Discussion:
The duration of the P wave is a result of the conduction velocity in the
atrial working myocardium and the distance the electrical activation has
to travel. Functional and structural changes in the atrial muscle affect
both of these parameters - they slow down conduction velocity and extend
the way to travel due to the enlargement of the atria. This results in
an extension of the P wave duration and a change in its morphology. The
same changes in structure and function are responsible for generating
atrial arrhythmias including atrial fibrillation [8]. Additionally,
the ongoing arrhythmia leads to progression of the above mentioned
changes. In particular the enlargement of left atrium is clearly
associated with an increase in filling pressure of the left ventricle
and probably dependent on the ventricular rate [12]. Data on the
effect of AF on muscle conduction are more scarce and equivocal
[13].
The main result of our study is to show a longer duration of the P wave
in patients with average long-term persistent atrial fibrillation
compared to patients with paroxysmal arrhythmia and sinus rhythm at the
time of the study. The degree of this elongation (about 10%) of the P
wave duration is not only statistically but also clinically significant.
It should be emphasized that the P waves measured by us in both groups
markedly exceed the normal values of 120 ms (144.6 vs 159.9 ms,
respectively). Similar comparisons are not numerous in the available
literature [14, 15]. As our subgroups of patients suffering from
paroxysmal and persistent AF are comparable according to age, gender
distribution, comorbidities and anti-arrhythmic medication, it indicates
that this additional prolongation is caused only by the presence of the
prolonged episodes of arrhythmia. Our measurements were not performed
immediately after the cardioversion shock, so the influence of direct
current can be skipped. Additionally the direct current flow during
cardioversion had little or no effect on the P wave duration in one
small study immediately after the procedure and on the next day
[16].
Even if diabetic patients were not frequently presented in our studied
group there was a noticeable difference between diabetics and
non-diabetics in terms of P wave duration. Those with DM were observed
to have a longer P wave than participants without it. This is in line
with the other clinical observations even the direct evidence lacks in
human. Diabetes is presumed to be a risk factor for atrial fibrillation
and the topic has been reviewed quite often. A meta-analysis of
different cohort and case control studies investigating the correlation
of DM and AF, showed that individuals with DM had a 40% greater risk of
AF compared to unaffected individuals [17]. There is only sparse
literature to be found about DM leading to electrical changes of the
atrial substrate [18]. In an experimental setting of DM it was
associated with increased atrial fibrosis, interatrial conduction delay
and greater inducibility of AF [19]. Another animal study confirmed
those results with additional interesting observations of either P wave
prolongation in diabetic rats without left atrial enlargement, for which
the authors accounted diabetic changes in the gap junction protein Cx
[20]. Similar outcomes were obtained in patients with impaired
fasting glucose leading to significantly prolonged interatrial
conduction times and consecutive decrease left atrial emptying volume
and fraction [21].
In another subgroup of our patients the chronic kidney disease was found
to be a predictor of longer P wave duration. In the literature some
researches made already the association between maximum P wave duration
and exacerbation of the renal condition until the defined end points of
hemodialysis, death or a specified decline in estimated glomerular
filtration rate [22. 23]. Based on our results it could be assumed,
that a vice versa influence of CKD on the P wave duration is occurring
as well, possibly because of a simple fluid overload. Referring to the
patients included in our study, only a small number of 9 (7.6%)
patients presented with CKD as a comorbidity but it was discovered to be
a statistically significantly related to the P wave duration. This needs
further investigation in other studies, not distorted by the small
number of CKD patients. Atrial fibrillation is frequently described
together with a renal dysfunction but mainly as a preceding comorbidity
but no relation was found for CKD being the reason of AF. Nevertheless
our results indicate such possibility making the subject worth to be
studied.
The anti-arrhythmic medication influences the electrophysiological
properties on the working myocardium, in particular the conduction speed
and refractory period which could influence the P wave duration. The
results of our study do not support such concept. Amiodarone is a class
III antiarrhythmic agent acting mainly as potassium channel blocker,
characterized by prolongation of the refractory period and atrial
repolarization. It has been shown to be effective in maintaining sinus
rhythm and preventing arrhythmia episodes in patients with paroxysmal
atrial fibrillations. Even if in one small study researchers described
the amiodarone-related increase in P wave duration, this was a small
experimental animal study and the conditions were not comparable in
sinus rhythm in human, present in our study [24]. The relationship
between P wave duration and amiodarone administration was similarly
negated in a study conducted by Sasaki et al. [25].
In contrast to amiodarone the treatment with sodium channel blocker
could theoretically influence the P wave duration. Propafenone is an IC
class agent which blocs the fast sodium channels, slowing down the
conduction velocity in the working myocardium. According to literature
data there is no direct relationship between the dose of propafenone and
the duration of the P wave, however the same study confirms a weak
correlation between the treatment with propafenone and the elongation of
the P wave duration [26]. Our data do not confirm this finding. One
should however emphasize that our propafenone treated patients’ group
was not large.
Based on our results the theoretical model resulting from ROC curves
indicated the estimated P wave duration differentiating patients between
sinus rhythm and persistent atrial fibrillation groups. In the
literature, this approach has not been presented so far, so our value of
P wave duration - 148 ms can only be referred to studies indicating the
importance of this parameter in the prediction of sinus rhythm
maintenance after electrical cardioversion. In 1999 Aytemir and
co-authors investigated the P wave signal-averaged ECG in 73 patients
after successful cardioversion. During 6 months follow-up period the
recurrence of AF was observed in 31 patients and in 42 patients sinus
rhythm was maintained. The researchers found no difference between the
groups according to gender, age, presence of organic heart disease, left
atrial diameter, left ventricular ejection fraction, use of
antiarrhythmic drug, and duration of atrial fibrillation. The filtered P
wave duration was statistically longer in patients with recurrence of
atrial fibrillation 138.4 vs. 112.5 ms. A filtered P wave duration of
128 ms was had a sensitivity of 70% and specificity of 76% for the
detection of recurrence of atrial fibrillation [27]. On the other
hand in the study of Perzanowski et al. the maximum duration of the P
wave did not differentiate patients who remained in sinus rhythm or
experienced a recurrence of arrhythmia (142 vs 145 ms; p=n.s.) [28].
As the authors did not mention the methodology of P wave duration
measurements it should be assumed that they used simple standard 12 lead
ECG without any more precise equipment. This lack of precision could be
the cause of their results. In the study of Gonna and co-workers a
12-lead ECG was recorded after electrical cardioversion for persistent
AF in 77 patients and repeated after 1 month. Compared with the sinus
rhythm group, the one with recurrent AF had more patients with P wave
duration exceeding 142 ms. Using a cutoff of <142 ms for P
wave duration the authors showed a sensitivity of 64.6% and specificity
of 62.1% for sinus rhythm maintenance. In multiple regression analysis
the P wave duration longer than 142 ms was the only independent
predictor of AF recurrence [29]. The above-mentioned considerations
indicate unequivocally that the prolongation of the P wave is clearly a
risk factor for paroxysm of atrial fibrillation and more advanced stages
of the arrhythmia, which is in line in our results. Moreover in
different settings we produced the evidence which supports the previous
findings. According to the higher values of the P wave duration obtained
by us, it should be remembered that the precise methodology used in our
study is qualitatively different from that of other researchers [28,
29]. This is a reason that already a few years ago we confirmed the
lack of P wave dispersion, assessed in some of the above papers, which
is related to the inaccuracy of the measurement [30].
In summary the ongoing atrial fibrillation in form of moderately long
persistent arrhythmia influences negatively the structural and
functional atrial remodeling. This occurs independently from age and
gender, sort of anti-arrhythmic treatment but can be slightly related to
some comorbidities.