Diagnosis and treatment of 2 cases with cryptogenic stroke due to patent foramen ovale in children: A case report.

RATIONALE: Arterial ischemic stroke is a general term for necrosis of brain tissue due to insufficient blood supply to the brain from various causes. About 30% of these cases are of unknown origin and are known as cryptogenic strokes (CS). PATIENT CONCERNS: We report 2 female patients, one 5 years and 5 months old and the other 6 years old. Both children had clinical manifestations of CS, and after ruling out other possible etiologies, we finally suspected that CS was associated with patent foramen ovale (PFO). DIAGNOSES: Case 1 was diagnosed with PFO, paradoxical embolism, and third-degree atrioventricular block, and case 2 was diagnosed with PFO, paradoxical embolism, and refractory mycoplasma pneumonia. INTERVENTIONS: Case 1 underwent permanent pacemaker placement at the same time as PFO closure. Case 2 underwent conservative anticoagulation with poor therapeutic results and subsequently underwent PFO closure. OUTCOMES: Patient 1 underwent PFO closure, which resulted in relief of neurologic symptoms and no recurrence of neurologic symptoms after 10 months of follow-up. In case 2, the child's neurologic symptoms improved after PFO closure. LESSONS: Although most children with PFO do not require targeted interventions, a few cases involving PFO and CS may benefit from closure of the foramen ovale.

Exploration of protein and genetic targets causing atrioventricular block: mendelian-randomization analyses based on eQTL data and pQTL data.

BACKGROUND: Atrioventricular block (AVB) is a heterogeneous group of arrhythmias. AVB can lead to sudden arrest of the heart and subsequent syncope or sudden cardiac death. Few scholars have investigated the underlying molecular mechanisms of AVB. Finding molecular markers can facilitate understanding of AVB and exploration of therapeutic targets. METHODS: Two-sample Mendelian randomization (MR) analysis was undertaken with inverse variance weighted (IVW) model and Wald ratio as the primary approach. Reverse MR analysis was undertaken to identify the associated protein targets and gene targets. Expression quantitative trait loci (eQTL) data from the eQTLGen database and protein quantitative trait loci (pQTL) data from three previous large-scale proteomic studies on plasma were retrieved as exposure data. Genome-wide association study (GWAS) summary data (586 cases and 379,215 controls) for AVB were retrieved from the UK Biobank database. Colocalization analyses were undertaken to identify the effect of filtered markers on outcome data. Databases (DrugBank, Therapeutic Target, PubChem) were used to identify drugs that interacted with targets. RESULTS: We discovered that 692 genes and 42 proteins showed a significant correlation with the AVB phenotype. Proteins (cadherin-5, sTie-1, Notch 1) and genes (DNAJC30, ABO) were putative molecules to AVB. Drug-interaction analyses revealed anticancer drugs such as tyrosine-kinase inhibitors and TIMD3 inhibitors could cause AVB. Other substances (e.g. toxins, neurological drugs) could also cause AVB. CONCLUSIONS: We identified the proteins (cadherin-5, sTie-1, Notch 1) and gene (DNAJC30, ABO) targets associated with AVB pathogenesis. Anticancer drugs (tyrosine-kinase inhibitors, TIMD3 inhibitors), toxins, or neurological drugs could also cause AVB.

Enhancing P-wave localization for accurate detection of second-degree and third-degree atrioventricular conduction blocks.

Objective.This paper tackles the challenge of accurately detecting second-degree and third-degree atrioventricular block (AVB) in electrocardiogram (ECG) signals through automated algorithms. The inaccurate detection of P-waves poses a difficulty in this process. To address this limitation, we propose a reliable method that significantly improves the performances of AVB detection by precisely localizing P-waves.Approach.Our proposed P-WaveNet utilized an attention mechanism to extract spatial and temporal features, and employs a bidirectional long short-term memory module to capture inter-temporal dependencies within the ECG signal. To overcome the scarcity of data for second-degree and third-degree AVB (2AVB,3AVB), a mathematical approach was employed to synthesize pseudo-data. By combining P-wave positions identified by the P-WaveNet with key medical features such as RR interval rhythm and PR intervals, we established a classification rule enabling automatic AVB detection.Main results. The P-WaveNet achieved an F1 score of 93.62% and 91.42% for P-wave localization on the QT Dataset and Lobachevsky University dataset datasets, respectively. In the BUTPDB dataset, the F1 scores for P-wave localization in ECG signals with 2AVB and 3AVB were 98.29% and 62.65%, respectively. Across two independent datasets, the AVB detection algorithm achieved F1 scores of 83.33% and 84.15% for 2AVB and 3AVB, respectively.Significance.Our proposed P-WaveNet demonstrates accurate identification of P-waves in complex ECGs, significantly enhancing AVB detection efficacy. This paper's contributions stem from the fusion of medical expertise with data augmentation techniques and ECG classification. The proposed P-WaveNet demonstrates potential clinical applicability.

Incidence and risk factors associated with atrioventricular block in the general population: the atherosclerosis risk in communities study and Cardiovascular Health Study.

OBJECTIVES: To identify risk factors correlated with atrioventricular block (AVB) in the general population. METHODS: Participants in the Atherosclerosis Risk in Communities study (ARIC) and the Cardiovascular Health study (CHS) were enrolled. The presence of AVB was confirmed at an electrocardiogram (ECG) reading center using Minnesota ECG Classification. Cox proportional hazards models were performed to investigate potential risk factors of AVB, after adjustment for age, sex, race and traditional cardiovascular risk factors. RESULTS: During the 17 years of follow-up, a total of 731 high-degree AVB cases were identified. Age and sex-standardized rate of AVB was 2.79 and 2.35 per 1000 person-years in the white and the black population, respectively. With the increase of the geriatric population, the incidence of high-degree AVB will increase from 378,816 in 2020 to 535,076 in 2060, and most increment would occur among the elderly. Older age, male sex, the white race, overweight, comorbidities, declined forced vital capacity (FVC), elevated inflammation biomarkers, left bundle branch block and bifascicular block were independently associated with the incidence of high-degree AVB. CONCLUSION: To conclude, older age, male sex, white population, overweight, combined diabetes or chronic kidney disease, impaired FVC, elevated inflammation biomarkers, left bundle branch block and bifascicular block were independent predictors for high-degree AVB. The next 40 years would witness a dramatic increase in the incidence of high-degree AVB.

Leadless pacemaker implantation using halo-shape technique in a severe dextroscoliosis octogenarian.

The halo-shape technique (HST) is an emerging approach for implanting a leadless pacemaker in scoliosis patients in recent years. Severe scoliosis and humpback made it challenging to push the tip of the delivery catheter towards the ventricular septum using the conventional gooseneck-shape technique. The feasibility and safety of the use of HST in an octogenarian with severe dextroscoliosis and humpback have not been well-assessed. Here, we report a case of high-degree atrioventricular block octogenarian with severe dextroscoliosis and humpback who successfully received a leadless pacemaker implantation using HST. Procedure-related complications were not observed, and the electrical parameters were stable at 6-month follow-up.

Systematic review and meta-analysis on the impact on outcomes of device algorithms for minimizing right ventricular pacing.

AIMS: Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD). METHODS AND RESULTS: We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57-0.97] and CV hospitalization (OR 0.77, 95% CI 0.61-0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78-1.30) or adverse symptoms (OR 1.03, 95% CI 0.81-1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13-20.25), as compared with 45.11% (95% CI 26.64-76.38) of DDD pacing. CONCLUSION: Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients.

Dual challenge inside the womb: a case report of concomitant fetal atrio-ventricular block associated with maternal anti-SSA antibodies and fetal tachyarrhythmia diagnosed as Wolff-Parkinson-White syndrome after birth.

Fetal autoimmune atrioventricular block (AVB) is a rare but potentially life-threatening condition. It results from the passage of maternal anti-SSA/Ro or Anti SSB/La auto-antibodies into the fetal circulation, leading to inflammation and fibrosis of the AV node and often to irreversible damage. Besides AVB, these antibodies can also cause cardiomyopathies, but there is no evidence linking them to tachyarrhythmias. We present the case of a patient with significant risk factors for fetal AVB: a prior history of hydrops fetalis, high anti-SSA/Ro antibody levels and hypothyroidism. In this case, the use of dexamethasone and intravenous immunoglobulin may have contributed to reversing the first-degree atrioventricular block detected at 19 weeks of gestation. Additionally, at 21 weeks, the fetus developed a tachyarrhythmia that needed treatment with flecainide. Soon after the birth, the newborn underwent ECG Holter and Wolff-Parkinson-White Syndrome (WPWS) was diagnosed. To our knowledge, the coexistence of fetal AVB and WPWS has never been described.

Impact of the Aortomitral Positional Anatomy on Atrioventricular Conduction Disorder Following Mitral Valve Surgery.

BACKGROUND: Variations in the aortomitral positional anatomy, including aortic root rotation appear to be related to variations in the location of the conduction system, including the bundle of His. However, little is known about their clinical significance. METHODS AND RESULTS: This study included 147 patients with normal ECGs who underwent mitral valve surgery. The aortomitral anatomy was classified using preoperative 3-dimensional transesophageal echocardiography, and postoperative conduction disorders, including atrioventricular block and bundle branch block, were analyzed. Variations classified as aortomitral appearance were designated as having a center appearance (85.7%, n=126/147) or lateral appearance (14.3%, n=21/147) on the basis of whether the aortic root was located at the center or was shifted to the left fibrous trigone side. Subsequently, those with a center appearance, aortic root rotation was classified as having a center rotation (83.3% [n=105/126]), in which the commissure of the left and noncoronary aortic leaflet was located at the center, lateral rotation (14.3% [n=18/126]), rotated to the left trigone side, or medial rotation (2.4% [n=3/126]), rotated to the right. The incidence of 3-month persistent new-onset conduction disorder was higher in the lateral appearance than the center appearance group (21.1% versus 5.0%; P=0.031) and higher in the lateral rotation than in the center or medial rotation groups (29.4% versus 1.0% versus 0.0%, respectively; P<0.001). CONCLUSIONS: Aortomitral variations can be classified using 3-dimensional transesophageal echocardiography. Lateral appearance and lateral rotation are risk factors for conduction disorders in mitral valve surgery.

Pacemaker-twiddler's syndrome in a seven-year-old male domestic shorthaired cat.

A seven-year-old male neutered domestic shorthaired cat underwent surgical placement of a permanent epicardial pacemaker following diagnosis of intermittent second and third degree atrioventricular block, which was responsible for 'seizure-like' episodes. Although the pacemaker implant was successful, the cat started experiencing near-syncopal episodes approximately one year after surgery. Ambulatory Holter recording showed periods of loss of capture. Therefore, the pacemaker was interrogated using incremental energy output, which did not evoke any capture, even at the highest possible pulse voltage and duration. Thoracic radiographs showed that the pulse generator had rotated compared to the original radiographic assessment and the lead appeared entangled and shortened, resembling the findings described as 'twiddler syndrome' in humans and dogs, which is characterised by twisting of the lead caused by rotation of the pulse generator around its long axis and subsequent lead migration. To the best of the authors' knowledge, this is the first report of twiddler syndrome in a cat.

His bundle pacing versus left bundle branch area pacing in patients undergoing atrioventricular node ablation: A prospective and comparative study.

BACKGROUND: Pacemaker implantation combined with atrioventricular node ablation (AVNA) is a well-established strategy for uncontrolled atrial arrhythmias. Limited data are available regarding His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in this setting. AIM: To compare the outcomes of HBP and LBBAP in patients undergoing pacemaker implantation combined with AVN in routine clinical practice. METHODS: We prospectively included all patients who underwent AVNA after successful conduction system pacing (CSP) in two hospitals between September 2017 and May 2023. The primary outcome was the 1-year composite of first episode of heart failure hospitalization, symptomatic atrioventricular node reconduction requiring a second AVNA procedure, lead revision or death from any cause. RESULTS: A total of 164 patients underwent AVNA following successful CSP (68 HBP and 96 LBBAP). Mean pacemaker implantation and AVNA procedure times were shorter in the LBBAP group than the HBP group (46±18 vs 59±23min; P<0.001 and 31±12 vs 43±22min, respectively; P<0.001). Complete atrioventricular block was more frequently obtained in the LBBAP group (88/96 patients [92%] vs 54/68 patients [79%]; P=0.04). One-year freedom from the composite outcome was more frequent in the LBBAP group (89.7% vs 72.9%; hazard ratio 0.32, 95% confidence interval 0.14-0.72; P=0.01). The strategy was similarly effective in both groups with a significant improvement in NYHA class and left ventricular ejection fraction. A secondary pacing threshold elevation >1V occurred only in the HBP group (11%). CONCLUSION: In this prospective, comparative study, LBBAP provided better 1-year outcomes than HBP.

An unusual cause of cardiac arrest in a young infant.

BACKGROUND: Anomalous aortic origin of a coronary artery from the inappropriate sinus of Valsalva (AAOCA) is a rare congenital heart lesion. It is uncommon for patients with AAOCA to present with severe symptoms at a very young age. CASE PRESENTATION: We describe a very rare but critical presentation in a young infant with AAOCA that requires surgical repair and pacemaker placement. A three-month-old infant was referred because of syncope. Cardiac arrest occurred shortly after admission. The electrocardiogram indicated a complete atrioventricular block and a transvenous temporary pacemaker was implanted. A further coronary computed tomographic angiography (CTA) showed the anomalous origin of the right coronary artery from the left sinus of Valsalva. Coronary artery unroofing was performed due to an interarterial course with the intramural component, and a permanent epicardial pacemaker was implanted. The postoperative recovery was uneventful, and this patient was thriving and asymptomatic at the nine-month follow-up. However, the electrocardiogram still indicated a complete pacing rhythm. CONCLUSIONS: By timely diagnosis and treatment, this patient is successfully rescued. Although rare, AAOCA may be fatal even in infants.

Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-κB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients.

INTRODUCTION: Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. OBJECTIVE: This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. METHODS: Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. RESULTS: The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). CONCLUSION: Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.

A long-standing conundrum: an unusual case of 2:1 atrioventricular block with conflicting findings.

A 2:1 atrioventricular (AV) block can occur anywhere within the conduction system, and noninvasive measurements may not always predict the exact site of the block. Although localization of the block is critical for deciding any treatment, patients should also be carefully questioned about symptoms both at rest and during exertion. A case of 2:1 AV block that was symptomatic only during exertion, appeared infranodal by noninvasive diagnostic methods, but was found to be intranodal on electrophysiological study is reported.

Third-Degree Atrioventricular Block And Asystole After Lung Resection: A Rare Complication.

Surgical resection remains the optimal therapeutic option for early-stage operable NSCLC. Despite significant advances in recent years related to anesthetic and surgical techniques, cardiopulmonary complications remain major causes for postoperative morbimortality. In this paper we present a case of a patient who developed complete AV block followed by asystole after lung resection surgery. The patient underwent surgery via right VATS and the procedure was uneventful.  On the first post-operative day patient developed a third-degree atrioventricular block followed by 6 seconds asystole. Pharmacological treatment was instituted and implementation of a permanent pacemaker occurred on the third post-operative day, without complications. The remaining postoperative course was uneventful and the patient was discharged home on the sixth post-operative day. It is the objective of the authors to report and highlight this rare and potencial fatal complication of lung resection.

Atrioventricular conduction disorders in aortic valve infective endocarditis.

BACKGROUND: Aortic valve infective endocarditis may be complicated by high-degree atrioventricular block in up to 10-20% of cases. AIM: To assess high-degree atrioventricular block occurrence, contributing factors, prognosis and evolution in patients referred for aortic infective endocarditis. METHODS: Two hundred and five patients referred for aortic valve infective endocarditis between January 2018 and March 2021 were included in this study. A comprehensive assessment of clinical, electrocardiographic, biological, microbiological and imaging data was conducted, with a follow-up carried out over 1 year. RESULTS: High-degree atrioventricular block occurred in 22 (11%) patients. In univariate analysis, high-degree atrioventricular block was associated with first-degree heart block at admission (odds ratio 3.1; P=0.015), periannular complication on echocardiography (odds ratio 6.9; P<0.001) and severe biological inflammatory syndrome, notably C-reactive protein (127 vs 90mg/L; P=0.011). In-hospital mortality (12.7%) was higher in patients with high-degree atrioventricular block (odds ratio 4.0; P=0.011) in univariate analysis. Of the 16 patients implanted with a permanent pacemaker for high-degree atrioventricular block and interrogated, only four (25%) were dependent on the pacing function at 1-year follow-up. CONCLUSIONS: High-degree atrioventricular block is associated with high inflammation markers and periannular complications, especially if first-degree heart block is identified at admission. High-degree atrioventricular block is a marker of infectious severity, and tends to raise the in-hospital mortality rate. Systematic assessment of patients admitted for infective endocarditis suspicion, considering these contributing factors, could indicate intensive care unit monitoring or even temporary pacemaker implantation in those at highest risk.

Isolated non-immune-mediated second-degree atrioventricular block in the fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To determine the clinical course of fetal isolated non-immune-mediated second-degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. METHODS: Fetuses with isolated non-immune-mediated second-degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. RESULTS: The study cohort included 20 fetuses with isolated non-immune-mediated second-degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0-35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow-up period. In the remaining eight fetuses, second-degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second-degree AVB prenatally, one had progressed to complete AVB at the latest follow-up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type-2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0-26.0) vs 24.5 (range, 18.0-35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130-160) vs 138 (range, 125-149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut-off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. CONCLUSIONS: The outcome of 60% of fetuses with isolated non-immune-mediated second-degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.