A 53 year-old female presents with transient left side weakness which slowly

improves over 3 days thereafter. Patient has a few years’ history of on and off
palpitations. Clinical examination reveals an irregular pulse, at 102 beats per
minute (bpm), pulse deficit of 6 bpm, and a 130/80mmHg blood pressure.
Peripheral pulses are normal. Cardiovascular system examination confirms
irregular heart. Although heart sounds are normal, a systolic click and a grade
iii/iv systolic murmur in the pulmonary area is heard. Central nervous system
examination reveals mild weakness in left lower limb. Patient is
nevertheless able to walk unsupported. Hemogram, serum lipids, kidney
function tests and liver function test results are within normal range. The
echocardiogram reveals atrial fibrillation with a ventricular rate of 90/min,
normal QRS and T waves. Chest X-Ray shows normal cardiac size and clear
lungs. Computerised tomography of the brain is normal and shows no evidence
of hemorrhage. Transthoracic echocardiography reveals normal-size chambers,
valves, and a prominent moderator band in right ventricle. Intra-ventricular
septum is intact. Intraatrial septum shows a large bulge in fossa ovalis area
towards right atrium with limited excursions of this part of the atrial septum. No
evidence of thrombus in any chamber or atrial appendage nor evidence of shunt
(Figures 1, 2, 3). Carotid Doppler and ultrasound studies are normal. 

Fig. 1 Transthoracic echocardiography of heart

a) Apical 4-C view 

b) Apical 4-C view, annotated. 

 

c) Sub costal view, annotated. 

 
Patient has ischemic cerebrovascular embolic stroke with left side hemiparesis,
atrial fibrillation with atrial septal aneurysm fossa ovalis. The ischemic
cerebrovascular accident- is most likely cardioembolic stroke.
Atrial septal aneurysm is rare (ASA) and is most often an accidental finding
however it could be a contributing factor to cardioembolic stroke even though
no thrombus in aneurysm or left atrium can be seen in transthoracic echo.
Patient was started on anticoagulants and rate control for atrial fibrillation.

Background

Although exact definitions of ASA vary according to size (2, 3, 7), and stage
(mobility) of the aneurysm (17, 18) atrial septal aneurysm is a localised
“saccular” deformity, generally at the level of the fossa ovalis, which protrudes
to the right or the left atrium or on both sides. Albeit rare, atrial septal aneurysm
is a well recognised cardiac abnormality. Previously diagnosed on autopsy only,
it is now frequently being picked up on routine echocardiography or during
evaluation of ischemic stroke. Studies link it with peripheral embolism and
cardioembolic stroke, pulmonary embolism and atrial arrhythmias, even though
clinical significance is uncertain. Further, it can be secondary to interatrial
pressure difference or may be the result of a primary malformation involving the
fossa ovalis region or the entire septum (1). In patients with chronically elevated
atrial pressures, as in mitral stenosis, atrial septal aneurysms are also rare
therefore acquired origin seems unlikely. Congenital malformation of the atrial
septum probably contributes to development of ASA, as was suggested by
Hanley PC and colleagues (2).

Associated cardiac abnormalities

Atrial septal aneurysm may be isolated or associated to another anomaly.

Commonest association is patent foramen ovale (PFO). Silver and Dorsy found
patent foramen ovale in 8 out of 16 patients (3). Other associations are atrial
septal defect (2), mitral valve prolapsed (4,5) tricuspid valve prolapse, marfans
syndrome, sinus of valsalva aneurysm and aortic dissection (1). Shunt across
ASA is more frequently detected with transesophageal echocardiography than
with transthoracic echocardiography (1). Association with mitral and tricuspid
valve prolapse and other abnormalities such as Marfans syndrome, sinus of
valsalva aneurysm may point to common inherent connective tissue deficiency
(6). Familial clustering of ASA has also been reported (13).

Clinical Manifestations

Manifestations attributed to ASA are 1) atrial arrhythmias and 2) arterial

embolism.
Interatrial septal aneurysm can act as an arrhythmic focus, generating focal
atrial tachycardias. Hanley et al (2) noted atrial arrhythmias in 20 out of 80
patients (25%). Mugge A et al., in a multicenter study of 195 patients found
atrial tachyarrhythmia in 47 patients (24%) and 28 patients (>14%) had atrial
fibrillation (1). Schneider B et al. reported prevalence of atrial tachyarrhythmia
in 26% of cases of ASA (8). Mechanism of increased prevalence of atrial
tachyarrhythmia in ASA is not clear though redundancy of atrial septum could
be responsible for pathogenesis of arrhythmia.
Arterial embolism is another complication associated with ASA. Presence of ASA
tends to aggravate stasis of left arterial (LA) blood flow and predispose to
minute LA clots and systemic thrombo embolism. 
With cardiac embolism reported in 20-52% cases of ASA, various studies have
found significant association between ASA and arterial embolism  (7,9,10). Most
patients (70%) had left to right shunt (7) and a higher prevalence of ASA was
reported in cerebrovascular accident patients compared to the general
population (7.9% vs. 2.2%) (11). A retrospective study by Mugge A et al.
reported that patients with ASA, and especially those with shunts showed
increased frequency of clinical events in their past compatible with cardiogenic
embolism. Atrial septal aneurysm was often the only source of embolism as
judged by transesophageal echocardiography (1). Salmasi AM reported higher
prevalence of ASA and patent foramen ovale in Afro-Caribbean population
compared to Indo-Asians, suggesting ASA as a possible cause for increased
incidence of stroke in Afro-Caribbeans (12). Mechanism of cardioembolic stroke
could be right to left shunting as is detected in most cases of ASA or in the
thrombogenic properties of aneurysm itself. A non ejection click may
occasionally be heard possibly as the IAS aneurysm bulges and tenses within
LA/RA cavity thus suggesting ASA as one of the causes of systolic click (20).

Diagnosis and treatment

Echocardiography is used to diagnose ASA, either during routine

echocardiography or in cases of cardioembolic cerebrovascular stroke and
peripheral embolism. Compared to transthoracic echo, transesophageal echo is
more sensitive in picking up ASA (1, 7). Cardiac computed tomography and
magnetic resonance imaging are also useful for diagnosis of ASA (14, 15).

 Uncomplicated and isolated ASA requires no specific treatment other than

follow up. Patients should be evaluated for presence of thrombus in
aneurysm. 
 Therapeutic options for prevention of recurrent stroke in patients with
atrial septal aneurysm as well as atrial septal abnormality - including
patent foramen ovale (PFO), ostium secundum atrial septal defect (ASD) -
are medical therapy with antiplatelet agents or anticoagulants and
surgical or percutaneous closure of the defect  
 To prevent recurrent paradoxical embolism, in presence of shunt, it is
preferable to close the shunt and transcatheter procedure is now safe and
effective and commonly used for this purpose (16) even though
superiority of closure over best medical therapy has not been established
(21). 
 In case of atrial arrhythmia, specific treatment is given. In case of embolic
episode patient needs antiplatelet drugs and preferably oral
anticoagulation for secondary prevention of cardioembolic episode. 
 The efficacy of aspirin therapy is suggested by the French PFO-atrial
septal aneurysm (ASA) study, in 216 patients with cryptogenic stroke and
PFO alone, recurrent stroke on aspirin was 2.3% after four years,
comparable to 4.2% in patients with neither a PFO nor an ASA (19).

Conclusion:

The case reports on the chance finding of atrial septal aneurysm in the case of
cerebral embolism. Although atrial fibrillation is well known cause of stroke,
presence of atrial septal aneurysm needs some attention as it could be
contributory. There is a possibility that atrial septal aneurysm could be a culprit
for strokes.

Mr Meraj-ud Din Shah. A look at atrial septal aneurysm

An article from the e-journal of the ESC Council for Cardiology Practice

Vol. 10, N° 17 - 03 Feb 2012. https://www.escardio.org/Journals/E-Journal-of-Cardiology-

Practice/Volume-10/A-look-at-Atrial-Septal-Aneurysm

Atrial Septal Aneurysm in Adult Patients

A Multicenter Study Using Transthoracic and Transesophageal
Echocardiography

Andreas Mügge Originally published1 Jun

1995https://doi.org/10.1161/01.CIR.91.11.2785Circulation. 1995;91:2785–2792

Abstract
Background  An atrial septal aneurysm (ASA) is a well-recognized
abnormality of uncertain clinical relevance. We reevaluated the
clinical significance of ASA in a large series of patients. The aims of
the study were to define morphological characteristics of ASA by
transesophageal echocardiography (TEE), to define the incidence of
ASA-associated abnormalities, and to investigate whether certain
morphological characteristics of ASA are different in patients with and
without previous events compatible with cardiogenic embolism.

Methods and Results  Patients with ASA were enrolled from 11 centers
between May 1989 and October 1993. All patients had to undergo
transthoracic and transesophageal echocardiography within 24 hours
of each other; ASA was defined as a protrusion of the aneurysm >10
mm beyond the plane of the atrial septum as measured by TEE.
Patients with mitral stenosis or prosthesis or after cardiothoracic
surgery involving the atrial septum were excluded. Based on these
criteria, 195 patients 54.6±16.0 years old (mean±SD) were included in
this study. Whereas TEE could visualize the region of the atrial septum
and therefore diagnose ASA in all patients, ASA defined by TEE was
missed by transthoracic echocardiography in 92 patients (47%). As
judged from TEE, ASA involved the entire septum in 100 patients (51%)
and was limited to the fossa ovalis in 95 (49%). ASA was an isolated
structural defect in 62 patients (32%). In 106 patients (54%), ASA was
associated with interatrial shunting (atrial septal defect, n=38; patent
foramen ovale, n=65; sinus venosus defect, n=3). In only 2 patients
(1%), thrombi attached to the region of the ASA were noted. Prior
clinical events compatible with cardiogenic embolism were associated
with 87 patients (44%) with ASA; in 21 patients (24%) with prior
presumed cardiogenic embolism, no other potential cardiac sources of
embolism were present. Length of ASA, extent of bulging, and
incidence of spontaneous oscillations were similar in patients with
and without previous cardiogenic embolism; however, associated
abnormalities such as atrial shunts were significantly more frequent in
patients with possible embolism.

Conclusions  As shown previously, TEE is superior to the transthoracic

approach in the diagnosis of ASA. The most common abnormalities
associated with ASA are interatrial shunts, in particular patent
foramen ovale. In this retrospective study, patients with ASA
(especially with shunts) showed a high frequency of previous clinical
events compatible with cardiogenic embolism; in a significant
subgroup of patients, ASA appears to be the only source of embolism,
as judged by TEE. Our data are consistent with the view that ASA is a
risk factor for cardiogenic embolism, but thrombi attached to ASA as
detected by TEE are apparently rare.

An atrial septal aneurysm (ASA) is a rare but well-recognized cardiac

abnormality of uncertain clinical significance.1234567 ASA has been
reported as an unexpected finding during autopsy1 but may also be
diagnosed in living patients by echocardiographic techniques. 2 ASA
formation can be secondary to interatrial pressure differences but may
also be a primary malformation involving the region of the fossa ovalis
or the entire septum.14 ASA may be an isolated abnormality but is
often found in association with other structural cardiac abnormalities,
eg, mitral valve prolapse89 or atrial septal defects.10

Several reports suggest a possible link between ASA and cardiogenic

embolism in patients with otherwise unexplained ischemic
stroke.4111213141516 Hanley and coworkers4 reported clinical events
compatible with cardiogenic embolism in 16 (20%) of 80 consecutive
patients with ASA; in 4 of these patients, ASA was the only apparent
cardiovascular abnormality. Belkin and coworkers12 reported
cerebrovascular events compatible with embolism in 10 (28%) of 36
patients with ASA. Using transesophageal echocardiography (TEE) for
the detection of ASA, Schneider and coworkers 14 observed
cerebrovascular events in 12 (52%) of 23 consecutive patients with
ASA and noted marked thickening of the atrial septum suggestive of
thrombus formation in 9 of the 12 patients. Furthermore, Pearson and
coworkers16 noted ASA more frequently in patients who were referred
for echocardiographic evaluation of potential sources of embolism (20
of 133 patients; 15%) than in patients who were referred to the
echocardiography laboratory for other reasons (12 of 277 patients;
4%).

In the present study, we reevaluated the clinical significance of ASA in

a large series of patients. Patients with ASA were recruited from the
echocardiography laboratory. The aims of the study were (1) to define
morphological characteristics of ASA by use of TEE, (2) to define
abnormalities associated with ASA and their incidence, and (3) to
investigate whether morphological characteristics of ASA are different
in patients with and without previous events compatible with
cardiogenic embolism. The present study was not designed to
establish ASA as a “novel” source of cardiogenic embolism.

Methods
The centers contributing to this study were selected by the initiating
institution (Hannover Medical School) between May 1989 and October
1993. Each of the 11 centers enrolled patients with an ASA detected
by echocardiography. The following criteria had to be fulfilled: (1)
transthoracic and transesophageal echocardiographic studies had to
be performed within 24 hours of each other; (2) ASA was defined as a
protrusion of the aneurysm of >10 mm beyond the plane of the atrial
septum as measured by TEE (Fig 1), (3) echocardiographic images had
to be of sufficient quality to allow precise measurements of
morphological characteristics of ASA, and (4) detailed patient records
had to be available. Patients with mitral stenosis or mitral prosthesis
or who had had any cardiothoracic surgery involving the atrial septum
were excluded from the study.

The patient records were evaluated for history, in particular clinical

events compatible with arterial embolism, cardiac rhythm (ECG), and
history of arrhythmias. The diagnoses of events compatible with
cardiogenic embolism were based on clinical criteria (sudden onset of
symptoms, exclusion of significant [>30% stenosis] carotid artery
disease by Doppler sonography), and technical investigations
(nonhemorrhagic stroke established by computed tomography,
peripheral arterial occlusion established by angiography and/or
surgery). The videotapes were carefully selected by an experienced
investigator from each center. The following parameters were
evaluated: length of the ASA in the plane of the atrial septum (Fig 1),
maximal excursion or protrusion of the ASA beyond the plane of the
atrial septum (Fig 1), direction of maximal protrusion (into the right or
left atrium), spontaneous oscillation of the ASA during normal
cardiorespiratory cycle, maximal extent of protrusion during
oscillation, other structural abnormalities associated with the atrial
septum, presence of patent foramen ovale (PFO) or atrial septal defect
(ASD) (tested either by color Doppler or contrast echocardiography, Fig
2), presence of thrombi attached to the ASA, presence of valve
abnormalities, presence of other cardiac abnormalities that might be
potential sources of cardiogenic embolism including the spontaneous
echo-contrast phenomenon, aortic plaques, and intracardiac
thrombi.1819 A “lone” ASA was defined as an ASA in a patient without
any other cardiac abnormalities and without a history of arrhythmias
as judged by TEE, ECG, and the patient’s records.

The data were analyzed by univariate ANOVA. The values presented

are mean±SD. A value of P<.05 was considered significant.

Results
A total of 195 patients met the inclusion criteria: 98 men and 97
women, with a mean age of 54.6±16.0 years (range, 18 to 85 years).
The indications for the echocardiographic examinations were
(n=number of patients): suspicion of cardiogenic embolism and/or
intracardiac masses (n=90), congenital heart disease (n=19), valvular
heart disease (n=16), infective endocarditis (n=15), aortic dissection
(n=10), before cardioversion for atrial fibrillation (n=9), and
miscellaneous (n=36).

At the time of the echocardiographic examination, 165 patients

(84.6%) were in sinus rhythm, 28 (14.4%) were in atrial fibrillation, and
2 had a pacemaker. The majority of patients for whom detailed
information was available had no history of arrhythmias (118 of 180
patients, 65.6%). Overall, atrial tachyarrhythmias were noted in 22.8%
of the patients (41 of 180 patients). Among 44 patients with ASA as the
only structural abnormality and without a history of coronary artery
disease or hypertension, 7 (15.9%) had atrial tachyarrhythmias (atrial
fibrillation).
Table 1 summarizes the morphological characteristics of the ASA as
determined by TEE. As judged by TEE, the ASA involved the entire
septum in 100 patients (51.3%) and was limited to the fossa ovalis in
95 (48.7%). Overall, ASA bulged predominantly toward the right atrium
in 130 patients (66.7%) and toward the left atrium in 65 (33.3%). In 132
patients (67.7%), the septum showed spontaneous oscillations
(between the two atria) during a normal cardiorespiratory cycle (Table
1).

ASA was often associated with other cardiac abnormalities, in

particular atrial septal defect, PFO, and mitral valve prolapse (Table 2).
In 62 patients (31.8%), ASA was an isolated structural abnormality, as
judged by TEE. In only 37 patients (18.9%) was the ASA considered a
“lone ASA,” ie, patients were in sinus rhythm and had no other cardiac
abnormalities and no history of hypertension or coronary artery
disease. Intracardiac thrombi were found by TEE in 18 patients;
thrombi were located within the left atrium or left atrial appendage in
15 patients and within the left ventricular cavity in 1 patient after
myocardial infarction. In the remaining 2 patients, thrombotic material
appeared to be attached to the septal aneurysm. In 1 of these 2
patients, ASA involved the entire septum, and thrombotic material
appeared to be attached to the left atrial side of the septum. In the
other, ASA was confined to the fossa ovalis and was associated with a
small type II atrial septal defect; in this patient, ASA bulged
predominantly into the left atrium, and the thrombotic material
appeared to be attached to the right atrial side of the septum.

The region of the atrial septum could be clearly visualized by TEE in all
patients, thereby allowing the diagnosis of ASA; in contrast, evidence
for ASA was not detected by transthoracic echocardiography in 92
patients (47%). In addition, PFO and atrial septal defects were missed
by transthoracic echocardiography in 64% and 19% of patients,
respectively.

Patients’ histories revealed no clinical evidence of cardiogenic

embolism in 108 patients (56%). Forty-three patients (22%) had
suffered a nonhemorrhagic stroke, 24 (12%) transient ischemic
attacks, 14 (7%) peripheral arterial embolism, 4 (2%) pulmonary
embolism, and 2 (1%) both stroke and peripheral arterial embolism.
Clinical events compatible with embolism had occurred on average
44±78 days (range, 1 to 450 days) before the echocardiographic
examination. Table 3 compares several clinical and
echocardiographic characteristics of patients with and without clinical
events potentially due to cardiogenic embolism. The two groups did
not differ with respect to cardiac rhythm at the time of the
echocardiographic examination. Interatrial shunting and intracardiac
thrombi were found more frequently in patients with possible
cardiogenic embolism. The two groups did not differ with respect to
several ASA characteristics, including the predominant side of bulging
(right or left atrium), length of ASA, maximal extent of protrusion, and
incidence of spontaneous oscillation of the ASA (Table 3). It is
interesting to note, however, that the majority of patients with lone
ASA had experienced a clinical event compatible with arterial
embolism (21 of 37 patients, 56.7%) before the echocardiographic
examination.

Discussion
An aneurysm of the interatrial septum is an infrequent finding in adult
patients. ASA formation may be secondary to raised interatrial
pressure gradients, producing a bulging septal shift toward the low-
pressure side1 ; however, it has been also found in patients with
normal atrial pressures,3 suggesting a primary (congenital?)
malformation.

Definition Criteria for ASA

The cutoff point between a slightly redundant atrial septum and an
ASA is somewhat arbitrary. In the present study, we used cutoff
criteria similar to those reported in an autopsy study by Silver and
Dorsey,1 ie, a protrusion of the aneurysm >10 mm beyond the plane of
the atrial septum into either the right or left atrium (Fig 1). We
excluded patients with previous cardiac surgery and those with mitral
stenosis so as to select predominantly those patients with a primary
ASA. These criteria are slightly different from those used in previous
echocardiographic studies. In the largest series of patients with ASA
diagnosed by transthoracic echocardiography, Hanley and
coworkers4 considered the atrial septum to be aneurysmal when a
dilated portion protruded at least 15 mm beyond the plane of the atrial
septum or when the atrial septum showed phasic excursions during
the cardiorespiratory cycle ≥15 mm with the base of the aneurysm ≥15
mm. In the largest series of cases of ASA diagnosed by TEE, Pearson
and coworkers16 considered a septum aneurysmal when it had an
excursion >10 mm into either the left or right atrium or a sum of the
total excursion into the left or right atrium >10 mm, with a base width
≥15 mm. Other authors112021 define ASA as a thin localized outpouching
of the middle portion of the atrial septum, but not the entire septum,
protruding at least 10 mm outside the plane of the atrial septum.
Because a “gold standard” is lacking for definition of true ASA, one
definition appears as arbitrary as the other. In the present multicenter
study, we used a simple and relatively less restrictive definition to
include a large number of patients with different types of atrial septal
redundancy.

Comparison of Transthoracic and Transesophageal Echocardiography

The transesophageal approach allows almost ideal imaging of the

interatrial septum. Several authors reported a more detailed and
superior characterization of the atrial septum morphology and
pathology by transesophageal compared with transthoracic
echocardiography.222324 In the present study, ASA as defined by TEE
was missed by surface (transthoracic) echocardiography in almost half
(47%) of the patients. Thus, the sensitivity for the detection of ASA
appears to be greatly enhanced with the use of TEE. These results are
in agreement with previous reports using both transthoracic and
transesophageal echocardiography. In the first report on both
techniques, ASA was demonstrated only by TEE in 6 of 7 patients. 5 In
a series of 23 patients communicated by Schneider et al,14 the surface
echocardiogram missed an ASA in 3 patients. In a series of 32 patients
reported by Pearson et al,16 transthoracic echocardiography missed an
ASA in the majority (62.5%) of patients. It should be mentioned again,
however, that a gold standard is lacking in the detection of ASA. Thus,
the discrepancy between transthoracic and transesophageal
echocardiography may be explained not only by false-negative
transthoracic echocardiographic findings but also by false-positive
TEE findings.

Arrhythmias Associated With ASA

Several authors have suggested an association between ASA and

atrial tachyarrhythmias.2526 Hanley and coworkers4 observed atrial
tachyarrhythmias in 20 of 80 patients (25%). Using Holter monitoring,
Schneider and coworkers27 reported recently in a preliminary
communication a prevalence of atrial tachyarrhythmias in 26 (52%) of
50 consecutive patients with ASA. In the present study, ambulatory
Holter monitoring was not performed systematically. Information
(patient’s history, ECG records) concerning cardiac arrhythmias was
available in 180 patients. In the majority of patients (65%), no
significant arrhythmias were noted. Twenty-eight of 195 patients
(14.4%) were in atrial fibrillation at the time of the echocardiographic
examination. It is unknown whether the redundancy of the atrial
septum itself or ASA-associated structural defects are related to the
pathogenesis of atrial arrhythmias. Overall, a relatively high
prevalence of atrial tachyarrhythmias was noted in the present study
(47 of 195 patients; 24%). This prevalence of atrial arrhythmias was
somewhat less but still relatively high (6 of 37 patients; 16%) in
patients without other detectable structural abnormalities and without
a known history of hypertension or coronary artery disease. This
relatively high prevalence of atrial tachyarrhythmias in patients with
ASA cannot as yet be explained and may be biased by the patient
selection criteria. Further studies are necessary to clarify whether
ASA is related to the pathogenesis of these arrhythmias.

Cardiac Abnormalities Associated With ASA

Several other cardiac (and noncardiac) abnormalities may be

associated with ASA. As noted in previous reports, 41015 ASA is often
associated with other atrial septal defects, in particular ASD type II
and PFO. At autopsy, Silver and Dorsey1 found a PFO in 8 of 16
patients (50%) with ASA, including 2 patients who also had a small
ASD due to fenestration of the septum primum. Hanley and
coworkers4 noted an ASD in 24 of 49 patients (49%) examined for
atrial shunting; they observed an ASD in all 12 patients in whom the
aneurysm involved the entire septum and in 6 of 8 patients (75%) in
whom an oscillating aneurysm involved the fossa ovalis. Using TEE,
Schneider and coworkers14 demonstrated atrial shunting in 17 of 22
patients (77%) with ASA. Zabalgoitia-Reyes et al15 found a small ASD
in 1 of 20 patients (5%) and, using contrast TEE, a PFO in 17 patients
(85%) with ASA. In the present study, interatrial shunting was noted in
106 of 195 patients (54.4%); this shunting was due to a type II ASD in
38 patients, a PFO in 65, and a sinus venosus defect in 3. Interatrial
shunting was noted with a similar frequency in both ASA involving the
fossa ovalis (52 of 95 patients) and involving the entire septum (54 of
100 patients). Whereas a sinus venosus defect or a large ASD can be
easily diagnosed by TEE,222328 differentiation between a small ASD and
PFO may be somewhat arbitrary in selected cases. In particular, it may
be difficult to visualize a small structural defect, allowing the ASD
diagnosis in patients with a highly mobile ASA. Therefore, the
differentiation between PFO and a small ASD was based on color
Doppler TEE demonstrating a continuous interatrial shunting
throughout the cardiac cycle in patients with ASD or an intermittent
right-to-left shunting provoked by Valsalva maneuver in patients with
PFO. These difficulties in a precise anatomic classification of
interatrial shunting, in particular in patients with ASA, may explain the
variation in the frequency distribution of different types of atrial septal
defects in previous studies.41415

A second type of cardiac abnormality often associated with ASA is

mitral valve prolapse.921 It has been suggested that the redundancy of
the atrial septum and the mitral (and/or tricuspid) valve may be
secondary to a similar inherent deficiency in the connective tissue. 8 In
the present study, a mitral valve prolapse was noted in 20.5% and a
tricuspid valve prolapse in 7.2% of the patients. It is interesting to
note that 2 of our patients had Marfan’s syndrome, 2 additional
patients had an aortic dissection, and 1 patient had a sinus of Valsalva
aneurysm, supporting the concept of an inherent connective tissue
abnormality as a possible cause of ASA.

ASA as a Possible Source of Arterial Embolism

Several authors have suggested that ASA (isolated or in combination

with other defects) may cause arterial embolism.1112131416 This
suggestion is based on clinical studies demonstrating a statistical
association between ASA and previous ischemic cerebral and/or
peripheral embolic events. In fact, the incidence of clinical events
compatible with cardiogenic embolism appears to be remarkably high
in patients with ASA, ranging from 20% to 52%.411121415 In the present
study, 87 of 195 patients (44.6%) with ASA had experienced clinical
events compatible with cardiogenic embolism before the
echocardiographic examination. This high percentage of possible
cardiogenic embolism in patients with ASA is certainly biased by the
patient selection criteria. Nevertheless, the association between ASA
and arterial embolism merits some consideration.

It has been speculated that ASA is a direct source of thrombus

formation.14 This is supported by anecdotal findings demonstrating
thrombotic material within the aneurysmal sac in patients at
autopsy1 or cardiac surgery.29 In addition, thrombotic material related
to an ASA has occasionally been visualized by TEE. Schneider et
al14 reported a thrombus in 2 of 23 consecutive patients with ASA; in 1,
thrombotic material appeared to override a PFO, suggesting
paradoxical embolism; in the second, a thrombus was attached to the
left atrial side of the aneurysm. In addition, these authors noted
thickening of the atrial septum in 9 of 12 patients with
cerebrovascular events. Pearson et al16 reported 1 patient (of 32) with
a thrombus on the right atrial side of the aneurysm. In the present
study, a mobile mass suggestive of thrombus formation was visualized
by TEE in only 2 of 195 patients. Echocardiographic differentiation
between ASA-attached thrombi and artifacts created by the mobile
and bulging part of the fossa ovalis may be difficult in some patients; a
tangential scan through a mobile ASA may create the false impression
of a thrombus (Fig 3). These difficulties in reliably differentiating
between true thrombi and artifact may explain the differences in the
reported incidence of thrombi attached to the ASA. Whether or not the
echo densities that appear attached to an ASA are truly clots, the
overall low incidence would suggest that an ASA on its own is unlikely
to be a common site of thrombus formation. It should be noted,
however, that TEE has a certain limit of resolution for thrombus
detection. This resolution limit has not as yet been defined and may be
influenced by several factors, such as density of the thrombus and its
relation to surrounding blood and tissue. Thus, this study does not
exclude the possibility that small (micro) thrombi are attached to or at
least generated in the region of ASA, subsequently causing
cardiogenic embolism.

It appears from this (retrospective) analysis that ASA is a risk factor

associated with previously occurring events compatible with
cardiogenic embolism. This association is certainly biased by the
patient enrollment criteria (90 of the 195 patients underwent TEE for
suspected cardiogenic embolism). Thus, the present study cannot
establish a scientifically proven link between ASA and cardiogenic
embolism. Furthermore, it is unclear whether ASA per se could be a
risk factor or whether the accompanying cardiac abnormalities are the
major determinant for this association. In fact, ASA is often associated
with other cardiac abnormalities that are independently recognized
causes of cardiogenic embolism, in particular PFO,243031 and, to a lesser
extent, mitral valve prolapse.3233 In the 87 patients with possible
cardiogenic embolism, ASA was an isolated finding in 21 patients
(24.1%) but was associated with other cardiac abnormalities
potentially related to embolism in the remaining 66 patients (75.9%).
The present study shows that lone ASA is associated with prior events
compatible with cardiogenic embolism, and it appears that this
association is more significant when ASA is accompanied by other
cardiac abnormalities, in particular those causing interatrial shunting.
It can only be speculated that this association with previous embolic
events also implies a future risk for cardiogenic embolism. However,
to define ASA as a marker of embolic risk, prospective studies with the
enrollment of appropriate control groups will be necessary.

A major finding of the present study is that morphological

characteristics of ASA based on TEE are not helpful for identifying a
subgroup of patients at increased risk of embolism. As shown in Table
3, patients with previous events compatible with cardiogenic
embolism had a higher incidence of left atrial thrombi, spontaneous
echo contrast phenomenon, and PFO compared with patients without
those events; however, patients with and without emboli did not differ
with respect to ASA characteristics such as extent of ASA, length of
ASA, maximal extent of bulging, and incidence of oscillations. This
negative finding indirectly supports the view that ASA per se is not a
direct source of cardiogenic embolism.

To exclude the possibility that the criteria of ASA definition in the

present study may have caused this negative result concerning the
association of morphological characteristics and incidence of
potential arterial embolism, we reanalyzed our data using the slightly
different criteria proposed by Hanley and coworkers4 (for criteria, see
above). According to these criteria, 138 patients could be included in
the reanalysis. As proposed by Hanley and coworkers, ASAs were
separated into two groups: those in which the aneurysm involved only
the region of the fossa ovalis and those in which the entire atrial
septum was involved. The fossa ovalis ASA type was subdivided
according to the direction of maximal excursion or protrusion during
the cardiorespiratory cycle: type 1, into the right atrium and type 2,
into the left atrium. Type 1 was further subdivided into groups A and B
on the basis of the maximal extent of phasic oscillations of the
aneurysmal membrane occurring during the cardiorespiratory cycle: A,
oscillations <0.5 cm and B, oscillations ≥0.5 cm. Table 4 summarizes
the incidence of possible arterial embolism in patients classified
according to the definition criteria proposed by Hanley and coworkers.
The incidence of possible cardiogenic embolism appears to be almost
equal for all subtypes.

Although the overall prevalence of clinical events compatible with

cardiogenic embolism appears to be high in patients with ASA, this
issue should not be overestimated. In recent studies using
TEE,1734353637383940414243444546 ASA was found and defined as a possible source
of embolism in 173 of 2037 patients (8.4%) with previous ischemic
stroke and/or peripheral arterial embolism (Table 5). Since more than
half of the patients with ASA had associated cardiac abnormalities
that also could have caused cardiogenic embolism, the importance of
ASA as an independent risk factor for arterial embolism appears to be
questionable in unselected patients with suspected or proven arterial
embolism.

Limitations and Clinical Implications

The present study has limitations. First of all, patient selection was
strongly biased by the TEE referral pattern. Thus, the study did not
allow the assessment of the true prevalence of ASA in unselected
patients, the true frequency of associated abnormalities, and more
important, the true prevalence of cerebral ischemia or peripheral
embolism in patients with ASA. Because of a multicenter design, the
same diligence in the echocardiographic examination and data
collection cannot be ensured for all participating centers. In addition,
the diagnosis “cardiogenic embolism” is not a definite diagnosis in
most cases, in particular in patients with cerebral ischemia. On the
one hand, it is difficult to prove a thromboembolic occlusion of
cerebral arteries without invasive techniques; on the other hand, it is
difficult if not impossible to prove a causal relation between cardiac
abnormalities and ischemic stroke, even in the presence of obvious
sources of cardiogenic embolism, eg, intracardiac thrombi.
Furthermore, although significant narrowing of the carotid arteries
was excluded by Doppler sonography, mobile or friable debris serving
as a nidus for cerebral embolism cannot be excluded in selected
patients. Consequently, this study does not allow us to draw
conclusions regarding the pathogenic mechanism of embolism in
patients with ASA. Nevertheless, the data are consistent with the view
that the presence of ASA may be a possible risk factor for cardiogenic
 embolism. In summary, although clinical implications are as yet
undefined, TEE is helpful to characterize different types of ASA and to
allow a careful search for additional sources of embolism, in particular
for associated interatrial shunting. The presence of ASA with
interatrial shunting may support the concept of cardiogenic embolism
due to paradoxical embolism. Other morphological characteristics of
ASA (length, bulging, oscillation) appear not to be important for
identifying patients at risk for arterial embolism.

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Figure 1. Original transesophageal echocardiogram demonstrating a

mobile atrial septal aneurysm (top); bottom, schematic showing the
various measurements. L indicates length of the aneurysm; a and b,
maximal extent of oscillation; LA, left atrium; and RA, right atrium.
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Figure 2. Original transesophageal echocardiogram demonstrating an

atrial septal aneurysm with a patent foramen ovale shown by color
Doppler flow (arrow, left) and contrast (right). Only during Valsalva
maneuver, a small right-to-left shunting was noted. LA indicates left
atrium; RA, right atrium.

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Figure 3. Original transesophageal echocardiogram demonstrating an
oscillating atrial septal aneurysm. A tangential scan through this
mobile aneurysm creates the false impression of a marked thickening
and/or thrombus (arrows, right). LA indicates left atrium; RA, right
atrium.