Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions. In this study, we describe an approach for optical mapping of the retrogradely perfused chick heart in the last third of the incubation period. This system showed stability for electrophysiological measurement for several hours. This feature allowed analysis of the number and functionality of the APs separately in each clinically relevant position. Under physiological conditions, we also recorded the shortening of the AV delay with annulus fibrosus maturation and analyzed ventricular activation patterns after conduction through APs at specific locations. We observed a gradual regression of AP with an area-specific rate (left-sided APs disappeared first). The results also revealed a sudden drop in the number of active APs between embryonic days 16 and 18. Accessory myocardial AV connections were histologically documented in all positions around the annulus fibrosus even after hatching. The fact that no electrically active AP was present at this stage highlights the necessity of electrophysiological evaluation of accessory atrioventricular connections in studying AP formation.NEW & NOTEWORTHY We present the use of retrograde perfusion and optical mapping to investigate, for the first time, the regression of accessory pathways during annulus fibrosus maturation, separately examining each clinically relevant location. The system enables measurements under physiological conditions and demonstrates long-lasting stability compared with other approaches. This study offers applications of the model to investigate electrical and/or functional development in late embryonic development without concern about heart viability.

BACKGROUND: Severe first-degree atrioventricular (AV) block may produce symptoms similar to heart failure due to AV dyssynchrony, a syndrome termed AV dromotropathy. According to guidelines, it should be considered for permanent pacemaker implantation, yet evidence supporting this treatment is scarce.
OBJECTIVE: This study aimed to determine the impact of AV-optimized conduction system pacing (CSP) in patients with symptomatic severe first-degree AV block and echocardiographic signs of AV dyssynchrony.
METHODS: Patients with symptomatic first-degree AV block (PR > 250 ms), preserved left ventricular ejection fraction, narrow QRS, and AV dyssynchrony were included in the study. In a single-blind cross-over design, patients were randomized to AV sequential CSP or backup VVI pacing with a base rate of 40 bpm. We compared exercise capacity, echocardiographic parameters, and symptom occurrence at the end of 3 months of each period.
RESULTS: Fourteen patients completed the study. During the AV-optimized CSP compared to the backup pacing period, patients achieved a higher workload on exercise test (147.2 ± 50.9 vs. 140.7 ± 55.8 W; p = .032), with a trend towards higher peak VO2 (23.3 ± 7.1 vs. 22.8 ± 7.1 mL/min/kg; p = .224), and higher left ventricular stroke volume (LVSV 74.5 ± 13.8 vs. 66.4 ± 12.5 mL; p < .001). Symptomatic improvement was recorded, with fewer patients reporting general tiredness and 71% of patients preferring the AV-optimized CSP (p = .008).
CONCLUSIONS: AV-optimized CSP could improve symptoms, exercise capacity and LVSV in patients with severe first-degree AV block.

UNASSIGNED: The heart conduction system is responsible for the occurrence of various types of cardiac arrhythmia. This study aimed to histologically and morphometrically describe damaged cardiac nodes during acute myocardial infarction and to compare them with normal tissues in dogs and horses.
UNASSIGNED: This study describes the morphometry of cardiac nodes in five dogs and five elderly horses that succumbed to sudden cardiac death (SCD). A computerized morphometric study was conducted to determine the number of cells composing the nodes, different shape and size parameters of nodes, and their relationship with degenerative changes due to cardiac conditions.
UNASSIGNED: In both species, the sinoatrial node (SAN) was ovoid in shape whereas the atrioventricular node (AVN) was pyramidal in shape. The percentage of collagen fibers inside the SAN of dogs (47%) and horses (50%) was found to be higher than that of cells. In contrast, the percentage of cells in the AVN of dogs (24%) and horses (16%) was higher than that of connective tissues. In the SAN, the area (p = 0.09), maximum diameter (<0.001), and mean diameter (0.003) of P cells were larger in dogs than in horses.
UNASSIGNED: Overall, the SAN cells and surrounding cardiomyocytes in dogs and horses as well as the AVN cells in dogs that succumbed to SCD decreased in size compared with those in normal hearts.

Background Self-administration of investigational intranasal L-type calcium channel blocker etripamil during paroxysmal supraventricular tachycardia (PSVT) appeared safe and well-tolerated in the phase 3 NODE-301 (Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia) trial of adults with sustained atrioventricular nodal-dependent PSVT. The NODE-302 open-label extension further characterized etripamil safety and efficacy. Methods and Results Eligible patients were monitored via self-applied cardiac monitoring system for 5 hours after etripamil self-administration. The primary end point was time-to-conversion of positively adjudicated PSVT to sinus rhythm after etripamil treatment. Probability of conversion to sinus rhythm was reported via Kaplan-Meier plot. Adverse events were based on self-reported symptoms and clinical evaluations. Among 169 patients enrolled, 105 self-administered etripamil ≥1 time for perceived PSVT (median [range], 232 [8-584] days\' follow-up). Probability of conversion within 30 minutes of etripamil was 60.2% (median time to conversion, 15.5 minutes) among 188 PSVT episodes (92 patients) positively adjudicated as atrioventricular nodal dependent by independent ECG analysis. Among 40 patients who self-treated 2 episodes, 75% had a significantly consistent response by 30 minutes; 9 did not convert on either episode, and 21 converted on both episodes (χ2=8.09; P=0.0045). Forty-five of 105 patients (42.9%) had ≥1 treatment-emergent adverse event, generally transient and mild-to-moderate, including nasal congestion (14.3%), nasal discomfort (14.3%), or rhinorrhea (12.4%). No serious cardiac safety events were observed within 24 hours of etripamil. Conclusions In this extension study, investigational etripamil nasal spray was well tolerated for self-treating recurrent episodes of PSVT without medical supervision. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635996.

OBJECTIVE: Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy.
RESULTS: The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too.
CONCLUSIONS: LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF.

During electrophysiological mapping of tachycardias, putative target sites are often only truly confirmed to be vital after observing the effect of ablation. This lack of mapping specificity potentiates inadvertent ablation of innocent cardiac tissue not relevant to the arrhythmia. But if myocardial excitability could be transiently suppressed at critical regions, their suitability as targets could be conclusively determined before delivering tissue-destructive ablation lesions. We studied whether reversible pulsed electric fields (PFREV) could transiently suppress electrical conduction, thereby providing a means to dissect tachycardia circuits in vivo.
PFREV energy was delivered from a 9-mm lattice-tip catheter to the atria of 12 swine and 9 patients, followed by serial electrogram assessments. The effects on electrical conduction were explored in 5 additional animals by applying PFREV to the atrioventricular node: 17 low-dose (PFREV-LOW) and 10 high-dose (PFREV-HIGH) applications. Finally, in 3 patients manifesting spontaneous tachycardias, PFREV was applied at putative critical sites.
In animals, the immediate post-PFREV electrogram amplitudes diminished by 74%, followed by 78% recovery by 5 minutes. Similarly, in patients, a 69.9% amplitude reduction was followed by 84% recovery by 3 minutes. Histology revealed only minimal to no focal, superficial fibrosis. PFREV-LOW at the atrioventricular node resulted in transient PR prolongation and transient AV block in 59% and 6%, while PFREV-HIGH caused transient PR prolongation and transient AV block in 30% and 50%, respectively. The 3 tachycardia patients had atypical atrial flutters (n=2) and atrioventricular nodal reentrant tachycardia. PFREV at putative critical sites reproducibly terminated the tachycardias; ablation rendered the tachycardias noninducible and without recurrence during 1-year follow-up.
Reversible electroporation pulses can be applied to myocardial tissue to transiently block electrical conduction. This technique of pulsed field mapping may represent a novel electrophysiological tool to help identify the critical isthmus of tachycardia circuits.

BACKGROUND: There is currently no particularly effective strategy for patients with persistent atrial fibrillation accompanying heart failure with preserved ejection fraction (HFpEF), especially with recurrent atrial fibrillation after ablation. In this study, we will evaluate a new treatment strategy for patients with persistent atrial fibrillation who had at least two attempts (≧2 times) of radio-frequency catheter ablation but experienced recurrence, and physiologic conduction was reconstructed after atrioventricular node ablation or drug therapy, to control the patient\'s ventricular rate to maintain a regular heart rhythm, which is called His-Purkinje conduction system pacing (HPCSP) with atrioventricular node ablation.
RESULTS: This investigator-initiated, multicenter prospective randomized controlled trial aimed to recruit 296 randomized HFpEF patients with recurrent atrial fibrillation. All the enrolled patients were randomly assigned to the pacing group or the drug treatment group. The primary endpoint is differences in cardiovascular events and clinical composite endpoints (all-cause mortality) between patients in the HPCSP and drug-treated groups. Secondary endpoints included heart failure hospitalization, exercise capacity assessed by cardiopulmonary exercise tests, quality of life, echocardiogram parameters, 6-minute walk distance, NT-ProBNP, daily patient activity levels, and heart failure management report recorded by the CIED. It is planned to compete recruitment by the end of 2023 and report in 2025.
CONCLUSIONS: The study aims to determine whether His-Purkinje conduction system pacing with atrioventricular node ablation can better improve patients\' symptoms and quality of life, postpone the progression of heart failure, and reduce the rate of rehospitalization and mortality of patients with heart failure.
BACKGROUND: ChiCTR1900027723, URL: http://www.chictr.org.cn/edit.aspx?pid=46128&htm=4.

Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT.
NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration.
NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events.
Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting.
URL: https://www.
gov; Unique identifier: NCT03464019.

The cardiac conduction system (CCS) is crucial for regulating heartbeats; therefore, clinicians and comedicals involved in cardiovascular medicine treatment must have a thorough understanding of the CCS structure and function. However, anatomical education of the CCS based on actual dissection and observation is uncommon, although such educational methodology promotes three-dimensional structural understanding of the observed object. Based on previous studies, we examined the CCS structure in the heart of a swine (pig, Sus scrofa domestica) which has been used in the biological, medical and anatomical curricula as science teaching materials, by using macroscopic dissection procedures. Most CCS structures in a young pig heart were successfully identified and illustrated on a macroscopic scale. The atrioventricular bundle (His bundle) was located on the lower edge of the membranous interventricular septum and was clearly distinguished from the general myocardial fibres by its colour and fibre arrangement direction. Following the atrioventricular bundle towards the atrium or ventricle with properly removing the endocardium and myocardium, the atrioventricular node or the right and left bundles appeared respectively. In contrast, the sinoatrial node was not identified. The anatomy of the CCS in young pig hearts was essentially similar to that previously reported in humans and several domestic animals. Our findings of the CCS in young pig hearts are expected to be useful for medical and anatomical education for medical and comedical students, young clinicians and comedical workers.

Interventional cardiology procedures may expose patients and staff to considerable radiation doses. We aimed to assess whether exposure to ionizing radiation during catheter ablation of supraventricular tachycardia (SVT) can be completely avoided.
In this prospective randomized study, patients with SVT (atrioventricular re-entrant tachycardia n = 94, typical atrial flutter n = 29) were randomly assigned in a 1:1 ratio to catheter ablation with conventional fluoroscopic guidance (CF group) or with the EnSite Precision mapping system [zerofluoro (ZF) group]. Acute procedural parameters, increased stochastic risk of cancer incidence and 6-month follow-up data were assessed. Between May 2019 and August 2020, 123 patients were enrolled. Clinical parameters were comparable. Median procedural time was 60.0 and 58.0 min, median fluoroscopy time and estimated median effective dose were 240 s vs. 0 and 0.38 mSv vs. 0 and arrhythmia recurrence was 5% and 7.9% in the CF and ZF groups, respectively. The acute success rate was 98.4% in both groups. No procedure-related complications were reported. At an average age of 55.5 years and median radiation exposure of 0.38 mSv, the estimate of increased incidence was approximately 1 in 14 084. The estimated mortality rate was 1 per 17 857 exposed persons.
The procedural safety and efficacy of the zero-fluoroscopic approach are similar to those of conventional fluoroscopy-based ablation for atrioventricular nodal re-entrant tachycardia and atrial flutter. Under the assumption of low radiation dose, the excessive lifetime risk of malignancy in the CF group due to electrophysiology procedure is reasonably small, whilst totally reduced in zero fluoroscopy procedures.