage range as those in SE. However, only 348 of 624 (55.8%) sites with the voltage 0.5-1.5 mV in NE stayed in the same range as those in SE. Local ventricular abnormal activities (LAVAs) were detected in 592 of 2042 (29.0%) sites in total, frequently distributed in the border area. A total of 177 (29.9%) LAVAs were missed in one direction and 180 (30.4%) in the other. When 415 (70.1%) LAVAs detected in NE are defined as the reference, 235 of 415 (56.6%) matched with those detected in SE., Conclusion: The bipolar voltage and distribution of LAVAs may differ significantly between diagonally orthogonal bipolar pairs at any given site., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

An early repolarization pattern can be observed in 1% up to 13% of the overall population. Whereas, this pattern was associated with a benign outcome for many years, several more recent studies demonstrated an association between early repolarization and sudden cardiac death, so-called early repolarization syndrome. In early repolarization syndrome patients, current imbalances between epi- and endo-cardial layers result in dispersion of de- and repolarization. As a consequence, J waves or ST segment elevations can be observed on these patients' surface ECGs as manifestations of those current imbalances. Whereas, an early repolarization pattern is relatively frequently found on surface ECGs in the overall population, the majority of individuals presenting with an early repolarization pattern will remain asymptomatic and the isolated presence of an early repolarization pattern does not require further intervention. The mismatch between frequently found early repolarization patterns in the overall population, low incidences of sudden cardiac deaths related to early repolarization syndrome, but fatal, grave consequences in affected patients remains a clinical challenge. More precise tools for risk stratification and identification of this minority of patients, who will experience events, remain a clinical need. This review summarizes the epidemiologic, pathophysiologic and diagnostic background and presents therapeutic options of early repolarization syndrome.

Introduction: Radiofrequency (RF) lesion metrics are influenced by underlying parameters like RF power, duration, and contact force (CF), and utilization of lesion metric indices (ablation index [AI]) is a proposed strategy to predict lesion quality. The aim of this study was to analyze the influence of underlying parameters on lesion metrics of high-power short-duration (HPSD) and standard RF applications using an in silico and ex vivo model., Methods and Results: An in silico simulation study was designed to simulate HPSD and standard ablations, in which ablation parameters could systematically be varied. For each simulated ablation process (n = 5732), the corresponding AI value was calculated. HPSD and standard RF settings were then applied in a porcine ex vivo model ( n = 120 lesions). The resulting lesion metrics were compared and analyzed regarding underlying parameters. RF applications of 50 W/13 seconds, 60 W/10 seconds, 70 W/7 seconds, and 80 W/6 seconds resulted in lesion volumes not significantly different from standard RF applications (30 W/30 seconds, P > 0.05). HPSD lesion diameters were significantly larger and lesion depths were significantly smaller ( P < 0.01) when compared with standard settings. Prolonging RF duration from 5 to 10 seconds resulted in a +27.5% increase, whereas a prolongation of RF duration from 35 to 40 seconds resulted in a +4.8% increase of AI value only. An increase of CF from 1 to 10 g resulted in a +73.0%, an increase of CF from 20 to 30 g resulted in a +10.1% increase of AI value., Conclusion: HPSD RF applications resulted in similar lesion volumes but significantly different lesion geometries when compared with standard setting RF applications., (© 2018 Wiley Periodicals, Inc.)

Background: Electrocardiographic mapping (ECM) expresses electrical substrate through magnitude and direction of the activation delay vector (ADV). We investigated to what extent the response to cardiac resynchronization therapy (CRT) is determined by baseline ADV and by ADV modification through CRT and optimization of left ventricular (LV) pacing site., Methods: ECM was performed in 79 heart failure patients (4 RBBB, 12 QRS < 120 ms, 23 non-specific conduction delay [NICD] and 40 left bundle branch block [LBBB]). 67 patients (QRS ≥ 120 ms) underwent CRT implantation and in 26 patients multiple LV pacing site optimization was performed. ADV was calculated from locations/depolarization times of 2000 virtual epicardial electrodes derived from ECM. Acute response was defined as ≥10% LVdP/dt max increase, chronic response by composite clinical score at 6 months., Results: During intrinsic conduction, ADV direction was similar in patients with QRS < 120 ms, NICD and LBBB, pointing towards the LV free wall, while ADV magnitude was larger in LBBB (117 ± 25 ms) than in NICD (70 ± 29 ms, P < 0.05) and QRS < 120 ms (52 ± 14 ms, P < 0.05). Intrinsic ADV accurately predicted the acute (AUC = 0.93) and chronic (AUC = 0.90) response to CRT. ADV change by CRT only moderately predicted response (highest AUC = 0.76). LV pacing site optimization had limited effects: +3 ± 4% LVdP/dt max when compared to conventional basolateral LV pacing., Conclusion: The baseline electrical substrate, adequately measured by ADV amplitude, strongly determines acute and chronic CRT response, while the extent of its modification by conventional CRT or by varying LV pacing sites has limited effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

AF is a heterogeneous rhythm disorder that is related to a wide spectrum of etiologies and has broad clinical presentations. Mechanisms underlying AF are complex and remain incompletely understood despite extensive research. They associate interactions between triggers, substrate and modulators including ionic and anatomic remodeling, genetic predisposition and neuro-humoral contributors. The pulmonary veins play a key role in the pathogenesis of AF and their isolation is associated to high rates of AF freedom in patients with paroxysmal AF. However, ablation of persistent AF remains less effective, mainly limited by the difficulty to identify the sources sustaining AF. Many theories were advanced to explain the perpetuation of this form of AF, ranging from a single localized focal and reentrant source to diffuse bi-atrial multiple wavelets. Translating these mechanisms to the clinical practice remains challenging and limited by the spatio-temporal resolution of the mapping techniques. AF is driven by focal or reentrant activities that are initially clustered in a relatively limited atrial surface then disseminate everywhere in both atria. Evidence for structural remodeling, mainly represented by atrial fibrosis suggests that reentrant activities using anatomical substrate are the key mechanism sustaining AF. These reentries can be endocardial, epicardial, and intramural which makes them less accessible for mapping and for ablation. Subsequently, early interventions before irreversible remodeling are of major importance. Circumferential pulmonary vein isolation remains the cornerstone of the treatment of AF, regardless of the AF form and of the AF duration. No ablation strategy consistently demonstrated superiority to pulmonary vein isolation in preventing long term recurrences of atrial arrhythmias. Further research that allows accurate identification of the mechanisms underlying AF and efficient ablation should improve the results of PsAF ablation.

Idiopathic ventricular fibrillation (IVF) is the main cause of unexplained sudden cardiac death, particularly in young patients under the age of 35. IVF is a diagnosis of exclusion in patients who have survived a VF episode without any identifiable structural or metabolic causes despite extensive diagnostic testing. Genetic testing allows identification of a likely causative mutation in up to 27% of unexplained sudden deaths in children and young adults. In the majority of cases, VF is triggered by PVCs that originate from the Purkinje network. Ablation of VF triggers in this setting is associated with high rates of acute success and long-term freedom from VF recurrence. Recent studies demonstrate that a significant subset of IVF defined by negative comprehensive investigations, demonstrate in fact subclinical structural alterations. These localized myocardial alterations are identified by high density electrogram mapping, are of small size and are mainly located in the epicardium. As reentrant VF drivers are often colocated with regions of abnormal electrograms, this localized substrate can be shown to be mechanistically linked with VF. Such areas may represent an important target for ablation.

Introduction: Recognition of implantable cardioverter defibrillator (ICD) lead malfunction before occurrence of life threatening complications is crucial. We aimed to assess the effectiveness of remote monitoring associated or not with a lead noise alert for early detection of ICD lead failure., Methods: From October 2013 to April 2017, a median of 1,224 (578-1,958) ICD patients were remotely monitored with comprehensive analysis of all transmitted materials. ICD lead failure and subsequent device interventions were prospectively collected in patients with (RMLN) and without (RM) a lead noise alert (Abbott Secure Sense™ or Medtronic Lead Integrity Alert™) in their remote monitoring system., Results: During a follow-up of 4,457 patient years, 64 lead failures were diagnosed. Sixty-one (95%) of the diagnoses were made before any clinical complication occurred. Inappropriate shocks were delivered in only one patient of each group (3%), with an annual rate of 0.04%. All high voltage conductor failures were identified remotely by a dedicated impedance alert in 10 patients. Pace-sense component failures were correctly identified by a dedicated alert in 77% (17 of 22) of the RMLN group versus 25% (8 of 32) of the RM group (P = 0.002). The absence of a lead noise alert was associated with a 16-fold increase in the likelihood of initiating either a shock or ATP (OR: 16.0, 95% CI 1.8-143.3; P = 0.01)., Conclusion: ICD remote monitoring with systematic review of all transmitted data is associated with a very low rate of inappropriate shocks related to lead failure. Dedicated noise alerts further reduce inappropriate detection of ventricular arrhythmias., (© 2018 Wiley Periodicals, Inc.)

Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported., Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations., Results: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm 2 ) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers ( P <0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, P =0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up., Conclusions: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism., (© 2018 The Authors.)

Background: Characteristics of multiple-loop atrial tachycardia (AT) circuits have never precisely examined., Methods: In 193 consecutive post-atrial fibrillation ablation patients with AT, 44 multiple-loop ATs including 42 dual-loop AT and 2 triple-loop AT in 41 (21.2%) were diagnosed with the high-resolution mapping system and analyzed off-line., Results: In dual-loop ATs, 3 types were identified: type M, a combination of 2 anatomic macroreentrant ATs (AMATs) in 19 (43.2%); type MN, with 1 AMAT and 1 non-AMAT in 12 (27.3%); and type N with 2 non-AMATs in 11 (25.0%). The remaining 2 triple-loop ATs (4.5%) were a combination of perimitral-, roof-dependent-, and non-AMAT. At least 1 AMAT was included in 33 (75.0%), and 1 non-AMAT in 25 (56.8%). Of the ATs with at least 1 non-AMAT circuit, a pulmonary vein formed part of the circuit in 16/25 (64.0%). The length of the common isthmus was 3.6±1.4 cm in type M, 1.6±0.7 cm in type MN, and 1.1±0.7 cm in type N ( P <0.0001). The area of the common isthmus was 12.92±7.68, 2.46±1.53, and 0.90±0.81 cm 2 , in Type M, MN, and N ( P <0.0001). The narrowest width of the common isthmus was 1.8±0.7 cm, 1.1±0.3 cm, and 0.7±0.3 cm in type M, MN, and N ( P <0.0001), respectively. The electrograms in the common isthmus showed longer duration and lower voltage in type N, type MN, and type M (duration: 106±25 ms, 87±27 ms, and 69±27 ms; P =0.006; and voltage: 0.06±0.02 mV, 0.22±0.21 mV, and 0.57±0.50 mV; P <0.0001), respectively., Conclusions: Multiple-loop ATs are complex, frequently including anatomic circuits. They have specific characteristics determined by the combination of AMAT and non-AMAT., (© 2018 American Heart Association, Inc.)

Pacemaker-induced arrhythmias represent a very rare complication. Algorithm-induced ventricular tachycardias have been described but this report is the first to describe a ventricular fibrillation caused by transient undersensing of the ventricular lead during an abdominal ultrasound., (© 2018 Wiley Periodicals, Inc.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) remains a new technology requiring accurate assessment of the various aspects of its functioning. Isolated cases of delayed sensing of ventricular arrhythmia have been described., Objective: The purpose of this multicenter study was to assess the quality of sensing during induced ventricular fibrillation (VF)., Methods: One hundred thirty-seven patients underwent induction of VF at the end of the S-ICD implantation., Results: VF induction was successful in 133 patients (97%). Mean time to first therapy was 16.2 ± 3.1 seconds, with a substantial range from 12.5 to 27.0 seconds. Four different detection profiles were arbitrarily defined: (1) optimal detection (n = 39 [29%]); (2) undersensing with moderate prolongation of time to therapy (<18 seconds; n = 68 [51%]); (3) undersensing with significant prolongation of the time to therapy (>18 seconds; n = 19 [14%]); and (4) absence of therapy or prolonged time to therapy related to noise oversensing (n = 7 [6%]). In some of the patients in the last group, despite induction of VF the initial counter was never filled, the device did not charge the capacitors, and the shock was not delivered because of a sustained diagnosis of noise (n = 5). A manual shock by the device or an external shock had to be delivered to restore the sinus rhythm., Conclusion: Our study demonstrated a marked sensing delay leading to prolonged time to therapy in a large number of S-ICD patients. A few worrisome cases of noise oversensing inhibiting the therapies were detected. These results support the need for systematic intraoperative defibrillation testing., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Anatomic macroreentrant atrial tachycardias (MATs) are conventionally reported to depend on the cavotricuspid isthmus, the mitral isthmus, or the left atrial roof, and are commonly seen following catheter ablation for atrial fibrillation., Objectives: To define the precise circuits of anatomic MAT with ultrahigh-resolution mapping., Methods: In 57 patients (mean age, 62 years; 10 female) who developed ≥1 anatomic MAT, we analyzed 88 MAT circuits including 16 peritricuspid, 42 perimitral, and 30 roof-dependent circuits, using high-density mapping and entrainment., Results: Of 16 peritricuspid atrial tachycardias (ATs), 8 (50.0%) showed a circuit not limited to the tricuspid annulus. However, cavotricuspid isthmus ablation terminated the tachycardia in all patients. Similarly, 26 of 42 perimitral ATs (61.9%) showed a circuit not limited to the mitral annulus, and a low-voltage zone <0.1 mV around the mitral annulus was associated with nontypical perimitral ATs (P < .0001). The practical isthmus was not in the mitral isthmus in 13 of these 26 perimitral ATs (50%). Finally, 22 of 30 roof-dependent ATs (73.3%) had a circuit not rotating around both pairs of pulmonary veins. Brief assessment of the activation direction on the posterior wall in relation to that on the septal, anterior, and lateral wall helped deduce the circuit of roof-dependent AT in 27 of 30 (90.0%). Practical isthmus was not in the roof in 8 of 22 (36.4%). Practical isthmuses mapped with the system were significantly shorter than the usual anatomic isthmuses (16.1 ± 8.2 mm vs 33.7 ± 10.4 mm) (P < .0001)., Conclusions: High-density mapping successfully identified the precise circuits and the practical isthmus of anatomic MATs in patients with prior atrial fibrillation ablation., (Copyright © 2017 Heart Rhythm Society. All rights reserved.)

Objectives: The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD)., Background: SD accounts for 11% to 25% of death in HD patients., Methods: Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed., Results: Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was <50% in 16%. Twelve patients (17%) had histories of atrial fibrillation or flutter at inclusion. During a mean follow-up period of 21.3 ± 6.9 months, 16 patients died (14% patient-years), 7 (44%) of cardiovascular causes. Four SDs occurred, with progressive bradycardia followed by asystole. The incidence of patients presenting with significant conduction disorder and with ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate survival frailty analyses, a higher risk for conduction disorder was associated with plasma potassium >5.0 mmol/l, bicarbonate <22 mmol/l, hemoglobin >11.5 g/dl, pre-HD systolic blood pressure >140 mm Hg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium <4.0 mmol/l, no antiarrhythmic drugs, and previous other arrhythmias. With ILR monitoring, de novo atrial fibrillation or flutter was diagnosed in 14 patients (20%)., Conclusions: ILR may be considered in HD patients prone to significant conduction disorders, ventricular arrhythmia, or atrial fibrillation or flutter to allow early identification and initiation of adequate treatment. Therapeutic strategies reducing serum potassium variability could decrease the rate of SD in these patients. (Implantable Loop Recorder in Hemodialysis Patients [RYTHMODIAL]; NCT01252823)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Biatrial tachycardia (BiAT) is a rare form of atrial macroreentrant tachycardia, in which both atria form a critical part of the circuit. We aimed to identify the characteristics and precise circuits of single-loop macroreentrant BiATs., Methods and Results: We identified 8 patients (median age, 59.5 years old) with 9 BiATs in a cohort of 336 consecutive patients from 2 institutions who had undergone AT catheter ablation using an automatic ultrahigh-resolution mapping system. Seven of the 8 patients had a history of persistent AF ablation, including septal or anterior left atrium ablation before developing BiAT. One of the 8 patients had a history of an atrial septal patch closure with a massively enlarged right atrium. Nine ATs (median cycle length, 334 ms; median 12 561 points in the left atrium; 8814 points in the right atrium) were diagnosed as single-loop macroreentrant BiATs. We observed 3 types of BiAT (1) BiAT with a perimitral and peritricuspid reentrant circuit (n=3), (2) BiAT using the right atrium septum and a perimitral circuit (n=3), and (3) BiAT using only the left atrium and right atrium septum (n=3). Catheter ablation successfully terminated 8 of the 9 BiATs., Conclusions: All patients who developed BiAT had an electric obstacle on the anteroseptal left atrium, primarily from prior ablation lesions. In this situation, mapping of both atria should be considered during AT. Because 3 types of single-loop BiAT were observed, ablation strategies should be adjusted to the type of BiAT circuit., (© 2018 American Heart Association, Inc.)

Neuromedin U (NMU) has been shown driving the progression of various tumor entities, including breast cancer. However, the expression pattern of NMU and its receptors in breast cancer tissues as well as systematic insight into mechanisms and downstream targets of the NMU-driven signaling pathways are still elusive. Here, NMU expression was found up-regulated in all breast cancer subtypes when compared to healthy breast tissue. Using an in silico dataset comprising 1,195 samples, high NMU expression was identified as an indicator of poor outcome in breast tumors showing strong NMUR2 expression. Next, the biological impact of NMU on breast cancer cells in relation to NMUR2 expression was analyzed. Ectopic NMU expression reduced colony growth while promoting a motile phenotype in NMUR2-positive SKBR3 but not NMUR2-negative Hs578T cells. To uncover signaling pathways and key molecules affected by NMU in SKBR3 cells, Affymetrix microarray analysis was applied. Forced NMU expression affected molecules involved in WNT receptor signaling among others. As such we demonstrated enhanced activation of the WNT/planar cell polarity (PCP) effector RAC1 and down-regulation of canonical WNT targets such as MYC. In summary, NMU might contribute to progression of NMUR2-positive breast cancer representing a potential druggable target for future personalized strategies.