METHODS
For this observational single-center study, approval was obtained from
the Local Ethics Committee before data collection began. Images of a
total of 720 ESUS and migraine patients who complied with the study
protocol between 2020 and 2022 were analyzed. For imaging purposes, two
TTE devices and one TEE probe were used in the same center.
The study included patients presenting with migraine and ESUS, along
with suspected PFO detection in color Doppler imaging within the
interatrial region using at least one transthoracic echocardiographic
window. We recorded parameters such as the basal right ventricular (RV)
and mediolateral right atrial (RA) diameters, as well as estimated
pulmonary artery (PA) systolic pressure for all patients. Additionally,
detailed examinations were conducted to assess the presence of
interatrial septal aneurysm, Chiari network, and Eustachian valve.
Transthoracic echocardiography was performed using various imaging
windows, including parasternal long axis (PLAX), parasternal short axis
(PSAX), apical four-chamber (A4C), apical three-chamber (A3C), apical
two-chamber (A2C), and subcostal four-chamber (SC4C) views. PSAX, A4C,
and SC4C windows were specifically used to detect Doppler blood flow in
the IAS. To rule out abnormal pulmonary venous return, we visualized the
entry of pulmonary veins into the left atrium using 2D and color Doppler
imaging in one or more transthoracic echocardiographic windows.
Identical color Doppler gain settings were applied to all patients.
Estimated pulmonary artery systolic pressures (PASP) were calculated
using the modified Bernoulli equation, considering the peak Doppler
velocity of the tricuspid regurgitation jet and the end-diastolic
velocity of the pulmonary regurgitation jet (PASP =
4V2 + right atrial pressure [mmHg]). Contrast
echocardiography was performed via the transthoracic A4C window
following 2D and Doppler TTE. Agitated saline was prepared by adding 9cc
of saline to a 10cc syringe. A positive finding was defined as the
presence of three or more microbubble transitions from the right atrium
to the left atrium during the first five beats of the cardiac cycle
following the Valsalva maneuver. TEE involved evaluating 2D and color
Doppler images of the IAS at 30-50 degrees mid-esophageal and in the
bicaval window. Defects in the fossa ovalis region were diagnosed clefts
were identified as PFO.
In this study, the TEE parameters used by Nakayama et al. to define the
anatomical and functional high-risk features associated with PFO were
used (13). A ’large’ PFO is characterized by a height of ≥ 2 mm,
measured as the maximum separation between the septum primum and septum
secundum in the end-systolic frame. Furthermore, a ’long’ PFO tunnel is
defined as having a length of ≥ 10 mm, measured by the maximum overlap
between the septum primum and septum secundum. High-risk PFO is further
defined by the presence of an atrial septal aneurysm (ASA), which
involves a septal excursion of ≥ 10 mm from the midline into either the
right or left atrium or a total excursion of ≥ 15 mm between the right
and left atrium. Another characteristic of high-risk PFO is a
hypermobile IAS, described as a septum with an excursion of ≥ 5 mm in
every heartbeat. Additional determinants associated with an increased
risk of cerebrovascular events through PFO include the presence of a
large right-to-left (RL) shunt, identified by the presence of ≥20
microbubbles in the left atrium during rest and the Valsalva maneuver.
Moreover, high-risk PFO is linked to anatomical factors such as the
presence of a prominent Eustachian valve or a Chiari’s network measuring
≥ 10 mm in the right atrium. Additionally, a sharp (≤10°) angle between
the inferior vena cava and the PFO flap is associated with a high-risk
PFO.
Using the noted anatomical and functional features of PFO determined by
TEE, Nakayama and colleagues developed a simple scoring system for
identifying high-risk PFO (14) (Table 1). When ESUS-related factors were
each scored as 1 point, a total score ≥ 2 points was strongly associated
with ESUS. A score of ≥2 points showed 91% sensitivity and 80%
specificity for association with ESUS.
Risk criteria for stroke in patients with PFO can be categorized as
clinical, anatomical, and functional criteria. The Risk of Paradoxical
Embolism (RoPE) score is based on 12 data and is used to distinguish
incidental PFO from clinically significant PFO in ESUS patients (15)
(Table 2).
We excluded patients with interatrial septal defects outside the fossa
ovalis region, and patients under 18 years and above 60 years of age
from the study. The primary endpoints of the study are the comparison of
atrial septum, PFO and accompanying anatomical variant of right atrial
structures in migraine and ESUS patients. Secondary endpoints were
comparison of RoPe and High-risk PFO scores in migraine and ESUS
patients.