Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

Multicurvature viscous streaming: Flow topology and particle manipulation.

Viscous streaming refers to the rectified, steady flows that emerge when a liquid oscillates around an immersed microfeature. Relevant to microfluidics, the resulting local, strong inertial effects allow manipulation of fluid and particles effectively, within short time scales and compact footprints. Nonetheless, practically, viscous streaming has been stymied by a narrow set of achievable flow topologies, limiting scope and application. Here, by moving away from classically employed microfeatures of uniform curvature, we experimentally show how multicurvature designs, computationally obtained, give rise, instead, to rich flow repertoires. The potential utility of these flows is then illustrated in compact, robust, and tunable devices for enhanced manipulation, filtering, and separation of both synthetic and biological particles. Overall, our mixed computational/experimental approach expands the scope of viscous streaming application, with opportunities in manufacturing, environment, health, and medicine, from particle self-assembly to microplastics removal.

Identification of Human Ventricular Tachycardia Demarcated by Fixed Lines of Conduction Block in a 3-Dimensional Hyperboloid Circuit.

BACKGROUND: The circuit boundaries for reentrant ventricular tachycardia (VT) have been historically conceptualized within a 2-dimensional (2D) construct, with their fixed or functional nature unresolved. This study aimed to examine the correlation between localized lines of conduction block (LOB) evident during baseline rhythm with lateral isthmus boundaries that 3-dimensionally constrain the VT isthmus as a hyperboloid structure. METHODS: A total of 175 VT activation maps were correlated with isochronal late activation maps during baseline rhythm in 106 patients who underwent catheter ablation for scar-related VT from 3 centers (42% nonischemic cardiomyopathy). An overt LOB was defined by a deceleration zone with split potentials (≥20 ms isoelectric segment) during baseline rhythm. A novel application of pacing within deceleration zone (≥600 ms) was implemented to unmask a concealed LOB not evident during baseline rhythm. LOB identified during baseline rhythm or pacing were correlated with isthmus boundaries during VT. RESULTS: Among 202 deceleration zones analyzed during baseline rhythm, an overt LOB was evident in 47%. When differential pacing was performed in 38 deceleration zones without overt LOB, an underlying concealed LOB was exposed in 84%. In 152 VT activation maps (2D=53, 3-dimensional [3D]=99), 69% of lateral boundaries colocalized with an LOB in 2D activation patterns, and the depth boundary during 3D VT colocalized with an LOB in 79%. In VT circuits with isthmus regions that colocalized with a U-shaped LOB (n=28), the boundary invariably served as both lateral boundaries in 2D and 3D. Overall, 74% of isthmus boundaries were identifiable as fixed LOB during baseline rhythm or differential pacing. CONCLUSIONS: The majority of VT circuit boundaries can be identified as fixed LOB from intrinsic or paced activation during sinus rhythm. Analysis of activation while pacing within the scar substrate is a novel technique that may unmask concealed LOB, previously interpreted to be functional in nature. An LOB from the perspective of a myocardial surface is frequently associated with intramural conduction, supporting the existence of a 3D hyperboloid VT circuit structure. Catheter ablation may be simplified to targeting both sides around an identified LOB during sinus rhythm.

Association between COVID-19 vaccination and atrial arrhythmias in individuals with cardiac implantable electronic devices.

INTRODUCTION: The impact of mRNA-based coronavirus disease-2019 (COVID-19) vaccines on atrial arrhythmias (AA) and ventricular arrhythmias incidence is unknown. METHODS: BIOTRONIK Home Monitoring data and Medicare Claims data were utilized to identify individuals implanted with a cardiac implantable electronic device (CIED) between 2010 and 2020 who received one or more doses of COVID-19 vaccine in 2021. The burden of AA (%) in the 3 months postvaccination was compared to those noted in the preceding 3 months using the Wilcoxon signed rank test. Sub-analyses comparing the effects of the influenza vaccine against the COVID-19 vaccine were also evaluated for individuals who received the influenza vaccine in 2020. A 1:1 propensity score match comparison between COVID-19 vaccine and non-vaccinated patients was also performed. RESULTS: First and second doses of the COVID-19 vaccine were administered to 7757 and 6579 individuals with a CIED (age 76.2 ± 9.0 years, 49% males), respectively. While a small but statistically significant increase in the burden of AA was noted in the 3 months postvaccination compared to the preceding 3 months after the first dose of the COVID-19 vaccine (0.43 ± 9.04%, p = .028) a similar rise in AA was found following the influenza vaccine and for matched patients who did not receive the COVID-19 vaccine. No significant difference in device therapies was seen pre- and postvaccination. CONCLUSIONS: Though we report a small but significant increase in the number of CIED-detected AAs following vaccination for COVID-19 over a 3-month window, we believe these results correlate more with time and the progressive nature of AF rather than the vaccine itself. While these data should not dissuade from the use of these vaccines, increased vigilance and prompt treatment of AF is required for high-risk groups, specifically males over 70 years of age, following vaccination.

Septal venous channel perforation during left bundle branch area pacing: a prospective study.

AIMS: To characterize the diagnosis, frequency, and procedural implications of septal venous channel perforation during left bundle branch area pacing (LBBAP). METHODS AND RESULTS: All consecutive patients undergoing LBBAP over an 8-month period were prospectively studied. During lead placement, obligatory septal contrast injection was performed twice, at initiation (implant entry zone) and at completion (fixation zone). An intuitive fluoroscopic schema using orthogonal views (left anterior oblique/right anterior oblique) and familiar landmarks is described. Using this, we resolved zonal distribution (I-VI) of lead position on the ventricular septum and its angulation (post-fixation angle θ). Subjects with and without septal venous channel perforation were compared. Sixty-one patients {male 57.3%, median age [interquartile range (IQR)] 69.5 [62.5-74.5] years} were enrolled. Septal venous channel perforation was observed in eight (13.1%) patients [male 28.5%, median age (IQR) 64 (50-75) years]. They had higher frequency of (i) right-sided implant (25% vs. 1.9%, P = 0.04), (ii) fixation in zone III at the mid-superior septum (75% vs. 28.3%, P = 0.04), (iii) steeper angle of fixation-median θ (IQR) [19 (10-30)° vs. 5 (4-19)°, P = 0.01], and (iv) longer median penetrated-lead length (IQR) [13 (10-14.8) vs. 10 (8.5-12.5) mm, P = 0.03]. Coronary sinus drainage of contrast was noted in five (62.5%) patients. Abnormal impedance drops during implantation (12.5% vs. 5.7%, P = NS) were not significantly different. CONCLUSION: When evaluated systematically, septal venous channel perforation may be encountered commonly after LBBAP. The fiducial reference framework described using fluoroscopic imaging identified salient associated findings. This may be addressed with lead repositioning to a more inferior location and is not associated with adverse consequence acutely or in early follow-up.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

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.

Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.

Coupled Dynamics of Droplet Impact on a Flexible, Hydrophilic Cantilever Beam.

We experimentally study the droplet impact on a flexible, hydrophilic cantilever beam. Droplets of water, water-glycerol (1:1 v/v), and glycerol were considered on a copper beam. Side visualization of the droplet impact on the cantilever was carried out by using a high-speed camera. We systematically vary cantilever stiffness to obtain a characteristic time scale of the beam dynamics, that is, shorter on the same order and longer than the characteristic time scale of droplet dynamics. Water droplet spreading reduces with an increase in the beam's flexibility, due to the "springboard effect". Results reveal that a threshold cantilever length exists beyond which the droplet vibration mode "locks-in" to the cantilever vibration mode. During lock-in, the bending energy of the beam increases with an increasing length or decreasing stiffness. The time-varying cantilever deflection exhibits an oscillatory, exponentially decaying response. However, in the case where both time scales are almost the same, we found a two-stage damping in the measurements: a fast, initial damping followed by a slower, damped response. We explain this damped response by the interplay of droplet and cantilever early dynamics. As expected, increasing the droplet viscosity dampens the magnitude of droplet spreading and displacement of the cantilever's tip due to a larger dissipation of kinetic energy in the bulk of the droplet. The decay is exponential in all cases, and the time taken to reduce the spreading and displacement is shorter with a larger viscosity. The damping coefficient is found to inversely scale with the cantilever length or mass. We corroborated the measurements with available analytical models, confirming the hypotheses used to explain the results. Overall, the present study provides fundamental insights into controlling the coupled dynamics of droplet and flexible substrates, with potential applications such as the design of efficient agricultural sprays and wings of microaerial vehicles.

Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS AND RESULTS: The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). CONCLUSION: This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.

Circuit Determinants of Ventricular Tachycardia Cycle Length: Characterization of Fast and Unstable Human Ventricular Tachycardia.

BACKGROUND: Fast ventricular tachycardias (VTs) have historically been attributed to shorter path lengths with smaller reentrant circuit dimensions in animal models. The relationship between the dimensions of the reentrant VT circuit and tachycardia cycle length (TCL) has not been examined in humans. This study aimed to analyze the determinants of the rate of human VT with comparison of circuit dimensions and conduction velocity (CV) across a wide range of both stable and unstable VTs delineated by high-resolution mapping. METHODS: Fifty-four VTs with complete circuit delineation (>90% TCL) by high-resolution multielectrode mapping were analyzed in 49 patients (men, 88%; age, 65 years [58-71 years]; nonischemic, 47%). Fast VT was defined as TCL <333 milliseconds (rate >180 bpm). Unstable VT was defined by hemodynamic deterioration with an intrinsic mean arterial pressure <60 mm Hg during a sustained episode. RESULTS: The median TCL of VT was 365 milliseconds (306-443 milliseconds), and 24 fast VTs were characterized. A wide range of CVs was observed within the entrance (0.03-0.55 m/s), common pathway (0.03-0.77 m/s), exit (0.03-0.53 m/s), and outer loop (0.17-1.13 m/s). There were no significant differences in the median dimensions of the isthmus and path length between fast and slow VTs and between unstable and stable VTs. The outer loop CV was the only circuit component that correlated with TCL in both ischemic cardiomyopathy (r=-0.5, P=0.006) and nonischemic cardiomyopathy (r=-0.45, P=0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length: r=-0.46, P=0.001, width: r=-0.3, P=0.047) and predictive of rapid VT termination by a single radiofrequency application (r=-0.41, P=0.023). CONCLUSIONS: Because of a wide spectrum of CV observed within the reentrant path during human VT, the dimensions of the circuit were not predictive of VT cycle length. For the first time, we demonstrate that the CV of the outer loop, rather than isthmus, is the principal determinant of the rate of VT. The size of the circuit was similar between fast and slow VTs and between unstable and stable VTs. Long, continuous electrograms were indicative of spatially confined isthmus dimensions, confirmed by rapid termination of VT during radiofrequency delivery.

Bradyarrhythmias and Physiologic Pacing in the ICU.

Bradyarrhythmias represent a common pathology in the intensive care unit (ICU) with etiologies of varying severity. Treatment has often been focused on correcting underlying causes and may require pacing for urgent hemodynamic support. In recent years, there has been interest in physiologic pacing modalities which avoid the dyssynchrony from right ventricular (RV) only pacing. Cardiac resynchronization therapy (CRT) through biventricular pacing is a well-established device-based electrical therapy in patients with wide QRS and heart failure. Recently, it has been shown that biventricular pacing may also be pursued for hemodynamic rescue in the ICU setting. Efforts to re-engage the conduction system with His bundle pacing or further downstream have also emerged as alternative means to deliver resynchronization, with early applications in the ICU now being reported. The goal of the review is to examine bradyarrhythmia causes and management in the ICU as well as investigate new approaches in physiologic pacing and their potential roles in critically ill patients.

Physiologic Pacing Targeting the His Bundle and Left Bundle Branch: a Review of the Literature.

PURPOSE OF REVIEW: Conduction system pacing (CSP) has emerged as a means to preserve or restore physiological ventricular activation via pacing at the His bundle or at more distal targets in the conduction system, including the left bundle branch area. This review examines strengths, weaknesses, and clinical applications of CSP performed via these approaches. RECENT FINDINGS: His bundle pacing (HBP) has been successfully utilized for standard bradyarrhythmia indications and for QRS correction among patients receiving devices for cardiac resynchronization therapy (CRT). Limitations of HBP pacing have included implant complexity and rising pacing thresholds over time. Left bundle branch area pacing (LBBAP) appears to deliver similar physiological benefits with shorter implant times and more stable thresholds. More recently, hybrid systems utilizing HBP or LBBAP in combination with left ventricular leads have been used to treat heart failure (HF) patients, and may be useful in multilevel or mixed conduction blocks. There is growing interest in CSP for bradycardia and HF indications, although high quality data with randomized controlled trials are needed to help guide future treatment paradigms.

Colloidal Deposits via Capillary Bridge Evaporation and Particle Sorting Thereof.

Evaporating droplets of colloidal suspensions leave behind particle deposits which could be effectively controlled via manipulating the surrounding conditions and particles and liquid properties. While previous studies extensively focused on sessile and pendant droplets, the present work investigates the evaporation dynamics of capillary bridges of colloidal suspensions formed between two parallel plates. We vary the wettability of the plates and the particle size and composition of the colloidal suspensions, keeping the same spacing between the plates. We employ side visualization, optical microscopy, fluorescence microscopy, and scanning electron microscopy and develop computational and theoretical models to collect the data. A computational model based on diffusion-limited evaporation is used to characterize the timescale of the evaporation of the capillary bridge. The model predictions are in good agreement with the present and prior experimental measurements. We discuss about the deposits of monodispersed particle suspension formed by the interplay of pinning of the contact line and evaporation dynamics. Multiple rings on the plates are observed due to the stick-slip motion of the contact line. The larger particles tend to form asymmetric deposits, with most particles concentrated on the bottom plates due to a considerably stronger gravitational pull than the hydrodynamic drag. This deposition is explained by estimating the competing forces on the particles during the evaporation. A regime map is proposed for classifying deposits on the particle size wettability plane. Lastly, we demonstrate size-based particle sorting of bidispersed colloidal suspensions in this framework. We describe two mechanisms: gravity-assisted and geometry-assisted sorting, which can be designed to sort particles efficiently. A regime map depicting the regions of influence of each mechanism is presented.

Atypical pathogens associated with cardiac implantable electronic device infections.

BACKGROUND: Cardiovascular implantable electronic device (CIED) infections are associated with significant morbidity and mortality making the identification of the causative organism critical. The vast majority of CIED infections are caused by Staphylococcal species. CIED infections associated with atypical pathogens are rare and have not been systematically investigated. The objective of this study is to characterize the clinical course, management and outcome in patients with CIED infection secondary to atypical pathogens. METHODS: Medical records of all patients who underwent CIED system extraction at the University of Chicago Medical Center between January 2010 and November 2020 were retrospectively reviewed to identify patients with CIED infection. Demographic, clinical, infection-related and outcome data were collected. CIED infections were divided into typical and atypical groups based on the pathogens isolated. RESULTS: Among 356 CIED extraction procedures, 130 (37%) were performed for CIED infection. Atypical pathogens were found in 5.4% (n = 7) and included Pantoea species (n = 2), Kocuria species (n = 1), Cutibacterium acnes (n = 1), Corynebacterium tuberculostearicum (n = 1), Corynebacterium striatum (n = 1), Stenotrophomonas maltophilia (n = 1), and Pseudozyma ahidis (n = 1). All patients with atypical CIED infections were successfully treated with total system removal and tailored antibiotic therapy. There were no infection-related deaths. CONCLUSIONS: CIED infections with atypical pathogens were rare and associated with good outcome if diagnosed early and treated with total system removal and tailored antimicrobial therapy. Atypical pathogens cultured from blood, tissue or hardware in patients with CIED infection should be considered pathogens and not contaminants.

Late presentation of recurrent syncope after permanent pacemaker implantation due to Lead-Header malapposition.

Permanent pacemaker (PPM) malfunction due to electrical connection problems such as a loose set screw or lead-header malapposition is extremely rare. We present a patient with complete heart block (CHB) who had PPM malfunction and recurrent syncope, late (14 months) after initial implantation, which was caused by the ventricular lead pin disengagement from the header resulting in oversensing due to noise, pacing inhibition and recurrent syncope. PPM due to lead-header malapposition this late after device implantation has previously not been reported.

Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns.

BACKGROUND: Septal activation in patients with left bundle-branch block (LBBB) patterns has not been described previously. We performed detailed intracardiac mapping of left septal conduction to assess for the presence and level of complete conduction block (CCB) in the His-Purkinje system. Response to His bundle pacing was assessed in patients with and without CCB in the left bundle. METHODS: Left septal mapping was performed with a linear multielectrode catheter in consecutive patients with LBBB pattern referred for device implantation (n=38) or substrate mapping (n=47). QRS width, His duration, His-ventricular (HV) intervals, and septal conduction patterns were analyzed. The site of CCB was localized to the level of the left-sided His fibers (left intrahisian) or left bundle branch. Patients with ventricular activation preceded by Purkinje potentials were categorized as having intact Purkinje activation. RESULTS: A total of 88 left septal conduction recordings were analyzed in 85 patients: 72 LBBB block pattern and 16 controls (narrow QRS, n=11; right bundle-branch block, n=5). Among patients with LBB block pattern, CCB within the proximal left conduction system was observed in 64% (n=46) and intact Purkinje activation in the remaining 36% (n=26). Intact Purkinje activation was observed in all controls. The site of block in patients with CCB was at the level of the left His bundle in 72% and in the proximal left bundle branch in 28%. His bundle pacing corrected wide QRS in 54% of all patients with LBBB pattern and 85% of those with CCB (94% left intrahisian, 62% proximal left bundle-branch). No patients with intact Purkinje activation demonstrated correction of QRS with His bundle pacing. CCB showed better predictive value (positive predictive value 85%, negative predictive value 100%, sensitivity 100%) than surface ECG criteria for correction with His bundle pacing. CONCLUSIONS: Heterogeneous septal conduction was observed in patients with surface LBBB pattern, ranging from no discrete block to CCB. When block was present, we observed pathology localized within the left-sided His fibers (left intrahisian block), which was most amenable to corrective His bundle pacing by recruitment of latent Purkinje fibers. ECG criteria for LBBB incompletely predicted CCB, and intracardiac data might be useful in refining patient selection for resynchronization therapy.

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy.

BACKGROUND: Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm. METHODS: Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed, and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality. RESULTS: One hundred twenty patients (median age 65 years [59-71], 15% female, 50% nonischemic, median ejection fraction 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2518 points [1615-3752] endocardial, 5049±2580 points epicardial) and identified an average of 2±1 DZ, which colocalized to successful termination sites in 95% of cases. The median total radiofrequency application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low-voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ischemic cardiomyopathy and 63% in nonischemic cardiomyopathy) was achieved. The overall survival rate was 87%. CONCLUSIONS: A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.

Keeping pace with the competition: His bundle versus biventricular pacing in heart failure.

PURPOSE OF REVIEW: His bundle pacing (HBP) has emerged as a novel method to achieve electrical resynchronization in bundle branch block and as an alternative means to deliver cardiac resynchronization therapy (CRT). There are now data on HBP in CRT-eligible patients from cohort studies and a single pilot randomized controlled trial (RCT). RECENT FINDINGS: Early clinical data regarding HBP in heart failure have demonstrated echocardiographic and functional improvement similar to traditional biventricular pacing (BiV), mostly when utilized as a bailout to traditional BiV-CRT. A single pilot RCT, His-SYNC, showed a trend toward greater echocardiographic response in an on-treatment analysis, but was underpowered. No large RCTs have reported long-term clinical outcomes. In order to realize any benefit from HBP, output-dependent morphology changes must be demonstrated to ensure the conduction system capture is present. There may be a role for corrective HBP in patients with right bundle branch block and after atrioventricular node ablation, which is theoretically more desirable than traditional BiV. Importantly, however, HBP is likely not to benefit patients with nonspecific intraventricular conduction delay. SUMMARY: HBP is emerging as an alternative strategy for CRT and may have a role in patients in whom traditional BiV is not achievable or ineffective.

Left ventricle and mitral valve reverse remodeling in response to cardiac resynchronization therapy in nonischemic cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves left heart geometry and function in nonischemic cardiomyopathy (NICMP). We aimed to detail the effects of CRT on left ventricular (LV) and mitral valve (MV) remodeling using 2-dimensional transthoracic echocardiography. METHODS: Forty-five consecutive patients with NICMP who underwent CRT implantation between 2009 and 2012, and had pre-CRT and follow-up echocardiograms available, were included. Paired t test, linear and logistic regression, and Kaplan-Meier survival analyses were used for statistical assessment. RESULTS: The mean age and QRS duration were 60 years and 157 ms, respectively, and 13 (28.9%) were female. At a mean follow-up of 3 years, there were 22 (48.9%) "CRT responders" (≥15% reduction in LV end-systolic volume index [LVESVi]). Significant improvements were observed in LV ejection fraction (26.3% vs 34.3%) and LVESVi (87.7 vs 71.1 mL/m2 ), as well as mitral regurgitation vena contracta width, MV tenting height and area, and end-systolic interpapillary muscle distance. Five-year actuarial survival was 87.5%. Multivariate regression analyses revealed the pre-CRT LVESVi (ß = 0.52), and MV coaptation length (ß = -0.34) and septolateral annular diameter (ß = 0.25) as good correlates of follow-up LVESVi. Variables associated with CRT response were pre-CRT MV coaptation length (OR 1.75, 95% CI 1.0-3.1) and posterior leaflet tethering angle (OR 1.07, 95% CI 1.0-1.14), irrespective of baseline QRS morphology and duration (all P < .05). CONCLUSIONS: Cardiac resynchronization therapy improves LV and MV geometry and function in half of patients with NICMP, which is paralleled by decreased mitral regurgitation severity. The extent of pre-CRT LV remodeling and MV tethering are associated with CRT response.