Functional characterization of atrial electrograms in sinus rhythm delineates sites of parasympathetic innervation in patients with paroxysmal atrial fibrillation.

OBJECTIVES: This study sought to characterize left atrial (LA) sinus rhythm electrogram (EGM) patterns and their relationship to parasympathetic responses during atrial fibrillation (AF) ablation. BACKGROUND: The mechanistic basis of fractionated LA EGMs in patients with paroxysmal AF is not well understood. METHODS: We analyzed 1,662 LA ablation sites from 30 patients who underwent catheter ablation for paroxysmal AF. Pre-ablation EGM characteristics (number of deflections, amplitude, and duration) were measured in sinus rhythm. Parasympathetic responses during radiofrequency application (increase of atrial-His interval by > or =10 ms or decrease of sinus rate by > or =20%) were assessed at all sites. We also prospectively studied the effect of adenosine, a pharmacological agent mimicking acetylcholine signaling in myocytes, on LA EGMs. Finally, we performed mathematical simulations of atrial tissue to delineate possible mechanisms of fractionated EGMs in sinus rhythm. RESULTS: A specific pattern of pre-ablation sinus rhythm EGM (deflections > or =4, amplitude > or =0.7 mV, and duration > or =40 ms) was strongly associated with parasympathetic responses (sensitivity 72%, specificity 91%). The sites associated with these responses were found to be located mainly in the posterior wall of the LA. Adenosine administration and mathematical simulation of the effect of acetylcholine were able to reproduce a similar EGM pattern. CONCLUSIONS: Parasympathetic activation during AF ablation is associated with the presence of pre-ablation high-amplitude fractionated EGMs in sinus rhythm. Local acetylcholine release could potentially explain this phenomenon.

Reduction of P-wave duration and successful pulmonary vein isolation in patients with atrial fibrillation.

INTRODUCTION: We hypothesize that successful pulmonary vein (PV) isolation can shorten the P-wave duration in patients with atrial fibrillation (AF). METHODS AND RESULTS: We recorded magnified surface electrocardiogram (ECG) and P-wave signal-averaged ECG using 12 electrode leads before and after 31 PV isolation procedures in 27 patients with AF. The patients were followed for 16 +/- 4 months. Repeat ablation studies documented failed PV isolation in seven patients with AF recurrences. At baseline, the maximal P-wave duration in patients without AF recurrence (161 +/- 7 msec) was slightly shorter than that in patients with AF recurrence (168 +/- 10 msec, P < 0.05). After ablation, patients without recurrence showed a significant reduction of P-wave duration from 161 +/- 7 msec to 151 +/- 8 msec (P < 0.0001). In contrast, no change of P-wave duration was noted in patients with recurrences. These findings were confirmed with signal averaged ECG of the P-waves. Three-dimensional (3-D) computer simulation using an atrial cell model showed that elimination of the muscle sleeves inside the PV resulted in a shortening of the P-wave duration and change of the terminal portion of the P-wave morphology. CONCLUSIONS: A significant shortening of P-wave duration by P-wave signal-averaged ECG can be used as an indicator for successful PV isolation. These findings suggest that activation of the PV muscle sleeves may be an important component of the terminal portion of the P-wave on surface ECG.

Ventricular fibrillation: new insights into mechanisms.

Device therapy with implantable cardioverter-defibrillators is currently the only proven effective therapy against sudden cardiac death due to ventricular fibrillation. However, the expanded clinical indications for device therapy come at a staggering cost to an already overburdened health care system. Given these statistics, it is both highly desirable and economically imperative to develop alternative therapies. New insights into the mechanisms of ventricular fibrillation, particularly the role of dynamic factors causing wave instability, are providing a promising avenue for developing novel therapies to prevent sudden cardiac death.