Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

BACKGROUND: A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. METHODS: Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. RESULTS: A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. CONCLUSIONS: In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. OBJECTIVE: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. METHODS: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. RESULTS: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%-3.6%] vs 2.6% [2.1%-6.4%], P = .541; CB: 1.7% [0.9%-3.1%] vs 1.5% [0.5%-2.8%], P = .600; LVA: 4.7% [1.6%-7.7%] vs 2.9% [2.1%-7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. CONCLUSION: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population.

Atrial extrasystoles enhance low-voltage fractionation electrograms in patients with atrial fibrillation.

BACKGROUND AND AIMS: Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy. METHODS AND RESULTS: Intra-operative high-resolution epicardial mapping of the right and left atrium, Bachmann's Bundle, and pulmonary vein area was performed during sinus rhythm (SR) in 287 patients (60 with AF). AES were categorized according to their prematurity index (>25% shortening) and degree of aberrancy (none, mild/opposite, moderate and severe). In total, 837 unique AES (457 premature; 58 mild/opposite, 355 moderate, and 154 severe aberrant) were included. The average prematurity index was 28% [12-45]. Comparing SR and AES, average voltage decreased (-1.1 [-1.2, -0.9] mV, P < 0.001) at all atrial regions, whereas the amount of LVAs and fractionation increased (respectively, +3.4 [2.7, 4.1] % and +3.2 [2.6, 3.7] %, P < 0.001). Only weak or moderate correlations were found between EGM morphology parameters and prematurity indices (R2 < 0.299, P < 0.001). All parameters were, however, most severely affected by either mild/opposite or severely aberrant AES, in which the effect was more pronounced in AF patients. Also, there were considerable regional differences in effects provoked by AES. CONCLUSION: Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. AF patients have more direction-dependent conduction disorders, indicating enhanced non-uniform anisotropy that is uncovered by spontaneous AES.

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology: Towards Patient-Tailored Cardiac Neuromodulation.

BACKGROUND: Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation. However, a lack in understanding of the exact antiarrhythmic properties of tLLVNS has hampered clinical implementation. OBJECTIVES: In this study, the authors aimed to study the effects of tLLVNS on atrial electrophysiology by performing intraoperative epicardial mapping during acute and chronic tLLVNS. METHODS: Epicardial mapping of the superior right atrium was performed before and after arterial graft harvesting in patients undergoing coronary artery bypass grafting without a history of atrial fibrillation. The time needed for arterial graft harvesting was used to perform chronic tLLVNS. Electrophysiological properties were compared before and during chronic tLLVNS. RESULTS: A total of 10 patients (median age 74 years [IQR: 69-78 years]) underwent tLLVNS for a duration of 56 minutes (IQR: 43-73 minutes). During acute and chronic tLLVNS, a shift of the sinoatrial node exit site toward a more cranial direction was observed in 5 (50%) patients. Unipolar potential voltage increased significantly during acute and chronic tLLVNS (3.9 mV [IQR: 3.1-4.8 mV] vs 4.7 mV [IQR: 4.0-5.3 mV] vs 5.2 mV [IQR: 4.8-7.0 mV]; P = 0.027, P = 0.02, respectively). Total activation time, slope of unipolar potentials, amount of fractionation, low-voltage areas and conduction velocity did not differ significantly between baseline measurements and tLLVNS. Two patients showed consistent "improvement" of all electrophysiological properties during tLLVNS, while 1 patient appeared to have no beneficial effect. CONCLUSIONS: We demonstrated that tLLVNS resulted in a significant increase in unipolar potential voltage. In addition, we observed the following in selective patients: 1) reduction in total activation time; 2) steeper slope of unipolar potentials; 3) decrease in the amount of fractionation; and 4) change in sinoatrial node exit sites.

Outcomes of concomitant surgical ablation in patients undergoing surgical myectomy for hypertrophic obstructive cardiomyopathy: A systematic review and meta-analysis.

OBJECTIVE: Studies investigating the efficacy of concomitant surgical atrial fibrillation (AF) ablation in hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing myectomy are scarce and limited in terms of sample size. We aim to summarize current outcomes of concomitant surgical AF ablation in HOCM patients undergoing surgical myectomy. METHODS: This systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included all studies reporting any of the following outcomes of concomitant surgical AF ablation in HOCM patients: freedom from recurrence of AF, overall survival and complications. Outcomes were evaluated using traditional meta-analysis at given time-points and using pooled Kaplan-Meier curves. RESULTS: A total of 13 studies were included, resulting in a total of 616 individual patients available for analysis. AF was paroxysmal in 68.1% of the patients (95% CI 56.0-78.2%; I2 = 87.1%; 8 studies, 583 participants). The majority of patients (86.2%) underwent either conventional Cox Maze III or IV (95% CI 39.7-98.3%; I2 = 92.4%; 8 studies, 616 patients) procedure. The incidence of early post-operative pacemaker implantation was 6.1% (95% CI 3.1-11.8%). Overall survival at 3, 5 and 7 years was 95.6% (95% CI 93.4-97.9%), 93.6% (95% CI 90.8-96.5%) and 90.5% (95% CI 86.5-94.6%), respectively. Freedom from recurrent AF at 3, 5 and 7 years was 77.6% (95% CI 73.7-81.7%), 70.6% (95% CI 65.8-75.7) and 63.2% (95% CI 56.2-73.8%), respectively. CONCLUSION: This meta-analysis supports concomitant surgical AF ablation at the time of surgical myectomy in HOCM patients, as it seems to be safe and effective in terminating AF.

Mapping-guided atrial lead placement determines optimal conduction across Bachmann's bundle: a rationale for patient-tailored pacing therapy.

AIMS: Conventional right atrial appendage (RAA) pacing is associated with increased atrial activation time resulting in higher incidences of atrial tachyarrhythmia. Optimal pacing sites ideally shorten inter-atrial conduction delay, thereby decreasing atrial excitation time. We therefore examined the impact of programmed electrical stimulation (PES) from the right atrium (RA) and left atrium (LA) on the electrophysiological properties of Bachmann's bundle (BB). METHODS AND RESULTS: High-resolution epicardial mapping of BB was performed during sinus rhythm (SR) and PES in 34 patients undergoing cardiac surgery. Programmed electrical stimulation was performed from the RAA, junction of the RA with inferior caval vein (LRA), and left atrial appendage (LAA). Pacing from either the RAA or LAA resulted in, respectively, right- and left-sided conduction across BB. However, during LRA pacing in most patients (n = 15), activation started in the centre of BB. The total activation time (TAT) of BB during RAA pacing [63 (55-78) ms] was similar to that of SR [61 (52-68) ms, P = 0.464], while it decreased during LRA [45 (39-62) ms, P = 0.003] and increased during LAA pacing [67 (61-75) ms, P = 0.009]. Reduction of both conduction disorders and TAT was most often achieved during LRA pacing (N = 13), especially in patients who already had a higher amount of conduction disorders during SR [9.8 (7.3-12.3) vs. 4.5 (3.5-6.6)%, P < 0.001]. CONCLUSION: Pacing from the LRA results in a remarkable decrease of TAT compared with pacing from the LAA or RAA. As the most optimal pacing site varies between patients, individualized positioning of the atrial pacing lead guided by mapping of BB may be one of the new frontiers for atrial pacing.

Case report: peri-device leakage after percutaneous left atrial appendage occlusion: plug, clip, or amputate?

Background: Although peri-device leakage is frequently observed after left atrial appendage occlusion (LAAO), there is no consensus on the optimal management strategy. It is unknown whether additional plugging should be preferred over surgical exclusion of the LAA, as experience with additional plugging is limited. Case summary: In this case report, we demonstrate the clinical implications of additional plugging and surgical exclusion in a 65-year-old male patient with peri-device leakage and recurrent thromboembolic events. After the recurrence of paroxysmal atrial fibrillation (AF) and a transient ischaemic attack despite adequate anticoagulation, the patient was opted for re-do pulmonary vein isolation and LAAO with a Watchman device. Due to multiple ischaemic strokes and recurrent AF in combination with significant peri-device leakage, additional plugging with a second device was performed. Post-procedurally, the patient had another ischaemic stroke and persisting peri-device leakage was observed during follow-up. Due to progressive symptoms of AF and patient's preference to discontinue DOAC, he underwent a Cox MAZE IV procedure, including amputation of the LAA with both devices. Within six months after surgery, the patient experienced two more ischaemic events. In the following two years, the patient remained free of any cerebrovascular accidents or recurrence of AF. Discussion: Additional plugging of peri-device leakage is not always successful in stroke prevention. In combination with recurrent AF, progressive symptoms, contraindication for oral anticoagulation, and patient's preference, surgical LAA exclusion could be preferred over additional plugging.

Premature atrial contractions promote local directional heterogeneities in conduction velocity vectors.

AIMS: Loss of cell-to-cell communication results in local conduction disorders and directional heterogeneity (LDH) in conduction velocity (CV) vectors, which may be unmasked by premature atrial contractions (PACs). We quantified LDH and examined differences between sinus rhythm (SR) and spontaneous PACs in patients with and without atrial fibrillation (AF). METHODS AND RESULTS: Intra-operative epicardial mapping of the right and left atrium (RA, LA), Bachmann's bundle (BB) and pulmonary vein area (PVA) was performed in 228 patients (54 with AF). Conduction velocity vectors were computed at each electrode using discrete velocity vectors. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. Five hundred and three PACs [2 (1-3) per patient; prematurity index of 45 ± 12%] were included. During SR, most LDH were found at BB and LA [11.9 (8.3-14.9) % and 11.3 (8.0-15.2) %] and CV was lowest at BB [83.5 (72.4-94.3) cm/s, all P < 0.05]. Compared with SR, the largest increase in LDH during PAC was found at BB and PVA [+13.0 (7.7, 18.3) % and +12.5 (10.8, 14.2) %, P < 0.001]; CV decreased particularly at BB, PVA and LA [-10.0 (-13.2, -6.9) cm/s, -9.3 (-12.5, -6.2) cm/s and -9.1 (-11.7, -6.6) cm/s, P < 0.001]. Comparing patients with and without AF, more LDH were found during SR in AF patients at PVA and BB, although the increase in LDH during PACs was similar for all sites. CONCLUSION: Local directional heterogeneity is a novel methodology to quantify local heterogeneity in CV as a possible indicator of electropathology. Intra-operative high-resolution mapping indeed revealed that LDH increased during PACs particularly at BB and PVA. Also, patients with AF already have more LDH during SR, which becomes more pronounced during PACs.

Unravelling early sinus node dysfunction after pediatric cardiac surgery: a pre-existing arrhythmogenic substrate.

Early post-operative sinus node dysfunction (SND) is common in paediatric patients undergoing surgical correction of congenital heart defects (CHD). At present, the pathophysiology of these arrhythmias is incompletely understood. In this case series, we present three paediatric patients in whom we performed intraoperative epicardial mapping and who developed early post-operative SND. All patients had either an inferior or multiple sinoatrial node (SAN) exit sites, in addition to extensive conduction disorders at superior and inferior right atrium. Our findings contribute to the hypothesis that pre-existing alterations in SAN exit sites in combination with atrial conduction disorders may predispose paediatric patients with CHD for early post-operative SND. Such insights in the development of arrhythmias are crucial as it may be the first step in identifying high-risk patients.

In-vivo Sino-Atrial Node Mapping in Children and Adults With Congenital Heart Disease.

Background: Sinus node dysfunction (SND) and atrial tachyarrhythmias frequently co-exist in the aging patient with congenital heart disease (CHD), even after surgical correction early in life. We examined differences in electrophysiological properties of the sino-atrial node (SAN) area between pediatric and adult patients with CHD. Methods: Epicardial mapping of the SAN was performed during sinus rhythm in 12 pediatric (0.6 [0.4-2.4] years) and 15 adult (47 [40-55] years) patients. Unipolar potentials were classified as single-, short or long double- and fractionated potentials. Unipolar voltage, relative R-to-S-amplitude ratio and duration of all potentials was calculated. Conduction velocity (CV) and the amount of conduction block (CB) was calculated. Results: SAN activity in pediatric patients was solely observed near the junction of the superior caval vein and the right atrium, while in adults SAN activity was observed even up to the middle part of the right atrium. Compared to pediatric patients, the SAN region of adults was characterized by lower CV, lower voltages, more CB and a higher degree of fractionation. At the earliest site of activation, single potentials from pediatrics consisted of broad monophasic S-waves with high amplitudes, while adults had smaller rS-potentials with longer duration which were more often fractionated. Conclusions: Compared to pediatric patients, adults with uncorrected CHD have more inhomogeneous conduction and variations in preferential SAN exit site, which are presumable caused by aging related remodeling. Long-term follow-up of these patients is essential to demonstrate whether these changes are related to development of SND and also atrial tachyarrhythmias early in life.

The First Evaluation of Remote Magnetic Navigation-Guided Pediatric Ventricular Arrhythmia Ablation.

Catheter ablation (CA) is an important treatment option for ventricular arrhythmias (VA) in pediatric cardiology. Currently, various CA techniques are available, including remote magnetic navigation (RMN)-guided radiofrequency (RF) ablation. However, no studies evaluate RMN-guided ablative therapy outcomes in children with VA yet. This study aimed to compare procedural and long-term outcomes between RMN-guided and manual (MAN)-guided VA ablation in children. This single-center, retrospective study included all CA procedures for VA performed in children with or without structural heart disease from 2008 until 2020. Two study groups were defined by CA technique: RMN or MAN. Primary outcome was recurrence of VA. Baseline clinical, procedural and safety data were also evaluated. This study included 22 patients, who underwent 30 procedures, with a median age of 15 (IQR 14-17; range 1-17) years and a mean weight of 57 ± 20 kg. In total, 14 procedures were performed using RMN and 16 using MAN (22 first and 8 redo procedures). Regarding first procedures, recurrence rates were significantly lower in RMN compared to MAN (20% versus 67%, P = 0.029), at a mean follow-up of 5.2 ± 3.0 years. Moreover, fluoroscopy dosages were significantly lower in RMN compared to MAN [20 (IQR 14-54) versus 48 (IQR 38-62) mGy, P = 0.043]. In total, 20 patients (91%) were free of VA following their final ablation procedure. This is the first study to investigate the use of RMN in pediatric VA ablation. RMN showed improved outcomes compared to MAN, resulting in lower VA recurrence and reduced fluoroscopy exposure.

Epicardial high-resolution mapping of advanced interatrial block: Relating ECG, conduction abnormalities and excitation patterns.

Background: Impairment of conduction across Bachmann's Bundle (BB) may cause advanced interatrial block (a-IAB), which in turn is associated with development of atrial fibrillation. However, the exact relation between a complete transverse line of conduction block (CB) across BB and the presence of a-IAB has not been studied. Objective: The aims of this study are to determine whether (1) a complete transversal line of CB across BB established by high resolution mapping correlates with a-IAB on the surface ECG, (2) conduction abnormalities at the right and left atria correlate with a-IAB, and (3) excitation patterns are associated with ECG characteristics of a-IAB. Methods: We included 40 patients in whom epicardial mapping revealed a complete transverse line of CB across BB. Pre-operative ECGs and post-operative telemetry were assessed for the presence of (a) typical a-IAB and de novo early post-operative AF (EPOAF), respectively. Total atrial excitation time (TAET) and RA-LA delay were calculated. Entry site and trajectory of the main sinus rhythm wavefront at the pulmonary vein area (PVA) were assessed. Results: Thirteen patients were classified as a-IAB (32.5%). In the entire atria and BB there were no differences in conduction disorders, though, patients with a-IAB had an increased TAET and longer RA-LA delay compared to patients without a-IAB (90.0 ± 21.9 ms vs. 74.9 ± 13.0 ms, p = 0.017; 160.0 ± 27.0 ms vs. 136.0 ± 24.1 ms, p = 0.012, respectively). Patients with typical a-IAB solely had caudocranial activation of the PVA, without additional cranial entry sites. Prevalence of de novo EPOAF was 69.2% and was similar between patients with and without a-IAB. Conclusion: A transverse line of CB across BB partly explains the ECG characteristics of a-IAB. We found atrial excitation patterns underlying the ECG characteristics of both atypical and typical a-IAB. Regardless of the presence of a-IAB, the clinical impact of a complete transverse line of CB across BB was reflected by a high incidence of de novo EPOAF.

Remote magnetic navigation shows superior long-term outcomes in pediatric atrioventricular (nodal) tachycardia ablation compared to manual radiofrequency and cryoablation.

BACKGROUND: Catheter ablation (CA) is the first-choice treatment for tachyarrhythmia in children. Currently available CA techniques differ in mechanism of catheter navigation and energy sources. There are no large studies comparing long-term outcomes between available CA techniques in a pediatric population with atrioventricular reentry tachycardia (AVRT) or atrioventricular nodal reentry tachycardia (AVNRT) mechanisms. OBJECTIVE: This study aimed to compare procedural and long-term outcomes of remote magnetic navigation-guided radiofrequency (RF) ablation (RMN), manual-guided RF ablation (MAN) and manual-guided cryoablation (CRYO). METHODS: This single-center, retrospective study included all first consecutive CA procedures for AVRT or AVNRT performed in children without structural heart disease from 2008 to 2019. Three study groups were defined by the ablation technique used: RMN, MAN or CRYO. Primary outcome was long-term recurrence of tachyarrhythmia. RESULTS: In total, we included 223 patients, aged 14 (IQR 12-16) years; weighting 56 (IQR 47-65) kilograms. In total, 108 procedures were performed using RMN, 76 using MAN and 39 using CRYO. RMN had significantly lower recurrence rates compared to MAN and CRYO at mean follow-up of 5.5 ± 2.9 years (AVRT: 4.3% versus 15.6% versus 54.5%, P < 0.001; AVNRT: 7.7% versus 8.3% versus 35.7%, P = 0.008; for RMN versus MAN versus CRYO respectively). In AVNRT ablation, RMN had significantly lower fluoroscopy doses compared to CRYO [30 (IQR 20-41) versus 45 (IQR 29-65) mGy, P = 0.040). CONCLUSION: In pediatric patients without structural heart disease who underwent their first AV(N)RT ablation, RMN has superior long-term outcomes compared to MAN and CRYO, in addition to favorable fluoroscopy doses.

First Evidence of Atrial Conduction Disorders in Pediatric Patients With Congenital Heart Disease.

This study sought to investigate whether pediatric patients with congenital heart disease (CHD) already have atrial conduction disorders early in life. The authors conducted first-in-children epicardial mapping in 10 pediatric patients with CHD undergoing primary open heart surgery. Areas of conduction delay (CD) and block (CB) were present in all patients and were particularly observed at Bachmann's bundle (CD: 4.9%; CB: 2.3%), followed by the right atrium (CD: 3.7%; CB: 1.6%) and, to a lesser degree, the left atrium (CD: 1.8%; CB: 1.0%). Conduction abnormalities may by aggravated over time (e.g., aging, residual lesions, or valvular dysfunction), predisposing these patients to atrial arrhythmias early in life.