Prevalence, Timing, and Impact of Early Recurrence of Atrial Tachyarrhythmias after Pulsed Field Ablation: A Secondary Analysis of the PULSED AF Trial.

BACKGROUND: Early recurrence of atrial tachyarrhythmias (ERATs) within three months following thermal ablation for atrial fibrillation (AF) is common and often considered transient. Pulsed field ablation (PFA) is a non-thermal energy source in which ERAT is not well described. OBJECTIVE: To analyze ERAT in AF patients undergoing PFA in the PULSED AF trial. METHODS: This analysis included 294 patients (154 paroxysmal, 140 persistent AF) that had ≥10 rhythm assessments during the 90-day blanking period. ERAT was defined as any instance of ≥30s of AF, atrial flutter, or atrial tachycardia on trans-telephonic monitoring (weekly and symptomatic) or ≥10s on ECG (at 3 months), both within 90 days. Late recurrence of atrial tachyarrhythmias (LRATs) was defined as observed atrial tachyarrhythmias between 90 days and 12 months. RESULTS: The overall prevalence of ERAT was 27.1% in paroxysmal and 31.6% in persistent AF patients. In patients with ERAT, 73% had ERAT onset within the first month post-procedure. Presence of ERAT was associated with LRAT in paroxysmal (HR 6.4 (95% c.i. 3.6-11.3)) and persistent (HR 3.8 (95% c.i. 2.2-6.6)) AF patients. Yet, in 29.4% of paroxysmal and 34.3% of persistent AF patients with ERAT, LRAT was not observed. LRAT was positively correlated with the number of ERAT observations. CONCLUSION: ERAT post PFA predicted LRAT in paroxysmal and persistent AF patients. However, the concept of a blanking period post PFA is still valid as approximately 1/3 of patients with ERAT did not continue on to LRAT during follow-up and may not need re-ablation.

Regional variations in patient selection and procedural characteristics for cryoballoon ablation of atrial fibrillation in the cryo global registry.

BACKGROUND: Cryoballoon ablation is a well-established anatomical approach for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Although widely adopted, regional variations in standards of care have not been well characterized. METHODS: Patients with AF were enrolled in the Cryo Global Registry (NCT02752737) from May 2016 to Sept 2021 at 128 sites in 37 countries and treated with cryoballoon ablation according to local clinical practice. Baseline patient and procedural characteristics were summarized for 8 regions (Central Asia & Russia, East Asia, Europe, Middle East, North America, South Africa, South America, and Southeast Asia). Serious procedure-related adverse events (SAEs) were evaluated in a subset of patients with ≥ 7 days of follow-up. RESULTS: A total of 3,680 patients undergoing initial PVI for AF were included. Cryoballoon ablation was commonly performed in patients with paroxysmal AF. Mean age ranged from 47 ± 12 years in the Middle East to 64 ± 11 years in East Asia. Mean procedure time was ≤ 95 min in all regions. Average freeze duration ranged from 153 ± 41 s in Southeast Asia to 230 ± 29 s in Central Asia & Russia. Acute procedural success was ≥ 94.7% in all geographies. In 3,126 subjects with ≥ 7 days of follow-up, 122 procedure-related SAEs were reported in 111 patients (3.6%) and remained low in all regions. One procedure-related death was reported during data collection. CONCLUSIONS: Despite regional variations in patient selection and procedural characteristics, PVI using cryoballoon ablation was performed with high acute success and short procedural times around the world. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

Impact of first-line cryoablation for atrial fibrillation on healthcare utilization, arrhythmia disease burden and efficacy outcomes: real-world evidence from the Cryo Global Registry.

BACKGROUND: Cryoballoon ablation (CBA) is an effective first-line treatment for symptomatic atrial fibrillation (AF), as recently demonstrated by three randomized trials. This sub-analysis of the Cryo Global Registry aims to examine current clinical practices of first-line CBA. METHODS: AF patients treated with first-line CBA were compared to CBA in antiarrhythmic drug (AAD)-refractory patients at 12 months. Efficacy was examined using time-to-first atrial arrhythmia recurrence following a 90-day blanking period. Healthcare utilization was evaluated by repeat ablations and hospitalizations. Disease burden was examined by assessing quality of life (QOL) and patients' reporting of symptoms. RESULTS: Of 1394 patients, 433 (31.1%) were treated with first-line CBA, which was more frequent in high-volume centers. Serious procedure-related adverse event rates were similar. Efficacy at 12 months was higher in the first-line group (87.8 vs. 81.6%, HRunadj 0.64 (95% CI 0.47-0.88); p < 0.01) regardless of the centers' CBA experience; when controlling for baseline characteristics, the difference was not significant (HRadj 0.87 (95% CI 0.56-1.37); p = 0.55). No difference was observed in repeat ablations and hospitalizations between cohorts. First-line patients experienced a larger mean reduction in symptoms and were prescribed AADs at a lower rate at 12-month follow-up (9.7 vs. 29.9%). QOL improved in both cohorts from baseline to 12 months with no significant difference between groups (p = 0.29). CONCLUSIONS: In this global real-world experience, first-line CBA in patients with symptomatic AF is effective, with a larger symptom reduction compared with CBA after AAD failure and without a difference in healthcare utilization at mid-term follow-up. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.

Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation.

Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation waves. Far less is known about the role of myocyte metabolism and tissue perfusion in the pathogenesis of AF. However, the rapid rates of electrical activity and contraction during AF must present an enormous challenge to the energy balance of atrial myocytes. This challenge can be met by scaling back energy demand and by increasing energy supply, and there are several indications that both phenomena occur as a result of AF. Still, there is ample evidence that these adaptations fall short of redressing this imbalance, which may represent a driving force for atrial electrical as well as structural remodelling. In addition, several 'metabolic diseases' such as diabetes, obesity, and abnormal thyroid function precipitate some well-known 'culprits' of the AF substrate such as myocyte hypertrophy and fibrosis, while some other AF risk factors, such as heart failure, affect atrial metabolism. This review provides an overview of metabolic and vascular alterations in AF and their involvement in its pathogenesis.

Dynamic regulation of atrial coronary blood flow in healthy adult pigs.

BACKGROUND: There are several indications for a mismatch between atrial oxygen supply and demand during atrial fibrillation (AF), but atrial coronary flow regulation has not been investigated extensively. OBJECTIVE: The purpose of this study was to characterize the dynamic regulation of atrial coronary flow in pigs. METHODS: In anesthetized open-chest pigs, Doppler flow probes were placed around left atrial (LA) and left ventricular (LV) branches of the circumflex artery. Pressures and work indices were measured simultaneously. Systolic and diastolic flow contribution, flow response kinetics, and relationship between pressures, work, and flow were investigated during sinus rhythm, atrial pacing, and acute AF. RESULTS: During atrial systole, LA flow decreased. Only 2% of total LA flow occurred during atrial systole. Pacing with 2:1 AV block and infusion of acetylcholine revealed that atrial contraction itself impeded atrial coronary flow. The response to sudden changes in heart rate was slower in LA compared to LV. Both LA and LV vascular conductance were positively correlated with work. After the cessation of acute AF, the LA showed a more pronounced phase of supranormal vascular conductance than the LV, indicating a period of atrial reactive hyperemia. CONCLUSION: In healthy adult pigs, atrial coronary flow is impeded by atrial contraction. Although atrial coronary blood flow is positively correlated with atrial external work, it reacts more slowly to changes in rate than ventricular flow. The occurrence of a pronounced hyperemic phase after acute AF supports the notion of a significant supply-demand mismatch during AF.

Atrial supply-demand balance in healthy adult pigs: coronary blood flow, oxygen extraction, and lactate production during acute atrial fibrillation.

AIMS: Little is known about how atrial oxygen supply responds to increased demand, and under which conditions it falls short (supply-demand mismatch). Here, we have investigated the vasodilator response, oxygen extraction, and lactate production of the left atrium (LA) and left ventricle (LV) in response to atrial pacing and atrial fibrillation (AF). METHODS AND RESULTS: Series A (n = 9 Dutch landrace pigs) was instrumented to measure LA and LV vascular conductance in branches of the circumflex artery. Coronary conductance reserve (CCR) was calculated as the ratio between conductance during adenosine infusion and baseline. Series B (n = 7) was instrumented with sampling catheters in LA and LV veins for determination of blood gases and lactate levels. LA CCR (1.76 ± 0.14) was significantly lower than LV CCR (3.16 ± 0.27, P = 0.002). However, basal oxygen extraction was lower in LA (27 ± 3%) than that in the LV (58 ± 6%, P = 0.0006), indicating a larger extraction reserve in the LA than that in the LV (4.68 ± 0.84 vs. 1.88 ± 0.26, P = 0.01). Atrial pacing caused an increase in LA conductance (Series A) and oxygen extraction (Series B). AF increased LA vascular conductance to 177 ± 14% at 1 min, 168 ± 14 at 5 min, and 164 ± 31% at 10 min of AF (P < 0.05 vs. baseline). Atrial oxygen extraction also increased from 26 ± 3% at baseline to 63 ± 5% (P < 0.01) at 5 min and 60 ± 11% (P < 0.01) at 10 min of AF. Arterio-venous lactate difference increased significantly (P = 0.02) during AF. CONCLUSIONS: In healthy pigs, the LA has a lower CCR, but a higher extraction reserve compared with the LV. Although both reserves were recruited during AF, atrial lactate production increased significantly.