Development of the Cardiac Conduction System.

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

An interesting electrocardiogram caused by lead reversal.

BACKGROUND: During normal sinus rhythm, atrial depolarization is conducted from right atrium to left atrium through Bachmann's bundle, and a normal P wave axis which is measured on the frontal plane is between 0º and + 75º. The change of P wave polarity is helpful for the analysis of origin point. CASE PRESENTATION: We report a patient with negative P wave in lead I. The characteristics of QRS complex in leads V1 to V6 are helpful to preliminarily differential diagnosis. The 12-lead electrocardiogram (ECG) with correct limb leads (right arm-left arm) placement shows sinus rhythm with complete right bundle branch block (RBBB). CONCLUSIONS: The change of P wave polarity as well as characteristics of QRS complex can help identify limb-lead reversals.

POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1S201F) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1S191F) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1S191F and popdc1 knock-out (popdc1KO) zebrafish larvae and adult isolated popdc1S191F hearts were studied by functional fluorescent analysis. It was found that in popdc1S191F and popdc1KO larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by ß-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1S191F zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1S191F hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.

Feasibility of a novel atrial mechanical sensing method for leadless atrioventricular synchronous pacing.

INTRODUCTION: Few studies have demonstrated a high degree of atrioventricular (AV) synchrony with a new leadless pacemaker called Micra AV. Our group previously reported a new and unique sensing method. We believe that this novel sensing method, "Simplified A3 method," might facilitate better AV synchrony than a conventional sensing method in almost all cases with Micra AV implantation. METHODS: We conducted a non-randomized retrospective study comparing the two pacing methods at two centers. From December 1, 2021 to October 31, 2022, Micra AV was implanted for 32 patients at the two centers. Twenty of the 32 patients with sinus rhythm and complete AV block were included in this study. In Group 1, the conventional setting was programmed as follows: auto A3 threshold, auto A3 window-end (WE), and auto A4 threshold turned on during hospitalization. In Group 2, the "Simplified A3 method" was programmed as follows: auto A3 threshold and auto A3WE turned off. Instead, an intentionally prolonged A3WE (850-1000 ms) and low A3 threshold (A3 signal amplitude + 0.5-1.0 m/s2) were programmed. RESULTS: Twenty patients were analyzed. In Group 2, AV synchrony (%AMVp) was significantly higher at the first outpatient clinic (63.0 ± 5.7% vs 81.0 ± 4.2%, p = .03). A3 threshold was significantly lower in Group 2 (5.9 ± 0.7 m/s2, p < .05 vs 2.3 ± 0.5 m/s2, p < .05). CONCLUSION: Our novel sensing method might be a more feasible sensing method for obtaining higher AV synchrony than the conventional algorithm.

Nonpharmacologic rate control of postoperative atrial fibrillation in the canine sterile pericarditis model.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is common following open heart surgery, and is associated with significant morbidity. Medications used for ventricular rate control of POAF may not be effective in controlling rapid ventricular rates during the postoperative period because of increased sympathetic tone. The purpose of this study was to develop nonpharmacologic rate control of POAF by atrioventricular node (AVN) fat pad stimulation using clinically available temporary pacing wires in the canine sterile pericarditis model. METHODS: We studied 10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-3. The AVN fat pad stimulation (amplitude 2-15 mA; frequency 20 Hz; pulse width 0.03-0.2 ms) was performed during sustained POAF (>5 min). We measured ventricular rate and inefficient ventricular contractions during sustained POAF and compared it with and without AVN fat pad stimulation. Also, the parameters of AVN fat pad stimulation to achieve a rate control of POAF were measured over the postoperative days. RESULTS: Eleven episodes of sustained POAF were induced in 5/10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-2. During POAF, the AVN fat pad stimulation decreased the ventricular rate from 178 ± 52 bpm to 100 ± 8 bpm in nine episodes. Nonpharmacologic rate control therapy successfully controlled the ventricular rate and eliminated inefficient ventricular contractions during POAF for the duration of the AVN fat pad stimulation. The AVN fat pad stimulation output remained relatively stable over the postoperative days. CONCLUSION: During sustained POAF, nonpharmacologic rate control by AVN fat pad stimulation effectively and safely controlled rapid ventricular rates throughout the postoperative period.

Voltage and propagation mapping: New tools to improve successful ablation of atrioventricular nodal reentry tachycardia.

INTRODUCTION: Mapping system is useful in ablation of atrioventricular nodal reentry tachycardia (AVNRT) and localization of anatomic variances. Voltage mapping identifies a low voltage area in the Koch triangle called low-voltage-bridge (LVB); propagation mapping identifies the collision point (CP) of atrial wavefront convergence. We conducted a prospective study to evaluate the relationship between LVB and CP with successful site of ablation and identify standard value for LVB. MATERIALS AND METHODS: Three-dimensional (3D) maps of the right atria were constructed from intracardiac recordings using the ablation catheter. Cut-off values on voltage map were adjusted until LVB was observed. On propagation map, atrial wavefronts during sinus rhythm collide in the site representing CP, indicating the area of slow pathway conduction. Ablation site was selected targeting LVB and CP site, confirmed by anatomic position on fluoroscopy and atrioventricular ratio. RESULTS: Twenty-seven consecutive patients were included. LVB and CP were present in all patients. Postprocedural evaluation identified standard cut-off of 0.3-1 mV useful for LVB identification. An overlap between LVB and CP was observed in 23 (85%) patients. Procedure success was achieved in all patient with effective site at first application in 22 (81%) patients. There was a significant correlation between LVB, CP, and the site of effective ablation (p = .001). CONCLUSION: We found correlation between LVB and CP with the site of effective ablation, identifying a voltage range useful for standardized LVB identification. These techniques could be useful to identify ablation site and minimize radiation exposure.

3D models of the cardiac conduction system in healthy neonatal human hearts.

Iatrogenic damage to the cardiac conduction system (CCS) remains a significant risk during congenital heart surgery. Current surgical best practice involves using superficial anatomical landmarks to locate and avoid damaging the CCS. Prior work indicates inherent variability in the anatomy of the CCS and supporting tissues. This study introduces high-resolution, 3D models of the CCS in normal pediatric human hearts to evaluate variability in the nodes and surrounding structures. Human pediatric hearts were obtained with an average donor age of 2.7 days. A pipeline was developed to excise, section, stain, and image atrioventricular (AVN) and sinus nodal (SN) tissue regions. A convolutional neural network was trained to enable precise multi-class segmentation of whole-slide images, which were subsequently used to generate high- resolution 3D tissue models. Nodal tissue region models were created. All models (10 AVN, 8 SN) contain tissue composition of neural tissue, vasculature, and nodal tissues at micrometer resolution. We describe novel nodal anatomical variations. We found that the depth of the His bundle in females was on average 304 µm shallower than those of male patients. These models provide surgeons with insight into the heterogeneity of the nodal regions and the intricate relationships between the CCS and surrounding structures.

Myocardial Injury Progression after Radiofrequency Ablation in School-Age Children. / Progressão da Lesão Miocárdica após Ablação por Radiofrequência em Crianças em Idade Escolar.

BACKGROUND: The past decades have seen the rapid development of the invasive treatment of arrhythmias by catheter ablation procedures. Despite its safety and efficacy being well-established in adults, to date there has been little data in pediatric scenarios. One of the main concerns is the possible expansion of the ablation procedure scar in this population and its consequences over the years. OBJECTIVES: This study aimed to analyze the risk of myocardial injury progression after radiofrequency catheter ablation in pediatric patients. METHODS: This is a retrospective study of 20 pediatric patients with previous ablation for treatment of supraventricular arrhythmia that underwent cardiac magnetic resonance and coronary angiography for evaluation of myocardial fibrosis and the integrity of the coronary arteries during follow-up. RESULTS: The median age at ablation procedure was 15.1 years (Q1 12.9, Q3 16.6) and 21 years (Q1 20, Q3 23) when the cardiac magnetic resonance was performed. Fourteen of them were women. Nodal reentry tachycardia and Wolf-Parkinson-White Syndrome were the main diagnosis (19 patients), with one patient with atrial tachycardia. Three patients had ventricular myocardial fibrosis, but with a volume < 0.6 cm 3 . None of them developed ventricular dysfunction and no patient had coronary lesions on angiography. CONCLUSION: Radiofrequency catheter ablation did not show to increase the risk of myocardial injury progression or coronary artery lesions.

FUNDAMENTO: As últimas décadas têm assistido ao rápido desenvolvimento do tratamento invasivo de arritmias por procedimentos de ablação por cateter. Apesar da sua segurança e eficácia bem estabelecida em adultos, até o momento, há poucos dados nos cenários pediátricos. Uma das principais preocupações é a possível expansão da cicatriz do procedimento de ablação nessa população e suas consequências ao longo dos anos. OBJETIVOS: Este estudo teve como objetivo analisar o risco da progressão da lesão miocárdica após ablação por cateter de radiofrequência em pacientes pediátricos. MÉTODOS: Este é um estudo retrospectivo de 20 pacientes pediátricos com tratamento prévio de arritmia supraventricular com ablação, submetidos à ressonância magnética cardíaca e angiografia coronária para avaliação de fibrose miocárdica e da integridade das artérias coronárias durante o acompanhamento. RESULTADOS: A idade mediana no procedimento de ablação foi 15,1 anos (Q1 12,9, Q3 16,6) e 21 anos (Q1 20, Q3 23) quando a ressonância magnética cardíaca foi realizada. Quatorze dos pacientes eram mulheres. Taquicardia por reentrada nodal e síndrome de Wolf-Parkinson-White foram os principais diagnósticos (19 pacientes), com um paciente com taquicardia atrial. Três pacientes apresentaram fibrose miocárdica ventricular, mas com um volume inferior a 0,6 cm 3 . Nenhum deles desenvolveu disfunção ventricular e nenhum paciente apresentou lesões coronarianos na angiografia. CONCLUSÃO: A ablação por cateter de radiofrequência não mostrou aumentar o risco de progressão de lesão miocárdica ou de lesões na artéria coronária.

Validation of dual atrioventricular nodal physiology in dual atrioventricular nodal non-reentrant tachycardia via adenosine triphosphate injection during atrial pacing: A novel insight into the role of leftward inferior extension.

INTRODUCTION: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) is a rare and challenging-to-diagnose arrhythmia, without previous reports associating it with a leftward inferior extension (LIE). METHODS: Diagnosis was made using adenosine triphosphate (ATP) injection during atrial pacing in a suspected DAVNNT patient. RESULTS: Ablation of the rightward inferior extension was unsuccessful in eliminating DAVNNT; however, subsequent ablation of the LIE successfully eradicated the arrhythmia. CONCLUSION: This unique case, marked by the first instance of DAVNNT caused by LIE, diagnosed through ATP injection, underscores the utility of this diagnostic approach and broadens the spectrum of our understanding and management of this condition.

High-density mapping of Koch's triangle during sinus rhythm and typical atrioventricular nodal re-entrant tachycardia, integrated with direct recording of atrio-ventricular node structure potential.

BACKGROUND: The mechanism of typical slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) and its anatomical and electrophysiological circuit inside the right atrium (RA) and Koch's Triangle (KT) are not well known. OBJECTIVE: To identify the potentials of the compact AV node and inferior extensions and to perform accurate mapping of the RA and KT in sinus rhythm (SR) and during AVNRT, to define the tachycardia circuit. METHODS: Consecutive patients with typical AVNRT were enrolled in 12 Italian centers and underwent mapping and ablation by means of a basket catheter with small electrode spacing for ultrahigh-density mapping and a modified signal-filtering toolset to record the potentials of the AV nodal structures. RESULTS: Forty-five consecutive cases of successful ablation of typical slow-fast AVNRT were included. The mean SR cycle length (CL) was 784.1 ± 6 ms and the mean tachycardia CL was 361.2 ± 54 ms. The AV node potential had a significantly shorter duration and higher amplitude in sinus rhythm than during tachycardia (60 ± 40 ms vs. 160 ± 40 ms, p < .001 and 0.3 ± 0.2 mV vs. 0.09 ± 0.12 mV, p < .001, respectively). The nodal potential duration extension was 169.4 ± 31 ms, resulting in a time-window coverage of 47.6 ± 9%. The recording of AV nodal structure potentials enabled us to obtain 100% coverage of the tachycardia CL during slow-fast AVNRT. CONCLUSION: Detailed recording of the potentials of nodal structures is possible by means of multipolar catheters for ultrahigh-density mapping, allowing 100% of the AVNRT CL to be covered. These results also have clinical implications for the ablation of right-septal and para-septal arrhythmias.

Variations in subtle cystic tumors of the atrioventricular node: Five autopsy cases.

Cystic tumor of the atrioventricular node (CTAVN) is the most common primary cardiac tumor cause of sudden death but is rarely found during forensic autopsy. We present five autopsy cases of sudden death from undiagnosed CTAVN. The tumors varied in their histological appearance, which may be related to their variation in clinical presentation. Some of the cases had been diagnosed with epilepsy before death; it seems that syncopal attacks caused by CTAVN may be misdiagnosed as epilepsy. When performing forensic autopsy, CTAVN should be considered in the differential diagnosis of sudden death. Careful examination of the cardiac conduction system is important in every sudden death case regardless of age.

Novel method to avoid serious injurious effects on the atrioventricular nodal (AVN) conduction during catheter ablation of the AVN slow pathway utilizing cryofreezing energy.

BACKGROUND: Slow pathway elimination of the atrioventricular node (AVN) is essential to treat AVN reentrant tachycardia (AVNRT). However, injury to the AVN conduction (IAVN) is one of the serious complications. Cryofreezing energy is expected to reduce the incidence of IAVN. This study aimed to investigate the usefulness of a novel method to avoid IAVN during cryoablation of AVNRT. METHODS: A total of 157 patients (average age, 65.8 years; male, 71) suffering from AVNRT were included. Once the AVNRT terminated during cryo-ablation, then rapid atrial constant pacing (RACP) was performed during freezing at a rate lower 10 bpm than that inducing Wenchebach AV block in 74 (47.1 %) patients (Group A). The RACP rate was decreasingly reduced by 10 bpm in case of the occurrence of IAVN. When the RACP reached 100 bpm, the cryoablation was prematurely terminated. Group B patients (83 = 52.9 %) underwent cryoablation during sinus rhythm. All patients were allocated in a randomized fashion. We compared the severity of the IAVN between Groups A and B. RESULTS: There were no significant differences at 12 months regarding the freedom from the AVNRT between Groups A and B. However, the duration of the IAVN was significantly longer in Group B than A (p = 0.02). There were no significant differences regarding the distance between the His recording sites and successful ablation sites between Groups A and B. No permanent IAVN requiring pacemaker implantation was provoked in either group. CONCLUSION: RACP was useful to avoid sustained and serious IAVN during cryoablation of AVNRT.

Site-specific effects of dobutamine on cardiac conduction and refractoriness.

BACKGROUND: Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature. OBJECTIVE: To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS. METHODS: From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing. RESULTS: For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted. CONCLUSION: In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.

The underrecognized and neglected compact atrioventricular nodal potential: clinical significance for preventing atrioventricular block during so-called slow pathway radiofrequency ablation.

BACKGROUND: The radiofrequency (RF) ablation target may be located at the compact atrioventricular node (AVN) region during so-called slow pathway (SP) RF ablation, potentially leading to transient or permanent atrioventricular block (AVB). However, related data are rare. METHODS: Among 715 index consecutive patients who underwent RF ablation for atrioventricular nodal re-entry tachycardia, 17 patients subsequently experienced transient or permanent AVB and were included in this retrospective observational study. RESULTS: Among the 17 patients, two patients (11.8%) developed transient first-degree AVB, four patients (23.5%) developed transient second-degree AVB, seven patients (41.2%) developed transient third-degree AVB, and four patients (23.5%) developed permanent third-degree AVB. During baseline sinus rhythm before the start of RF ablation, no His-bundle potential was recorded from the RF ablation catheter. During the so-called SP RF ablation that led to transient or permanent AVB, junctional rhythm with ventriculoatrial (VA) conduction block followed by subsequent AVB was observed in 14 of 17 patients (82.4%), and a low-amplitude, low-frequency hump-shaped atrial potential was recorded before the start of RF ablation in 7 of the 17 patients (41.2%). Direct AVB occurred in 3 of the 17 patients (17.6%), and a low-amplitude, low-frequency hump-shaped atrial potential was recorded before the start of RF ablation in all 3 patients. CONCLUSIONS: The low-amplitude, low-frequency hump-shaped atrial potential recorded at the so-called SP region may reflect the electrogram of compact AVN activation, and RF ablation to this site heralds impending AVB even when a His-bundle potential is not recorded.

Successful Catheter Ablation for Paroxysmal Supraventricular Tachycardia with Two Alternating Cycle Lengths.

A 62-year-old male was transferred to our hospital complaining of palpitations. His heart rate was 185/min. Electrocardiogram showed a narrow QRS regular tachycardia and the tachycardia changed spontaneously to another narrow QRS tachycardia with two alternating cycle lengths. The arrhythmia was stopped by the administration of adenosine triphosphate. Findings from electrophysiological study suggested that there was an accessory pathway (AP) and dual atrioventricular (AV) nodal pathways. After AP ablation, any other tachyarrythmias were not induced. We supposed that the tachycardia was paroxysmal supraventricular tachycardia involving AP and anterograde conduction alternating between slow and fast AV nodal pathways.