WSO - April 2023 - 401

Diener et al.
401
Keywords
Cryptogenic stroke, atrial fibrillation, patent foramen ovale closure, cardiac rhythm monitoring, stroke recurrence,
monitoring strategy
Received: 26 April 2022; accepted: 14 July 2022
Introduction
Percutaneous closure of patent foramen ovale (PFO) is a safe
and effective therapy to prevent recurrent stroke in selected
patients 18-60 years of age who had a cryptogenic stroke
(CS) with a suspected causal role of a PFO. Randomized trials1-6
have reported decreased recurrent stroke rates from
percutaneous PFO closure plus medical therapy compared to
medical therapy alone, particularly antiplatelet therapy.
Besides the term " cryptogenic stroke, " recent literature
often refers to the concept of " embolic stroke of undetermined
source " (ESUS). This concept was introduced to
have a well-defined diagnostic work-up leading to the diagnosis
of ESUS.7 ESUS is diagnosed if the stroke is nonlacunar,
and no cause of stroke is identified by a standardized
diagnostic work-up,7 including brain computed tomography
or magnetic resonance imaging, 12-lead electrocardiography,
precordial echocardiography, cardiac monitoring
for ⩾24 h with automated rhythm detection, and imaging of
extracranial and intracranial arteries supplying the area of
brain ischemia. While CS and ESUS are not interchangeable
concepts by definition, it is important to recognize that
the great preponderance of patients with CS diagnosed after
extensive diagnostic work-up also meet the criteria for
ESUS. Most recently, the term PFO-associated stroke was
proposed for superficial, large deep, or retinal infarcts in
the presence of a medium-risk to high-risk PFO and no
other identified likely cause.8 Any of these diagnoses cannot
be rendered until atrial fibrillation (AF) as a competing
cause has been appropriately excluded.
Cardiac rhythm monitoring is typically included in the
diagnostic work-up after a stroke to detect paroxysmal AF
as a potential cause. Moderate-to-high burden AF is a highrisk
source of cardioembolism, indicating guidelinedirected
chronic oral anticoagulation (OAC).9 Clinical
evidence does not support PFO closure in this situation. In
case of low burden AF, insufficient data are available to
indicate if anticoagulation, PFO closure, or both should be
pursued. While longer-term monitoring may be utilized to
obtain increased confidence about the absence of AF, there
is no consistent approach regarding the selection of CS
patients considered for PFO closure who are eligible for
monitoring and the optimal monitoring technology and
duration. A European survey10 reported various AF monitoring
approaches in CS patients, with most centers (85%)
using 24/48 h Holter monitoring and 30% using insertable
cardiac monitors (ICMs) in selected patients. This variability
is also reflected by current guidelines and consensus
statements11-17 (see Supplemental Table S1).
Because long-term monitoring in all patients is unlikely
to be cost-effective, it is reasonable to tailor the monitoring
strategy to the probability of AF detection in various patient
groups. The aim of this narrative review is to explore available
options for detecting AF and suggest a personalized
AF monitoring approach, accounting for the likelihood of
detecting AF.
Methods
As part of this review, a literature search was conducted to
identify scientific literature reporting on risk factors or predictors
for detection of AF in CS patients. The search strategy
is outlined in Table 1.
The search identified 22 articles reporting on studies
utilizing a systematic ECG monitoring approach and
reporting on risk factors or predictors for AF detection
in a CS population (Figure 1 and Supplemental Figure
S1 and Supplemental Table S2). These articles were
used as a starting point for this review. While Preferred
Reporting Items for Systematic Reviews and MetaAnalyses
(PRISMA) principles were followed as much
as possible, a number of PRISMA topics were not
applied systematically, such as assessments of bias, heterogeneity
of study results, confidence in the overall
body of evidence, or the evaluation of data in a formal
meta-analysis.
The review was conducted by neurologists, internists,
and cardiologists with relevant expertise, based on their
clinical experience and participation in clinical studies,
publications and development of guidelines, or consensus
statements related to (cryptogenic) stroke, ECG monitoring,
and/or PFO closure.
AF in CS and recurrent ischemic
stroke
Medium-to-high burden AF predisposes to recurrent
thromboembolic events. While there is evidence for a
weak temporal relationship between AF episodes lasting
<24 h and incident stroke,18,19 stroke risk was reported
to be substantially increased in patients with AF episodes
>24 h.20 Using monitoring by implantable cardiac
rhythm management devices, an atrial tachycardia/AF
burden of more than 5.5 h per day appeared to double the
risk of thromboembolic events.21 The risk of stroke
recurrence in the typically young CS patients considered
for PFO closure is relatively low. In the control arms of
International Journal of Stroke, 18(4)
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