From the Departments of Neurology (H.A., F.S.B., J.P.K., W.J.K.) and
Cardiology (S.A.A.), Massachusetts General Hospital, Stroke Service, Boston,
Mass.
Correspondence to Dr Ferdinando S. Buonanno, MD, Stroke Service, VBK-802, Massachusetts General Hospital, 32 Fruit St, Boston, MA 02114. E-mail buonanno{at}helix.mgh.harvard.edu
Methods—A conservative selection scheme was used to identify
patients likely to have had PFO-associated strokes (ie, cryptogenic)
and to exclude any structural, functional, or vascular heart disease
responsible for ECG changes. All patients had a standard 12-lead ECG.
The prevalence of crochetage in each group was determined.
Results—Sixty consecutive patients were studied (28 with
echo-documented PFO and 32 echo-negative control subjects). The
crochetage pattern was present in at least 1 inferior
limb lead in 10 of 28 PFO patients (36%) and 3 of 32 control subjects
(9%) (P<0.05). The sensitivity and specificity of the
crochetage pattern for diagnosis of PFO in cryptogenic stroke cases
were 36% and 91%, respectively; positive predictive value was
77%.
Conclusions—The finding of an ECG crochetage pattern may help to
identify stroke patients with PFO, may help to streamline their
diagnostic workup, and may warrant future studies to
determine its value in stratifying stroke risk in patients with PFO.
A notched pattern of the R wave, so called "crochetage," in the
inferior limb leads has recently been demonstrated to be
associated with ostium secundum-type atrial septal defect
(ASD).6 The exact mechanism leading to a
crochetage pattern in ASD is not known. Crochetage has not been
reported previously in patients with PFO. However, the similar location
of PFO and ostium secundum ASD, and the hemodynamic
similarities between a large PFO and an ASD, motivated us to
investigate the prevalence of crochetage in cryptogenic stroke patients
with PFO.
Our selection process sought to identify a patient cohort most likely
to represent PFO-associated strokes and a control group of
patients with no identifiable cause of stroke (in other words, a study
group of patients with cryptogenic strokes with PFO, and a control
group of patients with cryptogenic strokes without PFO). Excluded from
our study were: patients with any degree of stenosis or
occlusion of a major extracranial or intracranial vessel ipsilateral to
the symptomatic side, not only those stenoses that
may have caused hemodynamic abnormality but also those
that may have served as a source of emboli; patients with small
infarctions (less than 15 mm in diameter) in the territory of
perforating arteries either associated with 1 of the 4 classic lacunar
syndromes (pure motor hemiparesis, pure sensory stroke, ataxic
hemiparesis, and sensory-motor stroke) or with risk factors for small
vessel disease such as diabetes mellitus and hypertension; patients
with other rare causes of stroke such as vasculitis,
arterial dissection, or complicated migraine; and patients
with any structural, functional, or vascular heart disease that might
produce ECG changes or that may serve as a source of embolus. In
accordance with the latter criterion, we excluded all patients with any
history of clinical heart disease, with any ECG abnormality (myocardial
ischemia, infarction, atrioventricular or
intraventricular conduction block,
arrhythmia, pericarditis), or with any
echocardiography (ECHO)–documented cardiac
pathology (wall motion abnormality, cardiomyopathy,
pericardial effusion or tamponade, segmental left
ventricular hypertrophy, ASD,
ventricular septal defect, atrial septal aneurysm,
or heart valve disease with the exception of mitral valve prolapse.
All patients had a standard 12-lead ECG with a sensitivity of 10
mm/mV and paper speed of 25 mm/s. Crochetage pattern was described
as an M-shaped notch on the ascending branch, or at the top, of the R
wave in inferior limb leads (II, III, and aVF) (Figures 1
We compared cerebral ischemic lesion size in PFO patients with
or without crochetage by assuming that the size of the embolus would be
greater in larger infarctions, ie, involving cortical and subcortical
territories of a major intracerebral artery. This type
of distribution of infarction referred to the stem or main branch
occlusions of the anterior, middle, and posterior cerebral arteries.
Infarctions isolated either to cortex or subcortical structures, brain
stem, or cerebellum were assumed to be small.
All data were expressed as mean±SD. Frequency data were given as
percentage and the significance was assessed by
Clinical features of the study patients are summarized in the
Table
For each patient, at least 1 ECG was accessible from the cardiac
database unit; 2 or more tracings were available in 60% of PFO
patients and in 44% of the control patients. In 3 cases, ECGs were
obtained before the stroke (2 in the PFO group and 1 in the control
group). The time between stroke and the nearest ECG tracing varied from
1 day to 7 months, but it was less than 2 days in most instances.
Examiner 1 (S.A.A.) determined crochetage pattern in at least 1
inferior limb lead in 10 of 28 patients in the PFO group
and in 3 of 32 control patients. Examiner 2 (F.S.B.) rated a crochetage
in 11 patients in the PFO group and in 2 patients in the control group.
Concordance among the 2 examiners regarding the presence of a
crochetage was 90%. After adjustments were made based on interobserver
agreement (crochetage in 10 patients in the PFO group versus 3 patients
in the control group), the difference between the groups with respect
to the presence of crochetage was statistically significant
(P<0.05) (Figure 2
In the PFO group, crochetage was noted in 9 patients in only 1 lead,
and in 1 patient in 2 leads. Crochetage was present in 6 patients
in lead III, in 5 patients in aVF, and in 0 in lead II. In the control
group, all 3 patients with crochetage had it in only 1 lead. As defined
in the "Materials and Methods," crochetage was a consistent
finding from 1 ECG to the next. A PFO had been ruled out in these 3
patients of the control group (by a TEE in 1, a contrast TTE in 1, and
only by a color TTE in 1).
Large (ie, cortical-subcortical) cerebral infarction occurred in 60%
of PFO patients with crochetage (6 of 10 cases) but in only 39% (7 of
18) of PFO patients without crochetage. In contrast, small cerebral
lesions isolated either to cortical or to subcortical structures, or to
the brain stem or cerebellum, tended to be more frequent in PFO
patients without crochetage (9 versus 2 cases); however, this
difference did not achieve statistical significance
(P=0.15).
Although not a primary aim of the present study, we also determined
the frequency of incomplete right bundle branch block pattern
(incomplete RBBB) (R' or r' in lead V1 or
V2 and R' greater than R in
V1 and V2 and QRS duration
less than 120 milliseconds, or R peak time >50 milliseconds in lead
V1 or V2 when QRS duration
was < 120 milliseconds). There were 4 patients showing incomplete
RBBB both in the PFO group and in the control group. Three of 4
patients with the incomplete RBBB pattern in the PFO group, but only 1
in the control group, exhibited the crochetage pattern.
The actual role of PFO and the variables that determine its role in
paradoxical embolism are still not well understood. In addition to risk
factors for clotting in the pelvic and leg veins, major determinants
might include the size of defect, the degree of right-to-left shunting,
direction of current flow in the right heart, range of right-sided
heart pressures, and the variable degrees of closure that the valve
makes during different periods of the cardiac cycle. Moreover, for
paradoxical embolism to occur a thrombus in the venous circulation must
enter the right atrium and be directed through the foramen while it is
open. Many of the parameters that determine passage of
thrombus mentioned above are difficult to measure. Currently, the most
practical and sensitive diagnostic method is
transesophageal contrast
echocardiography, which can show the presence of a
PFO with approximately 80% sensitivity.5 19 20
Transcranial contrast Doppler sonography is also
sensitive in detecting PFO, comparable to that of
TEE.21 22 23 However, an
echocardiographically documented PFO may be incidental
rather than a causative finding. Determining more specific
echocardiographic, ECG, and deep venous system
characteristics for paradoxical embolus as the cause of stroke would
aid in the clinical decision of whether to anticoagulate or to close
the PFO.
The ECG pattern of incomplete RBBB has been known as a marker of ASD
for at least 40 years24–26; it has been
postulated to occur due to selective hypertrophy of the
basal portion of the right ventricle or to stretching of the
peripheral conduction fibers.27 28 29 30
Another ECG pattern, independent of incomplete RBBB, in ASD is
crochetage: an early M-shaped notch on the R wave of the QRS complex in
the inferior limb leads.31
Crochetage, when present in only 1 lead, has a sensitivity of
73.1%, a specificity of 92.6%, and a positive predictive value of
69% for the diagnosis of ostium secundum ASD, and achieves a
specificity of 100% if present in all 3 inferior
leads.6 Heretofore, the pattern has not been
associated with any other cardiac conditions, and the pathophysiology
is not known; however, it has been reported to disappear from 1 or more
leads after surgical closure of the ASD.6 To the
best of our knowledge, no specific ECG pattern has been associated with
PFO prior to the current report. Here, we demonstrate a statistically
significant increase in the prevalence of a crochetage pattern in the
inferior ECG limb leads in patients with PFO and
cryptogenic stroke as compared with control patients with cryptogenic
stroke without demonstrable PFO. Two blinded examiners detected
crochetage in at least 1 inferior ECG lead in 36% of PFO
patients as opposed to only 9% of control patients. The low
sensitivity suggests that a routine ECG would not be a useful screening
test for PFO. However, ECG is an almost uniformly available clinical
evaluation tool in all patients with stroke or TIA, principally to rule
out other cardiac abnormalities that may serve as potential sources of
emboli. Given the high specificity (91%) and moderately high positive
predictive value (77%), recognizing a crochetage pattern may increase
the clinical suspicion of paradoxical embolism. It may be helpful in
streamlining the diagnostic evaluation, especially in a
young, otherwise healthy patient with TIA or stroke; for example,
within minutes of a patient's evaluation in the emergency ward, a
certain degree of suspicion of PFO-related stroke can be generated, a
TEE can be requested with alacrity, and a search for the source of the
embolus is initiated with lower extremity ultrasound studies (and
magnetic resonance or contrast venography, if necessary). Detection of
crochetage does not preclude an echocardiographic
study. On the contrary, it may accelerate the clinical arrangements to
obtain early echocardiography with techniques more
sensitive for PFO (contrast TTE or TEE). Our results may also be
helpful in alerting the physician to perform a bedside
transcranial Doppler sonography study with contrast
injection,22 and–if applicable–to take
additional precautions, such as filtering all intravenous
lines or initiating early anticoagulation.
Heller et al6 reported that the presence of
crochetage, and the number of leads exhibiting it, correlated both with
the degree of left-to-right shunting and with the size of the ASD. It
had been previously shown32 33 that both the
degree of right-to-left shunting and size of the PFO are larger in
patients with arterial ischemic events. Our data
showed a trend toward larger infarct size in PFO patients with
crochetage than in PFO patients without crochetage. Three of 4 patients
who were finally referred to surgery for closure of PFO exhibited
crochetage. The reason for closure was coexisting fresh deep venous
thrombosis in 3 patients and recurrent cerebral embolism with multiple
infarctions in 1 patient. Unlike the reports from ASD studies, the
crochetage pattern remained unchanged after the closure in each of the
3 patients.
The current study was limited by the relatively small sample size that
resulted from very conservative selection criteria. Since patients with
any ECG abnormality or a known cardiac disease were excluded, the
impact of cardiac conditions on the ECG crochetage pattern remains to
be studied. Another limitation of this retrospective study is the
diverse methods of investigation used for the diagnosis of PFO. More
than 20% of patients in the control group were evaluated only by color
TTE. Because of the relatively lower sensitivity of this technique, PFO
might have been missed in some cases. However, we suspect that 2 of 3
patients with crochetage in the control group may have had PFO since
they did not have a TEE study. It is difficult to arrive at the true
predictive value of the crochetage pattern for stroke due to
paradoxical embolus without definitive knowledge about the incidence of
other causes of stroke in the patients with PFO, specifically in those
with and without crochetage.
In conclusion, the finding of a crochetage pattern may serve as a
readily available ECG marker to motivate the search for PFO or ASD in
patients with stroke or TIA. This study was performed in patients
without heart disease or stroke risk factors other than PFO. Future
prospective studies are needed to establish the relation of crochetage
to PFO in the general population. It will be especially important to
determine whether the presence or absence of the crochetage pattern
correlates with stroke risk in persons with PFO. The clinically
significant hypothesis raised by this study is whether the degree of
shunting in patients with PFO correlates with the presence of
crochetage, as it does in patients with secundum-type ASD.
Received February 16, 1998;
revision received March 27, 1998;
accepted April 16, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
An Electrocardiographic Criterion for Diagnosis of Patent Foramen Ovale Associated With Ischemic Stroke
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—An M-shaped
bifid notch on the ascending branch, or on the zenith, of the R wave in
inferior ECG leads (II, III, aVF), so called
"crochetage," is an indicator of ostium secundum atrial septal
defects. The pathophysiology underlying this finding remains unknown. A
crochetage pattern has not been previously reported in patients with
patent foramen ovale (PFO); however, the location of this defect and
the secundum atrial septum are similar. The purpose of this study was
to determine the prevalence of crochetage in cryptogenic stroke
patients with or without PFO.
Key Words: cerebral ischemia • cerebral infarction • electrocardiography • foramen ovale, patent
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Paradoxical embolus
through a PFO, a potential channel between the atria, has recently been
proposed as a major cause of otherwise cryptogenic embolic
stroke.1 The primary, but indirect, evidence
rests on the significantly higher prevalence of
echocardiographic diagnosis of PFO, especially in young
stroke patients without other known causes.1 2 3 4
Quick and accurate diagnosis of PFO is important in patients with
stroke or TIA to prevent early cerebral or systemic embolic
recurrences. However, in common practice, diagnosis of PFO is
usually delayed because patients are scheduled for
echocardiography days after the onset of stroke.
Furthermore, in most centers, transthoracic color
Doppler echocardiography is the choice in
routine evaluation of stroke patients, but its yield in detecting PFO
is very low.5 Moreover, the image quality of
color TTE is often degraded during the Valsalva maneuver, a maneuver
crucial for creating a right-to-left shunt in those persons without
spontaneous shunting. More sensitive, albeit more invasive, techniques
such as transthoracic contrast
echocardiography, transesophageal
contrast echocardiography, and
transcranial contrast Doppler ultrasonography are
required for the diagnosis of PFO. A readily available indicator of the
presence of PFO in stroke patients could streamline the
diagnostic evaluation and patient management.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We examined the hospital records of patients admitted
between March 1990 and March 1997 with the diagnosis of first-ever
ischemic stroke or TIA. The procedures followed were in
accordance with institutional guidelines and with the approval of the
Institutional Review Board. All patients had clinical symptoms
consistent with a specific arterial distribution in
the retina, cerebral hemisphere, or brain stem. Symptoms were transient
and lasted less than 24 hours in patients with TIA, or longer than 24
hours in those with ischemic stroke. All patients had brain CT
or MRI studies compatible with their diagnoses. All patients underwent
routine laboratory studies (blood chemistries, cell counts), 12 lead
ECG, TTE and/or TEE, and noninvasive vascular studies that included
duplex carotid Doppler ultrasonography and/or
transcranial Doppler sonography. Twenty-four-hour
Holter monitoring, conventional cerebral angiography and/or magnetic
resonance angiography, and blood tests for hypercoagulable states or
immunologic abnormalities were performed only in selected cases in whom
no other cause of stroke could be identified. 
and 2);
the notching must be persistent in all QRS complexes in an individual
lead in a given tracing, or—in the case of multiple tracings—across
the various studies. All ECG traces were analyzed with respect
to the absence or presence of the crochetage pattern and the number of
leads that exhibited notching. Analysis was performed by 2
examiners who were blind to the study groups. Contrast
echocardiography studies were performed by
injection of 7 mL of saline agitated with 1.0 mL of air into an
antecubital vein at rest and with Valsalva maneuver. A PFO was
diagnosed if at least 3 microbubbles were seen in the left atrium
within 3 cardiac cycles after maximum opacification of the right
atrium.
View larger version (112K):
[in a new window]
Figure 1. Examples of ECG tracings of 3 patients with PFO.
Evident notching on the ascending limb of the R wave ("crochetage")
in lead III can be noted in patients 1 (top row) and 3 (bottom).
Crochetage is seen in lead aVF in patient 2 (middle).
View larger version (30K):
[in a new window]
Figure 2. Prevalence of crochetage in cryptogenic stroke
patients with PFO and in control patients. 
2. This was replaced by Fisher`s exact test
when a cell frequency was less than 5. Results were considered
significant at P<0.05. Agreement between the examiners for
identifying a crochetage was evaluated using the 
statistic.7 A value of 1 indicates perfect
agreement, whereas 0 indicates only chance agreement. In general,
excellent agreement refers to values >0.81, 0.61 to 0.80 indicates
good agreement, and values <0.20 indicate poor agreement.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Among a total of 1470 patients with first-ever stroke or TIA,
there were 167 patients with cryptogenic strokes; of these, 60 cases
fulfilled our conservative eligibility criteria, and comprised 28
cryptogenic stroke patients with PFO and a control group of 32
cryptogenic stroke patients without PFO. . The mean age was lower in patients with PFO (45.0
versus 52.1 years). The male-female ratio and the clinical type of
ischemic attack between groups were not significantly
different. The mean number of cardiovascular risk
factors (including hypertension, hyperlipidemia,
obesity, smoking, and diabetes mellitus) was lower in the PFO group
(0.5±0.7 versus 1.0±0.9). There was a difference between the number
of TTEs and TEEs performed in each group; TEE examination was performed
in 11 patients in the PFO group and in 10 patients in the control
group. Moreover, low yield color TTE alone, rather than TTE study with
contrast injection, was performed more often in the control group (1
versus 9 patients). Thus, contrast TTE and/or TEE studies were obtained
in 96% of cases (27 patients) in the PFO group, whereas in only 72%
(23 patients) of patients in the control group (P<0.05). A
minimal degree of mitral valve prolapse was present in 3 patients
in the PFO group and in 1 of the control subjects. Deep venous
thrombosis was detected in 4 patients, all in the PFO group. Four
patients, 3 with deep venous thrombosis, eventually underwent surgical
closure of the PFO.
View this table:
[in a new window]
Table 1. Clinical Characteristics of the Study Patients 
). The sensitivity and specificity of
crochetage for the diagnosis of PFO in cryptogenic stroke patients were
found to be 36% and 91%, respectively. The positive predictive value
was 77%, and the negative predictive value was 62%. The difference in
prevalence of crochetage remained significant (P<0.05),
even after the exclusion of patients in each group evaluated only by
color TTE (sensitivity, specificity, positive predictive value, and
negative predictive value were 37%, 91%, 83%, and 62%,
respectively), or after exclusion of the patients with mitral valve
prolapse, ie, 3 patients in the PFO group (1 with crochetage) and 1
patient in the control group (who did not have crochetage) (36%
sensitivity, 90% specificity, 75% positive predictive value).
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The foramen ovale is a channel between the atria that enables
passage of blood from the inferior vena cava into the left
atrium in fetal life. After birth, pressure changes between the
pulmonary and systemic circulations can seal the opening by
keeping the valve of the foramen ovale opposed to the ostium secundum
septum. However, this is not always the case; autopsy studies
demonstrate patency in as many as 35% of
adults.8 9 10 A PFO has the potential to permit
passage of emboli from the venous into the arterial
circulation.11 12 13 14 15 Lechat et
al1 demonstrated an association between PFO and
cryptogenic strokes in patients less than 55 years old. The prevalence
of PFO was 24% in patients with an identifiable cause for stroke, 40%
in patients with no identifiable cause but risk factors, and 54% in
patients without identifiable cause or stroke risk factors. Other
studies also confirmed a similar association between PFO and otherwise
cryptogenic ischemic stroke.16 17 18 In the
present study, our strict inclusion criteria markedly reduced the
sample size but minimized contamination of the population with patients
who had stroke unrelated to PFO or ECG changes based on other cardiac
disease. We excluded all patients with either known or potential
cardiac disease.
Selected Abbreviations and Acronyms
ASD
=
atrial septal defect
PFO
=
patent foramen ovale
RBBB
=
right bundle branch block
TIA
=
transient ischemic attack
TEE
=
transesophageal echocardiography
TTE
=
transthoracic echocardiography
Acknowledgments
Dr Ay is the John Conway Fellow in cerebrovascular disease at
the Massachusetts General Hospital. We acknowledge the endowment
support of Paul O'Neill, the Latsis family, the Eliot B. Shoolman
fund, and the Merrill Lynch fund for clinical research in
cerebrovascular disease. Dr Buonanno is supported, in part, by NIH
grant RO1-NS28371. Dr Kistler is supported, in part, by NIH grant RO1
NS33765. Dr Koroshetz is supported, in part, by NIH grants 5 P50
NS108288–22 and 5 RO1 NS35284, and by an AHA grant.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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