Download Final Infarct Volume Is a Stronger Predictor of

Final Infarct Volume Is a Stronger Predictor of Outcome
Than Recanalization in Patients With Proximal
Middle Cerebral Artery Occlusion Treated With
Endovascular Therapy
Syed F. Zaidi, MD; Amin Aghaebrahim, MD; Xabier Urra, MD; Mouhammad A. Jumaa, MD;
Brian Jankowitz, MD; Maxim Hammer, MD; Raul Nogueira, MD; Michael Horowitz, MD;
Vivek Reddy, MD; Tudor G. Jovin, MD
Background and Purpose—The rationale for recanalization therapy in acute ischemic stroke is to preserve brain through penumbral
salvage and thus improve clinical outcomes. We sought to determine the relationship between recanalization, clinical outcomes,
and final infarct volumes in acute ischemic stroke patients presenting with middle cerebral artery occlusion who underwent
endovascular therapy and post-procedure magnetic resonance imaging.
Downloaded from http://stroke.ahajournals.org/ by guest on July 12, 2017
Methods—We identified 201 patients with middle cerebral artery occlusion. Patients with other occlusive lesions were
excluded. Baseline clinical/radiological characteristics, procedural outcomes (including thrombolysis in cerebral
infarction scores), clinical outcome scores (modified Rankin scores), and final infarct volumes on diffusion weighted
imaging were retrospectively analyzed from a prospectively collected database. Favorable outcome is defined as 90-day
modified Rankin score ≤2.
Results—Successful recanalization (thrombolysis in cerebral infarction grade 2b or 3) was achieved in 63.2% and favorable
outcomes in 46% of cases. Mean infarct volume was 50.1 mL in recanalized versus 133.9 mL in non-recanalized patients
(P<0.01) and 40.4 mL in patients with favorable outcomes versus 111.8 in patients with unfavorable outcomes (P<0.01).
In multivariate analysis, thrombolysis in cerebral infarction ≥2b, baseline National Institute of Health Stroke Scale,
Alberta Stroke Program Early Computed Tomography scores, and age were identified as independent predictors of
outcome. However, when infarct volumes were included in the analysis only final infarct volume and age remained
significantly associated.
Conclusions—Successful recanalization leads to improved functional outcomes through a reduction in final infarct volumes. In
our series, age and final infarct volume but not recanalization were found to be independent predictors of outcome, supporting
the use of final infarct volume as surrogate marker of outcome in acute stroke trials. (Stroke. 2012;43:3238-3244.)
Key Words: acute stroke ◼ infarct volume ◼ interventional treatment ◼ stroke outcome
T
here is a mounting evidence in support of the notion that
vessel recanalization has the most powerful effect on clinical outcomes in acute ischemic stroke.1 A concept fundamental
to the rationale for instituting reperfusion therapy is that of mismatch between ischemic core and ischemic penumbra. After
vessel occlusion, attribu table to progressive collateral failure,
there is continuous growth of the core at the expense of the
penumbra.2 The aim of recanalization therapy is to halt this process by salvaging the penumbra with the consequence of limiting final infarct size. Whereas final infarct volume represents
the accepted outcome measure in most experimental models
of focal ischemia,3 it is not the standard outcome measure in
human studies where scales assessing disability status are typically chosen for this purpose.4 This is in part attributable to the
fact that human studies attempting to correlate final infarct volumes to clinical outcomes have yielded contradictory results.5–8
Significant limitations of these studies include the heterogeneous nature of vascular occlusion sites particularly with
respect to anterior and posterior circulations and small sample
sizes. We sought to study the relationship between clinical
outcomes, recanalization, and final infarct volume in a homogenous patient population with regard to the territory at risk
composed of patients with middle cerebral artery (MCA)-M1
segment occlusion who underwent endovascular therapy.
Methods
This study represents a retrospective analysis of a prospectively
acquired database comprising 562 consecutive patients with acute
Received July 21, 2012; final revision received August 28, 2012; accepted September 12, 2012.
From the University of Toledo Medical Center, Department of Neurology, Toledo, OH (S.F.Z., M.A.J.); University of Pittsburgh Medical Center Stroke
Institute (A.A., X.U., M.H., V.R., T.G.J.), Department of Neurological Surgery (B.J., M.H.), University of Pittsburgh Medical Center, Pittsburgh, PA; and
Department of Neurology, Radiology, and Neurosurgery, Emory University School of Medicine, Atlanta, GA (R.N.).
Christoph Kleinschnitz, MD, was the guest editor for this article.
Correspondence to Tudor G Jovin, MD, UPMC Stroke Institute, 200 Lothrop St, Ste C400, Pittsburgh, PA-15213. E-mail [email protected]
© 2012 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.112.671594
3238
Zaidi etal Final Infarct Volume and Stroke Outcome 3239
Table. Baseline Clinical Variables, Treatment Modalities, and Univariate Analysis for Predictors of Good Outcome and Mortality at
90 Days
Variable
N (%)
mRS ≤2*
Median (IQR)
OR
P Value
Mortality*
95% CI
OR
P Value
95% CI
Age, y
70 (26–90)
0.93
<0.001
0.90–0.95
1.06
<0.001
1.03–1.09
NIHSS
16 (56–78)
0.92
0.002
0.87–0.97
1.13
<0.001
1.05–1.21
9 (8–10)
1.58
<0.001
0.39–0.86
0.81
0.09
0.63–1.01
Time to procedure, h
5.5 (0.5–35.5)
1.05
0.07
1.00–1.09
0.94
0.09
0.88–1.01
Treatment time, min
107 (72–136)
0.99
0.26
0.99–1.01
1.01
0.17
0.99–1.01
Baseline ASPECT
Female
109 (54.2)
0.53
0.034
0.33–0.95
1.43
0.28
0.74–2.71
Left MCA
106 (52.7)
1.18
0.56
0.67–2.07
0.73
0.3
0.38-.14
HTN
126 (62.6)
0.42
<0.006
0.22–0.78
1.37
0.38
0.66–2.8
DM
35 (17.4)
0.51
0.10
0.23–1.13
0.45
0.13
0.16–1.2
Afib
56 (27.8)
0.34
0.002
0.17–0.68
2.4
0.01
1.18–4.7
Smoking
47 (23.3)
5.6
<0.001
2.5–12.5
0.11
0.004
0.02–0.54
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CAD
48 (23.8)
0.68
0.27
0.34–1.35
2.04
0.05
0.99–4.1
Hyperlipidemia
56 (29.8)
0.67
0.23
0.35–1.29
2.11
0.033
1.06–4.23
PH
19 (11.05)
0.11
0.005
0.25–0.52
3.07
0.025
1.15–8.16
TICI>2b
127(63.2)
3.26
<0.001
1.73–6.15
0.29
<0.001
0.14–0.56
TICI>2a
159 (79.1)
Infarct volume
51.5 (21–111)
3.03
0.01
1.28–7.11
0.31
0.004
0.14–0.69
0.98
<0.001
0.97–0.98
1.01
0.009
1.01–1.02
General anesthesia
65 (32.3)
0.42
0.009
0.22–0.81
2.47
<0.001
1.24–4.9
IA lytic
90 (44.7)
1.09
0.76
0.61–1.9
0.82
0.56
0.42–1.59
1.2–8.03
144 (73.8)
0.68
0.25
0.35–1.31
3.18
0.014
GP IIb/IIIa inhibitors (IV or IA)
62 (32.1)
1.09
0.77
0.59–2.01
0. 54
0.11
0.25–1.16
Other mechanical interventions
(manual aspiration, penumbra,
stent)
85 (42.2)
1.24
0.79
0.72–2.15
0.86
0.67
0.45–1.66
Merci embolectomy
IQR indicates interquartile range; mRS, modified Rankin scores; NIHSS, National Institute of Health Stroke Scale; ASPECT, Alberta Stroke Program Early CT score;
MCA, middle cerebral artery; HTN, hemorrhagic transformation; DM, diabetes mellitus; CAD, coronary artery disease; PH, parenchymal hematoma; TICI, thrombolysis in cerebral infarction; IA, intra-arterial; and GP, glycoprotein.
*Significant associations are outlined in bold.
ischemic stroke treated with endovascular therapy at single high
volume academic center from 2000 to 2010. Patients receiving intraarterial (IA) stroke treatment at the University of Pittsburgh Medical
Center are included in an Institutional Review Board approved
prospective database after written informed consent is obtained by
the patient or proxies. All patient information was de-identified and
analyzed in compliance with the Health Insurance Portability and
Accountability Act. To study a homogeneous population with respect
to vascular occlusion site, only patients with MCA-M1 segment
occlusion were included and to determine final infarct volumes based
on the most accurate imaging method, only patients who underwent
post-procedure magnetic resonance imaging (MRI) were included.
Follow-up MRI was obtained within 24 to 48 hours after completion
of the procedure in all patients.
Patient Selection
All patients presenting with acute ischemic stroke symptoms underwent a baseline head Computed Tomography (CT) scan. In general,
as a first step, patients with anterior circulation stroke were selected
for IA therapy if CT showed an Alberta Stroke Program Early CT
score (ASPECTS) of >6 or less than one third of hypodensity of the
MCA territory. Most patients underwent additional imaging studies
(CT angiography/CT perfusion) or MRI/magnetic resonance angiography and were considered for interventional therapy based on assessment of mismatch between the extent of infarcted brain relative
to the extent of threatened but viable brain. In patients undergoing
CT/CT perfusion, the ratio of low cerebral blood volume (threshold
for infarct ≤2.0 mL× 100 gm-1)/elevated mean transit time maps and
to the severity of clinical deficit (National Institute of Health Stroke
Scale [NIHSS]) was factored in treatment decision. The minimum
amount of mismatch necessary for treatment selection varied according to patient specific considerations and stroke neurologist/interventionalist specific practice patterns. In general, patients with a core
volume of less than one third of MCA territory in the presence of M1
occlusion and corresponding clinical deficit (NIHSS >6–8) or severe
perfusion deficit (time to peak >6s) involving greater than or equal to
two third of the MCA territory were considered potential treatment
candidates. Computer-generated volumetric analysis was not available and manual calculation of volumes is too lengthy a process to be
useful for selection in the setting of acute stroke. Therefore, volumes
were estimated based on visual mismatch. Time from stroke onset
was not considered a limiting factor. All patients who underwent IA
treatment had baseline modified Rankin score (mRS) <2.
IA Treatment Protocol
The general approach regarding IA treatment at our center has been
described previously.9 In most cases, the procedure was performed
under conscious sedation. Subjects with airway compromise,
significantly impaired comprehension, and agitation were intubated
before the procedure. IA treatment was categorized as pharmacological
only, mechanical only, or combination pharmacological and
mechanical. If eligible, patients were administered IV tPA prior to
intervention. Mechanical thrombectomy was performed as first
line. In cases of unsuccessful recanalization with this approach,
3240 Stroke December 2012
a combination of IA pharmacological and mechanical treatment
was used. Sixty-six patients (33.1%) received IV tPA before the
procedure. Most patients underwent MERCI (Concentric Medical,
Mountain View, Ca) thrombectomy which was performed in 144 of
201 (71.6%) cases. Manual aspiration10 in conjunction with MERCI
thrombectomy was applied in 64 (31.9%) cases. Another 38 patients
(18.9%) underwent PENUMBRA (Penumbra Inc, Alameda, CA) clot
evacuation. Intracranial stenting was performed in 18 subjects (8.9%).
IA tPA was administered in 90 patients (47.1%). Sixty-two patients
(30.8%) received glycoprotein Ib/IIIa inhibitors. Combination
pharmacological and mechanical IA treatment was performed in
110 cases (54.7%). Successful recanalization was considered if
thrombolysis in cerebral infarction (TICI) 2b or 3 (defined according
to previously published TICI recanalization scores)11 was achieved.
Infarct Volume Calculation
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Post-treatment infarct volumes were calculated by vascular neurologists (S.Z. and M.J.), blinded to recanalization grade. The acute infarct was determined by visual inspection on the magnetic resonance
diffusion weighted imaging (DWI) sequence. Final outlines were
manually edited. If present, hemorrhagic changes were incorporated
in the final infarct volumes. Volume viewer 2 software (Voxtools; GE
Healthcare, Milwaukee, WI) on an Advantage Workstation 4.3 (GE
Healthcare) was used to calculate total infarct volume.
Patient Follow-Up
On discharge, patients were scheduled for follow-up appointments in
the stroke neurology clinic at 30 and 90 days and 90-day mRS was
charted on follow-up appointment. If patients were physically unable
to present for follow-up, they or next of kin were reached by a vascular
neurologist or other mRS certified investigator, and mRS was obtained
over the phone. Good clinical outcome was defined as mRS score of ≤2.
Symptomatic hemorrhage was defined as any parenchymal hematoma
(PH) according to European Cooperative Acute Stroke Study criteria.12
Statistical Analysis
Variables collected included patient demographics, stroke risk factors,
admission NIHSS score, ASPECT score, time from symptom onset to
first diagnostic baseline angiographic run, IA treatment used (pharmacologic, mechanical, or both), pre- and post-treatment TICI reperfusion grade, final DWI volumes, rates of symptomatic hemorrhage and
hemorrhagic transformation, inpatient mortality rate, and 90-day mRS.
All tests were performed using the STATA 10 software (StataCorp
LP, College Stanton, TX). Normal distribution of all variables was
assessed. We compared differences between patients with or without recanalization using t test or Mann–Whitney test for continuous variables and χ2 or Fisher exact tests for categorical variables.
In univariate analysis, several variables of interest were correlated to
good functional outcome as binary outcome measure. Subsequently
all covariates with a P value <0.2 were then entered into a multivariate stepwise logistic regression model. Significant association
was considered for a P value of <0.05. A multivariate logistic regression model was used to assess the effects of clinical and radiological
variables on functional outcome and mortality. Because ASPECTS
and final infarct volumes are related variables that are correlated to
each other (spearman ρ 0.68, P<0.01) multivariate analyses were performed, with and without inclusion of the ASPECT score. Level of
significance was established at a 2-tailed P value of <0.05.
Results
From January 2002 through December 2010, 562 endovascular stroke treatments were performed. Patients with posterior circulation (N=76, 14.1%), intracranial internal carotid
artery and internal carotid artery terminus (N=116, 21.6%),
proximal carotid (N=44, 8.1%), and isolated MCA M2 segment (N=50, 9.2%) occlusive lesions were excluded. A total
of 251 (46.7%) patients with MCA-M1 segment occlusion
were identified. Another 50 of these patients were excluded
because of lack of post-treatment MRI. Clinical and radiological characteristics of remaining 201 (35.7%) patients are outlined in Table. Five patients were lost to follow-up and 90-day
clinical outcomes are available for 196 patients (97.7%). The
median number of days from intervention to MRI was 1.
Nineteen patients (9.4 %) developed PH, of which 9 (47.3)
died and only 2 patients (10.5%) had favorable outcome at
90 days. The incidence of perforation was 5 of 201 (2.3%).
Overall mortality was 24.3% (49/201). TICI ≥2b and 3 recanalization was achieved in 127 patients (63.2%), whereas TICI
≥2a, b, and 3 was achieved in 159 cases (79.1%). Figure 1
shows an inverse linear association between TICI recanalization grade and infarct volume. Higher recanalization grades
corresponded to lower infarct volume (P<0.01 by ANOVA).
Recanalized patients had significantly lower mean infarct volumes as compared with non-recanalized patients irrespective
of their functional outcomes (mRS 0–2: 31.1 versus 74.9 mL,
P<0.01; mRS 3–6: 74.1 versus 154.9 mL, P<0.01).
Figure 2 shows the relationship between recanalization,
infarct volume, and 90-day clinical outcomes. Overall 90
patients (46.1%) had a favorable outcome at 3 months, of
which 71 (78.9%) recanalized and 19 (21.1%) did not recanalize (P<0.01). Irrespective of recanalization grade, patients
achieving functional independence at 3 months were younger
(mean age 60.1, 95% CI 57.0–62.9, versus 71.7, 95% CI
69.6–76.6, P<0.01) and had significantly lower mean infarct
volumes (40.4, 95% CI 31.8–49.7 mL versus 111.8 mL, 95%
CI 89.7–126.8, P<0.01).
In univariate analysis, older age, higher baseline NIHSS,
female gender, history of hypertension or atrial fibrillation,
intubated state during the procedure, and the development
of PH were associated with lower chances of independent
functional outcomes at 90 days. Conversely, higher baseline
ASPECT score, successful recanalization, lower final infarct
volumes, and current smoking status were associated with
higher chances of independent functional outcomes at 90 days.
We attributed the latter observation to the fact that current
smoking status was found predominantly in younger patients
(mean age in smoker versus nonsmokers 54 versus 71, P<0.01).
In multivariate logistic regression analysis TICI ≥2b,
baseline NIHSS, baseline ASPECT scores, and age were
identified as independent predictors of outcome. However,
when final infarct volumes were included in the model only
final infarct volume (mRS≤2: odds ratio [OR] 0.98, 95% CI
0.97–0.99, P<0.01; mortality: OR 1.01, 95% CI 1.01–1.02,
P=0.01) and age (mRS≤2: OR 0.93, 95% CI 0.88–0.95,
P<0.01; mortality: OR 1.07, 95% CI 1.03–1.08, P=0.016)
remained significantly associated with outcomes. These
predictors, that is, age (OR 0.91, 95% CI 0.87–0.94, P<0.01)
and infarct volume (OR 0.97, 95% CI 0.97–0.99, P<0.01)
remained significantly associated with outcome when baseline
ASPECTS and final infarct volumes were simultaneously
added in the model. A receiver operating characteristics curve
depicting various final infarct volume points as predictors
of favorable outcome was constructed (Figure 3). At 40 mL
infarct volume cutoff, the prediction sensitivity and specificity
for favorable outcome are 63% and 72%, respectively (area
under curve 0.75, 95% CI 0.38–0.72).
Zaidi etal Final Infarct Volume and Stroke Outcome 3241
TICI 2A
TICI 2B
TICI3
200
TICI 1
150
166.1
145.4
121.4
100
Figure 1. Recanalization and post-treatment DWI
infarct volume (mL). TICI indicates thrombolysis in
cerebral infarction.
50
53.9
36.2
0
MEAN POSTTREATMENT INFARCT VOLUME
TICI 0
P <0.001 BY ANOVA
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Of the 50 subjects excluded because of lack of post-treatment scan, 20 patients had MRI contraindication attributable
to cardiac pacemaker, shrapnel injury, etc. Eight patients
could not tolerate MRI scanning because of agitation or
claustrophobia. In the remaining 22 patients, there was no
evident contraindication to MRI. The recanalization and PH
rate for this cohort are 14 (66%) and 3 (14%), respectively.
Fifty-nine percent died (13/22) and only 5 subjects (23.8%)
were functionally independent at 90 days. These patients
had high-inpatient mortality 50% (11/22) and the lack of
MR imaging may be attributable to clinical instability, early
mortality, or withdrawal of care attributable to perceived
poor chances of meaningful recovery by the treating physicians or family members. Procedural results and outcomes
for the CT only group compared with the analyzed group
are as follows: TICI 2b and 3 recanalization: 14 (66%) versus 127 (63.2%), respectively, P= 0.78; PH: 3 (13.6%) versus 19 (9.4%), respectively, P=0.65; favorable outcomes: 5
(22.8%) versus 90 (46.1)%, respectively, P=0.03; mortality at
90 days: 13 (59%) versus 49 (24.3%), respectively, P=0.02.
Measurement of post-treatment CT infarct volume in these
patients yielded larger infarcts than in the analyzed group
(median post-treatment CT volume 126 mL (interquartile
range 50–355 mL) versus 51 mL, (interquartile range 21–111
mL), P=0.03.
Discussion
The main conclusion of this study is that in patients with
acute ischemic stroke because of MCA occlusion treated with
endovascular therapy, final infarct volumes in conjunction
with age are the strongest predictors of clinical outcomes.
Whereas this concept may be intuitive, it has not been
convincingly demonstrated previously, as studies investigating
the association between final infarct volumes and clinical
outcomes have yielded contradictory results.
Figure 2. Recanalization, infarct volume and 90-day functional outcome. TICI indicates thrombolysis in cerebral infarction; DWI, diffusion
weighted imaging.
1.00
3242 Stroke December 2012
0.75
85
Sensitivity
0.50
40
0.00
0.25
38
0.00
0.25
0.50
1 - Specificity
0.75
1.00
Area under ROC curve = 0.75
*Analysis adjusted for NIHSS, ASPECT and TIMI 2&3 recanalization
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Figure 3. Receiver operating characteristics (ROC) analysis—
Infarct Volume and favorable outcome. NIHSS, National Institute
of Health Stroke Scale; ASPECTS, Alberta Stroke Program Early
CT score; and TIMI, thrombolysis in myocardial infarction.
On the contrary, a strong relationship between prethrombolysis infarct volumes and outcome13–17 has been well established.
The DEFUSE investigators showed that among other MRI signatures, pretreatment DWI MRI volume of >100 mL predicts
a malignant clinical course.16 Among patients with anterior
circulation occlusions treated with endovascular therapy, Yoo
et al15 showed that regardless of recanalization results a preprocedure magnetic resonance DWI volume of ≥70 mL has a high
likelihood of yielding poor clinical outcomes. The EPITHET
investigators14 reported that in patients treated with intravenous
tPA between 3 and 6 hours from symptoms onset, a preprocedure DWI infarct volume of ≤25 mL is associated with a high
likelihood of obtaining a favorable outcome. The final infarct
volume cutoff of 40 mL found in our cohort to best differentiate
between favorable and unfavorable outcomes falls in the middle
of the final infarct volume range described by these studies.
Saunders et al18 using DWI MRI derived infarct volumes in
untreated patients with MCA distribution stroke but unspecified site of vascular occlusion reached similar results to those
noted in our study. These investigators reported that a final
infarct volume of 80 mL was found to best differentiate
between the likelihood of obtaining a good versus unfavorable
outcome. In keeping with our results, Yoo et al has also shown
an independent association between final infarct volume
together with age and outcomes.19 Other investigators have not
been able to detect a strong relationship between final infarct
and outcomes.6,20 We believe that this lack of association is
explained primarily by studying a heterogeneous patient
population with respect to vascular occlusion without knowledge of vessel patency status. To account for these important
confounding factors, we chose to study only patients with a
homogeneous vascular occlusion site whose vessel patency
status could be determined as all patients underwent endovascular therapy.
Because young patients can still achieve functional independence despite higher final infarct volumes the association
between final infarct volume and favorable clinical outcome
is influenced in a major way by age. The clinical outcome
measure captured in our database consisted of the mRS, which
primarily reflects physical disability status after stroke.4 This
scale was chosen because it is a widely used outcome measure
in endovascular acute stroke therapy trials. Other stroke related
sequelae, such as mood, cognition, and overall quality of life,
were not captured prospectively in our database and, as such,
our study could not assess the extent to which final infarct volumes may be correlated to these important patient-centered
outcome measures. We feel that this represents an important
question to be addressed by future prospective studies.
Previous studies21,22 have suggested that infarct location
enhance the predictive value of infarct volume with respect
to clinical outcomes. Consequently, the construction of topographic atlases was proposed to account for the different relevance in terms of outcomes of the regions affected. Unlike
our report, these studies did not limit inclusion criteria to the
presence of a single large artery occlusion (MCA) and as such
the volumes of infarct in the patients included were smaller
than those observed in our study. Because of the size of the
infarcts seen in our group of patients as well as the multiplicity of areas within the MCA territory involved, a detailed
topographical differentiation of ischemic lesions on follow-up
MRI would have posed significant challenges and, therefore,
an analysis of outcome prediction based on infarct location is
beyond the scope of this article. The extent to which infarct
location influences outcomes in patients with MCA occlusion
should be explored by future studies. With regard to side of
infarction, no relationship with outcomes could be found in
our study. Therefore, it appears that in patients with larger
infarcts, lesion side may not have a critical impact on outcome
especially when outcomes are measured in a rather crude way
through scales of disability such as the mRS. This contention
is supported by the findings from several randomized hemicraniectomy trials in which no association between infarct side
and likelihood of obtaining a favorable outcome was found.23
We were able to detect a strong association between degree
of recanalization and final infarct volumes with highest
recanalization scores translating into lowest infarct volumes.
These findings suggest that recanalization is a powerful means
of achieving a reduction in final infarct size, a mechanism that
explains why recanalization has a powerful effect on clinical
outcomes. Indeed recanalization has been shown in virtually
all IA thrombolytic trials to be a significant predictor of
favorable clinical outcome. This association was confirmed by
our study as we were able to detect a significant relationship
between vessel recanalization and clinical outcomes when
final infarct volume was not introduced in the statistical
model. However, when final infarct volumes are taken into
account they override the importance of recanalization. Thus
rather than independently predicting outcome, recanalization
appears to merely represent a means of achieving a small final
infarct volume which in turn is a strong predictor of outcome.
If for various reasons (mainly related to robust collateral
status) the final infarct volume is low, good clinical outcomes
can be obtained despite lack of recanalization. Conversely,
successful recanalization will not result in a good outcome,
if before recanalization a large infarct has already developed.
Stroke is a heterogeneous condition with multiple factors
determining eventual clinical outcomes. These include age,
premorbid functional status, comorbid conditions, as well as
Zaidi etal Final Infarct Volume and Stroke Outcome 3243
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poststroke care including access to rehabilitation and social
factors (family support, socioeconomic status, etc). Because
of the inherent complexities associated with clinical outcome measurement in IA thrombolytic stroke therapy trials,
recanalization scores are increasingly being used as surrogate
markers for efficacy of endovascular therapy. Our findings,
however, indicate that final infarct volumes may represent
a more accurate indicator of procedural success and, therefore, should be used in preference to recanalization scores as
surrogate markers of outcome in reperfusion trials for acute
stroke.
The main limitation of this study derives from its retrospective design. Patients were selected for endovascular treatment
based on different imaging methods with different selection
criteria, and treatment methods were heterogeneous. The heterogeneous nature both of imaging paradigms used for selection and of treatment modalities reflects the dynamic nature of
the rapidly evolving field of acute stroke interventions, over
the time span this study was conducted. We do not believe,
however, that this lack of uniformity affects the main message
of our article which, from an imaging standpoint, is based
mainly on calculation of follow-up infarct volumes that have
been obtained in a uniform fashion.
Patients were included in the study only if they underwent
a post-procedure MRI. We chose these inclusion criteria specifically to preserve uniformity in follow-up infarct assessment method and because it is well established that MRI is
more accurate than CT in delineating the extent of infarction.
As such, the possibility of selection bias is a valid concern.
However, we do not feel that this has altered the conclusions
of our study in a significant way because a post-procedure
MRI within the first 24 to 48 hours is performed as a matter
of standard of care at our center. Patients who did not undergo
an MRI scan were essentially those with contraindications
to the study. The fact that a large proportion (201 of 251) of
patients with MCA-M1 occlusion treated at our center during
the duration of the study was included supports this contention. In addition, patients who underwent follow-up CT only
had significantly larger follow-up infarcts along with significantly higher proportions of poor outcomes than those in the
analyzed group, a finding that is in keeping with the main conclusion of this study.
Because of the retrospective nature of our study a blinded
assessment of recanalization results by a core lab, whereas
optimal was not feasible. This represents another limitation of
this current study. Nonetheless, we feel that our prospectively
recorded recanalization scores at the end of the procedure are
validated by the infarct volume analysis performed by independent investigators, different from the interventionalist performing the procedure and blinded to recanalization results.
This analysis reveals a strong correlation between TICI scores
and final infarct volumes (Figure 1).
Another significant concern is the MRI sequence (DWI)
and timing (24–48 hours) used for final infarct assessment.
Several studies have shown that a FLAIR sequence performed
at 3 to 5 days may be the most accurate early indicator of
true infarct volume.24 However, the timing of this imaging
sequence may result in loss to follow-up as some patients
may not be available to undergo the study because of either
death or early discharge. In addition, at that point in time, the
FLAIR sequence incorporates a certain element of edema that
may result in overrepresentation of the final infarct lesion. To
explore ways to overcome these limitations, Campbell et al25
have investigated the accuracy of 24-hour DWI volume in predicting final infarct burden as assessed by FLAIR sequence at
90 days. The 2 sequences were found to be highly correlated
indicating that early DWI MRI may be comparable to FLAIR
at 5 days in outlining the final infarct. The timing of 24 hours
chosen for most of the patients in our study is likely to represent the earliest time point for accurate delineation of final
infarct volume. An earlier time point (eg, 6–12 hours) after
intervention would likely lead to underestimation of infarct
size because during this timeframe, continuous infarct growth
is still common.8,25 Although Campbell et al findings validate
our approach, the question of optimal sequences and timing
for infarct measurements on MRI can only be addressed by
conducting prospective studies with prespecified time points
for infarct measurement. Such studies are currently ongoing
and further light will be shed on whether differences in magnetic resonance sequence or timing of measurement have a
major impact on measurement accuracy and most importantly
whether these differences are clinically relevant in terms of
correlations with outcomes.
Disclosures
Dr Nogueira is on scientific advisory board for Concentric Medical,
Co-Axia, and eV3. Dr Jovin has received consulting and speaker fees
from Covidien, Stryker, Codman, and Silk Road. The other authors
have no conflicts to report.
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Final Infarct Volume Is a Stronger Predictor of Outcome Than Recanalization in Patients
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Stroke. 2012;43:3238-3244; originally published online November 15, 2012;
doi: 10.1161/STROKEAHA.112.671594
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