Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of AF. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews preclinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacological therapy, and ablative strategies for AF. Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate, so-called upstream therapy. Improved diagnostics, using imaging, genetics, and biomarkers, are needed to better identify subtypes of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel antiarrhythmics with more atrial specific effects may reduce limiting proarrhythmic side effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism-targeted approaches.

Background

Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for refractory ventricular tachycardia (VT). However, the current workflow is complicated, and the precision and safety in patients with significant cardiorespiratory motion and VT targets near the stomach may be suboptimal.

Objective

We hypothesized that automated 12-lead electrocardiogram (ECG) mapping and respiratory-gated therapy may improve the ease and precision of SAbR planning and facilitate safe radiation delivery in patients with refractory VT.

Methods

Consecutive patients with refractory VT were studied at 2 hospitals. VT exit sites were localized using a 3-D computational ECG algorithm noninvasively and compared to available prior invasive mapping. Radiotherapy (25 Gy) was delivered at end-expiration when cardiac respiratory motion was ≥0.6 cm or targets were ≤2 cm from the stomach.

Results

In 6 patients (ejection fraction 29% ± 13%), 4.2 ± 2.3 VT morphologies per patient were mapped. Overall, 7 out of 7 computational ECG mappings (100%) colocalized to the identical cardiac segment when prior invasive electrophysiology study was available. Respiratory gating was associated with smaller planning target volumes compared to nongated volumes (71 ± 7 vs 153 ± 35 cc, P < .01). In 2 patients with inferior wall VT targets close to the stomach (6 mm proximity) or significant respiratory motion (22 mm excursion), no GI complications were observed at 9- and 12-month follow-up. Implantable cardioverter-defibrillator shocks decreased from 23 ± 12 shocks/patient to 0.67 ± 1.0 (P < .001) post-SAbR at 6.0 ± 4.9 months follow-up.

Conclusions

A workflow including computational ECG mapping and protocol-guided respiratory gating is feasible, is safe, and may improve the ease of SAbR planning. Studies to validate this workflow in larger populations are required.