Introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with significant morbidity, including stroke, heart failure, and reduced quality of life. Pulmonary vein isolation (PVI) has become a cornerstone in the management of AF, particularly for patients who are refractory to antiarrhythmic drugs [1, 2]. Despite its proven efficacy, AF recurrence after PVI remains a significant challenge, with reported recurrence rates ranging from 25% to 40% within the first-year post-ablation [1].

The mechanisms underlying AF recurrence after ablation are multifactorial, involving a combination of patient-specific factors, procedural variables, and atrial substrate characteristics [1]. Among these, premature atrial contractions (PAC) have been implicated as potential triggers for AF, and its association with AF recurrence after ablation has been of recent interest [3–6]. PAC may reflect a diseased atrial substrate, characterized by increased fibrosis, electrical remodeling, or persistent ectopic activity, which predisposes patients to arrhythmia recurrence [3].

While previous studies have examined predictors of AF recurrence, the role of PAC burden following PVI has not been comprehensively evaluated. These PAC can reflect an underlying atrial substrate and potentially trigger arrhythmias. While smaller studies suggest that PAC burden correlates with AF recurrence, robust evidence remains limited, and optimal thresholds for prediction vary widely [4–8]. Furthermore, in these studies, the time of Holter monitoring ranges from the day of procedure to 6 months post ablation [4–8]. This study aims to investigate the predictive value of PAC burden for AF recurrence, as measured by 24-hour Holter monitoring at three months post-ablation, based on the 2017 guideline, leaving a blanking period for 3 months to allow dissipation of acute inflammatory effects [9]. Additionally, the study evaluates whether patient demographics, procedural details, or other clinical variables contribute to recurrence risk. Understanding these factors could help refine risk stratification and guide post-ablation management strategies.

Materials and methods

This single-center, retrospective observational study analyzed data from patients who underwent PVI at Jessa Hospital, Hasselt, Belgium, between July 2014 and January 2017. Initially, 416 patients were reviewed. Patients were included if they underwent their first endocardial AF ablation with PVI as the sole lesion set. Exclusion criteria were combined procedures, redo ablations, or the absence of a 24-hour Holter recording three months post-ablation. Lastly, patients with a presence of AF or atrial tachycardia on 24-hour Holter lasting more than 30 s were also excluded. The final analysis included 185 patients. Data was obtained from the C2M online patient database. This study was approved by the ethics committee of Jessa Hospital.

All procedures were performed under general anesthesia. An activated clotting time of ≥ 300 s was maintained throughout the procedure. Catheter choice depended on operator preference and patient-specific factors. Three distinct ablation techniques, all targeting PVI, were employed:

• 1.

  CARTO 3 Mapping System: Used to guide point-by-point radiofrequency ablation via detailed electro-anatomical mapping by making use of the ThermoCool SmartTouch catheter using standard radiofrequency energy settings, typically between 35 and 45 W in a power-controlled mode (Biosense Webster, Inc., Diamond Bar, CA, USA) [10, 11].

• 2.

  EnSite NavX Velocity Mapping System: Facilitated point-by-point radiofrequency ablation with precise mapping also by using the ThermoCool SmartTouch catheter (St. Jude Medical, Inc., St. Paul, MN, USA) [10, 11].

• 3.

  Laser Balloon Ablation: Utilized endoscopic laser energy for circumferential PVI (Cardiofocus, Inc., Marlborough, MA, USA) [12].

Anticoagulation was continued post-procedure and antiarrhythmic therapy was tapered, attempting discontinuation when clinically feasible. However, decisions were individualized according to the underlying substrate and patient tolerance. Follow-up was standardized according to current protocol with follow-up after three and twelve months with 24-hour Holter. Earlier consultations with electrocardiography were possible if the patient reported symptoms.

Demographic, clinical, procedural, and follow-up data were extracted from medical records. The PAC burden was assessed via 24-hour Holter monitoring, three months (±30 days) post-ablation. PAC were quantified by an automatic algorithm, which was verified by an experienced cardiac technician or cardiologist. The primary endpoint was freedom from atrial arrhythmia 12 months after ablation. Recurrence of arrhythmia was defined as any documented episode of AF or atrial tachycardia lasting at least 30 s after a 90-day blanking period, confirmed by electrocardiogram, Holter monitoring, or event recorders during follow-up [1, 9].

Continuous variables were summarized as means ± standard deviations or medians with interquartile ranges, depending on distribution. Categorical variables were expressed as frequencies and percentages. Comparisons between groups were conducted using t-tests, Mann-Whitney U tests, chi-squared tests, or Fisher’s exact tests, as appropriate. Receiver operating characteristic (ROC) analysis determined the optimal PAC threshold for predicting recurrence. Kaplan-Meier survival analysis estimated recurrence-free survival, with differences tested via the log-rank test. Multivariable Cox-regression analysis was performed to control for pre-defined potential confounders (PAC load, type AF, ablation system used, rhythm post-catheterisation, gender, age, left atrial volume, presence of obesity, presence of arterial hypertension). This was preferred to propensity score matching as Cox regression usually performs better in survival analysis [13–15]. All analyses were conducted using R software (The R Foundation for Statistical Computing, Vienna, Austria; version 4.3.2), with statistical significance set at p < 0.05.

Results

The median PAC burden three months post-ablation was 50 (16–145) beats/24 hours. ROC analysis established an optimal cut-off of 57 PAC/24 hours, yielding a sensitivity of 0.80, specificity of 0.59, positive predictive value (PPV) of 0.19, and negative predictive value (NPV) of 0.96 (Figure 1). Based on this cutoff, patients were classified into low (≤ 57 PAC/24 hours) and high (> 57 PAC/24 hours) PAC burden groups.

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Figure 1. Receiver operating curve (ROC) of premature atrial contraction/24h.

Baseline characteristics can be found in Table 1. Patients with high PAC burden were older and had larger left atrial diameters compared to those with low burden. Other patient characteristics were not significantly different. Procedural parameters were similar along both high and low PAC burden, with no significant difference in mapping method (p = 0.16). Kaplan-Meier analysis demonstrated significantly lower recurrence-free survival in the high PAC burden group (95% [95% confidence interval (CI): 0.91–0.99] vs. 80% (CI: 0.72–0.89), log-rank p = 0.004) (Figure 2). No significant differences in recurrence rates were observed across ablation techniques (p = 0.76) (Figure 3). Multivariable Cox proportional hazards analysis confirmed PAC burden as an independent predictor of AF recurrence [hazard ratio (HR) 3.38, CI: 1.20–9.50, p = 0.021], as illustrated in Figure 4. Patients who remained in AF immediately post-ablation and had an electrical reconversion demonstrated a borderline non-significant increase in risk of recurrence (HR 2.38, CI: 0.85–6.60, p = 0.099).

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Figure 2. Kaplan-Meier curve by PAC load for recurrence rate of atrial arrhythmia. Low PAC load: 95% vs. high PAC load: 80.4%. AF: atrial fibrillation; PAC: premature atrial contractions.

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Figure 3. Kaplan-Meier curve by ablation technique for recurrence rate of atrial arrhythmia. CARTO: 90% vs. EnSite: 82% vs. laser balloon: 86%. LBA: Laser Balloon Ablation.

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Figure 4. Multivariable Cox analysis evaluating predictors of AF recurrence after PVI. Variables included in the model were selected based on clinical relevance. Hazard ratios > 1 indicate increased risk of AF recurrence. Confidence intervals represent 95% bounds. AF: atrial fibrillation; AHT: arterial hypertension; PAC: premature atrial contractions; PVI: pulmonary vein isolation.

No significant differences in AF recurrence were observed between the three ablation techniques (CARTO^®, EnSite NavX™, and Laser Balloon Ablation). Similarly, other known risk factors, including left atrial size and type of AF, did not show statistical significance in this cohort.

Discussion

This study evaluated clinical and procedural predictors of AF recurrence after PVI, focusing on the burden of PAC three months post-ablation. PAC burden, as measured by 24-hour Holter monitoring, was a significant predictor of AF recurrence, with an optimal threshold of 57 PAC/24 hours. Patients with a PAC burden above this threshold demonstrated a higher risk of recurrence, whereas a low PAC burden was associated with a high NPV, suggesting a low likelihood of recurrence. PAC burden may reflect a more diseased atrial substrate, characterized by increased fibrosis or electrical remodeling, which predisposes to AF recurrence. In this study, a PAC burden > 57 was associated with an HR of 3.38 for recurrence, even after adjusting for known confounders.