Ablation of epicardial ventricular focus through coronary sinus using pulsed-field ablation. A case report.

INTRODUCTION: With the entry of pulsed-field ablation (PFA) into electrophysiology, new possibilities for ablation of different substrates such as epicardial foci of premature ventricular contractions (PVCs) from coronary venous system (CVS) have been opened. METHODS: This article focuses on a case of a 27-year-old patient with frequent monomorphic PVCs of epicardial origin, treated by radiofrequency ablation, followed by PFA. RESULTS: After unsuccessful focus ablation through CVS with RFA, successful ablations from the same region with PFA were achieved. CONCLUSION: This is the first described case of successful ablation of epicardial PVCs using PFA, which we hope will help in defining indications for this novel technology and enhance quality of treatment for patients with different arrhythmias.

Safety and effectiveness of additional left atrial posterior wall ablation using pulsed field ablation for persistent and long-standing persistent atrial fibrillation patients.

INTRODUCTION: The unique safety profile of pulsed field ablation (PFA) has made pulmonary vein isolation (PVI) + left atrial posterior wall (LAPW) ablation promising for treating persistent atrial fibrillation (PerAF). The goal of this study was to assess long-term freedom from atrial fibrillation, atrial flutter, and atrial tachycardia (AF/AFL/AT), as well as the safety and feasibility of LAPW PFA using multipolar, pentaspline Farawave catheter. METHODS: Retrospective observational study at a single institution. Data for 94 patients were collected from a prespecified intraprocedural registry. The long-term AF/AFL/AT recurrence assessment was based on an analysis of medical history; 24-h Holter ECGs at 3, 6, and 12 months postablation; and 12-lead ECGs recorded during symptomatic episodes or visits. RESULTS: Half of the patients had ls-PerAF, and half had a history of catheter ablation-mostly RF PVI. The acute ablation success rate was 100%, and the primary safety outcome was observed in 2 patients. Fifty patients experienced AF/AFL/AT recurrence (54.3%). An increase in LAPW low-voltage areas and AF classification were associated with arrhythmia recurrence. After a median follow-up of 13 months, the Kaplan‒Meier estimated median time free of AF/AFL/AT after a single procedure was 14.7 months. CONCLUSION: PFA PVI + PWA had the best outcome in perAF patients without extensive LA fibrosis. AF recurrence was paroxysmal in significant part of the cohort. The addition of PWA to PVI using multipolar PFA was safe and did not significantly influence the transpired ablation time.

Pulsed field ablation using focal contact force-sensing catheters for treatment of atrial fibrillation: acute and 90-day invasive remapping results.

AIMS: Pulsed field ablation (PFA) has emerged as a promising alternative to thermal ablation for treatment of atrial fibrillation (AF). We report performance and safety using the CENTAURI™ System (Galvanize Therapeutics) with three commercial, focal ablation catheters. METHODS AND RESULTS: ECLIPSE AF (NCT04523545) was a prospective, single-arm, multi-centre study evaluating safety and acute and chronic pulmonary vein isolation (PVI) durability using the CENTAURI System in conjunction with the TactiCath SE, StablePoint, and ThermoCool ST ablation catheters. Patients with paroxysmal or persistent AF were treated at two centres. Patients were analysed in five cohorts based upon ablation settings, catheter, and mapping system. Pulsed field ablation was performed in 82 patients (74% male, 42 paroxysmal AF). Pulmonary vein isolation was achieved in 100% of pulmonary veins (322/322) with first-pass isolation in 92.2% (297/322). There were four serious adverse events of interest (three vascular access complications and one lacunar stroke). Eighty patients (98%) underwent invasive remapping. Pulsed field ablation development Cohorts 1 and 2 showed a per-patient isolation rate of 38% and 26% and a per-PV isolation rate of 47% and 53%, respectively. Optimized PFA Cohorts 3-5 showed a per-patient isolation rate of 60%, 73%, and 81% and a per-PV isolation rate of 84%, 90%, and 92%, respectively. CONCLUSION: ECLIPSE AF demonstrated that optimized PFA using the CENTAURI System with three commercial, contact force-sensing, solid-tip focal ablation catheters resulted in transmural lesion formation and high proportion of durable PVI with a favourable safety profile, thus providing a viable treatment option for AF that integrates with contemporary focal ablation workflows.

Diagnostic and therapeutic pathways for the malignant left atrial appendage: European Heart Rhythm Association physician survey.

AIMS: Patients with atrial fibrillation who despite taking oral anti-coagulant therapy (OAT) suffer a stroke or systemic embolism (SSE) without vascular cause or who develop left atrial appendage (LAA) thrombus (LAAT) should be considered as having malignant LAA. The optimal treatment strategy to reduce SSE risk in such patients is unknown. The aim of the study is to investigate the diagnostic and therapeutic pathways for malignant LAA practiced in European cardiac centres. METHODS AND RESULTS: An 18-item online questionnaire on malignant LAA was disseminated by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee. A total of 196 physicians participated in the survey. There seems to be high confidence in transoesophageal echocardiography (TEE) imaging, considering LAAT diagnosis. Switching to another direct oral anti-coagulant (DOAC) is the preferred initial step for the treatment of malignant LAA followed by a switch to vitamin K antagonist (VKA), low-molecular-weight heparin, or continued/optimized DOAC dosage, whereas LAA closure is the last option. Left atrial appendage closure is a viable option in patients with embolic stroke despite OAT and no evidence of thrombus at TEE (empty LAA) after comprehensive diagnostic measures to exclude other sources of embolism. CONCLUSION: This EHRA survey provides a snapshot of the contemporary management of patients diagnosed with malignant LAA. Currently, the majority of patients are treated on an outpatient basis with either shifting from VKA to DOAC or from one DOAC to another. Left atrial appendage closure in this population seems to be reserved for patients with higher bleeding risk or complications of malignant LAA, such as stroke.

Comparison of procedural efficacy and biophysical parameters between two competing cryoballoon technologies for pulmonary vein isolation: Insights from an initial multicenter experience.

INTRODUCTION: Recently a novel cryoballoon system (POLARx, Boston Scientific) became available for the treatment of atrial fibrillation. This cryoballoon is comparable with Arctic Front Advance Pro (AFA-Pro, Medtronic), however, it maintains a constant balloon pressure. We compared the procedural efficacy and biophysical characteristics of both systems. METHODS: One hundred and ten consecutive patients who underwent first-time cryoballoon ablation (POLARx: n = 57; AFA-Pro: n = 53) were included in this prospective cohort study. RESULTS: Acute isolation was achieved in 99.8% of all pulmonary veins (POLARx: 99.5% vs. AFA-Pro: 100%, p = 1.00). Total procedure time (81 vs. 67 min, p < .001) and balloon in body time (51 vs. 35 min, p < .001) were longer with POLARx. After a learning curve, these times were similar. Cryoablation with POLARx was associated with shorter time to balloon temperature -30°C (27 vs. 31 s, p < .001) and -40°C (32 vs. 54 s, p < .001), lower balloon nadir temperature (-55°C vs. -47°C, p < .001), and longer thawing time till 0°C (16 vs. 9 s, p < .001). There were no differences in time-to-isolation (TTI; POLARx: 45 s vs. AFA-Pro 43 s, p = .441), however, POLARx was associated with a lower balloon temperature at TTI (-46°C vs. -37°C, p < .001). Factors associated with acute isolation differed between groups. The incidence of phrenic nerve palsy was comparable (POLARx: 3.5% vs. AFA-Pro: 3.7%). CONCLUSION: The novel cryoballoon is comparable to AFA-Pro and requires only a short learning curve to get used to the slightly different handling. It was associated with faster cooling rates and lower balloon temperatures but TTI was similar to AFA-Pro.

Pulsed field ablation: a promise that came true.

PURPOSE OF REVIEW: Pulsed field ablation is a nonthermal ablative modality that uses short living, strong electrical field created around catheter to create microscopic pores in cell membranes (electroporation). When adequately dosed/configured it shows a preference for myocardial tissue necrosis. Thus, it holds a promise to become a 'perfect' energy source for cardiac ablation to treat arrhythmias. Herein, we present update on platforms in clinical development. RECENT FINDINGS: First in human series using pulsed field ablation for atrial fibrillation ablation have been completed and data published for several platforms. Acute safety outcomes are similar across the platforms with exceptionally low rate of those complications that are typically reported for thermal ablation methods (esophageal injury, pulmonary vein stenosis, phrenic nerve palsy). Promising acute data on pulmonary vein isolation had been corroborated with satisfactory 1-year clinical follow-up for a single platform, whereas reports are pending for the rest. Research efforts are being expanded to a development of focal catheters, and therefore, pulsed field ablation application for ventricular arrhythmias. SUMMARY: As the reports confirming its safety and efficacy build up, there seems to be no way that the promise of pulsed field ablation could end in a blind alley.

Acute safety, efficacy, and advantages of a novel cryoballoon ablation system for pulmonary vein isolation in patients with paroxysmal atrial fibrillation: initial clinical experience.

AIMS: Cryoballoon pulmonary vein isolation (PVI) is a safe and effective treatment for atrial fibrillation (AF). Current limitations include incomplete vein occlusion due to balloon rigidity and inconsistent electrogram recording, which impairs identification of isolation. We aimed to evaluate the acute safety and performance of a novel cryoballoon system. METHODS AND RESULTS: The system includes a steerable sheath, mapping catheter, and a balloon that maintains uniform inflation pressure and size following initiation of ablation. Protocol-directed cryoablation was delivered for 180 s for isolation documented in ≤60 s, otherwise freeze duration was 240 s. Primary endpoints were acute safety and vein isolation. Pulmonary vein isolation was confirmed at ≥30 min post-isolation. Data were compared across vein locations. Thirty patients with paroxysmal AF were enrolled at two centres and underwent PVI. Pulmonary vein isolation was achieved with cryoablation only in 100% of veins (120/120). Nadir temperature was -53.1 ± 5.3°C. The number of applications to achieve PVI was 1.4 ± 0.4 per vein. Of the 120 veins, 89 were isolated with a single cryothermal application (10/30 patients required only 4 total cryoablations). There were no procedural- or device-related serious adverse events at 30 days post-procedure. A subset (24/30) of patients was followed for 1-year and 71% (17/24) remained free of atrial arrhythmias. Six patients with arrhythmia recurrence were remapped and three had durable PVI for all four veins. CONCLUSION: In this first human experience, the novel cryoballoon platform was safe, efficacious, and demonstrated a high proportion of successful single ablation isolation.

Ablation of accessory pathways in different anatomic locations using focal pulsed field ablation.

BACKGROUND: Ablation of accessory pathways (APs) is the cornerstone for treatment of patients with Wolff-Parkinson-White syndrome and manifestation of atrioventricular reentrant tachycardia. Pulsed field ablation (PFA) is a new type of nonthermal energy source delivered to the underlying tissue via the ablation catheter and used for ablation of arrhythmic substrates. OBJECTIVE: The purpose of this study was to determine the efficiency and long-term outcome of ablation of APs of different localizations using a focal pulsed electrical field. METHODS: Electrophysiological study was performed in patients with indication for AP ablation. An ablation catheter was used to map the position of AP insertion. Pulsed electric field was delivered through a standard ablation catheter. In left-sided APs, the first ablation attempt was within the coronary sinus (CS). Patient follow-up was scheduled 1-3 months after the ablation. Additional check-up was performed after 6 and 12 months. RESULTS: Fourteen 14 patients (3 pediatric) were treated. Termination of AP conduction was achieved in all procedures. The cohort consisted of 3 right free wall, 3 posteroseptal, and 8 left-sided APs. Ablation through CS was successfully used in 7 of 8 patients with left-sided APs. No complications were reported. Median follow-up was 5.5 months. Conduction recurrence through AP was documented in 1 patient. CONCLUSION: Focal PFA for AP shows promising results in terms of efficacy and safety. A high rate of successful termination of left-sided APs by ablation within CS may represent a new standard approach. The safety and efficacy profile of PFA seems to be transferable to the pediatric population.

Association of Electrical Cardioversion with Brain Perfusion and Cognitive Function in Patients with Atrial Fibrillation.

BACKGROUND: The association of atrial fibrillation (AF) and brain perfusion (BP) has not been well-defined. This study aimed to determine the association of persistent AF with BP and cognition, in comparison to control subjects and with regards to electrical cardioversion (ECV). METHODS: This study compared 25 patients with persistent AF undergoing elective ECV with 16 age/sex-matched controls. We measured regional BP by using the magnetic resonance (MRI) arterial spin labelling technique. Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function index. Measurements were performed at baseline and 6 weeks after ECV. RESULTS: There was no significant difference in BP between AF patients and control subjects (p > 0.05). Following the ECV, there was a significant improvement in BP in 15 patients who maintained sinus rhythm, while there was no significant change in the recurrence group (297 ± 24 before vs. 328 ± 37 after ECV, p = 0.008, and 297 ± 22 before vs. 307 ± 24 after ECV, p = 0.45, respectively). There was no difference in the cognitive assessment between AF patients and control subjects, as well as before and after ECV within the AF group (52.2 ± 9.6 vs. 51.2 ± 6.2, p = 0.71 and 53 ± 10 vs. 54 ± 9, p = 0.46, respectively). CONCLUSIONS: This study did not show difference in BP between persistent AF patients and matched control subjects. Restoration of sinus rhythm was associated with significantly improved BP. There was no association of ECV and changes in cognitive function.

Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation.

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.

Recruitment pattern of sympathetic muscle neurons during premature ventricular contractions in heart failure patients and controls.

Premature ventricular contractions (PVC) elicit larger bursts of multiunit muscle sympathetic nerve activity (MSNA), reflecting the ability to increase postganglionic axonal recruitment. We tested the hypothesis that chronic heart failure (CHF) limits the ability to recruit postganglionic sympathetic neurons as a response to PVC due to the excessive sympathetic activation in these patients. Sympathetic neurograms of sufficient signal-to-noise ratio were obtained from six CHF patients and from six similarly aged control individuals. Action potentials (APs) were extracted from the multiunit sympathetic neurograms during sinus rhythm bursts and during the post-PVC bursts. These APs were classified on the basis of the frequency per second, the content per burst, and the peak-to-peak amplitude, which formed the basis of binning the APs into active clusters. Compared with controls, CHF had higher APs per burst and higher number of active clusters per sinus rhythm burst (P < 0.05). Compared with sinus rhythm bursts, both groups increased AP frequency and the number of active clusters in the post-PVC burst (P < 0.05). However, compared with controls, the increase in burst integral, AP frequency, and APs per burst during the post-PVC burst was less in CHF patients. Nonetheless, the PVC-induced increase in active clusters per burst was similar between the groups. Thus, these CHF patients retained the ability to recruit larger APs but had a diminished ability to increase overall AP content.

Effects of successive air and nitrox dives on human vascular function.

SCUBA diving is regularly associated with asymptomatic changes in cardiac, pulmonary and vascular function. The aim of this study was to evaluate the changes in vascular/endothelial function following SCUBA diving and to assess the potential difference between two breathing gases: air and nitrox 36 (36% oxygen and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2 weeks pause in between. Arterial/endothelial function was assessed using SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite before and after diving was determined in venous blood. Production of nitrogen bubbles post-dive was assessed by ultrasonic determination of venous gas bubble grade. Significantly higher bubbling was found after all air dives as compared to nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after both air and nitrox diving, indicating an increase in arterial stiffness. However, augmentation index became significantly more negative after diving indicating smaller wave reflection. There was a trend for post-dive reduction of FMD after air dives; however, only nitrox diving significantly reduced FMD. No significant differences in blood nitrite before and after the dives were found. We found that nitrox diving affects systemic/vascular function more profoundly than air diving by reducing FMD response, most likely due to higher oxygen load. Both air and nitrox dives increased arterial stiffness, but decreased wave reflection suggesting a decrease in peripheral resistance due to exercise during diving. These effects of nitrox and air diving were not followed by changes in plasma nitrite.

Higher than recommended lesion size index target values for pulmonary vein isolation result in better clinical outcomes in paroxysmal atrial fibrillation patients.

PURPOSE: Catheter ablation is a cornerstone of the therapy for paroxysmal atrial fibrillation. The importance of effective lesion size formation during pulmonary vein isolation is gauged through conduction recovery and recurrence of arrhythmia. Therefore, the lesion size index (LSI) is designed to utilize traditional intraprocedural parameters and predict procedural success. The impact of the optimal LSI index and the respective segments of the pulmonary veins has not been commonly evaluated. We aimed to assess whether higher and targeted LSI on the different segments of pulmonary veins could actually lead to better clinical outcomes of paroxysmal atrial fibrillation ablation. METHODS: Retrospective analyses of drug-refractory paroxysmal atrial fibrillation patients who underwent first catheter ablation were conducted. Targeted LSI of 6.5 at the anterior wall and 5.2 at the posterior wall, roof, and floor of the pulmonary vein was applied. The primary endpoint was defined as arrhythmias recurrence assessed by routine electrocardiograms and 24-h ambulatory electrocardiographic monitoring at 3, 6, and 12 months post-ablation. RESULTS: Among the included 39 patients, the single-procedure 12-month freedom from arrhythmias was reached in 92.3% of patients. Interestingly, there was no tendency towards an increased number of adverse effects using a higher LSI index. CONCLUSIONS: Atrial fibrillation ablation guided by targeted LSI value showed efficiency on the freedom from arrhythmias during 1-year follow-up period without harmful effects.

Novel cryoballoon to isolate pulmonary veins in patients with paroxysmal atrial fibrillation: long-term outcomes in a multicentre clinical study.

BACKGROUND: Recently, a novel cryoballoon ablation catheter has demonstrated acute safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (PAF). However, there are limited studies demonstrating the long-term efficacy. The aim of this study was to evaluate the long-term safety and efficacy of this novel cryoballoon in treating PAF. METHODS: This was a non-randomized, prospective, multicentre study enrolling 58 consecutive patients. Cryoablation was delivered for 180 s if time to isolation was ≤ 60 s. Otherwise a 240-s cryoablation was performed. One centre performed pre- and post-ablation high-density mapping (n = 9) to characterize lesion formation. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. All patients were followed for 1 year. RESULTS: Acute PVI was achieved in 230 of 231 pulmonary veins (99.6%) with 5.3 ± 1.6 cryoablations per patient (1.3 ± 0.7 cryoablations per vein). Forty-three (77%) patients remained arrhythmia-free at 1-year follow-up. Four patients (6.9%) experienced phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post-index procedure. For patients who underwent high-density mapping, cryoablation was antral with 50% of the posterior wall ablated. CONCLUSIONS: Initial multicentre clinical experience with a novel cryoballoon has demonstrated safety and efficacy of PVI in patients with PAF. Ablation with this cryoballoon provides a wide, antral lesion set with significant debulking of the posterior wall of the left atrium.

A no-decompression air dive and ultrasound lung comets.

INTRODUCTION: Increased accumulation of extravascular lung water after repetitive deep trimix dives was recently reported. This effect was evident 40 min post-dive, but in subsequent studies most signs of this lung congestion were not evident 2-3 h post-dive, indicating no major negative effects on respiratory gas exchange following deep dives. Whether this response is unique for trimix dives or also occurs in more frequent air dives is presently unknown. METHODS: A single no-decompression field dive to 33 m with 20 min bottom time was performed by 12 male divers. Multiple ultrasound lung comets (ULC), bubble grade (BG), and single-breath lung diffusing capacity (DLCO) measurements were made before and up to 120 min after the dive. RESULTS: Median BG was rather high with maximal values observed at 40 min post-dive [median 4 (4-4)]. Arterialization of bubbles from the venous side was observed only in one diver lasting up to 60 min post-dive. Despite high BG, no DCS symptoms were noted. DLCO and ULC were unchanged after the dive at any time point (DLCO(corr) was 33.6 +/- 1.9 ml x min(-1) mmHg(-1) pre-dive, 32.7 +/- 3.8 ml x min(-1) x mmHg(-1) at 60 min post-dive, and 33.2 +/- 5.3 ml x min(-1) x mmHg(-1) at 120 min post-dive; ULC count was 4.1 +/- 1.9 pre-dive, 4.9 +/- 3.3 at 20 min post-dive, and 3.3 +/- 1.9 at 60 min post-dive. DISCUSSION: These preliminary findings show no evidence of increased accumulation of extravascular lung water in male divers after a single no-decompression air dive at the limits of accepted Norwegian diving tables.

Pulsed Field Ablation of Paroxysmal Atrial Fibrillation: 1-Year Outcomes of IMPULSE, PEFCAT, and PEFCAT II.

OBJECTIVES: This study sought to determine whether durable pulmonary vein isolation (PVI) using pulsed field ablation (PFA) translates to freedom from atrial fibrillation recurrence without an increase in adverse events. BACKGROUND: PFA is a nonthermal ablative modality that, in preclinical studies, is able to preferentially ablate myocardial tissue with minimal effect on surrounding tissues. Herein, we present 1-year clinical outcomes of PFA. METHODS: In 3 multicenter studies (IMPULSE [A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation], PEFCAT [A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation], and PEFCAT II [Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation]), paroxysmal atrial fibrillation patients underwent PVI using a basket or flower PFA catheter. Invasive remapping was performed at ∼2 to 3 months, and reconnected PVs were reisolated with PFA or radiofrequency ablation. After a 90-day blanking period, arrhythmia recurrence was assessed over 1-year follow-up. RESULTS: In 121 patients, acute PVI was achieved in 100% of PVs with PFA alone. PV remapping, performed in 110 patients at 93.0 ± 30.1 days, demonstrated durable PVI in 84.8% of PVs (64.5% of patients), and 96.0% of PVs (84.1% of patients) treated with the optimized biphasic energy PFA waveform. Primary adverse events occurred in 2.5% of patients (2 pericardial effusions or tamponade, 1 hematoma); in addition, there was 1 transient ischemic attack. The 1-year Kaplan-Meier estimates for freedom from any atrial arrhythmia for the entire cohort and for the optimized biphasic energy PFA waveform cohort were 78.5 ± 3.8% and 84.5 ± 5.4%, respectively. CONCLUSIONS: PVI with a "single-shot" PFA catheter results in excellent PVI durability and acceptable safety with a low 1-year rate of atrial arrhythmia recurrence. These data mitigate concern that the nonthermal ablative mechanism of PFA might mask undiscovered compromises to clinical success. (IMPULSE: A Safety and Feasibility Study of the IOWA Approach Endocardial Ablation System to Treat Atrial Fibrillation, NCT03700385; A Safety and Feasibility Study of the FARAPULSE Endocardial Ablation System to Treat Paroxysmal Atrial Fibrillation, NCT03714178; PEFCAT II Expanded Safety and Feasibility Study of the FARAPULSE Endocardial Multi Ablation System to Treat Paroxysmal Atrial Fibrillation [PEFCAT II], NCT04170608).

Sympathetic neural activation: an ordered affair.

Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new multi-unit action potential detection and analysis techniques we sought to determine whether the activation of sympathetic vasomotor neurones during stress is governed by the size principle of recruitment. Multi-unit postganglionic sympathetic activity (fibular nerve) was collected from five male subjects at rest and during periods of elevated sympathetic stress (end-inspiratory apnoeas; 178 ± 37 s(mean ± S.D.)). Compared to baseline (0.24 ± 0.04 V), periods of elevated stress resulted in augmented sympathetic burst size (1.34 ± 0.38 V, P < 0.05). Increased burst size was directly related to both the number of action potentials within a multi-unit burst of postganglionic sympathetic activity (r = 0.88 ± 0.04, P < 0.001 in all subjects), and the amplitude of detected action potentials (r = 0.88 ± 0.06, P < 0.001 in all subjects). The recruitment of larger, otherwise silent, neurons accounted for approximately 74% of the increase in detected action potentials across burst sizes. Further, action potential conduction velocities (inverse of latencies) were increased as a function of action potential size (R² = 0.936, P = 0.001). As axon diameter is positively correlated with action potential size and conduction velocity, these data suggest that the principle of ordered recruitment based on neuronal size applies to postganglionic sympathetic vasomotor neurones. This information may be pertinent to our understanding of reflex-specific recruitment strategies in postganglionic sympathetic nerves, patterns of vasomotor control during stress, and the malleability of sympathetic neuronal properties and recruitment in health and disease.

Ventilatory restraint of sympathetic activity during chemoreflex stress.

The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, with greater activity occurring during expiration and less during inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to-minute) regulation of MSNA has not been determined. We sought to define the specific role of ventilation in regulating sympathetic activation during chemoreflex activation, where both ventilation and MSNA are increased. Ten young healthy subjects performed both asphyxic rebreathing and repeated, rebreathing apneas to cause the same magnitude of chemoreflex stress in the presence or absence of ventilation. Both protocols caused increases in sympathetic burst frequency, burst amplitude, and burst incidence. However, burst frequency was increased more during repeated apneas (12 ± 6 to 25 ± 7 bursts/min) compared with rebreathing (12 ± 5 to 17 ± 7 bursts/min; P < 0.001) due to a greater burst incidence during apneas (36 ± 11 bursts/100 heart beats) vs. rebreathing (26 ± 8 bursts/100 heart beats, P < 0.001). The sympathetic gain to chemoreflex stress was also larger during repeated apneas (2.29 ± 1.29 au/% desaturation) compared with rebreathing (1.44 ± 0.53 au/% desaturation, P < 0.05). The augmented sympathetic response during apneas was associated with a larger pressor response and total peripheral resistance compared with rebreathing. These data demonstrate that ventilation per se restrains sympathetic activation during chemoreflex activation. Further, the augmented sympathetic response during apneas was associated with greater cardiovascular stress and may be relevant to the cardiovascular pathology associated with sleep-disordered breathing.

Peripheral chemoreflex regulation of sympathetic vasomotor tone in apnea divers.

OBJECTIVES: Involuntary apnea episodes in obstructive sleep apnea patients result in selective potentiation of peripheral chemoreceptor regulation of sympathetic vasomotor tone. Breath-hold diving is associated with repeated "voluntary" apnea episodes and massive arterial oxygen desaturation, which could also perturb chemoreflex function. METHODS: We measured ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 11 breath-hold divers and eleven matched control subjects. The study was carried out at least 1 month after intense apnea training. RESULTS: Baseline MSNA frequency was 30 +/- 4 bursts/min in control subjects and 31 +/- 7 bursts/min in divers (ns). During hypoxia MSNA frequency and total activity increased similarly in both groups (30 and 66% in controls and 27 and 60% in divers, respectively). MSNA remained increased after termination of hypoxia and approached baseline measurements after 20 min. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia-induced tachycardia drove an increase in cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. INTERPRETATION: We conclude that after the end of intensive training/competition periods, apnea divers show normal peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone. Although voluntary apnea may not lead to sustained changes in sympathetic nervous system regulation, we cannot exclude the possibility that repeated sympathetic activation elicited by voluntary apnea imposes a burden on the cardiovascular system.