This study helps elucidate the etiology of
cryptogenic ischemic stroke. As a result of our study,
we found that PWPT, which is a strong predictor of
AF, was significantly higher in cryptogenic ischemic
stroke patients at the time of diagnosis. This suggests
that the cause of cryptogenic ischemic stroke disease is
undetected AF.
Atrial fibrillation significantly increases the risk
of ischemic stroke in patients.[8] Atrial fibrillation
is known at the time of diagnosis in approximately
15 to 18% of patients with ischemic stroke or
transient ischemic attack.[9] Therefore, the cause
of stroke in the majority of these patients is AF.[9]
In another study, it was found that 30% of patients
who were diagnosed with AF before their stroke
diagnosis also had AF when they were admitted
to the hospital.[10] In the same study, it was found
that 4 to 13% of patients whose AF diagnosis
was unknown at the time of stroke had AF
attacks during their follow-up.[10] In another study
conducted independently of these, it was found that
the first AF attack was detected in the ECGs taken
at the time of diagnosis in 1.7 to 16% of patients
with acute ischemic stroke or transient ischemic
attack.[11] In the same study, the first AF attack was detected in approximately 0.2 to 13% of all patients
as a result of rhythm monitoring with an extra
24-h ECG.[11] In 72-h ECG rhythm monitoring,
the first AF attack was detected in approximately
2.3 to 11% of ischemic stroke patients.[11] After
rhythm monitoring with ECG for one week after
stroke diagnosis, AF was diagnosed in 1.7 to 14%
of all patients.[11] In a randomized controlled study
conducted with stroke patients, the first AF attack
was detected in 18 of 200 patients with 10-day
rhythm Holter monitoring.[12] In the 10-day rhythm
Holter follow-up performed after a three-month
interval, the first AF attack was detected in
10 patients.[12] In the 10-day rhythm Holter
follow-up performed after a six-month interval,
AF was not found in any of the remaining stroke
patients.[12] In a study conducted with patients
diagnosed with cryptogenic ischemic stroke, the
first AF attack was detected in 46 of 286 patients
after rhythm monitoring for 30 days.[13] All this
suggests that a new method is needed to find AF
in patients with cryptogenic ischemic stroke. In our
study, the prolonged detection of PWPT, which is
a predictor of AF, in cryptogenic ischemic stroke
patients should suggest AF. Patients with long
PWPT should be evaluated for anticoagulant use.
In addition, long-term and frequently intermittent
rhythm Holter should be recommended to these
patients. Already, the USA guideline recommends
rhythm monitoring with ECG for 30 days to detect
AF in patients diagnosed with cryptogenic ischemic
stroke (Class 2A, Level C).[14] The European Society
of Cardiology recommends rhythm monitoring
with ECG to detect AF for at least 72 h from the
moment of diagnosis in patients who have had a
stroke or transient ischemic attack but do not have
known AF (Class 1, Level B).[15] In our study, we
fitted patients with a rhythm Holter to detect AF
for 72 h from the stroke diagnosis. However, we
did not find AF in any patient. In the European
Stroke Organization guideline, it is recommended
that rhythm monitoring be performed for a long
time in stroke patients with the possibility of AF,
but there is no information about the duration in
acute strokes.[16]
Cryptogenic ischemic stroke accounts for
one-quarter of ischemic strokes.[17] Cryptogenic
ischemic stroke is more likely to be a recurrent stroke
than other strokes. The probability of recurrence
of ischemic stroke in these patients is between 3 and 6%.[18] Studies suggest new clinical scores
in cryptogenic stroke patients with no etiology
detected.[19] Although previous studies on this subject
suggested long-term heart rhythm monitoring with
implantable devices in cryptogenic stroke patients,
this cannot be fully implemented.[20] Since the required
effort and cost are quite high, the probability of being
diagnosed with AF in this patient group in one year
is approximately 10%.[20]
This supports the need to determine the
etiology in patients with cryptogenic ischemic
stroke. Although various risk factors for AF have
been identified in previous studies, the use of a
single predictor may not be sufficient to detect AF
in patients according to large population-based
studies.[21] For this reason, risk scores based on
imaging, clinical evaluation, and echocardiographic
features have been developed to detect AF in
patients.[21] Although these scores provide important
results for AF, such scores have not been developed
in cryptogenic ischemic stroke patients.[21]
In a study, PWPT-D2 was found to be a
significant predictor of paroxysmal AF in acute
ischemic stroke patients.[22] The P wave shows us
the conduction time between the sinoatrial node and
the atrioventricular node.22] There is restructuring
in the atria in paroxysmal AF patients.[22] In
addition, abnormal activities in the atria may cause
changes in the structure of the atrium and affect the
electrophysiological mechanism.[23] These changes
can make significant changes on the P wave.[23] P
wave parameters were found to predict poor clinical
outcomes, such as AF, cerebrovascular accident,
death, and heart failure.[24] P wave peak time is an
important ECG parameter that is the subject of many
articles.[22] In a study conducted on patients with
coronary artery disease, a significant correlation was
found between left atrial dysfunction and PWPT.[25]
Additionally, in another study, it was found that the
disease severity increased as the PWPT-D2 duration
increased in coronary artery patients admitted
with the diagnosis of non-ST-elevation myocardial
infarction.[26] In addition to these published studies,
another study conducted with hypertensive patients
observed that left ventricular end-diastolic pressure
increased as PWPT-D2 duration increased.[27] In a
study investigating the relationship between silent
ischemic stroke and PWPT, it was found that longer
PWPT in leads D2 and V1 was associated with silent
ischemic stroke, while PWPT-D2 was independently associated with silent ischemic stroke.[23] In our
study, PWPT-D2 and PWPT-V1 were found to be
higher in the cryptogenic ischemic stroke patient
group. Additionally, these two parameters were
found to be independent predictors in the diagnosis
of cryptogenic ischemic stroke.
Cardioembolic conditions constitute 25%
of total ischemic strokes.[28] Cardioembolic
strokes are associated with worse prognosis than
noncardioembolic strokes.[29] Since the cause of
the stroke in cryptogenic ischemic stroke patients
is not identified, it is unclear whether there is a
cardioembolic cause. However, as a result of our
study, we detected PWPT prolongation in these
patients and revealed the possibility of undetected
AF in the etiology of cryptogenic ischemic stroke.
In ischemic stroke patients, as the cardiovascular
risk status increases and the ECG follow-up period
increases, the probability of detecting AF also
increases.[30] In our study, the rates of hypertension,
coronary artery disease, hyperlipidemia, and
diabetes mellitus were higher in the group with
cryptogenic ischemic stroke, but there was no
statistical difference compared to the other group.
This situation may have caused the PWPT period to
extend slightly. Prospective randomized controlled
studies are needed to better understand this issue.
The main limitation of this study is the
retrospective design. Multicenter studies with
a large number of participants are needed to
better understand whether PWPT detects AF in
etiology in patients with cryptogenic ischemic
stroke. To determine whether PWPT truly detects
undetectable AF in cryptogenic ischemic stroke
patients, it needs to be compared with a group of
patients with ischemic strokes of different etiology
other than AF, in addition to the existing control
group. This situation creates a different limitation
that is important for our study. Additionally, there
was not enough follow-up time to detect AF in the
patients. The inability to wear a rhythm Holter
for longer than 72 h is also among the major
limitations.
In conclusion, the high PWPT in patients with
cryptogenic ischemic stroke of unknown etiology
suggests that these patients have undetected AF in
their etiology. Therefore, anticoagulant treatment may
be considered in these patients to prevent recurrent
strokes. Additionally, long-term rhythm Holter may
be considered to detect AF in these patients.
Ethics Committee Approval: The study protocol
was approved by the Uşak University Training and
Research Hospital Ethics Committee (date: 06.01.2021,
no: E-38824465-020-2221). The study was conducted
in accordance with the principles of the Declaration of
Helsinki.
Patient Consent for Publication: A written informed
consent was obtained from each patient.
Data Sharing Statement: The data that support the
findings of this study are available from the corresponding
author upon reasonable request.
Author Contributions: All authors contributed equally
to the article.
Conflict of Interest: The authors declared no conflicts
of interest with respect to the authorship and/or publication
of this article.
Funding: The authors received no financial support for
the research and/or authorship of this article.
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