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Self-treatment techniques in patients with paroxysmal atrial fibrillation and the probable influence of the autonomic nervous system


Anders Hansson, Pyotr Platonov, Jonas Carlson, Bjarne Madsen Hardig and S Bertil Olsson

Department of Cardiology, Lund University, SE-221 85 Lund, Sweden




Corresponding author
Anders Hansson
Department of Cardiology
Sk�ne University Hospital
SE-221 85 LUND, Sweden
Phone: +46 (0)46 171602
Fax: +46 (0)46 157857
E-mail: anders.p.hansson@skane.se
Abstract
Background: Self-treatment techniques in patients with paroxysmal atrial fibrillation (PAF) have seldom been described. It has been suggested that PAF attacks might be initiated by changes in the tonus of the autonomic nervous system. Our aim was to study patients� measures to terminate PAF attacks and to evaluate the possible influence of the autonomic nervous system on start and stop mechanisms. 
Methods: One hundred patients with PAF filled in a questionnaire on the circumstances under which attacks occurred and how they tried to stop them.  
Results: Thirty-nine per cent of the patients believed they could terminate episodes of PAF. Significantly more �terminators� described attacks of short duration, < 12 h, than �non-terminators� (31 of 39 vs. 23 of 61, p<0.0001). The majority of terminators, with known start times, had attacks that started in the time interval 2100-0900 h (24 of 29, p=0.0004). Parasympathetic stimulation was the most common way of terminating attacks ( 21 of 39, p = 0.0039), e.g. Valsalvae manoeuvre. A probable sympathetic or vagal influence on start mechanisms was equally common for terminators and non-terminators. In PAF with sympathetic start mechanisms, vagal ways of terminating dominated. For PAF of vagal type no difference was seen between vagal and sympathetic ways of terminating.
Conclusions: Patients often report that they are able to terminate their PAF attacks. Successful self-treatment techniques frequently include actions that involve vagal stimulation. Individuals with sympathetic start mechanisms may more often benefit from vagal stimulation, leading to termination. Patients who can treat themselves often have PAF attacks that start between late evening and early morning.

Key words: Paroxysmal atrial fibrillation, self-treatment, autonomic nervous system
Abbreviations: AF, atrial fibrillation; PAF, paroxysmal atrial fibrillation


Introduction
Nowadays, atrial fibrillation (AF) is divided into three different forms: paroxysmal, persistent, and permanent (1). The prevalence of the different forms of AF has earlier been described. In an out-of-hospital patient material, 35% of cases were paroxysmal AF, 18% were persistent AF, and 47% were permanent AF (2). Another study based on hospital observations showed that 35% of all AF was of paroxysmal (PAF) type (3).  
Despite the fact that PAF is common, surprisingly limited information is available about the different ways in which patients try to terminate an episode of PAF. In the clinic, it is generally believed that it is not possible for patients to terminate these attacks by themselves. Earlier studies have suggested that PAF attacks are initiated by changes in the tonus of the autonomic nervous system (4), and variation in vagal activity may be involved in termination (5,6). 
Our group has previously studied arrhythmia-provoking factors and symptoms at the onset of PAF. The most common symptoms were palpitations, physical tiredness, shortness of breath, and dizziness (7). In this report using the same patient material, we describe different ways of self-treatment reported by patients with PAF, which enabled them to terminate an attack into sinus rhythm. We investigated how these patients differed from those who did not have this ability, and studied the circumstances in which they managed to do it. We also looked at possible influences of the autonomic nervous system in start and stop mechanisms.
 
Materials and Methods
Study sample
A group of 100 patients with ECG-verified PAF were asked to fill in a structured questionnaire concerning their self-treatment techniques (Table 1). None of the patients declined participation. The same questionnaire had been used in our earlier publication describing PAF-provoking factors and symptoms (7). For some questions, extra information could be supplied by the patients in their own words.
In this report we selected those questions concerning the start mechanisms and the patient�s ability to terminate an attack (Table 1). At inclusion, the patients were given the questionnaire and interviewed by the investigating doctor, either at the time of visits to the Department of Cardiology or during hospitalisation following an acute episode of arrhythmia. Patients� journals were also available. 
Permission to carry out the investigation was obtained from the local Ethical Committee (LU 391-93) and all patients were informed about the investigation both verbally and in writing. 

Patients with diagnosed lone PAF were included (8). They were excluded if they had a history of myocardial infarction, pericarditis, thyroid disease, or diabetes, since these diseases are generally considered to cause atrial fibrillation (9-15).
One hundred completed questionnaires were filled in by 72 men and 28 women (Table 2). The median (min-max) age of the entire group was 60 (22-79) years, 68 (54-79) years for women and 58 (22-79) years for men. The patients had a PAF history of 3.9 (0-41.5) years from diagnosis to inclusion. Twenty-four per cent of the patients were treated for hypertension. The ages of patients with and without a previous history of hypertension were 65 (47-79) and 59 (22-79) years, respectively. Since patients with hypertension differed from the others only with regard to age, the analyses that followed were done without consideration of hypertension.
All the patients had had previous attacks of atrial fibrillation that stopped spontaneously or after medication, either by �pill in the pocket� strategy or given at the hospital. The symptoms patients interpreted as PAF were the same as those presented at diagnosis when AF was verified by ECG. 
Seventy-six per cent of all patients were already on treatment with anti-arrhythmic drugs (Table 2). Twenty-four per cent of the patients were not taking any anti-arrhythmic drugs.

Statistics
Continuous variables were compared using Mann Whitney U-test (StatView for Windows, SAS Institute Inc. Version 5.0.1). Values of p < 0.05 were considered significant. Comparisons between observed and expected frequencies were made using chi-squared test (www.graphpad.com/quickcalcs). For comparisons within a group ( e.g., male/ female distribution) a 50/50 distribution was expected. Analysis of 2x2 contingency tables were made using Fisher�s exact test.

Results
Thirty-nine of the 100 patients believed that they could terminate an episode of PAF by themselves. There were no statistically significant differences in gender, age, number of electrical cardioversions or treatment with anti-arrhythmic drugs between terminators and non-terminators (Table 2).

Diurnal variation and occurrence of PAF episodes
Of the terminators, 49% (19 of 39) had seven or more PAF episodes per year, as compared to 31% (19 of 61) of non-terminators (p=0.053). Distribution of and reported number of arrhythmia onset times (%) over 24 h are given in Figure 1. It can be seen that non-terminators had a peak of reported onset times in the time interval 1800-2100 h and terminators had a peak at 2100-2400 h and also at 0600-0900 h. Fourteen patients reported attacks in more than one time interval.
More than one third of the patients (n = 35) stated that they had PAF episodes when they woke up, but no significant difference was seen between terminators (38%; n = 15) and non-terminators (33%; n = 20).
In non-terminators, there were no significant differences in the number of patients who had episodes of PAF starting in the time interval 0900-2100 h (15 of 61) or 2100-0900 h (21 of 61) (p = 0.32). However, in terminators, a significant majority of the patients (24 of 29, Table 2), the PAF attacks started in the time interval 2100-0900 h (p = 0.0004). It was also significantly more common for terminators to have attacks during this time interval than non-terminators (24 of 39 as opposed to 21 of 61; p = 0.013). Only 25% of the patients (5 of 20) who had PAF that started in the time interval 0900-2100 believed that they could stop attacks.

Ways of terminating PAF attacks and the possible influence of the autonomic nervous system in start and stop mechanisms 
There were no significant differences between terminators and non-terminators regarding the various triggering factors that were reported in our previous study (e.g. mental stress, physical effort, alcohol, infections) (7). Depending on the circumstances in which the PAF attacks started and terminated, the material was analysed for probable vagal or sympathetic causes. If the patients woke up with or had PAF during rest, the attacks were considered to be of vagal type. Psychological stress and physical effort were defined as sympathetic causes.
In the study population, no significant differences were seen in vagal or sympathetic influence on the start mechanism (n = 30 vs. n = 25). In terminators, a vagal start mechanism for PAF was as common as a sympathetic start mechanism (n = 11 vs. n = 11, Table 3); nor were any significant differences seen for non-terminators (n = 19 vs. n = 14).
Parasympathetic stimulation was the most common way to succeed in stopping an attack (21 of 39, p = 0.0039) and most often by Valsalvae manoeuvre, which was mentioned by 9 patients. Other ways of terminating an attack were resting, drinking cold water, carotid massage, changing body position, and chest �knock� (Table 4). Of the twenty-one patients who pointed out probable vagal ways to self-terminate attacks, 14 patients responded that their episodes started in the time interval 2100-0900 h, one patient answered 0900-2100 h, and six could not specify any particular time. In terminators with PAF that started between 2100 h and 0900 h, it was significantly more common to have vagal ways of stopping the attacks ( 14 of 17, p = 0.0076, Table 3). 
Six patients pointed out probable sympathetic ways to self-terminate attacks and the most common way was exercising, which was mentioned by 5 patients (Table 4). Three of these 6 patients responded that their episodes usually started in the time interval 2100-0900 h, two responded that their episodes started between 0900 h and 2100 h, and one could not specify any particular time interval (Table 3).
Twelve patients pointed out ways of self-terminating attacks that could not be defined as vagal or sympathetic (Tables 3 and 4). 
In PAF of sympathetic type, it was more common to terminate in a vagal way (p = 0.034, Table 3). For PAF of vagal type, no difference was seen between sympathetic or vagal ways of stopping the attacks.

Attack duration in relation to ability to terminate attacks
For most patients (n = 64), attacks usually lasted less than 24 h, while 17 reported 1-7 days. No attack lasted more than one week (Fig. 2). It was also more common to have shorter attacks (<12h, n = 54) than longer attacks (e"12h, n = 42). Four patients could not specify the attack-duration.
Of the patients who could stop an attack, significantly more reported attacks shorter than 12 h (31 of 39) than those who could not stop their attacks (23 of 61, p < 0.0001). Significantly more terminators also described really short episodes (<15 min) than non-terminators (n = 9 vs. n = 5, p = 0,038).



Discussion
PAF is one of the most common cardiac arrhythmias requiring treatment. Despite this, surprisingly little information is available on how the patient can terminate attacks by themselves. Only case reports and treatment recommendations have been published, on how patients with PAF may be able to terminate attacks using Valsalva manoeuvre or exercise (16,17). In this study, we wanted to determine the ways in which the patients experienced that they could self-terminate attacks. 
Previously, studies with telephone-transmitted ECG have shown a high sensitivity (89%) of symptomatic registrations of patients with PAF (18). In this study, there was a strong correlation between the patient�s sensation of arrhythmia and an objectively observed PAF episode, thereby suggesting that the patients� experiences of PAF were reliable.
Recently, it has been reported that self-perception of arrhythmic sensations corresponds to objective verified AF in one third of cases (19). This was shown in a population that had undergone pulmonary vein ablation and received a subcutaneous event recorder. In this respect, the material is not comparable to ours, as our patients had not been exposed to any intervention. The patients could be more perceptive to both arrhythmic and non-arrhythmic sensations after intervention, and also by having a recorder, which might explain the low correlation.
The results of the present study show that a substantial proportion of the patients (39%) have the ability to succeed in different self-treatment methods to stop their PAF attacks. This seems to be a quite successful way of treatment, and is perhaps comparable or even better than different pharmacological therapies. The most common ways of stopping the attacks were of vagal type. Valsalvae manoeuvre appeared to be the best self-treatment technique, which enabled 9% of the patients to stop the attacks. However, some patients described sympathetic activities that resulted in termination.
In earlier studies, it has been described that attacks of PAF are often due to variations in the tonus of the autonomic nervous system. Arrhythmia is stimulated particularly when an initial adrenergic increase is followed by an abrupt change into vagal dominance (4). This is comparable with the findings in our study, as we could see peaks of reported PAF attacks in the time interval 1800-2100 h for non-terminators and 2100-2400 h for terminators (Fig. 1).
Nowadays, it is also generally accepted that most attacks of PAF are induced by ectopic impulses originating from the pulmonary veins (20, 21). The influence on this mechanism of the autonomic nervous system inducing arrhythmia is still uncertain.
Class I anti-arrhythmic drugs lower conduction velocity in the atrium (22), and termination of PAF with these drugs is preceded by an increase in fibrillation cycle length. Failure to increase the fibrillation cycle length correlates with failure to terminate PAF with medication (23).
Fujiki et al. have previously suggested that the role of the fibrillation cycle length in spontaneous termination may be different depending on the time of day (24). They have also shown that patients with PAF that terminates in the morning have a significant increase in the fibrillation cycle length, and they have stated that spontaneous termination in the morning may be caused by an abrupt increase in fibrillation cycle length related to a change in the vagolytic autonomic balance. A change in vagal activity during the day is one possible mechanism in spontaneous termination, as vagal tone promotes a shortening of the atrial refractory period (5,6). The same mechanism possibly explains why our patients� vagal ways of terminating attacks predominated.
From observations of heart rate in sinus rhythm shortly before onset of PAF, a separation into sympathetically mediated and vagal forms has been suggested (25). PAF of vagal type often starts at night and terminates in the morning. Earlier reports have suggested that this vagal type can be terminated by physical activity (25). PAF of sympathetic type mainly occurs during the day. Theoretically, those patients who specify sympathetically terminating mechanisms should have PAF of vagal type and should therefore have attacks that mainly start at night. Those who describe terminating mechanisms that are probably of vagal type should consequently have PAF of sympathetic type, and should therefore have episodes that start in daytime.
In our study, however, most patients mentioned probable vagal mechanisms that terminated the episodes of PAF. In PAF of sympathetic type, vagal stop mechanisms were most common but in PAF of vagal type, it was equally common to terminate by the vagal way or the sympathetic way. Vagal stop mechanisms predominated in PAF starting in the time interval 2100-0900 h, which contradicts the theory above. This raises the hypothetical question of whether it most often takes a vagal mechanism to terminate attacks, as most PAF episodes have a high frequency regardless of whether the trigger mechanism is vagal or sympathetic. In non-terminators, we did not find any difference in the time interval in which the PAF episodes started, but in terminators a highly significant majority of the patients the PAF attacks started in the time interval 2100-0900 h. It was also significantly more common for terminators than nonterminators to have attacks in this interval.
We have shown in this study that significantly more patients who could stop an attack described attacks with a duration of less than 12 h than non-terminators, and a significant proportion of these patients (29%) had attacks shorter than 15 min. In previous studies, it has been suggested that with increasing duration of attacks of PAF, the probability of successful cardioversion decreases irrespective of the technique used and the recurrence of arrhythmia becomes more and more likely (26). Thus, short attack duration is of importance for the ability to terminate PAF. Hypothetically, this could also mean that early attempts by the patient to terminate an attack should be encouraged.


Limitations
This material included only those patients seeking hospital treatment; thus, it was not representative of all patients with PAF. The symptoms of our patients were so advanced that hospitalisation or at least a visit to a hospital was required. We could presumably have missed a group of patients with PAF who were more successful in terminating attacks and who did not need to seek hospital treatment. 
The study shows the patients� experiences in how to terminate attacks, but no Holter registrations were performed to objectively verify attacks. Thus, we cannot rule out the possibility that some attacks might have been sensations originating from some other cause.

Conclusions
It is common that patients feel that they can sometimes stop an attack of PAF themselves.
Successful strategies reported by the patients most often included actions involving vagal stimulation, e.g. Valsalva manoeuvre, but sympathetic stimulation was not unusual. Sympathetic and vagal influences on the start mechanism of PAF were equally common for terminators and non-terminators. Sympathetic PAF was most often terminated in a vagal way, but in vagal PAF no difference was seen in which way it could be terminated.
Patients with the ability to self-terminate PAF more often had attacks that started between 2100 and 0900 h, and had shorter duration of attacks.

Competing interests
None



Acknowledgement
The authors wish to thank our colleague Fredrik Holmqvist for valuable intellectual input to this study.





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Table 1


Is it possible for you to stop the attacks by yourself?In what way can you stop the attacks?How long are the attacks in general?At what time does the attack start?How many times have you been treated with DC?When did you have the first episode of PAF?How often do you experience attacks?Under what circumstances do you experience attacks?























Table 2 

ObservationsCan stop
n = 39Can not stop
n = 61SignificanceAge (median(range))60.8 (33.2-77.9)59.6 (22.4-79.2)NsSex (men/women)27/1245/16NsStart time 0900-2100 h 515NsStart time 2100-0900 h2421p = 0.013Attack duration	< 12 h
                         	< 15 min79.5%
937.7%
5p = <0.0001
p = 0.038Medication:
Sotalol
Digoxin
Disopyramid
Calcium blocker
Beta blocker
Amiodarone
Flecainide
41%
18%
15%
8%
5%
3%
3%
39%
11%
11%
10%
15%
0%
7%
Ns
Ns
Ns
Ns
Ns
Ns
NsYears (mean � SD) from
diagnosis to inclusion5.8 � 6.65.8 � 6.8Ns
































Table 3 

Probable termination mechanism for PAFSympatheticn = 6Vagaln = 21Unknownn = 12Totaln = 39Start time interval2100-0900 h3147240900-2100 h2125Unknown16310Probable starting mechanism for PAFSympathetic17311Vagal44311Unknown110617 







Table 4

Reported self-treatment techniquesN = 39Probable mechanismValsalvae manoeuvre9VagalExercise5SympatheticRest2VagalCold water3VagalRelax2VagalCarotid massage2VagalChange body position2UnknownChest �knock�1UnknownRed wine1UnknownPull up knees1UnknownBurp1VagalWake up1SympatheticMeditate1VagalSamarin	(Sodium bicarbonate)1VagalSotalol3UnknownDiazepam1UnknownFurosemid1UnknownFlekainid1UnknownPropranolol1Unknown
Table legends

Table 1
Questions included in the patient questionnaire regarding start mechanisms and termination of PAF attacks.

Table 2
Patient characteristics

Table 3
Probable autonomic neural terminating mechanisms in relation to diurnal variation of the attacks. Vagal mechanisms were most common, and the majority of these patients had attacks starting 2100-0900 h. (Unknown: > 1 or no specific interval reported). 
Probable starting- and termination mechanisms for PAF. Vagal stop mechanisms predominate in sympathetic PAF. For vagal PAF, sympathetic and vagal termination mechanisms are equally common.

Table 4
Different attack-termination techniques tried by the patients and probable mechanisms behind them.





Figures



Figure 1
 SHAPE  \* MERGEFORMAT 

Figure 2
 SHAPE  \* MERGEFORMAT 


Figure legends

Figure 1
Distribution of onset times for reported arrhythmias as percentage of terminators (n = 39) and non-terminators (n = 61), respectively. Fourteen patients reported more than one onset time. NOS, no onset time specified. Onset time 1800-2100 h was most common for non-terminators and 2100-2400 h was most common for terminators.



Figure 2
Duration of attacks in relation to the ability to terminate attacks. Patients with the ability to self-terminate PAF had significantly shorter duration of attacks.









Hansson et al

PAGE  


PAGE  14


Hansson et al

PAGE  


PAGE  25



Non-terminators

Terminators

time

NOS

21-24

18-21

15-18

12-15

09-12

06-09

03-06

00-03

35%

30%

25%

20%

15%

10%

5%

0%

Number of onset times (%)                    

Patients who cannot terminate [n = 61]

Patients who can terminate [n = 39]

number of patients

determine

Cannot

> 1 week

4-7 days

1-3 days

12-23 h

3-11 h

1-2 h

30-59 min

15-29 min

< 15 min

20

18

16

14

12

10

8

6

4
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