TAIPEI, TAIWAN. In 1994 Professor Philippe Coumel of the Lariboisiere Hospital in Paris (who wrote the foreword to my first book) postulated that disturbances in autonomic nervous system (ANS) balance may be involved in the initiation of atrial fibrillation (AF). He coined the terms vagal (parasympathetic) and adrenergic (sympathetic) AF to distinguish between episodes initiated by excessively dominant vagal activity and those initiated by excessively dominant adrenergic activity. He noted that vagal AF is preferentially observed in the absence of detectable heart disease, whilst adrenergic AF is mostly accompanied by heart disease. Vagally-mediated episodes usually occur at night or after rest or a heavy meal when vagal dominance is common. In contrast, adrenergically-mediated episodes occur almost exclusively during daytime and are often associated with physical or emotional stress. However, most AF patients experience random episodes that cannot be clearly classified as either vagal or adrenergic. Whether or not an episode is vagally- or adrenergically-mediated can be ascertained by observing heart rate variability (HRV) about 10 minutes prior to the onset of an episode.

Pr. Coumel warned that beta-blockers and digoxin are contraindicated for patients with vagal AF since they would suppress adrenergic activity and thus exacerbate the ANS imbalance. Unfortunately his findings and warnings were largely ignored by cardiologists and electrophysiologists, particularly in North America. Our 2nd LAF Survey reported in March 2001 found that 54% of vagal afibbers were on contraindicated drugs resulting in a very significant increase in their AF burden (episode frequency multiplied by episode duration). A Dutch study published 7 years later found 72% of vagal afibbers were prescribed contraindicated drugs.

Now a group of electrophysiologists at the Taipei Veterans General Hospital further confirm the existence of the two forms of AF and conclude that they are associated with different electrophysiological properties of the left atrium. Their study involved 190 patients with frequent episodes of symptomatic, paroxysmal AF. During the month prior to a scheduled catheter ablation, all patients underwent 24-hour Holter monitoring to determine if their AF was adrenergically or vagally mediated as indicated by heart rate variability 10 minutes before the onset of an episode.

Heart rate variability (the variation in the interval between heart beats) is a powerful indicator of the state of the autonomic nervous system (ANS). The variation in the heart beat interval is usually measured via a 5-minute electrocardiogram or 24-hour Holter monitoring. The original and still commonly used measure for the variation is referred to as SDNN which is the standard deviation of the heart beat intervals, that is, the square root of the variance. Most scientific work on heart rate variability (HRV) now uses power spectral density (PSD) analysis to relate the relatively simple measurement of beat to beat variability to the state of the autonomic nervous system. PSD analysis uses a mathematical technique (fast Fourier transform) to determine how the power (variance in heart beat interval) is distributed across different frequency bands. There is now general agreement that the power in the low frequency band (LF) from 0.04 to 0.15 Hz (cycles/second) is an indication of sympathetic (adrenergic) branch activity and that the power in the high frequency band (HF) from 0.15 to 0.40 Hz is primarily an indication of parasympathetic (vagal) activity. It follows that the ratio of LF/HF is a measure of the balance of the autonomic nervous system with a higher number indicating an excess of adrenergic activity and a lower number indicating an excess of vagal activity.

Thirty of the patients (16%), with an average age of 53 years and 87% male, met the criteria for pure vagal or pure adrenergic AF and were included in the subsequent study. In 12 of the patients the onset of AF episodes were preceded by an increased HF component and a decreased LF/HF ratio. These patients were classified as vagal. In the remaining 18 patients episodes were preceded by a decreased HF component and an increased LF/HF ratio. They were classified as adrenergic. Electrical and structural properties of the atria were evaluated during the ablation procedure and revealed the following differences between the two groups:

• All patients had AF originating from the pulmonary veins (PVs), but vagal afibbers had far fewer non-PV triggers than did adrenergic afibbers (8% vs. 44%).
• Bipolar peak-to-peak voltages (PPV), as measured in the left atrium by electroanatomical mapping (using the NavX system), were substantially higher in the vagal group, whilst the area of low voltage zones (bipolar PPV less than 0.5 mV) was more extensive in the adrenergic group (29% vs. 18%). NOTE: Low voltage zones are likely associated with atrial fibrosis.
• The average volume of the left atrium as determined with a CT scan was significantly smaller in the vagal group.
• There was no difference in electrical or structural properties of the right atrium between the two groups.
• During a 15-month follow-up after a single catheter ablation procedure, 8% of vagal afibbers experienced recurrence as compared to 50% amongst adrenergic afibbers.

The authors conclude that electrical properties and left atrial volume, as well as ablation outcome, are more favourable for patients with vagal AF.
Lo, L-W, et al. Differences in the atrial electrophysiological properties between vagal and sympathetic types of atrial fibrillation. Journal of Cardiovascular Electrophysiology, January 22, 2013 [Epub ahead of print]

Editor's comment: It is interesting that 84% of the 190 patients originally screened for the study did not exhibit the clear pre-onset HRV change associated with either vagal or adrenergic AF. In other words, as measured by pre-onset HRV, only 6% of the 190 patients had vagal AF, 9% had adrenergic AF, and the remaining 84% had random (mixed) AF. These numbers are in sharp contrast to the data for 584 afibbers participating in the 2008 Ablation/Maze Survey. Here 33% reported that their AF corresponded to the definition of vagal (occurring during the night, after a heavy meal or after alcohol consumption), 7% reported that their AF indicated an adrenergic association (stress-related), and 60% could not specify their AF as either vagal or adrenergic, and were therefore classified as having random (mixed) AF. In considering this significant difference in classification, it should be kept in mind that the 2008 Ablation/Maze Survey involved lone AF patients only, whilst the Taiwan study included patients with coronary artery disease and heart failure. Thus 25% of the 12 patients classified as vagal and 44% classified as adrenergic had either heart disease or heart failure. This may also help explain the relatively poor ablation outcome for adrenergic afibbers.