Electrical remodeling in arial fibrillation - assessment using surface electrocardiograms, prognostic implications and potential reversal

Abstract: The fibrillatory rate of the surface ECG during atrial fibrillation (AF) has been suggested for quantification of the individual atrial remodeling, to monitor interventions and to predict the response to different therapies. In this dissertation, the relation between fibrillatory rate of the surface ECG and (1) clinical and echocardiographic variables, (2) the outcome of cardioversion, (3) circulating markers of inflammation and hemostasis, (4) the risk of left atrial thrombus formation, (5) the risk of stroke, and (6) the effects of candesartan on the fibrillatory rate were investigated in human persistent atrial fibrillation (AF). Fibrillatory rate (in fibrillations per minute, fpm) was determined from the surface ECG using spatiotemporal QRST cancellation and time-frequency analysis. In 124 patients, multivariate linear regression analysis revealed age, gender, left atrial diameter and use of verapamil to be independently related with fibrillatory rate. Fibrillatory rate was reduced by candesartan, but not by placebo with dominant effects in patients with a high fibrillatory rate at baseline. In 123 patients treated with candesartan or placebo but not with class I or III antiarrhythmic drugs, cardioversion success was 100% in patients with a fibrillatory rate < 360 fpm as opposed to 83% in patients with higher rates. In successfully cardioverted patients, risk for AF recurrence was similar in patients with low (64%), intermediate (75%) or fibrillatory rates (63%). In contrast, in 44 patients treated with class I or III antiarrhythmic drugs, uni- and multivariate regression analysis revealed larger systolic left atrial area obtained by precardioversion echocardiogram from the apical 4-chamber view and higher fibrillatory rate to be independent predictors for AF recurrence after two weeks. Negative correlations were found between fibrillatory rate and C-reactive protein, von Willebrand factor, soluble tissue factor and plasminogen activator inhibitor-1 activity. However, these relations were lost after adjustment for age, gender, body mass index and left atrial diameter, except for a weak inverse relation between fibrillatory rate and soluble tissue factor. Fibrillatory rates were similar in patients with or without left atrial thrombus, and also in patients with or without stroke. In conclusion, (1) aging is associated with a fibrillatory rate decrease that may be a sign for advanced atrial remodeling. (2) Candesartan decreases fibrillatory rate, but this effect is restricted to patients with high baseline fibrillatory rates and offers no obvious clinical benefit. (3) Fibrillatory rates lower than 360 fpm are associated with successful cardioversion using monophasic shocks but not with AF recurrence in patients without specific antiarrhythmic treatment. (4) In contrast, in patients treated with class I or III antiarrhythmic drugs, fibrillatory rate and systolic left atrial area obtained by echocardiography may predict early AF recurrence in patients with persistent AF. (5) Fibrillatory rate does not correlate with inflammatory and hemostatic markers after adjustment for age, gender, body mass index and left atrial diameter, and (6) is not a risk marker for left atrial thrombus formation or (7) stroke.