Contact force and catheter stability are predictive metrics of successful pulmonary vein isolation with high-power short duration ablation in atrial fibrillation.

INTRODUCTION: Preliminary data suggest that high power short duration (HPSD) ablation for pulmonary vein isolation (PVI) are safe. Limited data are available on its effectiveness. Aim was to evaluate HPSD ablation in atrial fibrillation ablation using a novel Qdot Micro catheter. METHODS AND RESULTS: Prospective multicenter study evaluating safety and efficacy of PVI with HPSD ablation. First pass isolation (FPI) and sustained PVI was assessed. If FPI was not achieved additional ablation index (AI)-guided ablation with 45 W was performed and metrics predictive of this were determined. Sixty-five patients and 260 veins were treated. Procedural and LA dwell time was 93.9 ± 30.4 and 60.5 ± 23.1 min, respectively. FPI was achieved in 47 (72.3%) patients and 231 veins (88.8%) with an ablation duration of 4.6 ± 1.0 min. Twenty-nine veins required additional AI-guided ablation to achieve initial PVI with 24 anatomical sites ablated with the right posterior carina being the most common site (37.5%). A contact force of ≥8 g (area under the curve [AUC]: 0.81; p < 0.001) and catheter position variation of ≤1.2 mm (AUC: 0.79; p < 0.001) with HPSD were strongly predictive of not requiring additional AI-guided ablation. Out of the 260 veins, only 5 (1.9%) veins showed acute reconnection. HPSD ablation was associated with shorter procedure times (93.9 vs. 159.4 min; p < 0.001), ablation times (6.1 vs. 27.7 min; p < 0.001), and lower rates of PV reconnection (9.2% vs. 30.8%; p = 0.004) compared to moderate power cohort. CONCLUSIONS: HPSD ablation is an effective ablation modality which results in effective PVI whilst maintaining a safety profile. Its superiority needs to be evaluated in randomized controlled trials.

ECG-I phenotyping of persistent AF based on driver burden and distribution to predict response to pulmonary vein isolation (PHENOTYPE-AF).

BACKGROUND: This prospective trial sought to phenotype persistent atrial fibrillation (AF) based on AF mechanisms using electrocardiographic imaging (ECGI) mapping to determine whether this would predict long-term freedom from arrhythmia after pulmonary vein isolation (PVI). METHODS: Patients with persistent AF of <2 years duration underwent cryoballoon PVI. ECGI mapping was performed before PVI to determine potential drivers (PDs) defined as rotational activations completing ≥1.5 revolutions or focal activations. The coprimary endpoint was the association between (1) PD burden (defined as the number of PD occurrences) and (2) PD distribution (defined as the number of segments on an 18-segment model of the atria harboring PDs) with freedom from arrhythmia at 1-year follow up. RESULTS: Of 100 patients, 97 completed follow up and 52 (53.6%) remained in sinus rhythm off antiarrhythmic drugs. Neither PD burden nor PD distribution predicted freedom from arrhythmia (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 0.99-1.03, p = .164; and HR: 1.04, 95% CI: 0.91-1.17, p = .591, respectively). Otherwise, the burden of rotational PDs, rotational stability, and the burden of PDs occurring at the pulmonary veins and posterior wall all failed to predict arrhythmia recurrence (all p > .10). CONCLUSIONS: AF mechanisms as determined using ECGI mapping do not predict outcomes after PVI for persistent AF. Further studies using different methodologies to characterize AF mechanisms are warranted (NCT03394404).

Impact of pulmonary vein isolation on mechanisms sustaining persistent atrial fibrillation: Predicting the acute response.

BACKGROUND: Noninvasive mapping identifies potential drivers (PDs) in atrial fibrillation (AF). We analyzed the impact of pulmonary vein isolation (PVI) on PDs and whether baseline PD pattern predicted termination of AF. METHODS: Patients with persistent AF less than 2 years underwent electrocardiographic imaging mapping before and after cryoballoon PVI. We recorded the number of PD occurrences, characteristics (rotational wavefronts ≥ 1.5 revolutions or focal activations), and distribution using an 18-segment atrial model. RESULTS: Of 100 patients recruited, PVI terminated AF in 15 patients; 21.3% ± 9.1% (8.7 ± 4.8) of PDs occurred at the pulmonary veins (PVs) and posterior wall. PVI had no impact on PD occurrences outside the PVs and posterior wall (33.2 ± 12.9 vs 31.6 ± 12.5; P = .164), distribution over the remaining 13 segments (9 [8-11] vs 9 [8-10]; P = .634), the proportion of PDs that was rotational (82.9% ± 9.7% vs 83.6% ± 10.1%; P = .496), or temporal stability (2.4 ± 0.4 vs 2.4 ± 0.5 rotations; P = .541). Fewer focal PDs (area under the curve, 0.683; 95% CI, 0.528-0.839; P = .024) but not rotational PDs (P = .626) predicted AF termination with PVI. CONCLUSIONS: PVI did not have a global impact on PDs outside the PVs and posterior wall. Although fewer focal PDs predicted termination of AF with PVI, the burden of rotational PDs did not. It is accepted though not all PDs are necessarily real or important. Outcome data are needed to confirm whether noninvasive mapping can predict patients likely to respond to PVI.

Noninvasive electrocardiographic imaging-guided targeting of drivers of persistent atrial fibrillation: The TARGET-AF1 trial.

BACKGROUND: Mechanisms sustaining persistent atrial fibrillation (AF) remain uncertain. OBJECTIVES: The purpose of this study was to use electrocardiographic imaging (ECGI) mapping to guide localized driver ablation in patients with persistent AF. METHODS: Patients undergoing catheter ablation for persistent AF <2 years were included. Patients were enrolled consecutively between 2018 and 2020. ECGI mapping was used to identify focal and rotational potential drivers (PDs). PDs were ablated after pulmonary vein isolation (PVI). The ablation response and freedom from AF/atrial tachycardia (AT) at 1 year were assessed. RESULTS: Forty patients were enrolled. AF terminated with PVI in 8 patients, and 32 underwent ECGI-guided driver ablation. Average procedural duration was 228.8 ± 66.7 minutes, with a total radiofrequency delivery time of 38.9 ± 14.1 minutes. During 1 year of follow-up, the primary endpoint of freedom from AF/AT was achieved in 26 patients (65%). The secondary endpoint of freedom from AF was achieved in 30 patients (75%). AF termination was achieved in 20 of 40 patients (50%). The composite endpoint of an ablation response (AF termination or cycle length slowing ≥10%) occurred in 37 of 40 patients (92.5%). In total, 181 drivers (48 focal and 133 rotational) were ablated, with an ablation response achieved in 59 (32.6%). Focal drivers and drivers with a higher recurrence rate and greater temporal stability were more likely to be associated with an ablation response including AF termination (P <.001). CONCLUSION: ECGI-guided ablation plus PVI results in high freedom from AF during follow-up and an ablation response in a large proportion of patients. Using driver type and characteristics may facilitate a hierarchical ablation approach.

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure.

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Impact of adenosine on mechanisms sustaining persistent atrial fibrillation: Analysis of contact electrograms and non-invasive ECGI mapping data.

BACKGROUND: We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping. METHODS: Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model. RESULTS: 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11-14) vs 12 (10-14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003). CONCLUSION: Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404.

Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.

Background: Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods: We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results: Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions: This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/.