Atrial Fibrillation. Modulation of the atrial fibrillatory frequency. A non-invasive approach

Abstract: Aim: To non-invasively detect and explore the changes in atrial fibrillatory cycle length (i.e. changes in the atrial refractory period) in humans with chronic atrial fibrillation (CAF) following autonomic modulation and pharmacological intervention. Furthermore we investigated if the value of the atrial fibrillatory cycle length could predict outcome following DC-cardioversion. Methods: The study enrolled patients with persistent or permanent AF. Data was acquired using 12-lead standard ECG equipment, a unipolar oesophageal lead or digital Holter recorders. Assessment of atrial fibrillatory electrophysiology was made non-invasively with power spectrum frequency analysis of QRST cancelled ECG using the frequency analysis of fibrillatory ECG methodology (FAF-ECG). The peak frequency was converted to a cycle length, termed dominant atrial cycle length (DACL), which is a validated index of atrial refractoriness. Results: In the first study (I) the DACL derived from both surface and oesophageal ECG as well as additional parameters of the FAF-ECG methodology were evaluated in clinical practice. The second study (II) showed that oral treatment with verapamil increases DACL (and therefore by inference atrial refractory period) in patients with chronic AF. The two following studies (III, IV) investigated the effects of autonomic modulation on atrial fibrillatory electrophysiology. The first of these (III), demonstrated that adrenergic stimulation decreases the DACL and that vagal withdrawal initially increases the DACL. The other study (IV) found that atrial fibrillatory cycle length shows significant diurnal variation, with shorter cycle lengths during day and consequently longer cycle lengths during night. Finally, we demonstrated that the ratio of DACL and left atrial diameter is higher in patients maintaining in sinus rhythm after DC-cardioversion of persistent AF (V). Conclusion: The FAF-ECG method can estimate DACL in the majority of patients, allowing non-invasive assessment of atrial refractoriness and of spatial dispersion in DACL, power maximum and spectral width of DACL (I). Since DACL is recognised as an index of refractoriness, we have demonstrated that already established electrical remodelling can be attenuated/partly reversed with calcium channel blockade (II). Changes in the electrophysiological properties of the fibrillating atrium during pharmacological autonomic modulation are detectable by the FAF-ECG method, and sympathetic modulations appear to be more pronounced than vagal ones during chronic AF (III). DACL, and hence atrial refractoriness, exhibits significant diurnal fluctuations during chronic AF, with a shorter mean DACL during daytime (IV). Prediction of sinus rhythm maintenance following cardioversion is optimised by combining electrophysiological and anatomical measurements, but the absolute predictive accuracy is modest, suggesting other etiological factors than absolute degree of electrical remodelling are important (V).