Cost, Efficiency and Outcomes of Pulsed Field Ablation versus Thermal Ablation for Atrial Fibrillation: A Real World Study.

BACKGROUND: With the exponential growth of catheter ablation (CA) for atrial fibrillation (AF), there is increasing interest in associated healthcare costs. Pulsed field ablation (PFA) using a single-shot pentaspline multi-electrode catheter has been shown to be safe and effective for AF CA, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. OBJECTIVE: To compare cost, efficiency, effectiveness and safety between PFA, CB and RF for AF ablation. METHODS: We studied 707 consecutive patients (208 PFA, 325 CB, 174 RF) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, lab utilisation and hospital stay, and compared between ablation modalities, as effectiveness and safety. RESULTS: Skin-to-skin times and catheter lab times were significantly shorter with PFA (68min/102min) vs CB (91min/122min) and RF (89min/123 min); p<0.001. General anaesthesia utilisation differed across modalities (PFA 100%, CB 10.2%, RF 61.5%); p<0.001. Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and lab costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) vs CB (£8,106) and RF (£8,949); p<0.001. CONCLUSION: In this contemporary real-world study of the three major AF CA modalities used concurrently, PFA had shorter skin-to-skin and catheter lab times than CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely due to higher equipment cost.

Durability of Thermal Pulmonary Vein Isolation in Persistent Atrial Fibrillation Assessed by Mandated Repeat Invasive Study.

BACKGROUND: No study has assessed durability of pulmonary vein isolation (PVI) with radiofrequency (RF) and Cryoballoon (CB) in patients with persistent AF. These data are especially lacking for those with significantly diseased left atria (LA). OBJECTIVE: To assess PVI durability in patients with significant LA disease and compare reconnection rates between RF and CB. METHODS: 44 Patients (mean age 63, 77% male, median time since AF diagnosis 22.5 months, median indexed LA volume 36 ml/m2) were randomised 1:1 to RF (StablePoint catheter, Boston Scientific) or CB (Arctic Front Advance, Medtronic) PVI. A redo procedure using ultra high-density electroanatomic mapping (Rhythmia, Boston Scientific) was mandated at 2 months, where PV reconnections were identified and re-isolated. RESULTS: 38 patients underwent both procedures (n=17 CB, n=21 RF). Index RF procedures were longer (median 158 vs 97min; p<0.001) but required less fluoroscopy (9.5 vs 23min; p<0.001). At the index RF procedure, median 47% of LA myocardium had voltage <0.5mV, suggesting half of the mapped LA comprised scar. PV reconnection was observed in 73/152 (48.0%) PVs and was more frequent with CB (58.8%) vs RF (39.3%), p=0.022. Reconnection of at least 1 PV was detected in >75% of patients. Significantly more ablation was required at redo to reisolate PVs in the CB arm (median 10.8 vs 1.2min; p<0.001). CONCLUSION: PVI durability may be poor in those with significant LA scarring and dilatation, even with modern thermal ablation technologies. RF resulted in significantly better PVI durability than CB in this complex population. CLINICAL TRIAL REGISTRATION: NCT04111731.

Silent pulmonary veins at redo ablation for atrial fibrillation: Implications and approaches.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Despite promising success rates, redo ablation is sometimes required. At redo, PVs may be found to be isolated (silent) or reconnected. We studied patients with silent vs reconnected PVs at redo and analysed associations with adverse outcomes. METHODS: Patients undergoing redo AF ablations between 2013 and 2019 at our institution were included and stratified into silent PVs or reconnected PVs. The primary outcome was a composite of further redo ablation, non-AF ablation, atrioventricular nodal ablation, and death. Secondary outcomes included arrhythmia recurrence. RESULTS: A total of 467 patients were included with mean 4.6 ± 1.7 years follow-up, of whom 48 (10.3%) had silent PVs. The silent PV group had had more often undergone >1 prior ablation (45.8% vs 9.8%; p<0.001), had more persistent AF (62.5% vs 41.1%; p=0.005) and had more non-PV ablation performed both at prior ablation procedures and at the analysed redo ablation. The primary outcome occurred more frequently in those with silent PVs (25% vs 13.8%; p=0.053). Arrhythmia recurrence was also more common in the silent PV group (66.7% vs 50.6%; p=0.047). After multivariable adjustment, female sex (aHR 2.35 [95% CI 2.35-3.96]; p=0.001) and ischaemic heart disease (aHR 3.21 [95% CI 1.56-6.62]; p=0.002) were independently associated with the primary outcome, and left atrial enlargement (aHR 1.58 [95% CI 1.20-2.08]; p=0.001) and >1 prior ablation (aHR 1.88 [95% CI 1.30-2.72]; p<0.001) were independently associated with arrhythmia recurrence. Whilst a finding of silent PVs was not itself significant after multivariable adjustment, this provides an easily assessable parameter at clinically indicated redo ablation which informs the clinician of the likelihood of a worse future prognosis. CONCLUSIONS: Patients with silent PVs at redo AF ablation have worse clinical outcomes.

The Oral Microbiome Profile of Water Polo Players Aged 16-20.

OBJECTIVES: Chlorine has a strong antibacterial property and is the disinfectant most frequently used in swimming pools. Therefore, the microbiota community in the oral cavity of those who practice water sports is assumed to be special due to their regular immersion in water. Adverse changes in the composition of oral cavity microbiota may have serious health consequences. We aimed to compare the oral microbiome between water polo players and non-athletes. We hypothesized that the oral cavity microbiota community differed between water polo players and non-athletes. MATERIALS AND METHODS: Altogether, 124 water polo players (62 males and 62 females, aged between 9 and 20 years) and 16 non-athlete youths (control group, eight males and eight females, aged between 16 and 20 years, mean age + SD = 17.1 + 1.4 years) who participated in body structure examinations voluntarily agreed to participate in the study. In a randomly selected subsample of water polo players (n: 29, aged between 16 and 20 years, mean age + SD = 17.3 + 1.0 years), saliva samples were also collected. Saliva samples were collected from all non-athlete youths (n: 16, aged between 16 and 20 years). The oral microbiome was determined from a saliva sample, and DNA was isolated using the QIAmp DNA Blood Mini Kit. The 16S rRNA gene amplicon sequencing method was used to analyze the microbiome community. PCR primers were trimmed from the sequence reads with Cutadapt. R library DADA2 was used to process reads in the abundance analysis. RESULTS: In general, Streptococcus, Veilonella, and Prevotella genera constituted more than 50% of the oral microbiome community in the two participant groups combined (n = 45). The oral microbial profile had significant sexual dimorphism and differed between water polo players and the non-athletes. Compared to females, males had a higher (p < 0.05) relative abundance of the Atopobium (medium effect size) and Pravotella_7 (very large effect size) genera and a lower (p < 0.05) relative abundance of the Fusobacterium (large effect size), Gemella (large effect size), and Streptococcus (large effect size) genera. Compared to non-athletes, water polo players had higher (p < 0.05, medium effect size) relative abundance of the genus Veillonella and lower (p < 0.05, large effect size) relative abundance of the genus Gemella. CONCLUSIONS: The results suggest that regular water training can unfavorably alter the composition of the oral microbial community.

Incidence of vascular complications for electrophysiology procedures in the ultrasound era: a single-centre experience over 10,000 procedures in the long term.

BACKGROUND: Ultrasound (US) is being increasingly used to guide vascular access for electrophysiology (EP) procedures in many centres. Nonetheless, the incidence and predictors of vascular complications in the US era are limited. In this study, we describe our experience of vascular access-related complications associated with EP procedures which were performed with the routine use of US-guided vascular access. METHODS: A total of 10,158 consecutive EP procedures in 8361 patients performed from April 2014 (when our centre moved to a policy of routine US-guided vascular access for EP procedures) to March 2022 were included. The outcome of interest was any vascular access-related complication that occurred within 7 days of the procedure; these were classified as severe if surgical intervention and/or blood transfusion was required, major if non-surgical intervention or delayed hospital discharge was required, or minor if it did not fulfil the criteria for severe or major. RESULTS: During the study period, 2 (0.02%) severe vascular complications occurred, including 1 pseudo-aneurysm requiring surgery and 1 retroperitoneal haemorrhage requiring blood transfusion. Nine (0.09%) major complications occurred, including 6 hematomas managed by compression devices, 1 type B aortic dissection, 1 AV fistula managed conservatively and 1 haematoma managed conservatively but delayed hospital discharge. Eighteen (0.18%) minor haematomas were seen that did not require any intervention or delayed hospital discharge. On multivariable analysis, female sex [OR (95% CI): 2.5 (1.2, 5.4)] and use of an arterial access [OR (95% CI): 19.3 (7.1, 52.3)] were seen to be independent predictors of the 29 vascular complications. CONCLUSION: With the use of US-guided vascular access in EP procedures, major vascular complications are exceedingly rare, particularly those needing surgical intervention. Our results provide additional evidence for scientific guidelines to support US use.

Impact of COVID-19 on patients awaiting ablation for atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) ablation services were significantly affected by the COVID-19 pandemic. We aimed to evaluate a symptom-based clinician prioritisation scheme for waiting list management compared with patient-completed quality of life (QoL) scores. We also sought to understand factors influencing QoL, particularly the impact of COVID-19, on patients awaiting AF ablation, via a bespoke questionnaire. METHODS: Patients awaiting AF ablation were sent two QoL questionnaires (Atrial Fibrillation Effect on QualiTy of Life (AFEQT) and EuroQol 5D (EQ5D-5L)) and the bespoke questionnaire. At a separate time point, patients were categorised as C1-urgent, C2-priority or C3-routine by their cardiologist based on review of clinic letters. RESULTS: There were 118 patients included with priority categorisation available for 86 patients. Median AFEQT scores were lower in C2 (30.4; 17.2-51.9) vs C3 patients (56.5; 32.1-74.1; p<0.01). Unplanned admission occurred in 3 patients in C3 with AFEQT scores of <40. Although 65 patients had AF symptoms during the pandemic, 43.1% did not seek help where they ordinarily would have. An exercise frequency of ≥3-4 times a week was associated with higher AFEQT (56.5; 41.2-74.1; p<0.001) and EQ5D (0.84; 0.74-0.88; p<0.0001) scores. CONCLUSION: The QoL of patients awaiting AF ablation is impaired and AFEQT helps to identify patients at risk of admission, over and above physician assessment. COVID-19 influenced patients seeking medical attention with symptomatic AF when they normally would. Regular exercise is associated with better QoL in patients awaiting AF ablation.

Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease.

BACKGROUND: The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases. METHODS: A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques. RESULTS: When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT). CONCLUSIONS: SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.

Structural and functional remodeling of the atrioventricular node with aging in rats: The role of hyperpolarization-activated cyclic nucleotide-gated and ryanodine 2 channels.

BACKGROUND: Aging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVE: The aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging. METHODS: Electrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, while ryanodine (2 µM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology. RESULTS: Without drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content. CONCLUSION: Heterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging.

Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues.

It is now over 100years since the discovery of the cardiac conduction system, consisting of three main parts, the sinus node, the atrioventricular node and the His-Purkinje system. The system is vital for the initiation and coordination of the heartbeat. Over the last decade, immense strides have been made in our understanding of the cardiac conduction system and these recent developments are reviewed here. It has been shown that the system has a unique embryological origin, distinct from that of the working myocardium, and is more extensive than originally thought with additional structures: atrioventricular rings, a third node (so called retroaortic node) and pulmonary and aortic sleeves. It has been shown that the expression of ion channels, intracellular Ca(2+)-handling proteins and gap junction channels in the system is specialised (different from that in the ordinary working myocardium), but appropriate to explain the functioning of the system, although there is continued debate concerning the ionic basis of pacemaking. We are beginning to understand the mechanisms (fibrosis and remodelling of ion channels and related proteins) responsible for dysfunction of the system (bradycardia, heart block and bundle branch block) associated with atrial fibrillation and heart failure and even athletic training. Equally, we are beginning to appreciate how naturally occurring mutations in ion channels cause congenital cardiac conduction system dysfunction. Finally, current therapies, the status of a new therapeutic strategy (use of a specific heart rate lowering drug) and a potential new therapeutic strategy (biopacemaking) are reviewed.

Simplified electrocardiogram sampling maintains high diagnostic capability for atrial fibrillation: implications for opportunistic atrial fibrillation screening in primary care.

AIMS: Atrial fibrillation (AF) is a major cause of morbidity, mortality, and health resource consumption. However, as many patients with chronic AF are asymptomatic, rapid, accurate opportunistic screening is needed in primary care to detect AF. Conventional electrocardiogram (ECG) technology is too clumsy and time consuming for mass opportunistic screening, thus technology that allows easy, rapid, yet accurate AF screening is required. To address this requirement a prototype hand-held electrode assembly was developed. We hypothesized that a 6-lead frontal-plane ECG acquired from this apparatus in a seated, clothed patient would be as accurate at detecting AF as conventional 12-lead ECG in the undressed, supine patient (the 'gold standard'). METHODS AND RESULTS: Electrocardiograms were obtained from 78 patients with AF and 79 with sinus rhythm (SR). All had a conventional 12-lead ECG, a 6-lead ECG from conventionally positioned limb electrodes, a supine 6-lead recording using the prototype recorder placed on the lower thorax/upper abdomen, and a 6-lead prototype recording in the seated patient, the latter with loosened clothing only. Electrocardiograms were randomly and blindly assessed by two cardiologists for (i) diagnosis of AF vs. SR and (ii) tracing quality (subjectively assessed as good, adequate, or bad). Compared with conventional 12-lead ECG recordings, all 'new' recording methods performed satisfactorily with sensitivities ≥90% (90-99%), specificities ≥94% (94-100%), positive predictive values ≥94% (94-100%), negative predictive values ≥90% (90-99%), and accuracies ≥93% (93-99%). Tracing quality was higher in conventional 12-lead recordings (71 and 80% were assessed as good by the two observers) compared with conventional 6-lead (57 and 59%), supine prototype (41 and 31%), and sitting prototype (39 and 19%). CONCLUSIONS: Despite inferior electrocardiographic quality a 6-lead frontal plane ECG acquired by a simple prototype hand-held electrode assembly allowed reliable differentiation of AF from SR compared with standard 12-lead ECG.