Ventricular Conduction Research Articles

Nurses’ Knowledge and Attitudes toward Pacemaker: A Cross-Sectional Study

Despite the critical role of pacemakers in managing symptomatic atrioventricular and ventricular conduction abnormalities, there remains a significant gap in the knowledge and attitudes of nurses towards these devices. This study assesses the understanding and perceptions of pacemakers among nurses in Al-Basrah Governorate hospitals, exploring associations with demographic factors such as age, gender, educational level, years of experience, and training. Employing a descriptive methodology, a non-probability sample of 200 nurses from five hospitals (Abi Al-Khasib General Hospital, Umm Qasr General Hospital, Al-Zubair General Hospital, Al-Shifaa Hospital, and Al-Mawani Teaching Hospital) was surveyed from October 15, 2022, to August 15, 2023. Content validity was ensured by engaging eleven professionals, while reliability was assessed using Cronbach's Alpha. Results indicate a concerning deficiency in pacemaker-related knowledge, with 79.5% of nurses demonstrating poor knowledge, 18% showing intermediate knowledge, and only 2.5% exhibiting high knowledge. Similarly, attitudes were predominantly negative, with 81.5% of nurses expressing low enthusiasm towards pacemakers, while 11% and 7.5% displayed intermediate and high attitudes, respectively. These findings highlight the need for targeted educational interventions aimed at enhancing nurses' competence and attitudes concerning pacemakers to improve postoperative care and management outcomes for patients with these devices. Highlights: Knowledge Gap: A significant 79.5% of nurses show insufficient knowledge of pacemakers, indicating a critical need for improved medical education. Attitudinal Barriers: Over 81% of nurses have negative attitudes towards pacemakers, which may affect patient care quality. Training Requirement: There's a clear need for specialized training programs for nurses on pacemakers to enhance their knowledge and attitudes, ultimately improving patient care. Keywords: Pacemaker Knowledge, Nursing Attitudes, Educational Interventions

Long-term outcome after catheter ablation for fascicular ventricular tachycardia in a single high-volume center in Germany

Abstract Background Idiopathic Fascicular Ventricular Tachycardia (IFVT) accounts for less than 10% of all VTs and represents the most common idiopathic ventricular tachycardia of the left ventricle. This study reports on clinical and procedural characteristics and the long-term outcome of patients undergoing catheter ablation of premature ventricular complexes (PVC) and ventricular tachycardias (VTs) arising in proximity of the left ventricular conduction system. Methods and results This study includes 27 patients (17 male, 45 ± 17 years; 10 females, 50 ± 11 years) who underwent electrophysiological examinations at a tertiary ablation center over a period of 14 years (2009 to 2022). Follow-up was performed via regular Holter-ECGs and clinical evaluations, or via structured follow-up within the prospective TRUST registry. In 21/27 patients (77.8%), the left posterior fascicle (LPF) was involved in the IFVT. In 4 (14.8%) the left anterior fascicle (LAF) was involved and in 2 (7.4%) patients an origin in the upper septal (US) area was demonstrated. 22/27 (81.5%) patients had a preserved left ventricular ejection fraction (LVEF) and only 5 (18.5%) patients had a LVEF less than 50% at the time of presentation. 14/27 (51.9%) patients presented with PVC or non-sustained VTs with the following distribution: 10 (71.4%) originating from the LPF, 3 (21.4%) from the LAF and 1 (7.1%) from the US. 21/27 (77.8%) patients presented with sustained VTs: 16 (76.2%) arising from the LPF, 4 (19%) from the LAF and 1 (4.8%) from the US. However, only 2 (7.4%) patients presented in sustained VT at the beginning of the EP procedure. In 16 (59.3%) patients a sustained VT was induced during the EP study via isoprenaline and/or programmed ventricular stimulation. Mean QRS duration of the VT was 124.5 ± 14.6 msec. In 21 (77.7%) patients only a retrograde approach was used, in 3 (11.1%) patients a retrograde and an additional transeptal approach and in only 3 (11.1%) patients solely a transeptal approach. Mean number of radiofrequency applications was 11.8 ± 12.6 (30 to 40 Watts, 27545.6 ± 30524.4 Joules). FVT ablation was acutely successful in 24 patients (88.9%). In 2 patients (7.4%) no ablation was performed due to inability to induce VT under sedation. 3/27 patients (11.1%) underwent re-ablation due to FVT recurrence after previous ablation procedures. Moreover, 3 (11.1%) additional patients underwent repeated VT ablations during follow-up, but the arrhythmia originated from a different LV area. No procedure-related complication occurred. In 4 patients (14.8%) left fascicular posterior block was caused by ablation and in 3 (11.1%) patients a complete left bundle block. Mean procedure time was 130 ± 48.9 minutes. Conclusion Ablation of FVT in a tertiary ablation center is associated with a high single procedural success rate of 88.9% during long-term follow-up, with a mild risk of fascicular injury. 11.1% of patients underwent re-ablation due to FVT recurrence.

Swiss national cardiac device registry: changing trends in pacemaker and ICD procedures over the last two decades

Abstract Background The Swiss National Device and Ablation Registry (SwissEPnet) provides a comprehensive database for cardiac pacemaker and ICD procedures. All Swiss centers performing device implantations are obliged to provide their data in this web-based platform. The purpose of this study was to provide an in-depth look at pacemaker and Implantable -defibrillator (ICD) statistics and changing trends over the course of the last 20 years. Methods and Results We analyzed the database of pacemaker and ICD procedures between January 1, 2003, and December 31, 2022. During the study period, a total of 124 458 pacemaker and cardiac resynchronization (CRT) procedures (mean age 77.7 years; 59.7% male) were performed in 73 centers while 29 133 ICDs and CRT-D procedures (mean age 63.63 years; 80.2 % male) were performed in 56 centers in Switzerland. While the number of pacemaker procedures doubled in 20 years and there has been a constant increase in the mean age of patients receiving a pacemaker, the number of ICD procedures has more than tripled and now plateaued with a mean age which remained stable over time. Throughout the study period, the main indications for de novo pacemaker implantations were AV block in 41.7% of patients, followed by sick sinus syndrome combined with tachy-bradycardia syndrome (29.6%) and atrial fibrillation (AF) with slow ventricular conduction (13.7%). The main indication for ICD implantation was primary preventive (66.7%). Since 2016 there has been a decline in primary preventive interventions. Fluoroscopy and procedure durations remained stable over time in pacemaker and ICD procedures. Newer technologies, such as leadless pacemakers and CRT procedures required more fluoroscopy time, but this has also decreased over time. While regular battery changes remained stable (80% in pacemakers, 68% in ICDs), the proportion of DDD and CRT upgrades has increased. The overall reintervention rate due to device-associated infections was 2.4% in pacemaker- and 2.8% in ICD procedures. Since 2013, there has been a steady increase in lead removals/extractions, which were performed mainly due to device-related infections, but also because of lead dysfunctions and worsening electrical parameters. Conclusions In the last 20 years, there was a pronounced increase in the number of pacemaker procedures and a marked increase in the number of ICD procedures which has plateaued now. In younger technologies there is decreasing trend in fluoroscopy time by stable procedure times. Overall, there is a constant increase in mean age of patients receiving a pacemaker, while the mean age of patients receiving an ICD did not change during follow up. Female patients are constantly younger and undergo ICD implantation significantly less often than men. Despite of a stable infection rate, there has been a significant increase in lead removal and extractions in Switzerland.

Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts.

Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts.

Ablate and pace with conduction system pacing, Rovigo's experience

Abstract Background Several clinical data demonstrate that atrio ventricular junction (AVJ) ablation, followed by cardiac pacing, in atrial fibrillation (AF) with uncontrollable heart rate is beneficial. There are still limited data about conduction system pacing (CSP) in that setting. Aims To analyse if this “ablate and pace” strategy is feasible with good electrical results (ECG and parameters) and clinical outcomes (heart failure (HF) admission, ejection fraction (EF) and NYHA class). To analyse also differences between his bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in this setting. Methods. This is an observational retrospective single center study involving 30 patients of which 11 had a HBP and 19 a LBBAP from March 2019 to June 2023 (medium follow up 33 ± 18 month). The implant procedure was performed with both stylet driven or lumenless lead. After 2 ± 2 weeks was performed the AVJ ablation. The electrical parameters were measured at the implant and every 6 – 12 months. The patients had an echocardiographic and clinical evaluation every 6 – 12 months. There was nobody with a NYHA class IV. Results The procedure was performed without complication in all patients. There were a rising in the EF (49,9 ± 14,6 vs 54,2 ± 10,4% p = 0.004). There weren’t HF admission and only 2 patients died (not for cardio–vascular causes) during follow up. There were also a decrease in NYHA class in every patient (at least one NYHA class less). 17 (57%) patients had normal ventricular conduction, only 4 (13%) had LBBB, 4 (13%) RBBB. There were not statistical difference between the QRS duration pre and after implant (129 ± 35 vs 125 ± 24 ms p = 0,06). The threshold measured at the implant were stable both in the HBP (0,75 ± 0,34 vs 1,3 ± 0,8 V @ 0,4 ms p = 0,14) and in the LBBAP (0,93 ± 0,3 vs 0,89 ± 0,3 V @ 0,4 ms p = 0,49). The LBBAP presented higher values of sensing compared with HBP (17,5 ± 7,4 vs 6,3 ± 3,3 mV p = 0,04) and less procedural (63 ± 32 vs 95 ± 41 min, p = 0,02) and fluoroscopic time (2,6 ± 2,4 vs 7,5 ± 4,1 min, p = 0,04) compared with HBP. Conclusion The CSP is feasible and safe in the setting of “ablate and pace” and results in a clear increasing in EF and clinical status of patients with good and stable ECG features and electrical parameters during follow up; the CSP indeed represent a valuable alternative to BVP in this setting. LBBAP performed better than HBP in terms of procedural and fluoroscopic time and of higher sensing values.

Abstract 3105: Lamin Mutations: Single Nuclei Multiomic Analysis Reveals Endothelial Cell Dysfunction And Its Cardiovascular Implications

Background: LMNA-related dilated cardiomyopathy (DCM) or cardiolaminopathy is an autosomal dominant trait with complete penetrance resulting in left ventricular enlargement and cardiac dysfunction. LMNA mutations in DCM have been shown to cause to ventricular arrythmias and conduction deficits. The interplay between the LMNA gene and other cell types have yet to be fully elucidated. Notably, cardiolaminopathy patients present with prominent cardiac fibrosis, but the mechanistic link between LMNA mutations and the development of fibrosis remains inconclusive. Additionally, LMNA is expressed in the endothelium, and patients with cardiolaminopathy exhibit distinct endothelial dysfunction. Hypothesis: We hypothesize that LMNA mutations prompt a cascade of pathological alterations on the endothelium, causing vascular dysfunction and fibrosis through endothelial to mesenchymal transition (EndoMT). Aims: Next generation sequencing platforms are critical to identifying these epigenetic and transcriptomic changes in the endothelium. Combining sequencing technology with our iPSC platform, we aim to unravel the mechanism behind vascular dysfunction and fibrosis in LMNA-DCM to uncover novel therapeutic targets and treatment strategies. Methods: We performed single nuclei multiome (RNA and ATAC) on cardiac tissue from one patient with LMNA-dilated cardiomyopathy. Frozen tissues were minced into pieces before digestion. We then utilized patient-specific induced pluripotent stem cells (iPSCs) and CRISPR-generated isogenic controls. We differentiated to endothelial cells (iPSC-ECs) and nuclei capture was performed after 24hr flow. Results: Endothelial cell clusters from cardiac tissue exhibit increased stress and mesenchymal markers. Phenotypic shift and EC dysfunction was corroborated with iPSC-ECs derived from two LMNA-DCM patients. Conclusion: These results present important considerations highlighting vascular dysfunction in LMNA-DCM and notes the importance of the endothelium in cardiac health. By analyzing these datasets produced from LMNA-DCM cardiac tissue and our iPSC-EC platform, there is opportunity to both define the mechanisms that causes cardiac fibrosis and to develop new therapeutic strategies.

Cardiac resynchronization therapy for patients with mild to moderately reduced ejection fraction and left bundle branch block

BackgroundIt is unknown whether cardiac resynchronization therapy (CRT) would improve or halt the progression of heart failure (HF) in patients with mild to moderately reduced ejection fraction (HFmmrEF) and left bundle branch block (LBBB). ObjectiveThis study aimed to investigate the outcomes of CRT in patients with HFmmrEF and left ventricular conduction delay. MethodsA prospective, randomized clinical trial sponsored by the National Heart, Lung, and Blood Institute included 76 patients who met the study inclusion criteria (left ventricular ejection fraction [LVEF] of 36%–50% and LBBB). Patients received CRT-pacemaker and were randomized to CRT-OFF (right ventricular pacing 40 beats/min) or CRT-ON (biventricular pacing 60–150 beats/min). At a 6-month follow-up, pacing programming was changed to the opposite settings. New York Heart Association class, N-terminal pro–brain natriuretic peptide levels, and echocardiographic variables were collected at baseline, 6 months, and 12 months. The primary study end point was the left ventricular end-systolic volume (LVESV) change from baseline, and the primary randomized comparison was the comparison of 6-month to 12-month changes between randomized groups. ResultsThe mean age of the patients was 68.4 ± 9.8 years (male, 71%). Baseline characteristics were similar between the 2 randomized groups (all P > .05). In patients randomized to CRT-OFF first, then CRT-ON, LVESV was reduced from baseline only after CRT-ON (baseline, 116.1 ± 36.5 mL; CRT-ON, 87.6 ± 26.0 mL; P < .0001). The randomized analysis of LVEF showed a significantly better change from 6 to 12 months in the OFF-ON group (P = .003). LVEF was improved by CRT (baseline, 41.3% ±.7%; CRT-ON, 46.0% ± 8.0%; P = .002). In patients randomized to CRT-ON first, then CRT-OFF, LVESV was reduced after both CRT-ON and CRT-OFF (baseline, 109.8 ± 23.5 mL; CRT-ON, 91.7 ± 30.5 mL [P < .0001]; CRT-OFF, 99.3 ± 28.9 mL [P = .012]). However, the LVESV reduction effect became smaller between CRT-ON and CRT-OFF (P = .027). LVEF improved after both CRT-ON and CRT-OFF (baseline, 42.7% ± 4.3%; CRT-ON, 48.5% ± 8.6% [P < .001]; CRT-OFF, 45.9% ± 7.7% [P = .025]). ConclusionCRT for patients with HFmmrEF significantly improves LVEF and ventricular remodeling after 6 months of CRT. The study provides novel evidence that early CRT benefits patients with HFmmrEF with LBBB.

Signal-averaged electrocardiography as a noninvasive tool for evaluating the ventricular substrate in patients with nonischemic cardiomyopathy: reassessment of an old tool.

Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

Assessment of left ventricular activation conduction during left bundle branch area pacing in heart failure patients: A novel criterion to determine left bundle branch capture

Assessment of left ventricular activation conduction during left bundle branch area pacing in heart failure patients: A novel criterion to determine left bundle branch capture

Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart.

Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function. To address this, we have generated a mouse model with a cardiomyocyte-specific knockout of PFKFB2 (cKO). Using 9-month-old cKO and control mice, we characterized the impacts of PFKFB2 on cardiac metabolism, function, and electrophysiology. cKO mice have a shortened life span of 9 months. Metabolically, cKO mice are characterized by increased glycolytic enzyme abundance and pyruvate dehydrogenase activity, as well as decreased mitochondrial abundance and beta oxidation, suggesting a shift toward glucose metabolism. This was supported by a decrease in the ratio of palmitoyl carnitine to pyruvate-dependent mitochondrial respiration in cKO relative to control animals. Metabolomic, proteomic, and Western blot data support the activation of ancillary glucose metabolism, including pentose phosphate and hexosamine biosynthesis pathways. Physiologically, cKO animals exhibited impaired systolic function and left ventricular dilation, represented by reduced fractional shortening and increased left ventricular internal diameter, respectively. This was accompanied by electrophysiological alterations including increased QT interval and other metrics of delayed ventricular conduction. Loss of PFKFB2 results in metabolic remodeling marked by cardiac ancillary pathway activation. This could delineate an underpinning of pathologic changes to mechanical and electrical function in the heart.

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

Defining Transcriptomic Heterogeneity between Left and Right Ventricle-Derived Cardiac Fibroblasts.

Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV- and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy murine left and right ventricles indicated that LV-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the RV. Single-cell RNA-sequencing analysis of the two populations confirmed that Postn+ CFs were more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed a unique expansion of two less-well-characterized CF subpopulations (Igfbp3+ and Inmt+). These findings demonstrate that LV- and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform on whether LV and RV fibrosis require distinct treatments.

Chemical ablation of the left ventricular endocardium reduces ventricular fibrillation inducibility in acute ischemic canine heart.

Ventricular fibrillation remains as the major cause of death in patients with acute myocardial infarction. Effects of trans-atrial chemical ablation of the left ventricular (LV) endocardium with Lugol's solution on ventricular fibrillation inducibility and ventricular conduction were examined in canines with acute myocardial ischemia. Chemical ablation of the LV endocardium with Lugol's solution or normal saline was preformed through a left atrial appendage in 14 canines 30 min after occlusion of the left anterior coronary artery. Ventricular fibrillation threshold decreased after the coronary artery occlusion and increased after endocardial chemical ablation. There was a significant difference in the ventricular fibrillation threshold after chemical ablation between with Lugol's solution and with normal saline (25.9 ± 9.2 mA vs. 11.3 ± 2.7 mA, p < .01). QRS width significantly increased from 88 ± to 116 ± (p < .01) after the chemical ablation with Lugol's solution, and the activation map of the ventricles demonstrated a left bundle branch block ventricular conduction pattern. Histological examination of the LV endocardium showed lymphocyte infiltration for a depth of 1 mm. Chemical ablation of the LV endocardium with Lugol's solution injures endocardial conduction system and increases ventricular fibrillation threshold in the early phase of myocardial ischemia in canines. The procedure may be useful in suppressing intractable ventricular tachyarrhythmias in patients with acute myocardial ischemia.

Mannitol and hyponatremia regulate cardiac ventricular conduction in the context of sodium channel loss of function.

Scn5a heterozygous null (Scn5a+/-) mice have historically been used to investigate arrhythmogenic mechanisms of diseases such as Brugada syndrome (BrS) and Lev's disease. Previously, we demonstrated that reducing ephaptic coupling (EpC) in ex vivo hearts exacerbates pharmacological voltage-gated sodium channel (Nav)1.5 loss of function (LOF). Whether this effect is consistent in a genetic Nav1.5 LOF model is yet to be determined. We hypothesized that loss of EpC would result in greater reduction in conduction velocity (CV) for the Scn5a+/- mouse relative to wild type (WT). In vivo ECGs and ex vivo optical maps were recorded from Langendorff-perfused Scn5a+/- and WT mouse hearts. EpC was reduced with perfusion of a hyponatremic solution, the clinically relevant osmotic agent mannitol, or a combination of the two. Neither in vivo QRS duration nor ex vivo CV during normonatremia was significantly different between the two genotypes. In agreement with our hypothesis, we found that hyponatremia severely slowed CV and disrupted conduction for 4/5 Scn5a+/- mice, but 0/6 WT mice. In addition, treatment with mannitol slowed CV to a greater extent in Scn5a+/- relative to WT hearts. Unexpectedly, treatment with mannitol during hyponatremia did not further slow CV in either genotype, but resolved the disrupted conduction observed in Scn5a+/- hearts. Similar results in guinea pig hearts suggest the effects of mannitol and hyponatremia are not species specific. In conclusion, loss of EpC through either hyponatremia or mannitol alone results in slowed or disrupted conduction in a genetic model of Nav1.5 LOF. However, the combination of these interventions attenuates conduction slowing.NEW & NOTEWORTHY Cardiac sodium channel loss of function (LOF) diseases such as Brugada syndrome (BrS) are often concealed. We optically mapped mouse hearts with reduced sodium channel expression (Scn5a+/-) to evaluate whether reduced ephaptic coupling (EpC) can unmask conduction deficits. Data suggest that conduction deficits in the Scn5a+/- mouse may be unmasked by treatment with hyponatremia and perinexal widening via mannitol. These data support further investigation of hyponatremia and mannitol as novel diagnostics for sodium channel loss of function diseases.

Development of the Cardiac Conduction System.

The electrical impulses that coordinate the sequential, rhythmic contractions of the atria and ventricles are initiated and tightly regulated by the specialized tissues of the cardiac conduction system. In the mature heart, these impulses are generated by the pacemaker cardiomyocytes of the sinoatrial node, propagated through the atria to the atrioventricular node where they are delayed and then rapidly propagated to the atrioventricular bundle, right and left bundle branches, and finally, the peripheral ventricular conduction system. Each of these specialized components arise by complex patterning events during embryonic development. This chapter addresses the origins and transcriptional networks and signaling pathways that drive the development and maintain the function of the cardiac conduction system.

Visualization of Left Ventricular Endocardium Activation Time during Cardiac Conduction System Pacing

Introduction. Right ventricular myocardial pacing leads to asynchronous contraction of the left ventricle (LV) and can impair its contractility over time. Stimulation of the conduction system of the heart ensures physiological activation of the ventricles.&#x0D; The aim. To visualize the pattern of propagation of the electrical front on the activation map of the LV endocardium during conduction system pacing and during right ventricular myocardial pacing.&#x0D; Materials and methods. In two patients with the conduction system pacing, who were operated at the National Amosov Institute of Cardiovascular Surgery, invasive LV activation mapping was performed on various options of cardiac pacing using the EnSite Precision TM navigation system. One patient with complete atrioventricular block had nonselective His bundle pacing. The second patient had dilated cardiomyopathy and indications for cardiac resynchronization therapy and ablation of the atrioventricular junction due to chronic tachyform of atrial fibrillation. After an unsuccessful attempt to place LV lead in coronary sinus, a lead for left bundle branch pacing was implanted. Different activation maps of the LV endocardium were built in two patients with two types of cardiac pacing: right ventricular myocardial pacing and cardiac conduction system pacing.&#x0D; Results. The total LV endocardial activation time was significantly different in the two studied patients with different pacing options. In a patient with non-selective stimulation of His bundle, the total LV endocardial activation time was 43 ms (QRS width 126 ms, the interval from the stimulus to the peak of the R wave in lead V6 78 ms). After switching to right ventricular myocardial pacing with a decrease in the pacing amplitude, the total LV endocardial activation time prolonged to 90 ms (QRS width 165 ms, the interval from the stimulus to the peak of the R wave in lead V6 117 ms). In a patient with left bundle branch pacing, total LV endocardial activation time was 51 ms (QRS width 160 ms, the interval from the stimulus to the peak of the R wave in lead V6 66 ms). With switching exclusively to right ventricular pacing the total LV endocardial activation time prolonged to 93 ms (stimulated QRS width 180 ms). At the same time, the activation pattern of the LV endocardium was significantly different, since the right ventricular lead was located closer to the apex.&#x0D; Conclusions. Conduction system pacing provides rapid physiological LV activation and potentially avoids the negative consequences of asynchronous slow ventricular activation during right ventricular pacing.

Is left bundle branch pacing (LBBP) associated with better depolarization and repolarization kinetics than right ventricular mid septal pacing (RVSP)? - Comparison of frontal QRS -T angle in patients with LBBP, RVSP and normal ventricular conduction

AimsTo assess the frontal QRS- T angle (f QRS- T angle) in patients with left bundle branch pacing (LBBP) as compared to right ventricular mid septal pacing (RVSP) implanted for symptomatic high degree atrioventricular (AV) block and to compare with control subjects with normal ventricular conduction (CSNVC) MethodsA total of one-fifty subjects were chosen (50 patients with LBBP, 50 patients with RVSP and 50 CSNVC). The indication for pacemaker implantation was symptomatic high degree AV block. Baseline clinical and electrocardiogram (ECG) parameters like QRS duration (QRSD), QRS axis and f QRS-T angle and Ejection Fraction (EF) were assessed. f QRS-T angle was measured as the difference between the computerised mean frontal QRS and T wave axes in the limb leads. If the difference between the QRS axis and T-wave axis exceeds 180°, then the resultant QRS-T angle would be calculated as 360° minus the absolute angle to obtain a value between 0° and 180°. Baseline, immediate post procedural and 6 month follow up (f/u) ECGs and EF were chosen for the analysis. ResultsPatients who underwent LBBP had significantly shorter paced QRSD than patients who had undergone RVSP (112 ± 12 ms vs 146 ± 13 ms; 95 % confidence interval (CI): 43, −31; p<0.001). There was no significant difference in the QRSD before and after LBBP. The QRSD before and after pacing in RVSP was 111 ± 27 ms and 146 ± 13 ms; 95 % CI: 43, −28; p < 0.001. The QRSD in control patients with NVC was 82.94 ± 9.59 ms.RVSP was associated with wider f QRS-T angle when compared with LBBP (103 ± 53° vs 82 ± 43°; 95 % CI: 39, −1.0; p = 0.037). The baseline and immediate post procedure f QRS-T angle in LBBP was 70 ± 48° and 82 ± 43°; 95 % CI: 31, 5.3; p = 0.2. At 6 months f/u, the f QRS-T angle was 61 ± 43°; 95 % CI: 8.5, 35; p=0.002. The baseline and immediate post procedure f QRS-T angle in RVSP was 67 ± 51° and 103 ± 53°; 95 % CI: 54, −17; p < 0.001. At 6 months f/u, the f QRS-T angle in RVSP group was 87 ± 58°; 95 % CI: 2.6, 29; p = 0.020. The f QRS T angle in control patients with NVC was 24 ± 16°. When subgroup analysis was done the difference in the f QRS-T angle was significant between RVSP and LBBP groups only in patients who had wide QRS escape.The mean LVEF at 6-month follow-up in LBBP vs RVSP was 61 ± 3.7 % vs 57.1 ± 7.8 %; 95 % CI:1.48, 6.32, p = 0.002. In the RVSP group, three patients developed pacing induced cardiomyopathy (PIC) whereas no patients in the LBBP group developed PIC at 6-month follow-up; p=0.021. One patient with PIC had deterioration of functional status with new onset HF symptoms. The patient symptoms improved with medical therapy and needed no hospitalisation. The patient declined further interventions including upgradation to CRT or LBB pacing. No deaths or ventricular arrhythmias were observed during the study period. ConclusionLBBP is associated with narrower f QRS-T angle as compared to RVSP both at post implant period and at 6 month f/u period. These findings might be due to the more physiological depolarization and repolarization kinetics associated with LBBP. RVSP was associated with 6 % incidence of PIC. Hence wide f QRS-T angle might be a predictor of PIC.

Navigating the Complexity: A Comprehensive Review of Managing Pregnancy in Complete Heart Block Cases.

This review explores the comprehensive management of pregnancy in cases of complete heart block, a cardiac condition characterized by the dissociation between atrial and ventricular conduction. The review begins with a thorough examination of preconception counseling, emphasizing the assessment of maternal health, the evaluation of cardiac function, and the identification of potential risks. Subsequently, the medical management section delves into using beta-blockers, pacemakers, and antiarrhythmic drugs to monitor cardiac function during pregnancy and adjust medication regimens. Obstetric considerations highlight the importance of antenatal care, fetal monitoring, and thoughtful delivery planning, including the choice between vaginal delivery and cesarean section. The section on complications underscores the risks of arrhythmias, heart failure, premature birth, and neonatal cardiac issues. Looking ahead, the future directions and research section explores ongoing studies in genetics, pharmacology, and technological innovations, envisioning potential advancements in pacing technology and personalized medicine approaches. The conclusion synthesizes key findings, offering recommendations for clinical practice and reflecting on the challenges and opportunities inherent in managing pregnancy in complete heart block cases. The multidisciplinary approach emerges as paramount, with collaborative efforts paving the way for improved patient outcomes and advancements in the field.

Empagliflozin treatment rescues abnormally reduced Na+ currents in ventricular cardiomyocytes from dystrophin-deficient mdx mice.

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle illness caused by mutations in the gene encoding for the intracellular protein dystrophin. A major source for arrhythmia vulnerability in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant circuits. Using the dystrophin-deficient mdx mouse model for human DMD, we previously reported that the lack of dystrophin causes a significant loss of peak Na+ current (INa) in ventricular cardiomyocytes. This finding provided a mechanistic explanation for ventricular conduction defects and concomitant arrhythmias in the dystrophic heart. In the present study, we explored the hypothesis that empagliflozin (EMPA), an inhibitor of sodium/glucose cotransporter 2 in clinical use to treat type II diabetes and nondiabetic heart failure, rescues peak INa loss in dystrophin-deficient ventricular cardiomyocytes. We found that INa of cardiomyocytes derived from mdx mice, which had received clinically relevant doses of EMPA for 4 wk, was restored to wild-type level. Moreover, incubation of isolated mdx ventricular cardiomyocytes with 1 µM EMPA for 24 h significantly increased their peak INa. This effect was independent of Na+-H+ exchanger 1 inhibition by the drug. Our findings imply that EMPA treatment can rescue abnormally reduced peak INa of dystrophin-deficient ventricular cardiomyocytes. Long-term EMPA administration may diminish arrhythmia vulnerability in patients with DMD.NEW & NOTEWORTHY Dystrophin deficiency in cardiomyocytes leads to abnormally reduced Na+ currents. These can be rescued by long-term empagliflozin treatment.

The Role of MAPRE2 and Microtubules in Maintaining Normal Ventricular Conduction.

Brugada syndrome is associated with loss-of-function SCN5A variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within MAPRE2, which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome. A mapre2 knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with cdh2 tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with MAPRE2 knockdown and knockout, respectively. Voltage mapping of mapre2 knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with mapre2 loss of function, associated with a decrease of detyrosinated tubulin. MAPRE2 knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of ttl encoding tubulin tyrosine ligase in mapre2 knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential. Genetic ablation of mapre2 led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with ttl knockdown led to rescue of voltage-gated sodium channel-related functional parameters in mapre2 knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction.