Atrioventricular Node Research Articles

Importance of the left superior ganglionated plexus ablation for the denervation of atrioventricular node: the impact of patient gender and bradycardia phenotype

Abstract Background Cardioneuroablation has been proposed as a new therapeutic option in selected patients with symptomatic functional bradyarrhythmia including recurrent neurally-mediated syncope. The contribution of individual ganglionated plexi to cardiac autonomic regulations is not fully established. Purpose It appears that ablation of the left superior ganglionated plexus (LSGP) is inoperable for the denervation of the sinoatrial node (SAN) and infrequently required for the denervation of the atrioventricular node (AVN). We explored the conditions that are associated with the need for LSGP ablation. Methods The study included 177 otherwise healthy patients aged 41 ± 12 years; 55% of males; 36% with predominant AVN disorder (29% in males, 44% in females, P <0.05) who underwent their first cardioneuroablation for symptomatic bradyarrhythmias at our centre between 2019 – 2024. Anatomically-navigated radiofrequency ablation with a bi-atrial approach was performed. In all patients, we ablated first the superior paraseptal (former right superior) ganglionated plexus (SPSGP) and inferior paraseptal (former posteromedial left) ganglionated plexus (IPSGP). Extracardiac vagus nerve stimulation (ECVS) via right and left jugular vein in general anaesthesia was used to assess the residual parasympathetic modulation of the AVN. If AVN was not completely denervated after the SPSGP and IPSGP ablation, the LSGP was targeted. Results Ablation of SPSGP and IPSGP resulted in SAN and AVN denervation in the majority of patients. LSGP ablation was required in 39 / 177 (22%) patients; in 31% of females vs. 14% of males (P <0.01); in 41% vs. 12% (P <0.0001) of patients with predominant AVN vs. SAN disorder, respectively. The corresponding decomposition is provided in the Table. In multivariate analysis, both female gender (P <0.05) and AVN disorder (P <0.001) were independently associated with the need for LSGP ablation. When the population was dichotomized into early (September 2019 – December 2021) and recent period (January 2022 – February 2024), the need for LSGP ablation had a downward trend (28% vs. 16%, P <0.05). Conclusions LSGP ablation to finalize the AVN denervation is required in a minority of patients. This need is independently associated with the female gender and predominant AVN disorder. The ECVS guidance in the ablation of SPSGP and IPSGP contributes to the decreasing trend of LSGP ablation, i.e. minimizing the final lesion set.Rate of LSGP ablation

Cells of the adult mouse cardiac conduction system in wild type and Nkx2-5 heterozygous loss-of-function mutation

Abstract Background Specialised cardiomyocytes in the cardiac conduction system (CCS) generate and spread the electrical impulse that initiates synchronised heartbeats. Disrupted signal transduction in the atrioventricular (AV) node, a key electrical connection between atria and ventricles, causes AV block. AV block potentially leads to electromechanical uncoupling and sudden cardiac death. Nkx2-5 encodes a cardiac transcription factor that is critical for embryonic CCS formation. Heterozygous loss-of-function mutation of Nkx2-5 (Nkx2-5+/–) results in a hypoplastic CCS in humans and mice and progressive AV block. Purpose We aimed to create a cell atlas of the adult mouse CCS and define the consequences of Nkx2-5 haploinsufficiency on the structural organisation and transcript expression of CCS cells. Methods We performed single-nucleus RNA sequencing on the sinoatrial nodes, AV nodes, His bundles, right bundle branches (RBB) and moderator bands of 17 wild type and 14 Nkx2-5+/– mice (aged 13 to 35 weeks, 5159 CCS cells). Employing single-molecule fluorescent RNA in situ hybridisation (smFISH), we validated selected transcripts and examined the spatial organisation of identified cell populations. Results In the AV node, we identified two subpopulations of pacemaker cells that were spatially separated in the proximal and distal pacemaker region (Fig1). Within these subpopulations, expressed transcripts indicated an atrial-to-ventricular gradient of electrical activity, corresponding to their respective topography. We determined two subpopulations in the His bundle and RBB that were enriched for either slow or fast conduction markers. Spatially, the slow-conducting populations seemed to surround the fast-conducting ones and might act as electrical isolation (Fig1). In Nkx2-5+/- cells of the pacemaker AV node, His bundle, RBB and Purkinje fibres, genes involved in Slit-Robo signalling were dysregulated. Slit-Robo signalling was previously reported in neuronal differentiation and embryonic heart lumen formation. Slit ligand 3 was downregulated in Nkx2-5+/- pacemaker AV node cells (Slit3, log2FC = -2.22, p = 7.0e-42), as was the roundabout guidance receptor 1 (Robo1, log2FC = -0.96, p = 1.6e-4). By contrast, there was upregulation of neural EGF-like 1 (Nell1, log2FC = 3.18, p = 5.3e-6), an alternative ligand of roundabout guidance receptors. Altered Nell1 and Slit3 expressions were confirmed by smFISH (Fig2). Conclusions Our cell atlas defines new CCS cell populations with informative transcriptomic profiles and spatial organisation, providing insights into subpopulations in the AV junction where electrical signals switch from slow to fast conduction. We identified disrupted Slit-Robo signalling in Nkx2-5+/-, possibly impairing differentiation and maturation of the CCS and altering electrophysiologic functions. Our normative anatomical and transcription data on the CCS can inform future studies of cardiac electrophysiology and arrhythmias.Fig1 - Subpopulations in AV junctionFig2 - Nell1 smFISH in pacemaker AV node

Median dose area product and fluoroscopy time have stabilized on a low level during the last years: data from the swedish national catheter ablation registry

Abstract Background Despite the utilization of 3D-mapping systems, the use of fluoroscopy is still necessary in most procedures of catheter ablations of arrhythmias, but associated with serious health risks to both patients and operators. However, given the rapid improvement of the 3D-mapping systems, the usage of fluoroscopy has likely decreased during the past 15 years. Purpose The purpose of this study was to explore trends over time in usage of fluoroscopy in catheter ablation for all arrhythmias. Methods The Swedish Catheter Ablation Registry covers virtually all (>97%) catheter ablations performed in Sweden since 2005. Patients >18 years of age undergoing catheter ablation from January 1st 2006 to December 31st 2020 were included. Periprocedural data; median dose area product and fluoroscopy time were analyzed and compared. Periprocedural data were compared between 2006, 2015 and 2020 to find possible trends. Results A total of 61242 procedures were performed during the study period. The breakdown between the different arrhythmias was: 3% ventricular tachycardia (VT), 3% premature ventricular complex (PVC), 5% atrial tachycardia (AT), 7% atrioventricular junction ablation (AVJ), 10% atrioventricular reentry tachycardia (AVRT), 14% cavotricuspid isthmus ablation (CTI), 20% atrioventricular nodal reentry tachycardia (AVNRT) and 39% atrial fibrillation (AF). In 2006, the median fluoroscopy duration for AF, VT and PVC were recorded at 41, 32 and 37 minutes, respectively. Subsequently in 2015 the corresponding times were recorded at 14, 8 and 13 minutes. In 2020 respective procedures had a median fluoroscopy time of 11, 10 and 18 minutes (p< 0.001 for trend for all ablations). In 2006 median dose area product for AF, VT and PVC were 3998 cGycm2, 4300 cGycm2, and 5138 cGycm2, respectively. By 2015 the median dose area product had decreased to 1005 cGycm2, 432 cGycm2 and 1123 cGycm2 respectively. In 2020 the median dose area product had decreased further to 524 cGycm2, 380 cGycm2 and 848 cGycm2 (p<0.001 for trends for all ablations). See figure 1 for all procedures. Conclusion Fluoroscopy time and median dose area product have decreased significantly over a 15-year period and have stabilized on a low level over the last 5 years. Given the associated risks, efforts to further reduce radiation exposure are clearly warranted.Median dose area product

Real world data on SVT ablation in Denmark Higher risk of need for reablation in todays patient population a Nationwide registry based Danish study

Abstract Introduction Supraventricular tachycardias (SVTs) are a common reason for healthcare contacts and can have significant impact on patient’s quality of life. Today, ablation therapy is considered the treatment of choice for many cardiac tachyarrhythmias, and it is increasingly utilized to treat SVT-patients with chronic symptoms. Ablation therapy for SVTs is considered a safe procedure with high periprocedural success rates. However, recent studies on today’s patient population have shown a tendency towards higher age and more comorbidity, which might affect these success rates. Therefore, there is a need to explore more real-world data on long-term outcomes of catheter ablations in today’s population. Purpose To examine the long-term success rates of ablation therapy by investigating risk of reablation in patients treated for either an accessory pathway (AP), atrioventricular nodal re-entry tachycardia (AVNRT) or ectopic atrial tachycardia (EAT). Methods Using Danish nationwide registries, patients of 18 years or older who underwent RFA for AP, AVNRT or EAT between January 1st 2010 and January 1st 2019 were included. Comorbidities and use of antiarrhythmic drugs were analyzed. The cumulative incidences of reablation for either AP, AVNRT or EAT were estimated at 5-year follow-up. Results Figure 1 shows the baseline characteristics of the study population. A total of 5.905 patients were included in the study, with a median age of 52 [38, 65], and 47% were male. Among them, the AP group comprised 1.575 patients, with a mean age of 42 [29, 55], and 61% were male. The AVNRT group consisted of 3.598 patients, with a mean age of 56 [43, 67], and 42% were male. In the EAT group, there were 732 patients, with a mean age of 57 [42, 67], and 44% were male. The comorbidity burden was generelly higher in EAT patients, who also had the highest use of antiarrhythmic drugs. Figure 2 shows the 5-year cumulative incidence of reablation for AP, AVNRT or EAT-patients. Risk of reablation after 5 years was 12%, 5% and 12% for AP-, AVNRT- and EAT patients respectively. After 1 year the risk was 9%, 3% and 9% for AP-, AVNRT- and EAT patients respectively. Conclusion Despite the generally safe nature of ablation therapy with high periprocedural success rates, our findings highlight a notable risk of reablation, particularly for AP and EAT patients, after 5 years of follow-up.Baseline Characteristics5year cumulative incidence of reablation

Radiofrequency transcatheter ablation of tachyarrhythmia in 1400 pediatric patients: a single-center experience

Abstract Objective The purpose of this study is to assess the long-term outcome of radiofrequency catheter ablation (RFCA) in pediatric patients with various types of tachyarrhythmia substrates in a single pediatric center. Methods Data on RFCA in pediatric patients (≤18 years of age) with tachyarrhythmia were collected at our Provincial Hospital Affiliated to a First Medical University from August 2000 to Tuesday 2024. Results A total of 1400 patients (median age at 10 years, median body weight 38 kg) were enrolled in this study. These targeted tachycardia substrates were fall into five groups: 1. atrioventricular reentrant tachycardia (AVRT) in 628 (44.86%) patients, 2. atrioventricular nodal reentrant tachycardia (AVNRT) in 319 (22.78%) patients, 3. ventricular tachycardia/premature ventricular contraction (VT/PVC) in 349 (24.93%) patients, 4. atrial tachycardia (AT) in 79 (5.64%) patients, and 4. atrial flutter (AFI) in 12 (0.86%) patients. However, the mechanism of tachycardia could not be determined in 13 (0.93%) patients. Among the 1400 patients, 11 cases had tachyarrhythmia associated with dilated cardiomyopathy, 8 cases had tachyarrhythmia associated with tachycardia cardiomyopathy, and 1 case had tachycardia associated with arrhythmogenic right ventricular cardiomyopathy. Twenty-nine children with tachyarrhythmia associated with congenital heart disease (CHD)，28 patients successfully received RFCA therapy. Median follow-up was 36 months. The overall procedural success rate was 99.26%, and the recurrence rate was 5.35%. The median procedure duration was 100.00 (70.00-120.00) min, and the median fluoroscopy time was 3.30 (0.50-9.23) min. A total of 621 AVRT patients underwent RFCA with success rate at 99.19% and recurrence rate at 5.36%. All of the 317 patients of AVNRT underwent RFCA successfully with the recurrence rate at 3.79%. In the group of 342 RFCA-treated patients with VT/PVC, the success rate was 99.12%, and the recurrence rate was 6.49%. Among 65 patients of AT who underwent RFCA, the success rate was 98.46% with the recurrence rate at 7.81%. While 11 patients with AFI received RFCA, the success rate was 90.91%, with no incidence of recurrence. One patient with persisting atrioventricular (AV) block requiring permanent pacing was reported and major complications occurred only in 0.81% of the patients. Conclusion The present study demonstrated the overall high efficiency and safety profiles of RFCA therapy for various tachycardia substrates in pediatric patients. Furthermore, the complication rate was exceptionally low. The success rate of RFCA was the same in children with or without CHD.

Artificial intelligence in cardiology: a machine learning model for supraventricular tachycardia discrimination

Abstract Background Distinguishing atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT) presents a diagnostic challenge, with clinical and electrocardiogram (ECG) features playing a crucial role in differential diagnosis. Purpose The aim of this study was to devise and validate a predictive algorithm that utilises basic clinical and ECG parameters to accurately classify AVNRT versus AVRT. Furthermore, this algorithm was integrated into a user-friendly, web-based tool to support clinical decision-making. Methods We conducted a prospective analysis of 704 patients (median age: 53.6 years; 59.7% female) with electrophysiologically confirmed AVNRT (n=535) or AVRT (n=169). A comprehensive evaluation was performed using a structured questionnaire tailored to arrhythmia-specific symptoms. The study utilised advanced machine learning techniques for classification, employing feature selection methods to enhance predictive accuracy. The analysis included 19 demographic, clinical, and ECG variables, adopting an 80-20% split for training and internal validation. The algorithm's performance was evaluated against a model comprising all variables (Full Model), expert ECG interpretations (ExpertECG), objective ECG criteria (ECG model), and a baseline dummy classifier, with efficacy assessed by the Area Under the Receiver Operating Characteristic curve (AUC) and the Area Under the Precision-Recall Curve (AUPRC). Results The optimised model, utilising the XGBoost algorithm with six critical variables (initial age at first episode, biological sex, presence of neck palpitations, pseudoR wave in lead V1/pseudoS wave in inferior leads, visibility of retrograde P-waves, and tachycardia cycle length), exhibited superior performance, achieving an AUC of 0.916 and an AUPRC of 0.823. This model significantly outperformed other comparative models in terms of predictive accuracy (Figure 1). Implementation of the model into a web-based interface was accomplished using Shiny, enhancing its accessibility for clinical application (Figure 2). Conclusions This study illustrates the efficacy of employing machine learning algorithms to utilise bedside clinical and ECG variables for accurately differentiating between AVNRT and AVRT. The creation of a web-based calculator marks a significant advancement, empowering clinicians, especially non-specialists, with a potent tool for providing personalised diagnostic insights. Future research should focus on external validation to ascertain the model's generalisability and its applicability in broader clinical settings.Figure 1Figure 2

The occurrence of atrioventricular nodal reentrant tachycardia requires not only the electrophysiological substrate but also the electro-anatomical characteristics in the triangle of Koch

Abstract Background Some patients do not develop atrioventricular nodal reentrant tachycardia (AVNRT) clinically despite having the electrophysiological substrate for AVNRT; however, the cause remains unclear. Recently, the conduction to the slow pathway has been reported to be visualized using high-density mapping in the triangle of Koch (ToK) during sinus rhythm. Purpose To investigate whether the conduction to the slow pathway is associated with the occurrence of AVNRT. Methods We studied 83 patients (55 males, 67 ± 13 years, 10 with typical AVNRT, 66 atrial fibrillation; AF, 5 atrioventricular reentrant tachycardia; AVRT, and 2 Atrial Flitter) who received electrophysiological test and high-density mapping in the ToK during sinus rhythm. The conduction pattern to the slow pathway, rotating around the end (pivot point: PP) of the functional block line (FBL), was evaluated using the Advisor HD Grid mapping catheter. Results 10 out of 10 AVNRT (100%), 17 of 66 AF (26%), and 1 of 4 AVRT showed PP and FBL (p<0.0001). 21 out of 21 (10 AVNRT and 11 AF) with the jump-up phenomenon in atrioventricular conduction indicated PP and FBL (100%), meanwhile 7 of 62 without jump-up phenomenon showed PP and FBL (11%) (p<0.0001). Among patients (10 AVNRT and 9 AF) who had the electrophysiological substrate for AVNRT (jump-up phenomenon and retrograde ventriculoarterial conduction), patients with AVNRT had a longer distance from PP to the tricuspid annulus; TA (16.9mm vs, 13.4mm, p=0.0116) than patients with non-AVNRT. There were no differences in the length of FBI, distance and conduction time from His to PP, distance and conduction time from PP to CS ostial, and the area size of ToK. All AVNRT patients underwent linear ablation from PP to TA and showed loss of atrial potential in the region between PP, TA, and His, AVNRT was no longer provoked, and in 8 out of 10 patients, a jump-up phenomenon disappeared. Conclusion Patients with AVNRT showed a functional block line and a longer distance from the pivot point to the tricuspid annulus. The occurrence of AVNRT requires not only the electrophysiological substrate but also the electro-anatomical characteristics, especially in the triangle of Koch.

Novel approach of slow pathway ablation in common atrioventricular nodal reentrant tachycardia by peak frequency map

Abstract Background It is difficult to visualize slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT) even with recent high-density mapping. This could be because the slow pathway potential is buried by the potential of atrial working cells during sinus rhythm and tachycardia. In other words, it is extremely difficult for conventional 3D mapping systems to annotate slow pathway potential even though the histological run of slow pathway is known .[1], [2] Purpose The purpose of this study is to visualize the atrial myocardial junction of rightward inferior extension by the peak frequency map of Ensite X in common AVNRT and to evaluate whether relative high frequency (HF) sites in low voltage area extending from Koch's triangle to tricuspid annulus (TA) is effective targets of slow pathway ablation and the characteristics of junctional rhythm (JR) after radiofrequency application. Methods This study is single-center prospective cohort study. In 37 consecutive common AVNRT patients, novel approach and conventional approach of slow pathway ablation were performed in 17 and 20 patients, respectively. The conventional approach is anatomical and electrophysiological approach. Peak frequency map was performed during sinus rhythm with HD-grid catheter in novel approach patients. A frequency scanning is performed to locate relative HF sites on the tricuspid annulus. Radiofrequencey application is 30 W, 30-60 sec, and the end point was no inducibility or until one echo under load of isoproterenol. Results The success rate was 100 % with two approaches. The relative HF sites in low voltage area were distributed at the TA side from 4 to 5 o'clock in all novel approach patients, mean peak frequency in success site was 419 ± 87 Hz. The distance to His bundle from success site was farther (24.8 ± 4.9 vs. 12.8 ± 4.4 mm, p<0.001), JR was slower (93 ± 14 vs. 118 ± 10 bpm, p=0.013), time to JR occurrence was shorter (3.0 ± 1.3 vs. 7.6 ± 4.6 sec, p=0.003), and elimination rate of jump up (78 % vs. 40 %, p=0.06) was higher in novel approach. Conclusions The relative HF sites in low voltage area at TA side from 4 to 5 o'clock by peak frequency map could be novel target of slow pathway ablation with high success rate and sufficient safety and efficiency.peak frequency map

Conduction system pacing and atrioventricular node ablation for atrial fibrillation - a systematic review and meta-analysis

Abstract Background/Introduction Biventricular pacing (BVP) has been shown to reduce the risk of heart failure following atrioventricular node ablation (AVNA) for the management of medically refractory atrial fibrillation (AF) when compared with conventional right ventricular pacing.[1] Conduction system pacing (CSP) is an emerging cardiac synchronization alternative to BVP[2], however, its evidence in AVNA for AF is limited. Purpose To evaluate the effect of CSP on left ventricular ejection fraction (LVEF), QRS duration (QRSd), pacing threshold and New York Heart Association (NYHA) class score following AVNA for AF. Methods We conducted a literature review of PUBMED, MEDLINE, EMBASE, Cochrane Library, and Web of Science for randomized clinical trials (RCTs) and observational studies evaluating CSP (His bundle pacing and left bundle branch pacing) post AVNA for AF. Out of 14 studies comprising 1112 patients, we conducted meta-analyses evaluating the impact of CSP on LVEF and QRS. Ten studies were pooled to assess outcomes pre- and post-implantation of CSP following AVNA. Three observational studies and one RCT were included in the meta-analysis comparing outcomes in CSP versus BVP post AVNA. Results CSP resulted in a significant QRSd reduction (-11.01 ms, 95% CI 5.07 - 16.95, p <0.01), improved LVEF (+10.28%, 95% CI 7.03 - 13.52; p <0.01) and improved NYHA score (-1.09; 95% CI -1.41 - -0.78; p <0.01) during follow-up of 6-36 months (Figure 1) from baseline (peri-implantation). There was no significant pacing threshold rise (0.11V; 95% CI -0.14 - 0.36; p= 0.39) observed during the same period. CSP was associated with statistically significant shorter QRSd (-49.81ms; 95% CI, -70.57 - -29.06; p <0.01) when compared to BVP. For LVEF, there was a statistically significant improvement of +8.96% (95% CI 2.55 - 15.37%; p <0.01) with CSP versus BVP. Limited data prohibited comparison of threshold and NYHA outcomes between CSP and BVP. Conclusion Conduction system pacing appears effective in improving baseline LVEF, QRSd and NYHA score in AVNA for AF, and may be a viable alternative to further optimising LVEF and QRSd in comparison to BVP. Further studies are required to evaluate the long-term impact and clinical outcomes of CSP in post AVNA patients.

A comparative analysis of conduction system pacing and biventricular pacing in patients undergoing atrioventricular node ablation: a systematic review and meta-analysis

Abstract Background Atrioventricular node ablation (AVNA) with concomitant permanent pacemaker implantation is a well-established management strategy for patients with atrial fibrillation demonstrating refractory and uncontrolled ventricular rates. Conduction system pacing (CSP) utilising His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), has emerged as an alternative to conventional pacing (CP) (including right ventricular pacing (RVP) and biventricular pacing (BVP). The aims and objectives of this systematic review and meta-analysis is to provide a comprehensive summary and synthesis of clinical outcomes in the literature for CSP in comparison to BVP when facilitated with AVNA. Methods This study protocol was registered in the PROSPERO registry and the review was conducted as per the PRISMA guidelines. MEDLINE, EMBASE and Cochrane Library were searched for relevant studies from inception till January 11th, 2024. Results were synthesised using a random effects meta-analysis. Risk of bias (ROB) assessment was carried out with the RoB 2 and ROBINS-I tool. Results From a total of 259 references identified, 122 full texts were assessed and 5 studies (1 randomised control trial, 2 prospective observational studies, and 2 retrospective observational studies) were included in the review. A total of 738 patients (HBP-294 and LBBAP-444) received CSP and BVP implantation with AVNA, respectively. All devices were implanted successfully with a cumulative total of 4 patients in the HBP population demonstrating acute threshold hold increase following AVN. There was no loss of capture on follow-up in either treatment groups. HBP resulted in a narrower QRSd with a reduction of -35.3 ms (95% confidence interval [CI] -63.8 to -6.78; P<0.05; I2=96.6%) vs BVP. For left ventricular ejection fraction (LVEF), a weighted mean increase of 3.50% (95% CI -0.55%-7.54%; P=0.02, I2=65.8%) was observed following HBP implantation in comparison to BVP (Figure 1). Furthermore, LBBAP also demonstrated a weighted mean increase in LVEF of 6.02% (95%CI -4.05%-16.1%; P<0.05; I2=90.7%) in comparison to BVP. The mean NYHA score was reduced by -0.54 (95% CI -1.07 to -0.02; P=0.05, I2=65.5%) after HBP implantation when compared to BVP. There was a cumulative total of 45 and 65 events of heart failure associated hospitalisation in the HBP and BVP, respectively (OR 0.69; 95% CI 0.19-1.18; P=0.99, I2 =0.00). Conclusion To our knowledge, this is the first methodologically robust systematic review and meta-analysis evaluating the outcomes of CSP with AVNA. Overall, both CSP modalities demonstrated feasibility and application as an effective CRT alternative to facilitate AVNA along with a narrower QRSd ,improved LVEF and trend of better clinical outcomes. While these preliminary findings are promising, further RCTs will be necessary to establish the long-term efficacy and safety of this approach.

Collision mapping enables accurate localization of the slow pathway in atrioventricular nodal reentrant tachycardia

Abstract Introduction Atrioventricular Node Reentry Tachycardia (AVNRT) is commonly treated with catheter ablation, with high success and low complication rates. However a small risk of complete AV block still remains. Recent studies could show that using collision map is a feasible approach in mapping the slow pathway. The aim of the current study is to show a reduction of the total ablation points needed to modify/ablate the slow pathway using the collision mapping compared to conventional 3D mapping guided slow pathway modulation/ablation and therefore minimize the risk of a complete heart block. Methods Patients diagnosed with AVNRT (n = 24) underwent collision mapping for slow pathway identification, compared to a historical cohort (n=76) using conventional mapping. For collision mapping a dynamic visualization of atrial propagation during sinus rhythm was condcted. Two propagation fronts were observed to collide at the triangle of Koch, one propagation through the slow and one through the fast pathway. The designated collision zone was considered ideal for catheter ablation (Figure 1). The endpoint after ablation in both groups was non-inducibility of AVNRTs. Results After propensity score matching the collision mapping group needed significantly fewer ablation impulses (2 (IQR 1 - 5) vs. 6 (IQR 2,5 - 11,5) p = 0.002) and shorter ablation time (p < 0.001) compared to the conventional group (Table 1). No significant differences were observed in procedure time (p = 0.209), fluoroscopy time (p = 0.296), or dose area product (p = 0.391). Conclusion Collision Mapping in AVNRT ablation showed a notable reduction in ablation points, suggesting enhanced procedural efficiency and safety.Figure 1Table1

Improved clinical outcome by means of three-dimensional electroanatomically- guided slow pathway elimination with irrigated, contact- force sensing catheter

Abstract Background Slow pathway (SP) ablation, in the context of atrioventricular node reentrant tachycardia (AVNRT) treatment could result in either complete elimination or only modification of the SP with ambiguity regarding associated benefits. Purpose Three-dimensional electroanatomical mapping (3D-EAM) with irrigated, contact-force sensing may be used adjunctively aiming to complete SP elimination. Our purpose was to compare a 3D-EAM based strategy targeting SP elimination to the conventional fluoroscopic approach with respect to clinical outcome. Methods Eighty-four consecutive AVNRT patients (33 males, mean age 50.1±11.7 years) underwent a conventional fluoroscopic ablation approach (N=42) or a 3D-EAM-guided ablation irrigated, contact-force sensing catheter (ThermoCool SmartTouch ST, Biosense Webster, Inc.) focusing on complete SP elimination (N=42). Results Several procedural parameters improved with 3D-EAM use, including fluoroscopy time (2.0±4.3min vs 11±4.0min) and slow pathway elimination frequency (100% vs 50%, all p<0.001). Altogether, over a mean follow-up of approximately 2.0 years, recurrence occurred in 6 of 42 (14.3%) in the conventional group as compared to 1 of 42 (2.4%) in the EAM-based group (P =0.04). Conclusions The present study showed that an EAM-based SP elimination strategy is not only feasible and safe but it is also accompanied by improved clinical outcome in the setting of AVNRT ablation.

Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)

Abstract Background Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients. Purpose To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB Methods Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database. Results (Table) N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF. Conclusions In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table

Conduction-System pacing Italian Network Group (C-SING): insights from a Nationwide Multicenter Observational Study

Abstract Background/Introduction Conduction system pacing (CSP), encompassing His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has gained prominence in treating bradycardia and heart failure in recent years. Despite its increasing utilization, data on real-world adoption of CSP are limited. Purpose The C-SING study aimed at assessing patient characteristics, implant success, procedural details, and safety of CSP when performed in routine clinical practice. Methods Periprocedural data from 27 experienced CSP centers across Italy were collected on patients undergoing CSP implantation for various indications between January 2021 and January 2024. Results The study comprised 1,317 patients (median age 78 years [interquartile range, 71-83], male 66.2%). Leading indications included atrioventricular (AV) block (40.8%), sinus node dysfunction (12.1%), atrial fibrillation with bradycardia (9.7%), AV node ablation (9.5%), and heart failure (12.5%). Pacemakers were implanted in 77.3% of patients, cardiac resynchronization devices in 21.7%, and implantable cardioverter-defibrillators in 1.0%. Stylet-driven and lumenless CSP leads were utilized in 64.7% and 35.3% of procedures, respectively. Final 12-lead ECG assessment revealed LBBAP capture in 88.7% patients, HBP in 8.4% (selective 4.2%, non-selective 4.2%), and no CSP capture in 3.0%, resulting in a 97.0% CSP lead implantation success rate. In patients with LBBAP, predominant capture types were left bundle branch pacing (19.6%), left posterior fascicular pacing (19.2%), and left septal fascicular pacing (14.8%). Comparing HBP to LBBAP, the latter showed shorter procedural time (60 minutes [45-80] vs. 70 minutes [60-95], p=0.003), but similar fluoroscopy time (6.0 minutes [3.3-10.8] vs. 6.1 minutes [4-10], p=0.735). Paced QRS duration was longer in LBBAP (118 ms [105-130]) compared to HBP (110 ms [101-122], p<0.001). LBBAP showed lower capture thresholds (0.6 V [0.5-0.9] @0.4 ms vs. 0.8 V [0.5-1.5] @1.0 ms, p<0.001) and higher R-wave sensing (10.7 mV [8-16] vs. 4.5 mV [2.4-9.9], p<0.001). The rate of periprocedural complications was higher in patients with LBBAP than HBP (7.3% vs. 1.8%, p=0.03), with the most frequent events being intraprocedural perforation into the left ventricular cavity during lead screwing (2.6%) and CSP lead dislodgment before hospital discharge (1.4%). These occurrences necessitated lead repositioning without additional complications. Conclusion CSP demonstrated feasibility as a primary pacing strategy for various indications in a real-world, multicenter setting. LBBAP, more frequently used than HBP, exhibited shorter procedural time and superior acute electrical parameters. LBBAP revealed a higher rate of minor procedural complications than HBP. Further investigations, supported by additional long-term outcome data, are essential to comprehensively assess CSP performance.

Temporal trends of catheter ablation procedures in patients with atrial fibrillation and atrial flutter: A nationwide cohort study

BackgroundCatheter ablation is a well-established treatment to prevent atrial fibrillation (AF) and atrial flutter (AFL) recurrences and to relieve symptoms, whereas pacemaker implantation and atrioventricular node (AVN) ablation is used for rate control when medical therapy fails. AimsWe investigated temporal trends and patient characteristics in catheter ablation procedures for AF, AFL and AVN in Finland between 2012–2018. MethodsFinnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a registry-based study including all patients with AF or AFL in Finland between 2012–2018. ResultsThe number of patients with AF or AFL diagnosis in Finland increased from 185057 to 243802 between 2012–2018 and a total of 8954 first-time catheter ablation procedures were performed. Of them, 4909 (54.8 %) were AF ablations, 2731 (30.5 %) AFL ablations and 1314 (14.7 %) AVN ablations. The procedural numbers increased from 457/year to 934/year for AF, from 223/year to 553/year for AFL and from 114/year to 238/year for AVN. Altogether, 0.65% of all patients with diagnosed AF or AFL underwent AF, AFL or AVN ablation in 2018. The mean age of the patients increased in all ablation groups. Patients undergoing AF and AFL ablations were predominantly men (69.7 % and 74.6 % respectively) whereas patients undergoing AVN ablation were more often women (56.9%). ConclusionsThe use of catheter ablation more than doubled during 2012–2018 and the increase was particularly seen in the elderly patients. Nevertheless, only a minority of AF and AFL patients were treated with catheter ablations.

Comparing Low-to-Zero Fluoroscopic Navigation Systems for AVNRT Catheter Ablation: A Network Meta-Analysis.

Low-to-zero fluoroscopic navigation systems lower radiation exposure which improves health outcomes. Conventional x-ray fluoroscopy (CF) has long been the standard to guide to catheter location for cardiac ablation. With advancements in technology, alternative safety navigation systems have been developed. Three primary modalities commonly utilized are three-dimensional electroanatomic mapping (3D-EAM), magnetic navigation system (MNS), and intracardiac echocardiography (ICE), all of which can reduce radiation exposure during the procedure. We aim to compare the efficacy and safety among ICE, EAM, MNS, and CF in ablation of atrioventricular nodal reentrant tachycardia (AVNRT). This is a meta-analysis consisting of observational studies and randomized controlled trials, which evaluated the performance of navigation systems of catheter ablation in AVNRT patients. Primary endpoint was to access the AVNRT recurrence after the procedure during follow-up periods. Secondary endpoints were technical success, fluoroscopic time, fluoroscopic dose area product, radiofrequency ablation time, and adverse events. Random-effect model was applied for pooled estimated effects of included studies. A total of 21 studies (21 CF, 2 ICE, 9 EAM, 11 MNS) including 1716 patients who underwent catheter ablation for AVNRT treatment were analyzed. Of these, 16 were observational studies and 5 were randomized controlled trials. Point estimation of AVNRT recurrence showed ICE exhibited a pooled odds ratio (ORs) of 1.06 (95% confidence interval [CI]: 0.064-17.322), MNS with ORs of 0.51 (95% CI: 0.214-1.219], and EAM with ORs of 0.394 (95% CI: 0.119-1.305) when compared to CF. EAM had significant higher technical success with ORs of 2.781 (95% CI: 1.317-5.872) when compared to CF. Regarding fluoroscopy time, EAM showed the lowest time with mean differences (MD) of -10.348 min (95% CI: -13.385 to -7.3101) and P-score of 0.998. It was followed by MNS with MD of -3.712 min (95% CI: -7.128 to -0.295) and P-score of 0.586, ICE with MD of -1.150 min (95% CI: -6.963 to 4.662) with a P-score of 0.294 compared to CF, which has a P-score of 0.122. There were insignificant adverse events across the procedures. AVNRT ablation navigated by low-to-zero fluoroscopic navigation systems achieves higher efficacy and comparable safety to conventional fluoroscopywhile also reducing risk of radiation exposure time.

His bundle pacing is continually relevant for patients with atrial fibrillation and bradycardia without prior atrioventricular nodal ablation, data from mid-term follow-up.

In patients with atrial fibrillation (AF) and symptomatic bradycardia, His Bundle pacing (HBP) is used to achieve an appropriate heart rate and physiological depolarization of the left ventricle (LV). We aimed to evaluate the impact of HBP on LV function in two different populations: normal LV ejection fraction (LVEF) and low LVEF (<50%). Patients who received HBP as de novo therapy or as an upgrade were divided into two groups based on initial LVEF, followed by echocardiographic and device monitoring. One hundred and twenty three patients (aged 76.0 [69.2-79.8] years, 74.0% men) with AF and bradycardia received HBP and completed follow-up with a median of 6.2 months (6.0-8.0). LV function remained unchanged in initially normal LV function patients (65 participants, LVEF 59.0% [55.0 - 62.0] vs. 58.0% [55.0-63.0]). In patients with low LVEF (58 participants), there was an increase in LVEF (37.5% [30.0-43.0] vs. 44.0% [35.0-50.0]; p < 0.0001), reduction of indexed LV end-systolic volume (62.4 [20.7] ml vs. 51.5 [21.5] ml; p = 0.001) and indexed LV end-diastolic volume (97.5 [26.2] ml vs. 88.1 [25.1] ml; p = 0.009), and improvement in the New York Heart Association class (2.3 [0.71] to 1.6 [0.9]; p < 0.0001). With permanent HBP, patients with AF and bradycardia and without prior atrioventricular nodal ablation did not experience LV systolic function deterioration. Those with reduced baseline LVEF experienced improvements in LV function and its reverse remodeling at the mid-term follow-up.

Clinical features of suspected and unsuspected fatal pulmonary emboli in hospitalized patients.

Pulmonary embolism (PE) is often unsuspected by treating clinicians. Since the adoption of clinical prediction scores for PE and the widespread availability of computed tomography (CT)-pulmonary angiogram, there are few reports of clinical presentations of hospitalized patients who died of PE. To compare the clinical signs, symptoms, and comorbidities of hospitalized patients who died of PE for whom PE was suspected versus not suspected antemortem. Case-control study from January 1999 to December 2018 in one Veterans Affairs (VA) hospital. We compared groups to examine differences in clinical presentations of fatal PE over the two decades. Among 1345 autopsies performed during the study period, 52 patients (4%) with fatal PE were included in the final analyses. PE was unsuspected before death in 29/52 patients (56%). Comparing groups, there were significant differences for: dyspnea (suspected 91%; unsuspected: 59%, p = 0.01); active malignancy (suspected 74%; unsuspected: 28%, p = 0.002); and atrioventricular (AV) nodal blocking treatment (suspected: 62%; unsuspected 30%,p= 0.03). A greater proportion of patients with unsuspected PE lacked symptoms of PE (suspected 0%; unsuspected: 31%, p = 0.003). Fatal PE remains a common, unsuspected cause of inpatient death in the modern era. Symptoms of PE, active malignancy, and potentially confounding AV nodal blocking treatment were less frequent in patients with unsuspected PE. These data highlight the variation in presentation and the challenge of making the diagnosis in many hospitalized patients, particularly those without typical symptoms.

Relevance of Anatomical Significance of AV Nodal Structures within Koch's Triangle and Pyramid.

The exploration of the cardiac conduction system evolved over a century, marked by groundbreaking discoveries in atrioventricular (AV) nodal physiology. Atrioventricular nodal re-entrant tachycardia (AVNRT), the most prevalent regular tachycardia in humans, remains enigmatic despite extensive research. Detailed examinations of AV nodal anatomy and histology reveal variations in location and shape, influencing electrophysiological properties. Variability in AV nodal extensions and their embryological origins contribute to the complexity of the conduction system. Physiologically, the AV node plays a crucial role in modulating AV conduction, introducing delays for ventricular filling and filtering atrial impulses. Dual-pathway physiology involving fast and slow pathways further complicates AVNRT circuitry. Integrated approaches combining pre-procedural imaging with electroanatomical mapping enhance our understanding of AV nodal structures and high-definition mapping improves precision in identifying ablation targets. Electrophysiological-anatomical correlations may unveil the specific roles of conduction axis components, aiding in the optimization of ablation strategies. This review traces the historical journey from Tawara's pioneering work to recent integrated approaches aimed at unraveling the intricacies of AV nodal structures while emphasizing the importance of a multidimensional approach, incorporating technological advancements, anatomical understanding, and clinical validation in human mapping studies.

Formulation, Optimization, and Evaluation of Solid-lipid Formulation for Bioavailability Enhancement Utilizing Diltiazem Hydrochloride

Background: Cardiac arrhythmia is a health concern, requiring effective medication for proper treatment. Diltiazem hydrochloride (DTZ.HCL), a class IV anti-arrhythmic calcium channel blocker, was used as a model drug due to its ability to block Ca++ channels in the SA and AV nodes, reducing calcium entry into cardiac cells and subsequently decreasing the force of contraction and oxygen consumption by the heart. Despite its good oral absorption, DTZ.HCL bioavailability is reduced to approximately 40% due to extensive first-pass metabolism. A nano-enabled drug delivery system has the advantage of incorporating both lipophilic and hydrophilic drugs with improved physical stability and enhanced bioavailability. Objective: The objective of this study was to develop a solid-lipid formulation utilizing diltiazem hydrochloride and evaluate it for its bioavailability enhancement. Method: In the experimental study, SLNs were prepared using the microemulsion technique. A blend ratio (1:1) of lipid (stearic acid: compritol 888 ATO), span 80, PEG 200, and water was selected based on the microemulsion region obtained from the Triplot (4.1) ternary phase diagram. The hydrophilic drug diltiazem hydrochloride was incorporated into the lipid blend, and a preheated Smix was maintained at 80°C to obtain a transparent microemulsion, which then crystallized to form SLNs upon subsequent dispersion in cold water (1:25). Critical process parameters, including magnetic stirring speed, homogenizer speed, and probe sonication cycle, were optimized using Design Expert 10 software to achieve the desired particle size diameter, PDI, and entrapment efficiency. Results: The results revealed that the particle size and PDI were significantly influenced by the span 80 and PEG 200. An increase in the concentration of the lipid blend resulted in large particle sizes. The optimized formulation showed a particle size of 415.4±0.2 nm, PDI of 0.184±0.01, and zeta potential of -24.19±0.12 mV. These results were corroborated by DSC thermograms, which indicated reduced enthalpy associated with the reduced particle size of SLNs. Given that diltiazem hydrochloride is a hydrophilic drug with high water solubility, the entrapment efficiency was relatively 30.6% ±0.45. In vitro release studies demonstrated an initial burst release, followed by a sustained release of 85% over 24 hours. The optimized SLNs followed the Higuchi matrix model, with a coefficient of correlation (R²) value of 0.9369. Conclusion: Results concluded successful development of SLNs with improved bioavailability when compared by way of in-vitro method with marketed preparations.