Catheter ablation of atrial fibrillation : methods for improving outcome

Introduction: The most common arrhythmia world-wide is atrial fibrillation (AF). The arrhythmia is diagnosed through an electrocardiogram (ECG). Patients with AF often experience symptoms including palpitations, dyspnoea, fatigue, and an overall reduced quality of life. Patients with AF also face a higher risk of stroke, which is due to thrombus formation in the left atrial appendage, and heart failure, attributable to a fast heart rate. Numerous risk factors for the development of AF have been identified, including advanced age, male sex, underlying heart disease, obstructive sleep apnoea syndrome (OSAS), and intensive prolonged physical activity, among others. Additionally, epidemiological studies have shown a relationship between gastroesophageal reflux disease (GERD) and AF. The two main treatments for AF are catheter ablation and antiarrhythmic drugs, with catheter ablation being the more effective option. Catheter ablation of AF is known to be associated with certain complications, and as a result, the traditional approach in most centres has been to keep patients hospitalised overnight to monitor for any complications that may occur following the ablation procedure. The cornerstone of catheter ablation of AF is pulmonary vein isolation (PVI). However, this treatment does not benefit all patients, especially those with persistent AF. Approximately 60% of patients with persistent AF achieve arrhythmia freedom through PVI. Fibrosis in the left atrium (LA), when detected through voltage mapping, showing low voltage zones (LVZ), is known to be associated with an even poorer prognosis. Therefore, it is essential to further investigate the mechanisms of AF and to develop additional ablation methods, to help a larger proportion of patients.

The aims of this thesis are: 1) to determine the safety of same-day discharge after the ablation procedure, aiming to increase the overall effectiveness of this treatment; 2) to evaluate, in a randomised controlled trial (RCT), whether ablation of LVZs in addition to PVI increases arrhythmia-free survival, compared to PVIonly; 3) to validate the accuracy of an ECG device, the Coala Heart Monitor (CHM), in detecting atrial arrhythmias; 4) to identify independent predictors of the presence of LVZs; and 5) to assess whether symptoms of GERD is a predictor of LVZs in the posteroinferior part of the LA.

Methods and results: Study I was a registry-based study that included all AF ablations performed at Karolinska University Hospital over the 2001-2020 period, encompassing a total of 5414 procedures. All complications were registered, and the medical records of patients who suffered from a complication were thoroughly reviewed. The complications were categorised based on the time of occurrence: from intraprocedural up to six hours post-ablation, and from six hours post-ablation until discharge the following day. We found that most complications occurred either intraprocedurally or within the first six hours following ablation. Furthermore, 73 complications were observed between six hours after the ablation until discharge, of which 12 were severe. Of these 12, it appears unlikely that a longer hospital admission would have altered the outcomes.

Study II outlines the protocol for an RCT where we aim to randomise 206 patients with LVZs in the LA to PVI-only or to PVI + LVZ ablation. The primary outcome is freedom from atrial arrhythmias at 12 months following one or two ablation procedures conducted within a six-month period with a blanking period of 3 months after the first procedure. As of now, we have randomised 166 patients, however, as the study is still ongoing, the results are not yet available.

Study III is a validation study in which a handheld ECG device, the CHM, was validated for detecting AF and atrial tachyarrhythmia (ATA), encompassing both AF and atrial flutter, with a 12-lead ECG serving as the reference standard. A total of 200 12-lead ECGs and simultaneous CHM registrations were collected. All registrations were interpreted in a blinded fashion by two electrophysiologists. The sensitivity and specificity for detecting ATA were found to be 98.9% (95% confidence interval (CI): 94.0–100) and 100% (95% CI: 96.6–100), respectively. The sensitivity and specificity for detecting AF were 100% (95% CI: 95.3–100) and 97.5% (95% CI: 93.0–99.5), respectively.

In Studies IV and V, we utilised a subset of the cohort from Study II, which comprised both randomised and non-randomised patients. In Study IV, we conducted a comparison between patients with LVZs in the LA and those without LVZs, with the aim of identifying independent predictors for the presence of LVZs. We discovered that female sex (odds Ratio (OR): 4.83, 95% CI: 2.66–8.76, P <0.001), age (OR: 1.08, 95% CI: 1.03–1.13, P =0.002), coronary artery disease (CAD) (OR: 3.20, 95% CI: 1.32–7.77, P =0.010), and an enlarged LA (OR: 1.10, 95% CI: 1.04–1.17, P=0.001) were independent predictors of the presence of LVZs. In Study V, we conducted a comparison between patients with and without symptoms of GERD. We found that patients with symptoms of GERD exhibited significantly higher odds of possessing LVZs in the posteroinferior wall of the LA, with an OR of 2.26 (95% CI: 1.24-4.13, P =0.008) in the adjusted analysis.

Conclusions: Same-day discharge after AF ablation appears to be safe six hours after ablation. The CHM demonstrates high accuracy, in detecting ATA and AF when compared to a 12-lead ECG, suggesting its suitability for follow-up in AF patients, and for screening purposes. Female sex, advanced age, CAD, and an enlarged LA were identified as independent predictors of LVZs. This information can be valuable in the planning process for AF ablation. Patients with symptoms of GERD exhibit increased odds of presenting with LVZs in the posteroinferior wall of the LA, which may partially explain the observed higher risk of AF in patients with GERD.

List of scientific papers

I. Paul Nordin, A., Drca, N., Insulander, P., Bastani, H., Bourke, T., Braunschweig, F., Kennebäck, G., von Olshausen, G., Sadigh, B., Saluveer, O., Tapanainen, J., Schwieler, J., Åkerström, F., Jensen-Urstad, M. Low incidence of major complications after the first six hours post atrial fibrillation ablation: Is same-day discharge safe and feasible in most patients? Journal of Cardiovascular Electrophysiology. 2021, Sep 17; 32(11): 2953- 2960.
https://doi.org/10.1111/jce.15243

II. Paul Nordin, A., Jensen-Urstad, M., Charitakis E., Åkerström, F., Almroth, H., Herczku, C., Tapanainen, J., Höglund, N., Drca, N. Individually DEsigned Ablation of Low voltage areas in persistent Atrial Fibrillation — a randomised controlled trial (IDEAL-AF): Study design. [Manuscript]

III. Paul Nordin, A., Carnlöf, C., Insulander, P., Mohammad Ali, A., JensenUrstad, M., Saluveer, O., Drca, N. Validation of diagnostic accuracy of a handheld, smartphone-based rhythm recording device. Expert Review of Medical Devices. 2023, Jan 25; 20(1): 55-61.
https://doi.org/10.1080/17434440.2023.2171290

IV. Paul Nordin, A., Jensen-Urstad, M., Charitakis, E., Carnlöf, C., Drca, N. Predictors of low voltage zones in patients with persistent atrial fibrillation eligible for catheter ablation: An observational study. Journal of Cardiovascular Electrophysiology. 2024, April 1; 35(5).
https://doi.org/10.1111/jce.16264

V. Paul Nordin, A., Charitakis, E., Carnlöf, C., Åkerström F., Drca, N. Symptoms of gastroesophageal reflux disease predicts low voltage zones in the posteroinferior left atrium in patients with persistent atrial fibrillation. [Submitted]