3.1 Sinus and paced P-wave duration analysis
The distribution of sinus P-wave duration was as follows: <
120 ms (64%), 120-139 ms (26%), and ≥ 140 ms (10%); and for paced
P-wave, < 120 ms (11%), 120-159 ms (49%), and ≥ 160 ms
(40%). Table 1 reflects sinus and paced P-wave duration (ms) according
to the presence of AHRE. Mean paced P-wave was significantly longer than
sinus P-wave (154±27 vs 115±18 ms; p < 0.001), both in
patients with AHRE (161±29 ms vs 119±20 ms; p < 0.001) and
without AHRE (148±23 ms vs 112±16 ms; p < 0.001). IAB was
present in 36% of the patients in sinus rhythm (31% partial, 5%
advanced) and 89% during atrial stimulation (p = 0.011). IAB in sinus
rhythm was present in 43% of the patients with AHRE and 30% of the
patients without AHRE (p = 0.039) and i4% and 86%, respectively,
during atrial stimulation (p = 0.034).
ROC curves showed the following values for area under the curve (AUC):
sinus P-wave: 0.594 ± 0.038 (p = 0.016) and paced P-wave: 0.635 ± 0.038
(p < 0.001) (Figure 2). No significant difference between
sinuthe s and paced P-wave duration for AHRE development was found,
although paced P-wave showed a better performance.
In a subgroup analysis dividing the population according to paced P-wave
duration (Table 3), a paced P-wave ≥ 160 ms showed the strongest
association with AHRE development, especially for those lasting
> 24 h (OR 4.2; 95% CI [1.6-11.4] p < 0.004)
Table 4 shows the results of a univariate analysis in which several
cut-off points in sinus/paced P-waves and clinical factors were
included. Among the statistically significant predictors for AHRE, a
paced P-wave ≥160 ms, a CHA2DS2-VASc
score ≥4, and a LA SI dimension ≥ 55 mm were included in a multivariable
model which yielded the following 3 independent predictors augmenting
AHRE: paced P-wave ≥160 ms (OR: 1.84; 95% CI [1.03–3.28];
p = 0.038), CHA2DS2-VASc score ≥4 (OR:
2.01; 95% CI [1.13–3.55]; p = 0.016), LA dimension ≥55 (OR 2.69;
95% CI [1.48–4.90]; p = 0.001).
DISCUSSION
We have found that patients with CIED using right atrial stimulation in
conventional atrium lead location presented significant prolongation of
the P-wave duration and a higher prevalence of IAB. Furthermore, our
results show that a longer P-wave duration and a higher presence of IAB
are significantly related to the development of AHRE during long-term
follow-up. A paced P-wave duration ≥160 ms had the highest predictive
value for AHRE of any duration, especially for those lasting
>24 h. Only patients without prior known AF were included,
since a history of this entity is considered an independent risk factor
for the development of AHRE.
The development of AHRE is relatively common among patients with CIED13, 14. In the recently published IMPACT study, AHRE
episodes of >6 min to <6 h were the most
prevalent among all duration categories, and age, history of AF, and
hypertension were the most important risk factors 14.
Although they have been related to the development of clinical AF, their
clinical implications are not yet sufficiently clarified15. Even so, finding prognostic markers for the
development of AHRE and therefore of possible clinical AF is currently
an important goal due to the possible therapeutic implications,
especially as concerns anticoagulation 16.
Our group previously analyzed 380 patients who had undergone CIED
implantation, showing that IAB is a significant predictor of AHRE, both
in subjects with and without a previous history of AF8. Tekkesin et al included 367 patients with CIED with
no previous history of AF, and 32% of them had IAB (29% partial and
3% complete) 10. This proportion was also higher in
patients who developed AHRE during follow-up (12). In the present study,
this proportion was similar: 36% of the patients had IAB, and its
presence was significantly higher in patients with AHRE than without it
(43% vs 30%; p = 0.039). Ariyarajah et al found a higher IAB
prevalence in patients with previous embolic stroke than in patients
with a non-embolic stroke (61% vs. 41%;
p < 0.05)5. Some other studies also support
the same relation between the presence of advanced IAB and the
development of AF and ischemic stroke 17. Tse et al.
carried out a meta-analysis of 16 studies with 18204 patients in which
they found that IAB, especially advanced IAB, was a significant
predictor of de novo and recurrent AF 18. In the study
by Lehtonen et al with 5667 patients, AF, male sex, hypertension, age,
and obesity were identified as clinically significant factors that
prolonged the duration of the P-wave 19. The REGICOR
registry showed a higher IAB prevalence in patients with AF vs. without
AF (63% partial and 11% advanced vs 46% partial and 9% advanced;
p = 0.0006) 3.
However, there are almost no studies analyzing the paced P-wave, the
incidence of IAB, and the development of AHRE. Only Kristensen et al.20 conducted a study with 109 patients who had
undergone CIED implantation due to sinus node disease or brady-tachy
syndrome, in which the duration and dispersion of the sinus and paced
P-waves were measured, analyzing their relationship with AHRE and AF
during follow-up. Although the paced P-wave was wider than the sinus
P-wave during high atrial pacing (155 ± 27 ms vs 117 ± 26 ms), there was
no significant difference in the paced P-value duration between patients
with and without AHRE, and it was not a significant predictor of
AHRE/AF. Only a previous diagnosis of brady-tachy syndrome was a
significant predictor. These findings differ from ours since we
demonstrated that the paced P-wave duration or the presence of IAB
during atrial pacing are significant predictors of AHRE during
follow-up. In addition, as in the study by Kristensen et al, we found
that with atrial stimulation the duration of the P-wave increases by 39
± 29 ms on average and, consequently, the proportion of patients with
IAB (89% with stimulation vs. 36% without stimulation).
All traditional works define the presence of IAB by taking a P-wave
duration ≥ 120 ms, though this value may not be appropriate if atrial
stimulation alone increases the duration of the P-wave and generates a
greater degree of IAB or develops a previously nonexistent IAB. Perhaps
values greater than 120 ms should be considered to define IAB in the
presence of atrial stimulation, making them better predictors of AHRE.
That is why we have carried out a predictive analysis of AHRE as a
function of the width of the paced P-wave, finding that a greater width
increases the risk of presenting AHRE of longer duration. A paced P-wave
≥160 ms has the best prognostic value for any duration of AHRE episodes,
but especially for those lasting >24 h, which are perhaps
those with the most important clinical implications.
We found that in addition to paced P-wave duration, the presence of left
atrial enlargement and a CHA2DS2-VASc
scale ≥4 are significant independent predictors of AHRE development in
the general population with CIED. Atrial enlargement by itself is
associated with IAB 2, 21, 22. All these findings may
have an important clinical impact since some studies have shown that a
higher percentage of atrial pacing is associated with an increased risk
of AHRE 23. This could also explain why the vast
majority of studies on the prevention of AHRE/AF with different lead
atrial placements have failed 24. Whether atrial
stimulation itself could be also pro-arrhythmogenic, especially in
patients with previous IAB, is subject to debate, and better control of
the paced P-wave duration during implantation and follow-up of patients
with CIED would be necessary to avoid future episodes of AHRE.