Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Effects and pharmacological mechanism of Zhigancao Decoction on electrical and structural remodeling of the atrium of rabbits induced by rapid atrial pacing.

BACKGROUND: Zhigancao decoction (ZD) has a long history in China as a traditional Chinese medicine compound for the treatment of tachyarrhythmias. This study mainly explored the pharmacological mechanism of Zhigancao Decoction in preventing atrial fibrillation by altering the electrical and structural remodeling of the atrial in rabbits. METHODS: In total, 30 male New Zealand white rabbits were randomly divided into 3 groups (ten rabbits for each). The first group was sham-operated (control group). The second group was intervened by the rapid right atrium pacing (RAP) to induce atrial fibrillation (AF group), while the third group was given ZD gavage and RAP (AF + ZD group). All rabbits were anesthetized before two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. After 8 h of rapid right atrial pacing, the electrophysiological indexes and the induction rate of atrial fibrillation were observed in the three groups of rabbits, and the left atrial myocardium samples were taken to observe the ultrastructure. Single atrial myocytes were separated by enzymolysis, and the L-type calcium current (ICa-L) of atrial myocytes in different experimental groups was observed by whole-cell patch clamp technique. The fluorescence intensity of Ca2+ in atrial myocytes was observed after Fluo-3/AM fluorescent staining. The main components of ZD were identified by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS/MS) method. RESULTS: Compared with the AF group, the maximum ascent rate (Max dV/dt) and plateau potential were significantly reduced in the ZD group, the action potential duration at 10% and 20% (APD10, APD20) were significantly shortened (P < 0.01), action potential duration at 50%, 70%, and 90% (APD50, APD70, APD90) were significantly prolonged, and atrial effective refractory period (AERP) was significantly prolonged (P < 0.01) in the ZD group. In the ZD group, the ICa-L amplitudes of rabbit atrial myocytes under each clamping voltage were significantly smaller than those in the AF group (P < 0.01) and the control group (P < 0.05). The Ca2+ fluorescence intensity in the rabbit atrial myocytes in the ZD group was significantly weaker than that in the AF group (P < 0.01) and the control group (P < 0.05). Electron microscopy displayed that the control group had neatly arranged atrial tissue myofilaments and intact mitochondria. However, the ultrastructural damage of the AF group was severe compared with that of the ZD group. LC-MS/MS analysis confirmed that ZD contained several antiarrhythmic compounds including ginsenoside, isoliensinine, catalpol, glycyrrhizinate and hesperetin. CONCLUSION: Rapid atrial pacing (RAP) could cause the electrical and structural remodeling of rabbit atrial myocytes. ZD might reverse the atrial electrical remodeling but could have little effect on structural remodeling, which might be the mechanism of ZD treatment on atrial fibrillation.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

The history of cardiac pacing in the young and a look to the future.

PURPOSE OF REVIEW: The purpose of this review is to explore the historical and serendipitous events that led to the creation of modern-day pacemakers. In addition, this review will explore how contemporary conduction site-specific pacing has overcome some of the deleterious effects from historical chronic right ventricular apical pacing. RECENT FINDINGS: Recently, there have been tremendous advances in not just the lead design but the tools required to promote more physiologic pacing. Although cardiac resynchronization pacing has been around for nearly 2 decades, this review also introduces and discusses the early results of His-bundle pacing and left bundle branch pacing and some of the potential applicability of this technology for our children. SUMMARY: Pacemakers have evolved significantly in the last 30 years through collaborative partnerships between physicians and engineers. The future of cardiac pacing is bright compared to the field of electrotherapy 50 years ago. Future iterations of pacemakers must consider unusual anatomy and growing children. Pediatric patients contribute to a small percentage of the overall device volume, but the majority of these patients will have a pacemaker for life. We need to be proactive and consider what are the best short and long-term solutions for this cohort.

Characteristics of intracardiac electrogram of the interventricular septum in the left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) has become a hot topic in the field of physiological pacing. However, only a few studies have described the characteristics of the intrinsic intracardiac electrogram (EGM) while placing the left bundle branch (LBB) lead. CASE PRESENTATION: Herein, we reported a case with atrial premature contractions to the ventricle during the LBBP procedure. Paced and intrinsic (supraventricular) EGMs were recorded and analyzed. CONCLUSIONS: The myocardium of the interventricular septum could be divided into four regions based on electrophysiology: the right septal area, the left septal area, the endocardium of the left ventricular septum, and the LBB area. This might guide the electrophysiological localization of the LBB lead in the septum.

A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Recording an isoelectric interval as an endpoint of left bundle branch pacing with continuous paced intracardiac electrogram monitoring.

BACKGROUND: The present study aimed to evaluate the feasibility and safety of the novel left bundle branch pacing (LBBP) procedure that uses isoelectric interval as an endpoint for lead implantation. METHODS: A total of 41 patients with indications for pacing were enrolled. All patients underwent a novel LBBP procedure guided by recording an isoelectric interval as an endpoint for lead implantation. The procedural details and electrophysiological characteristics were then analyzed. RESULTS: A total of 38/41 (92.7%) cases were confirmed of left bundle branch (LBB) capture. An isoelectric interval was observed in 36/41 cases (87.8%). A total of 36/41 (87.8%) cases with LBB potential were observed. The mean unipolar LBBP threshold at the implant was 0.5 ± 0.2 V. The mean sensed amplitude of the R wave and the pacing impedance at the implant were 12.9 ± 5.0 mV and 723.5 ± 117.1 Ω. During the final threshold testing, a transition from non-selective to selective LBBP (S-LBBP) was demonstrated in 26 patients. A transition from non-selective LBBP (NS-LBBP) to left ventricular septal myocardial capture was observed in 12 patients. CONCLUSION: Using an isoelectric interval as an endpoint to guide the LBBP was feasible in a high proportion of captured LBB cases.

Septal versus apical pacing sites in permanent right ventricular pacing: The multicentre prospective SEPTAL-PM study.

BACKGROUND: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative. AIM: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up. METHODS: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead. RESULTS: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival. CONCLUSION: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period.

Regularly irregular atrial rhythm after superior vena cava isolation: Another manifestation of sinoatrial node injury?

The present case described an unusual clinical manifestation of the sinoatrial node (or sinoatrial junction) injury during superior vena cava isolation.

Outcomes of supraventricular tachycardia ablation: Results from the Singapore ablation and cardiac devices registry.

BACKGROUND: The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS: Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT), or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, postoperative pacing requirement, arrhythmic recurrence and 1-year all-cause mortality. RESULTS: Among 2260 patients (mean age 45 ± 18 years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT, and AVNRT (p < .001). Periprocedural cardiac tamponade occurred in two AVRT patients. A total of 15 pacemakers (6 within first 30-days, 9 after 30-days) were implanted (seven AV block, eight sinus node dysfunction [SND]), with the highest incidence of pacemaker implantation after AT-ablation (5% vs. 0.6% AVNRT vs. 0.1% AVRT, p < .001). Repeat ablations (0.9% AVNRT, 7% AVRT, 4% AT, p < .001) were performed in 78 (3.5%) patients and 13 (0.6%) patients died within a year of ablation. Among outcomes considered adjusting for age, sex, PSVT-type and procedure-time, AT was independently associated with 6-fold increased odds of total (adjusted odds ratio [AOR] 6.32, 95% confidence interval [CI] 1.95-20.53) and late (AOR 6.38, 95% CI 1.39-29.29) pacemaker implantation, while AVRT was associated with higher arrhythmic recurrence with repeat ablations (AOR 4.72, 95% CI 2.36-9.44) compared to AVNRT. CONCLUSIONS: Contemporary PSVT ablation is safe with high acute success rates. Long-term outcomes differed by nature of the PSVT.

His bundle pacing: A promising alternative strategy for anti-bradycardic pacing - report of a single-center experience.

His bundle pacing (HBP) is proven to be a safe and effective alternative pacing modality that, in addition, avoids pacemaker-induced cardiomyopathy (PICM) by achieving a "physiological" ventricular stimulation, via the native conduction system. Indications include various causes of bradycardia requiring anti-bradycardic pacing, inadequately controlled atrial fibrillation requiring AV node ablation and established PICM. In addition, HBP may also be used as an alternative therapy for patients with heart failure (HF) and an indication for cardiac resynchronization therapy (CRT). Available data show several advantages of HBP with regard to preservation or restoration of intra- and inter-ventricular synchronization; improvement in left ventricular ejection fraction, functional status and quality of life; decrease in atrial fibrillation incidence and improvement in HF hospitalization rates, compared with conventional pacing. Nevertheless, superiority in terms of mortality rates has not been consistently demonstrated, and the long-term efficacy and safety of HBP remain to be proven. In the present manuscript, we review the status of HBP and present our current experience with this novel pacing modality.

Physiologic lead placement with electroanatomic mapping: A case series.

INTRODUCTION: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) have emerged as attractive alternatives to traditional biventricular pacing to achieve cardiac resynchronization therapy. Early reported results have been inconsistent, particularly amongst patients in whom initial placement with traditional approaches has been unsuccessful or those with complex anatomy or congenital abnormalities. In this report, we describe the use of three-dimensional electroanatomic mapping (EAM) in five selected cases. METHODS: Five patients from multiple clinical sites underwent EAM-guided HBP or LBBAP by highly trained electrophysiologists with significant experience with conduction system pacing. Each patient in this series underwent EAM-guided conduction system pacing due to complex anatomy and/or prior failed lead implantation. RESULTS: EAM-guided lead implantation was successful in all five cases. Capture thresholds were relatively low and patients continued to have evidence of successful lead implantation with minimum 1-month follow-up. The fluoroscopy time varied, likely owing to the variable complexity of the cases. CONCLUSIONS: The use of EAM, in combination with traditional intracardiac electrograms with or without fluoroscopy, allows more targeted and precise placement of leads for HBP and LBBAP pacing. Further investigation is needed to determine this strategy's long-term performance and to optimize patient selection.

Permanent His-bundle pacing using distal His-bundle electrogram-guided approach in patients with atrioventricular block.

BACKGROUND: Permanent His-bundle pacing (HBP) is effective and safe; however, the success rate of HBP is low, especially in patients with infranodal block. This study aimed to assess the efficacy and feasibility of HBP implantation using an electrophysiological guided approach targeting a distal His-bundle electrogram (HBE) in patients with atrioventricular block (AVB). METHODS: Thirty-four consecutive patients with AVB (infranodal block in 28 patients) who underwent HBP were enrolled. During implantation, we attempted to target the distal part of the HBE (distal HBE) beyond the block site based on unipolar mapping. The His-capture threshold was evaluated for 1 year after implantation. RESULTS: HBP was achieved in 26 patients and in 21 patients (75%) with infranodal block. Detection of distal HBE was significantly higher in the successful HBP group than in the HBP failure group (65.4% vs. 0%, p = .001). Among 15 patients with intra-Hisian block, 14 patients (93%) successfully achieved HBP with distal HBE detection. During the 1-year follow-up period, an increase in His-capture threshold by ≥1.0 V at 1.0 ms occurred in five (19.2%) of 26 patients. The increased His-capture threshold group exhibited significantly less detection of distal HBE (20% vs. 76.2%; odds ratio 0.078, 95% confidence interval 0.07-0.87, p = .038) and a higher His-capture threshold at implantation (2.0 ± 1.1 V vs. 1.1 ± 0.9 V; odds ratio 1.702, 95% confidence interval 1.025-2.825, p = 0.04) than the non-increased His-capture threshold group. CONCLUSION: HBP implantation guided by distal HBE approach may be feasible with subsequent stable pacing in patients with intra-Hisian and atrioventricular nodal block.

Pseudo-elevation of conduction system pacing threshold through parallel connection of an intracardiac electrogram recording system.

Parallel connection of an electrophysiology recording system (EP system) to equipment for conduction system pacing (CSP) has been widely used for fine monitoring of intracardiac electrograms and pacing evaluation. We experienced a case showing unexpected pacing threshold exacerbation under specific conditions when the EP system was connected in parallel. We evaluated the underlying mechanism using an ex vivo model. An ex vivo pacing and intracardiac electrogram monitoring model was generated using an oscilloscope, pacing system analyzer (PSA), EP system, and simulated heart. The discrepancy between expected output at the PSA and the actual measured output value at the simulated heart was measured under various conditions and using various combinations of pacing equipment. Parallel connection of the EP system was associated with reduced electrical output from the PSA as recorded at the simulated heart. The unexpected adverse effects were particularly noticeable when using an RMC-5000 EP system with the pacing function on. The trouble is completely resolved by simply turning off the pacing function of the system. There is a possibility that the EP system might increase the pacing threshold in CSP when the PSA and EP system is are deployed in parallel. The issue may provoke pseudo failure of CSP due to the high pacing threshold. When the RMC-5000 is used for conduction system pacing in parallel with a PSA for the pacing test, the pacing function of RMC-5000 should be turned off.