Cardiac Conduction Disorders Research Articles

Long-term prognosis of patients with an SCN5A loss-of-function variant and progressive cardiac conduction disorder or Brugada syndrome

The long-term prognosis of patients with a loss-of-function variant in the cardiac sodium channel gene SCN5A is unknown. This study aimed to evaluate the long-term arrhythmic risk in patients with an SCN5A loss-of-function variant to identify predictors of arrhythmic events. Probands and family members with (likely-)pathogenic SCN5A loss-of-function variants were retrospectively included. Clinical and ECG data at baseline and last follow-up were collected. Patients with a history of cardiac arrest, sustained ventricular tachycardia, symptomatic or documented atrial tachy- or bradyarrhythmia, or arrhythmogenic syncope, were categorized as symptomatic. Arrhythmic events at follow-up were defined as sudden death, aborted cardiac arrest, documented ventricular fibrillation and/or sustained ventricular tachycardia. We included 615 patients (349 males, 242 probands, 157 spontaneous type-1 Brugada-ECG and 111 symptomatic at baseline). During 9.5 (5.0-14.3) years follow-up, arrhythmic events occurred in 41 patients (6.7%), equating an overall event rate of 0.7%/year; 2.0%/year in symptomatic and 0.3%/year in asymptomatic patients. In the overall study population, symptoms at baseline, male sex, and QRS prolongation were identified as independent predictors of arrhythmic events. In asymptomatic patients, also male sex and QRS prolongation were identified as predictors. Asymptomatic women with QRS <100ms did not experience arrhythmic events at follow-up. Key predictors of arrhythmic risk in patients with an SCN5A loss-of-function variant, regardless of a Brugada syndrome diagnosis, are symptoms at baseline, male sex, and prolonged QRS. Our findings may enable more tailored management strategies in patients with an SCN5A loss-of-function variant based on their individual risk profiles.

Improved outcomes with leadless vs. single-chamber transvenous pacemaker in haemodialysis patients.

Cardiac conduction disorders are common in haemodialysis patients, with a relatively high rate of pacemaker implantations. Pacemaker-related complications, especially lead infections and central venous stenosis, pose significant challenges in this population. This study aims to compare single-chamber leadless pacemaker to single-chamber transvenous pacemakers in terms of survival and related complications in haemodialysis patients. This retrospective study included adult haemodialysis patients who received a first single-chamber transvenous or leadless pacemaker between January 2017 and December 2020. Data were obtained from the French national REIN registry matched to the national health databases (Système National des Données de Santé). Propensity score matching was used to balance baseline characteristics. Survival and complications were compared between groups by Cox regression and by competitive risk models, respectively. One hundred and seventy-eight patients were included after propensity score matching, with 89 patients in each group. The median follow-up time was 24 (range 7-37) months. Leadless pacemakers were associated with significantly lower all-cause mortality rates compared to transvenous pacemakers [hazard ratio (HR) = 0.68, 95% confidence interval (CI) (0.47-0.99)]. Device-related infections are significantly lower with leadless pacemakers throughout the follow-up period (HR 0.43, 95% CI 0.21-0.86). Leadless pacemaker recipients also required fewer vascular access interventions [odds ratio 0.53, 95% CI (0.33-0.68)] on arteriovenous fistula. With the limitations of its observational design, this study suggests that leadless pacemakers are associated with a lower rate of complications and better survival as compared with transvenous VVI pacemakers in haemodialysis patients, supporting to consider their preferential use in this population.

Temporal Changes in Cardiac Conduction Disorders in Patients with ESKD on Long-Term Hemodialysis

Temporal Changes in Cardiac Conduction Disorders in Patients with ESKD on Long-Term Hemodialysis

Editorial: Is There a Relationship/An Association Between ABO Blood Group System and Cardiac Conduction Disorders?

Abstract Introduction Data from the literature suggest a slight increase in cardiovascular risk for people with non-O blood types. The purpose of the study was to evaluate if there is an association between advanced cardiac conduction disorders and blood groups. Material and methods In this retrospective study, a group of patients with atrio-ventricular conduction disorders or sinus node disease, having an indication for permanent cardiostimulation, was analyzed and compared with a control group consisting of patients who underwent coronary angiography or elective peripheral angiography. The blood group was determined in all patients. Univariate and multivariate statistical methods were used. Results Six hundred forty patients, mean age 72±11y, 55.3% men, were included: 320 patients with advanced atrio-ventricular conduction disorders or sinus node dysfunction in the study group and 320 patients in the control group. Blood type A had the highest prevalence (46.8%), followed by blood types O (28.95%), B (16.74%) and AB (7.51%). In the group with heart rhythm disorders, patients with blood type A had an increased risk of atrio-ventricular block (OR 1.38, p= 0.02), but not with sinus node disease (OR 1.02, p= 0.98). Blood type O had a protective role both for atrio-ventricular block and for sinus node dysfunction (OR 0.65, p= 0.01). Conclusion Blood type A proved to be an independent predictor for atrio-ventricular conduction disorders in patients with severe heart rhythm disorders with indication for permanent cardiostimulation.

Possibilities of predicting the risk of developing cardiac conduction disorders after transcatheter aortic valve replacement

Introduction. Cardiac conduction disturbances with the subsequent need for pacemaker implantation are a major clinical problem in the postoperative period of transcatheter aortic valve implantation (TAVI). The aim of the study. To develop multifactorial models for predicting the risk of developing cardiac conduction disturbances and pacemaker implantation after TAVI in the early postoperative period on a "training" sample of patients with an assessment of the diagnostic accuracy of the developed model on a "control" sample of patients. Material and methods. The study included 337 patients with severe or critical aortic stenosis who underwent TAVI from 2021 to 2022 in the laboratory of hybrid methods in the Department of cardiovascular surgery, Chazov National Medical Research Center, Ministry of Health of the Russian Federation Results. In constructing a model for predicting new (not registered before the operation) cardiac conduction disturbances after TAVI, the most significant predictors were: intraventricular conduction disturbances, the size of the aortic root, and the end-diastolic size of the left ventricle. The quality indicators of the model: AUC 0.711 (95 % CI: 0.644-0.778), sensitivity 77.7 % (95 % CI: 67.9-85.6), specificity 56.6 % (95 % CI: 47.8-65.1), PPV 55.3% (95 % CI: 46.5-67.9), NPV 78.5% (95 % CI: 69.1-84.0). Results of testing in the "control" sample: AUC 0.723 (95 % CI: 0.615-0.832). For the pacemaker implantation risk model predictors were: right bundle branch block, coronary heart disease and atrioventricular conduction disturbances. Model quality indicators: AUC 0.789 (95 % CI: 0.683-0.894), sensitivity 94.1 % (95% CI: 71.3-99.8), specificity 53.9 % (95 % CI: 47.0-60.7), PPV 13.8 % (95% CI: 10.8-87.0), NPV 99.2 % (95 % CI: 94.7-99.4). Results of verification on the control sample: AUC 0.795 (95 % CI 0.664-0.925). Discussion. The proposed models can be used in practice to assess the risk of developing cardiac conduction disorders and pacemaker implantation in patients who are scheduled to TAVI.

Diagnostic capability of long-term electrocardiographic telemonitoring for detection of heart rhythm disorders

prevalence of cardiac rhythm and conduction disorders is increasing and associated with the growing amount of people of older age groups. The extended use of traditional electrocardiography (ECG) recorders is currently limited due to duration of the investigation, possible skin irritation and withdrawal of consent by the patients. The aim: evaluation of the frequency of arrythmia incidents in adult patients of different ages by assessing the patch monitoring results, and the impact of the monitoring duration on the possibility of diagnosis. Materials and methods: study included 1123 patients aged from 18 to 99 (599 women and 524 men), data about whom was collected in 2021-2022. ECG was recorded by the «Mawi Heart patch» – a single-use dual-channel device for continuous ECG recording for up to2 7 days. Results: the average ECG monitoring time was 81,03±18,5 hours or 3,37±0,7 days. The majority of the participants (74,35%) received the continuous 3-day ECG monitoring. Most rhythm disorders were recorded in the first 24 hours, but over the next 2 days, atrial fibrillation (AF) was detected in 7,66%, more often in men (48 participants, p=0,048) and with some differences in age groups. Starting above 50 years of age, the frequency of AF diagnosing on the first monitoring days is decreased and it is significantly statistically lower (61,11%, p&lt;0,05). Three-day ECG monitoring is associated with a higher chance of detecting AF (OR=2,03; 1,53-3,02, p=0,031) regardless of gender, while the 5-day monitoring wasn’t as effective. The prolonging of the monitoring time increased the number of diagnosed supraventricular tachycardia (SVT) cases by 5,53% in men and 8,35% in women. The 3 days of monitoring are associated with a higher chance of SVT detection (OR = 4,18; 3,32–4,95, p=0,009). There is a direct correlation between SVT detection and the older age groups (r=0,53, p&lt;0,05). SVT detection is higher in patients of 71-80 years old (OR = 2,71; 2,35–3,75, p=0,0041), and of 81-99 years (OR = 2,92; 2,56–3,49, p=0,0039). Conclusion: The frequency of arrhythmia detection, in patients referred to long-term patch monitoring, is high both for AF and SVT. The sex and age patterns for the prevalence of the described arrhythmias were statistically confirmed. The use of long-term ECG patch monitoring increases the chance of arrhythmia detection, primarily for older patients.

Improved diagnostic performance of high-sensitivity cardiac troponins in muscle dystrophies using comprehensive definition criteria for cardiac involvement: A longitudinal study on 35 patients.

Sparse information is available on the correct interpretation of elevated high-sensitivity cardiac troponin (hs-cTn) in confirmed muscular dystrophies. Serum concentrations of hs-cTn T (hs-cTnT) and hs-cTn I (hs-cTnI) were determined in 35 stable outpatients with confirmed skeletal muscle dystrophies. We calculated sensitivities, specificities, and positive and negative predictive values of hs-cTnT and hs-cTnI for identification of cardiac involvement using a comprehensive definition that included diastolic left ventricular and right ventricular function, strain analysis using two-dimensional transthoracic echocardiogram and magnetic resonance imaging, myocardial biopsies, and consideration of a variety of triggers for cardiac injury, including arrhythmias, conduction disorders, and hypoxemia due to respiratory failure. Cardiac involvement was diagnosed in 34 of 35 cases. Specificities of hs-cTnT increased from 12.5% to 100% (p = 0.0006) applying the comprehensive definition compared to a definition based on electrocardiography and echocardiography alone. At the recommended 99th percentile upper limit of normal, sensitivities were significantly lower for hs-cTnI than for hs-cTnT (29.4% vs. 100%, p = 0.0164). Conversely, the specificities of hs-cTnT and hs-cTnI increased to 100% when using the comprehensive definition criteria for diagnosing cardiac involvement. Elevated hs-cTnT but not hs-cTnI discriminates cardiac involvement in cases with confirmed skeletal muscle dystrophies with very high sensitivity and 100% specificity. Prior reports on worse performance may be explained by the use of less sensitive imaging methods or incomplete assessment of cardiac involvement.

Arrhythmias in Children with Acute Respiratory Viral Infections: Prevalence and Causes

The article presents literature review about arrhythmias in children with acute respiratory viral infections (ARVI). The search was carried out in such databases as PubMed, CyberLeninka, RSCI, etc. ARVI is the most common infectious disease in children and adults, and it can have severe course and various complications. Arrhythmias can be frequently revealed in children with ARVI, and most of them are transient. Life-threatening cardiac rhythm and conduction disorders (CRCD) may occur more rarely, especially in severe cases. Knowledge and interest in the pathophysiology of viral infections have increased significantly, including CRCD risk factors in ARVI, thanks to the data obtained during the analysis of COVID-19 clinical course and outcome. This review summarizes and analyzes data on CRCD prevalence and arrhythmogenesis causes in ARVI.

Coordinated Tbx3 / Tbx5 transcriptional control of the adult ventricular conduction system.

The cardiac conduction system (CCS) orchestrates the electrical impulses that enable coordinated contraction of the cardiac chambers. The T-box transcription factors TBX3 and TBX5 are required for cardiac conduction system development and associated with overlapping and distinct human cardiac conduction system diseases. We evaluated the coordinated role of Tbx3 and Tbx5 in the murine ventricular conduction system (VCS). We engineered a compound Tbx3:Tbx5 conditional knockout allele for both genes located in cis on mouse chromosome 5. Conditional deletion of both T-box transcriptional factors in the ventricular conduction system, using the VCS-specific Mink:Cre, caused loss of VCS function and molecular identity. Combined Tbx3 and Tbx5 deficiency in the adult VCS led to conduction defects, including prolonged PR and QRS intervals and elevated susceptibility to ventricular tachycardia. These electrophysiologic defects occurred prior to detectable alterations in cardiac contractility or histologic morphology, indicative of a primary conduction system defect. Tbx3:Tbx5 double knockout VCS cardiomyocytes revealed a transcriptional shift towards non-CCS-specialized working myocardium, suggesting reprogramming of their cellular identity. Furthermore, optical mapping revealed a loss of VCS-specific conduction system propagation. Collectively, these findings indicate that Tbx3 and Tbx5 coordinate to control VCS molecular fate and function, with implications for understanding cardiac conduction disorders in humans.

Physical Activity Modifies the Risk of Incident Cardiac Conduction Disorders Upon Inflammation: A Population-Based Cohort Study.

Emerging evidence suggests a central role for inflammation in cardiac conduction disorder (CCD). It is unknown whether habitual physical activity could modulate the inflammation-associated risks of incident CCD in the general population. This population-based cohort was derived from the China Kailuan study, including a total of 97 192 participants without prior CCD. The end points included incident CCD and its subcategories (atrioventricular block and bundle-branch block). Systemic inflammation was indicated by the monocyte-to-lymphocyte ratio (MLR). Over a median 10.91-year follow-up, 3747 cases of CCD occurred, with 1062 cases of atrioventricular block and 2697 cases of bundle-branch block. An overall linear dose-dependent relationship was observed between MLR and each study end point (all P-nonlinearity≥0.05). Both higher MLR and physical inactivity were significantly associated with higher risks of conduction block. The MLR-associated risks of developing study end points were higher in the physically inactive individuals than in those being physically active, with significant interactions between MLR levels and physical activity for developing CCD (P-interaction=0.07) and bundle-branch block (P-interaction<0.05) found. Compared with those in MLR quartile 2 and being physically active, those in the highest MLR quartile and being physically inactive had significantly higher risks for all study end points (1.42 [95% CI, 1.24-1.63], 1.62 [95% CI, 1.25-2.10], and 1.33 [95% CI, 1.13-1.56], respectively, for incident CCD, atrioventricular block, and bundle-branch block). MLR should be a biomarker for the risk assessment of incident CCD. Adherence to habitual physical activity is favorable for reducing the MLR-associated risks of CCD.

Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation

BackgroundGenetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. ObjectivesThis study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. MethodsWe performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). ResultsAmong 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). ConclusionsUnrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.

Requirement of β subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A.

Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.

A rare presentation of infective endocarditis: Phase 4 block of the left bundle branch as key for the diagnosis. A case report

Definitive diagnosis of infective endocarditis (IE) is mainly based on microbiological and imaging criteria. In a minority of cases, particularly when perivalvular area is involved, cardiac conduction disorders (CCD) may appear, which implies worse prognosis. In this scenario, different degrees of auriculoventricular block can occur, but development of bundle branch block is rare. Herein, we present a case of IE with negative initial imaging tests, where the occurrence of phase 4 bundle branch block after a sequence of type I second degree AV block was crucial to establish a definitive diagnosis and an optimal therapeutic approach.

Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices.

This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (ICa,L) in Guinea pig ventricular cardiomyocytes. Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated ICa,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes. Light pulses activated ICa,L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered ICa,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. OEPC-mediated activation of ICa,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of ICa,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.

Clinico-demographic Profile of Patients Receiving Permanent Pacemakers as Bradyarrhythmia Therapy: The Srinagar Registry

Introduction Cardiac conduction disorders can interrupt the normal electrical conduction in the heart and cause a decrease or cessation of pulse generation and a fall in organ perfusion in the body. This can lead to significant morbidity and mortality. This study was conceived to illustrate the clinical profile, presentation, management, and complications of bradyarrhythmia therapy in this population. Methods This descriptive cross-sectional study included prospective and retrospective data over a period of 16 years. All patient’s demographic data and data of any complications and adverse outcomes were documented. Results A total of 3489 cases having permanent pacemakers (PPMs) implanted in them were included in this study. There were 2254 (64.6%) men and 1235 (35.4%) were women. Age of the patients ranged from 25 to 100 years with a mean age of 62.9 ± 11.14 years. Mean ejection fraction of patients was 59.3 ± 2.57%. The indication for PPM implantation was complete heart block in 2079 (59.6%), sick sinus syndrome in 422 (12.1%), Mobitz type 2 heart block in 345 (9.9%), symptomatic left bundle branch block in 295 (8.5%), symptomatic bifasicular block in 176 (5.0%), symptomatic trifascicular block in 109 (3.1%), vasovagal syncope with symptomatic sinus bradycardia in 21 (0.6%), left anterior hemiblock with syncope in 3 (0.1%), and atrial fibrillation with heart block in 11 (0.3%) patients. Cardiac syncope was presented in 80%, presyncope in 15%, and 5% presented with features of chronotropic incompetence. No significant seasonal variation was observed in the incidence of PPM implantation. Single-chamber PPM was implanted in 58.8% and dual-chamber PPM in 41.2% of the cases. PPM-related complications were seen in 139 (3.98%) of the cases. Pneumothorax was seen in 21 (0.6%) of the cases, lead displacement in 39 (1.12%), lead replacement in 31 (0.89%), pocket site infection in 20 (0.57%), generator extrusion in 25 (0.70%), and lead extrusion in 3 (0.08%). Conclusion Conduction disorders affect men more than women and complete heart block is the most common form of conduction disorder in our population. There has been a significant improvement in bradyarrhythmia detection and its management, leading to wider penetration and safety of device therapy provided to the patient population.

Cardiac manifestations in myotonic dystrophy type 1

Aim. To characterize cardiac damage in myotonic dystrophy type 1 (MD1), which is the most common form of hereditary primary muscular pathology in adults.Material and methods. Forty-eight patients with MD1 (31 men, 17 women, mean age 39,2±9,3 years) underwent clinical examination, neuropsychological examination, lipid profile assessment, electrocardiography (ECG), Holter ECG monitoring, and echocar-diography. Four clinical cases are presented that demonstrate clear cardiac manifestations of MD1.Results. The patients did not complain of arrhythmias or chest pain, while 7 (14,6%) had complaints of exercise shortness of breath. Cardiac conduction disorders occurred in 18 (37,5%) patients, which were represented by firstand second-degree atrioventricular (AV) block, his bundle and intraventricular conduction disturbances. According to Holter monitoring, heart rate &lt;60 bpm was recorded in 46 (95,8%) patients, of which 2 (4,2%) were &lt;30 bpm. One (2.1%) patient had atrial fibrillation. According to echocardiography, ventricular enlargement was detected in 3 (6,3%) patients, and atrial enlargement — in 8 (16,7%). None of the patients had an ejection fraction &lt;50%.Conclusion. Cardiac involvement is a common manifestation of MD1. Full cardiac examination can help not only improve the quality of life of patients, but also avoid possible side effects of the prescribed treatment.

His bundle pacing implantation in octogenarian patients: a substudy of the PACE-CONDUCT trial

Abstract Background His bundle pacing (HBP) is gaining recognition as a valuable alternative for the management of various cardiac conduction disorders. This substudy, conducted within the framework of the PACE-CONDUCT trial, investigates the outcomes of HBP implantation in patients aged 80 years and older, comparing them with a younger cohort. Methods We examined a total of 61 consecutive patients who underwent HBP implantation, utilizing DDD pacemakers, CRT-P, or CRT-D devices, during the years 2021 to 2023. Patients were categorized into two subgroups: those aged younger than 80 years and those aged 80 years or older. The mean age of the entire cohort was 73 years, spanning from 51 to 86 years, with 15 patients (comprising 24.6% of the total) falling into the octogenarian category. His bundle threshold was assessed on the day of implantation, one day post-implantation, and four weeks post-implantation. All HBP implantations were deemed successful, incorporating both selective and non-selective His bundle pacing. Complications were classified as major (necessitating lead or pocket revision) or minor (requiring no revision). Threshold values were converted to volts per milliseconds (volts x milliseconds) for statistical analysis, conducted with IBM SPSS Statistics 29.0. Results Initial analysis revealed a consistent success rate of HBP implantation across all patients, with no discernible differences between the two age groups. Threshold measurements at the day of implantation and after one day indicated no differences between the younger and the older group. However, at the four-week mark, a statistically significant lower threshold of His bundle pacing was observed in the octogenarian group (one-sided p-value 0.028), suggesting a faster stabilization to the chronic threshold of the active fixation His Bundle lead. The comparison of major and minor complications between the age groups, conducted using chi-square tests, revealed no age-related discrepancies. Conclusions This substudy of the PACE-CONDUCT trial underscores the feasibility and safety of His bundle pacing implantation in octogenarian patients, comparable to their younger counterparts. While no initial threshold variations are observed, the octogenarian group demonstrated improved His bundle pacing thresholds approximately four weeks post-implantation. Importantly, the study revealed no heightened complication risk associated with advanced age, affirming that very old patients aged 80 or older can derive the benefits of His bundle pacing without increased complication rates. Given the relatively modest patient cohort in this study, further investigations are warranted to validate and extend these findings.T-tests and Chi square tests

Clinical characteristics and genetic substrate of lone atrial fibrillation: a single center experience

Abstract Background Juvenile-onset lone atrial fibrillation (LAF) may be the initial manifestation of a concealed channelopathy or cardiomyopathy (CMP) or it may be due to an atrial specific genetic susceptibility. Clinical characteristics, genetic background and proper management are still largely unknown. Purpose Aim of the present study is to describe the clinical and genetic characteristics of patients with juvenile-onset LAF. Methods We enrolled patients referred to our center for ablation between 1/2018 and 11/2023 with a first diagnosis of LAF before the age of 60, a structurally normal heart (absence of known CMP, ischemic, valvular, congenital heart disease) and no overt channelopathy. A concealed Brugada syndrome was systematically excluded. Genetic testing was performed using Next Genome Sequencing and a dedicated gene panel. Results 89 patients were included (84% male, LAF onset 43 ± 8 years, BMI 25 ± 7 kg/m2): 32% had a first-degree family history of AF (including 15% below 60 years), 18% of sudden death, 8% of cardiac conduction disorders and 2% of CMP. Cardiovascular risk factors included arterial hypertension in 24%, smoking in 47% and obstructive sleep apnea syndrome in 4%; 20% were competitive athletes. Most patients (89%) presented with paroxysmal AF and 92% were symptomatic (mainly palpitations). At presentation LVEF was 61±5% and LAVI 35±14 ml/m2. Median follow-up time after the first AF episode was 6 years (IQR 4-10). Most patients (81, 91%) underwent at least one transcatheter ablation procedure after failed anti-arrhythmic drug (AAD) therapy (mostly IC). The first procedure (73% radiofrequency, 27% cryoablation) included pulmonary veins isolation (PVI) in all and additional lesions in 5%; the second procedure (n=18, 22% of the ablation group) included PV re-isolation in all (mostly due to multiple vein reconnections) and additional lesions in 17%; the third procedure (n=8, 10% of the ablation group) included PV re-isolation in 25% and additional lesions in 75%. The remaining 8 patients were treated with AAD only (mostly IC). By the last follow-up, 7% of patients in the ablation group and 25% in the AAD group had documented recurrences (even though 50% of those who received ablation were still on AAD). Among the 35 patients subjected to genetic investigation, 10 have available results: 30% tested positive for C4-C5 variants (2 for KCNQ1, 1 for TTN), 50% for C3 variants (RYR2, ABCC9, LMNA, KCNH2 and RMB20) and 20% were negative. Conclusions In the present single center cohort of patients with juvenile-onset LAF, a positive family history was found in almost one third of patients. Despite prompt diagnosis and treatment (including &amp;gt;1 ablation in 20% of patients), recurrences rate is not trivial. The yield of genetic test so far is high, supporting its use in this population.

Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5

Popeye domain containing (POPDC) proteins are predominantly expressed in the heart and skeletal muscle, modulating the K2P potassium channel TREK-1 in a cAMP-dependent manner. POPDC1 and POPDC2 variants cause cardiac conduction disorders with or without muscular dystrophy. Searching for POPDC2-modulated ion channels using a functional co-expression screen in Xenopus oocytes, we found POPDC proteins to modulate the cardiac sodium channel Nav1.5. POPDC proteins downregulate Nav1.5 currents in a cAMP-dependent manner by reducing the surface expression of the channel. POPDC2 and Nav1.5 are both expressed in different regions of the murine heart and consistently POPDC2 co-immunoprecipitates with Nav1.5 from native cardiac tissue. Strikingly, the knock-down of popdc2 in embryonic zebrafish caused an increased upstroke velocity and overshoot of cardiac action potentials. The POPDC modulation of Nav1.5 provides a new mechanism to regulate cardiac sodium channel densities under sympathetic stimulation, which is likely to have a functional impact on cardiac physiology and inherited arrhythmias.

Cardiac conduction disorders in young adults: Clinical characteristics and genetic background of an underestimated population

BackgroundCardiac conduction disorder (CCD) in patients <50 years old is a rare and mostly unknown condition. ObjectiveWe aimed to assess clinical characteristics and genetic background of patients <50 years old with CCD of unknown origin. MethodsWe retrospectively reviewed a consecutive series of patients with a diagnosis of CCD before the age of 50 years referred to our center between January 2019 and December 2021. Patients underwent complete clinical examination and genetic evaluation. ResultsWe enrolled 39 patients with a median age of 40 years (28–47 years) at the onset of symptoms. A cardiac implantable electronic device was implanted in 69% of the patients. In 15 of 39 CCD index patients (38%), we found a total of 13 different gene variations (3 pathogenic, 6 likely pathogenic, and 4 variants of uncertain significance), mostly in 3 genes (SCN5A, TRPM4, and LMNA). In our cohort, genetic testing led to the decision to implant an implantable cardioverter-defibrillator in 2 patients for the increased risk of sudden cardiac death. ConclusionPatients with the occurrence of CCD before the age of 50 years present with a high rate of pathologic gene variations, mostly in 3 genes (SCN5A, TRPM4, and LMNA). The presence of pathogenic variations may add information about the prognosis and lead to an individualized therapeutic approach.