From the Society for Vascular Surgery

The utility of intravascular ultrasound comparedto angiography in the diagnosis of blunt traumaticaortic injuryAli Azizzadeh, MD,a Jaime Valdes, MD,a Charles C. Miller III, PhD,b

Louis L. Nguyen, MD, MBA, MPH,c Anthony L. Estrera, MD,a Kristofer Charlton-Ouw, MD,a

Sheila M. Coogan, MD,a John B. Holcomb, MD,a and Hazim J. Safi, MD,a Houston and El Paso, Tex; andBoston, Mass

Background: Blunt traumatic aortic injury (TAI) refers to a spectrum of pathology that ranges from intimal tears to aorticrupture. Computed tomography angiography (CTA) has been widely used as a diagnostic tool in this setting. Additionalimaging is required when CTA studies are equivocal. The purpose of this study is to evaluate the utility of intravascularultrasound (IVUS) versus angiography in the diagnosis of TAI.Methods: We performed an analysis of prospectively collected trauma registry data. CTA was used as the initial screeningtest. Patients with a positive or equivocal CTA underwent angiography and IVUS. Injuries were classified into Grades 1to 4 (intimal tear, intramural hematoma, pseudoaneurysm, and rupture). Patients with Grade 1 injuries were managedmedically. Patients with Grade 2 to 4 injuries underwent repair. A blinded randomized retrospective review of positiveand equivocal imaging studies was performed. Standard screening test assessments (sensitivity, specificity), inter-rateragreement (Kappa), and frequency (Chi-square for the difference) were computed to evaluate the measurementcharacteristics of the multiple imaging techniques.Results: Between May 2008 and August 2009, 7961 patients were admitted to our trauma center, and 2153 (27%)underwent a chest CTA. Twenty-five (0.3%) patients (21 males, mean age 21.9 years) had a positive or equivocal study forTAI. The mean Injury Severity Score was 33.9. Ten patients underwent repair (nine endovascular, one open), and 15patients were managed medically. The 30-day mortality, paraplegia, and stroke rates were zero. Equivocal results weremore common with CTA images than with either IVUS or angiography (27% vs 2.5 and 5%, respectively; overall P �.0002). Compared with angiography, IVUS changed the diagnosis in 13% of cases; identifying injuries in 11% and rulingthem out in 2%. Sensitivity and specificity of angiography with respect to IVUS was 38% and 89%, respectively.Conclusions: CTA is useful as a screening test in suspected TAI. When additional imaging is required after an equivocalCTA, IVUS is better than angiography. Therefore, we advocate the use of IVUS in potential TAI patients in whom

angiography is being considered. (J Vasc Surg 2011;53:608-14.)

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Blunt traumatic aortic injury (TAI) is the second mostcommon cause of death after blunt trauma.1,2 The mecha-nism is likely related to a complex combination of bothrelative motion of the structures within the thorax and localloading of the tissues, either as a result of the anatomy orthe nature of the impact.3 In the aorta, the greatest strainoccurs at the isthmus.4 A 1958 article by Parmley reportedan 85% pre-hospital mortality in patients with TAI.5 Pa-tients who survive transportation to the hospital may pres-ent with a spectrum of pathologies that include intimaltear, intramural hematoma, pseudoaneurysm, and rupture.

From the University of Texas Medical School Houston, Memorial HermannHeart and Vascular Institute;a the Texas Tech University Health SciencesCenter, Paul L. Foster School of Medicine;b and the Harvard MedicalSchool, Brigham and Women’s Hospital.c

Competition of interest: none.Presented at the 2010 Vascular Annual Meeting, Society for Vascular

Surgery, Boston, Mass, June 10-13, 2010.Reprint requests: Ali Azizzadeh, MD, Associate Professor, 6400 Fannin,

Ste. 2850, Houston, TX 77030 (e-mail: Ali.Azizzadeh@uth.tmc.edu).The editors and reviewers of this article have no relevant financial relationships

to disclose per the JVS policy that requires reviewers to decline review of anymanuscript for which they may have a competition of interest.

0741-5214/$36.00

dCopyright © 2011 by the Society for Vascular Surgery.doi:10.1016/j.jvs.2010.09.059

608

omputed tomography angiography (CTA) has beenidely used as a diagnostic tool in this setting.6 AlthoughTA provides great sensitivity for diagnosis of TAI, there

re a significant number of equivocal scans that requiredditional imaging.7 The purpose of this study is to evalu-te the utility of intravascular ultrasound (IVUS) versusngiography in the diagnosis of TAI after a positive orquivocal CTA.

ETHODS

We performed an analysis of prospectively collectedrauma registry data at an urban Level I center. This studyas approved by the Committee for the Protection ofuman Subjects, which acts as the institutional review

oard. TAI patients were screened with CTA on arrival.nitial management included resuscitation, blood pressureontrol, and treatment of associated injuries. Patients withCTA read as positive or equivocal in the report of the

ttending radiologist underwent both angiography andVUS after stabilization. Therefore, the data analyzed arisenly from cases where work-up beyond CTA was clinically

ndicated. The population of patients with negative CTAid not receive further studies and is not included in the

ata analysis. Angiography was performed in a hybrid

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JOURNAL OF VASCULAR SURGERYVolume 53, Number 3 Azizzadeh et al 609

endovascular operating room using a fixed Siemens Ax-iom Artus (Munich, Germany) system. Intravascular ul-trasound was performed concurrently using a Volcano s5imaging system and a Visions PV 8.2 French Catheter(San Diego, Calif).

Based on the combination of imaging modalities, inju-ries were classified into Grade 1, intimal tear; Grade 2,intramural hematoma; Grade 3, aortic pseudoaneurysm;and Grade 4, free rupture (Fig 1).8 Patients with Grade 1injuries were managed medically with a follow-up CTAstudy at 6 weeks. Patients with Grade 2 to 4 injuriesunderwent endovascular repair with the off-label use of aFood and Drug Administration (FDA) approved thoracicdevice. The suitability of a patient for endovascular repairwas based on aortic diameter according to the manufactur-er’s sizing recommendations for thoracic devices as well asthe location of the injury. Our technique for both open andthoracic endovascular repair of TAI has been describedpreviously.8 The primary outcome measures were mortal-ity, stroke, and paraplegia.

A retrospective review of positive and equivocal imag-ing studies (CTA, angiography, and IVUS) was performedby a two-member panel consisting of a vascular surgeon

Fig 1. Classification

and a cardiothoracic surgeon, with the review conducted in d

blinded fashion, and the order in which studies wereresented was randomized. Uninjured control studies werelso introduced into the case review as described below.ach reviewer was initially presented with the CTA imagesf a patient. Following that, either the angiography or theVUS studies of the same patient were presented. The orderf the patients, as well as the order of the secondary andertiary studies (IVUS vs angiography) was randomized.esults were recorded as positive, negative, or equivocal byach reviewer. Reviewers were instructed to respond “pos-tive” when an injury was present, “negative” when nonjury was identified, and “equivocal” when an injury couldot be ruled in or ruled out. “Equivocality” of ratings washerefore a clinical judgment about the interpretation of anmage and not a statistically-derived determination. Imagesrom 10 patients without traumatic aortic injury were useds control. Since IVUS is the only measure of the three ableo image all layers of the aorta simultaneously, it was used ashe standard against which the other two tests were judgedor purposes of estimating sensitivity and specificity.

Agreement by the expert raters on the diagnostic im-ging tests was assessed two ways; by Kappa statistic as aeasure of inter-rater agreement, and by frequency test, to

umatic aortic injury.

etermine which tests most often caused raters to change

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JOURNAL OF VASCULAR SURGERYMarch 2011610 Azizzadeh et al

their ratings. The effect of order in which the tests werepresented to the raters was assessed by Kappa as well. Allcomputations were performed using SAS software version9.1.3 (SAS Institute, Inc, Cary, NC). The null hypothesiswas rejected at a nominal P � .05.

RESULTS

Between May 2008 and August 2009, 7961 patientswere admitted to our Level I Trauma Center, and 2153(27%) underwent a chest CTA. Of the 2153 CTA examsperformed, 2128 were deemed negative by the attendingradiologist. Positive or equivocal results were obtained in25 (0.31%) patients (21 males, mean age 21.9 years). Themean Injury Severity Score was 33.9. The official radiologyreport for the 25 studies revealed: TAI (n � 14), suspectedTAI or TAI cannot be excluded (n � 6), and periaorticmediastinal hematoma (n � 5).

Following stabilization, all 25 patients underwent an-giography and IVUS. Aortic injury was ruled out in 10patients with angiography and IVUS. No further interven-tion was done in these patients. Five patients with Grade 1injuries were managed medically using anti-impulse ther-apy. This consisted of short-acting intravenous �-blockeradministration to maintain a systolic blood pressure of�120 mm Hg and heart rate �90 beats per min. Patientswere weaned to oral therapy when possible. A follow-upCT scan at 6 weeks confirmed healing in all patients.

Ten patients with Grade 2 to 4 injuries underwentrepair (nine endovascular, one open). The detailed treat-ment algorithm is described in Fig 2. The 30-day mortality,

Fig 2. Treatment algorithm describing the study patithoracic endovascular aortic repair.

paraplegia, and stroke rates were zero. There was no mor- c

ality from aortic rupture or any other cause in this cohortfter admission to the hospital. One patient underwentpen repair after failure of medical management. This was a0-year-old man after a motor vehicle accident who had aTA that demonstrated an intramural hematoma (Grade 2AI). He underwent angiography and IVUS per protocol.he angiography was negative. The IVUS confirmed therade 2 aortic injury. He did not meet sizing criteria for thenly FDA-approved thoracic device at the time, so he wasollowed with serial imaging. His follow-up CTA at 1 weekhowed an enlargement of the injury. Our attempts tobtain an investigational device exemption for endovascu-

ar repair using a smaller diameter device were unsuccessful.e subsequently underwent open repair without compli-

ation.Agreement between raters under various conditions as

ssessed by Kappa is shown in the Table. Agreement be-ween raters about whether studies were positive, negative,r equivocal was good (Kappa 0.77) when the CTA wasonsidered by itself. Addition of IVUS to this determina-ion did not affect rater agreement on diagnostic findingsCTA � IVUS also 0.77). Addition of angiography read-ngs reduced rater concordance regardless of how the otherests were presented in combination with angiography.imply stated, raters were more likely to agree about thenterpretation of IVUS findings than angiographic find-ngs, so that addition of angiography tended to introduce

ore disagreement between raters about the diagnosis thanTA or IVUS. Comparing the findings of the imaging

tudies, expert readings of studies as “equivocal” were more

CTA, Computed tomography angiography; TEVAR,

ents.

ommon with CTA images than with either IVUS or

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JOURNAL OF VASCULAR SURGERYVolume 53, Number 3 Azizzadeh et al 611

angiography (27% vs 2.5 and 5%, respectively; overall P �.0002; Fig 3). Compared with angiography, IVUS changedthe diagnosis in 13% of cases; identifying injuries in 11% andruling them out in 2%. Sensitivity and specificity of angiog-raphy with respect to IVUS was 38% and 89%, respectively.Fig 4 shows CTA, angiography, and IVUS studies of apatient after a motor vehicle accident. CTA shows irregularcontour of the lesser curvature of the descending thoracicaorta at the isthmus consistent with a TAI. Although theangiogram was read as equivocal, IVUS clearly shows aGrade 2 TAI.

DISCUSSION

TAI is a major cause of mortality after blunt trauma.Those surviving hospital admission require rapid and accu-rate diagnosis, which is crucial to appropriate treatment.

Table. Agreement among raters assessed by Kappastatistic

Test (order) Kappa

Overall 0.68CTA alone 0.77CTA � (angio) 0.57CTA � (angio � IVUS) 0.61CTA � (IVUS) 0.77CTA � (IVUS � angio) 0.44

CTA, Computed tomography angiography; IVUS, intravascular ultrasound.CTA and IVUS show good agreement. Angiography reduces agreementmarkedly, presumably by introducing ambiguity to an otherwise generallyagreed-upon finding. Notably, CTA was the most-often equivocal test, butthe raters agreed that it was equivocal.

Fig 3. Percentage of equivocal results with computed tomogra-phy angiography (CTA), angiography (Angio), and intravascularultrasound (IVUS).

Diagnosis can be initially suspected based on the finding of p

n abnormal mediastinum on plain chest x-ray.9 In a studyf 656 patients with TAI, Woodring found that 93% had anbnormal mediastinum on initial chest radiograph.10 Thisighlights that in up to 7% of patients with a normalediastinum on chest x-ray, additional imaging was doneased on mechanism of injury or clinical suspicion. CTAas been widely adopted as a screening tool for patientsuspected of having TAI.9 This is due to the very highensitivity (95% to 100%) and a high negative predictivealue (99% to 100%).7,11-13 However, CTA can have aelatively low specificity (40%) and positive predictive value15%).7 In simple terms, CTA produces few false negativeesults at the expense of having a large number of falseositives. Therefore, patients with an equivocal CTA studyften require additional imaging including aortography,VUS, or transesophageal echocardiography.14 In our earlyxperience with TAI, we made the clinical observation thatome patients with a positive CTA had a negative angio-ram. As a result, we started relying on IVUS as an addi-ional imaging modality in these patients. This study wasesigned to mirror the standard clinical algorithm whereTA is primarily used as a screening test. Patients withegative CTA did not receive additional imaging and wereot included in the analysis. The study was limited to theases where work-up beyond CTA was clinically indicated.e compared the utility of IVUS versus angiography for

he diagnosis of TAI in patients who had positive or equiv-cal CTA.

In the present study, of the 7961 patients admitted tohe emergency center, 2153 (27%) underwent a CTAtudy, with 14 (0.18%) positive and 11 (0.14%) equivocalesults. The most common CTA finding in patients withquivocal results was a periaortic mediastinal hematoma.ll patients underwent angiography and IVUS. Our com-arative study found equivocal results twice as often inngiography (5%) as compared with IVUS (2.5%). Thessessment of agreement between raters (Kappa) showedhat the experts were more likely to agree about the inter-retation of IVUS findings than angiographic findings. As aesult, the addition of angiography tended to introduceore disagreement between raters about the diagnosis thanT or IVUS. It is important to keep in mind that Kappaoes not measure the character or quality of the diagnosis,ut only consistency among raters about the call. That is, an

dentical Kappa (0.77) for CT and IVUS does not mean theiagnoses were the same with both modalities; it meanshat the raters agreed about the diagnoses for each, even ifhey were different between modalities. For example, twoaters might have agreed that a CT was equivocal and aollow-up IVUS was positive for injury, so that their agree-ent is the same, but IVUS is enhancing the CT diagnosis

ather than confirming it. The IVUS is adding additionaliagnostic information that the CT is unable to provide by

tself. Based on these findings, IVUS is very helpful inefining TAI in patients who have equivocal CTA or an-iography.

IVUS, first developed in the 1960s by Born et al,

rovides real-time 360° images of the vessels using a min-

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JOURNAL OF VASCULAR SURGERYMarch 2011612 Azizzadeh et al

iature sonographic probe.15 The role of IVUS in thediagnosis of TAI has been previously reported.14,16-19 Inaddition, the interpretation of IVUS has yielded excellentinter- and intraobserver agreement as an adjunct to angiog-raphy for the diagnosis of TAI.20 We utilized a 10 MHzVisions PV 8.2 French (Volcano) catheter that incorporatesa cylindrical ultrasound transducer array. The catheter isintroduced over a guidewire to avoid the risk of perforationof an injured aortic wall. When combined with angiogra-phy, the IVUS catheter can be positioned in the area ofinjury using fluoroscopy for detailed assessment. IVUSdoes not require contrast or radiation and can be performedconcurrently using the same femoral puncture as angiogra-phy. The disadvantages of IVUS are additional cost (capitalequipment and disposable catheter), larger sheath, andoperating room time. However, the information that it canprovide can be invaluable in properly identifying TAI.

In the present series, we used a combination of angiog-

Fig 4. Computed tomography angiography (CTA), anpatient with traumatic aortic injury. CTA shows irregulaaorta at the isthmus consistent with a traumatic aortic inIVUS clearly shows a Grade 2 TAI.

raphy and IVUS to rule out aortic injury in 10 of the 25 s

atients with equivocal CTAs. These patients did not un-ergo any further follow-up imaging or intervention. Theomplementary use of both modalities was helpful in rulingut TAI with a high degree of certainty. Reporting equiv-cal results to patients is very troublesome and frustrating.his is especially important in the setting of TAI when aissed injury can have devastating consequences.

Five of the 25 patients were diagnosed with a Grade 1ortic injury. Two of these patients had a negative angio-ram. In other words, if angiography had been used as theold standard, two Grade 1 TAIs would have been missed.he disadvantages of angiography for identification of aor-

ic injuries have been previously described.14,16,21 Malho-ra et al reported a sensitivity of 37.5% for angiographiciagnosis of minimal aortic injury (defined as a �1-cm

ntimal flap with no or minimal peri-aortic hematoma)omparable to a Grade 1 injury in the present series. Re-arkably, the sensitivity of angiography in the present

ram, and intravascular ultrasound (IVUS) images of atour of the lesser curvature of the descending thoracic(TAI). Although the angiogram was read as equivocal,

giogr conjury

eries was also 38%. TAI lesions that do not cause an

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JOURNAL OF VASCULAR SURGERYVolume 53, Number 3 Azizzadeh et al 613

abnormality in the contour of the aortic wall (Grade 1 andsome Grade 2) are inherently difficult to see on angiogra-phy. In addition, several normal variants including ductusdiverticulum, bronchial artery diverticulum, aortic spindle,and penetrating aortic ulcer can produce false-positive re-sults on angiography.14,21-23 IVUS, on the other hand,provides a two-dimensional axial view of the lumen and theaortic wall without the interference of intraluminal con-trast, motion artifacts, or volume averaging. All five patientswith Grade 1 TAI were managed medically with intrave-nous anti-impulse therapy. Follow-up CTA at 4 to 6 weeksdemonstrated healing in all five patients. CTA was used asthe only follow-up imaging modality in this group ofpatients due to cost constraints. The medical managementof minor TAIs (Grade 1) has been previously repor-ted.14,16,24 Several animal studies have demonstrated spon-taneous healing of arterial injuries that are limited to theintima and the internal elastic lamina (inner media).25-28

The current data support non-operative treatment of se-lected patients with Grade 1 TAI who are compliant withmedical therapy and follow-up imaging.

The remaining 10 patients with Grades 2 to 4 TAIunderwent repair. The utility of angiogram and IVUS inthis group of patients who had a definitive diagnosis onCTA is limited. The additional imaging studies were usuallydone at the time of definitive repair. The only exception wasthe case of the patient with a Grade 2 TAI who failedmedical therapy. If angiography had been used as the goldstandard in this patient, a Grade 2 TAI would have beenmissed. The remainder of the patients in the study withGrades 2 to 4 TAI underwent endovascular repair with theoff-label use of approved devices.

Limitations of this series include the relatively smallsample size and the non-randomized nature of the study.A future study design could prospectively randomizepatients with equivocal CTA studies to two arms: IVUSfirst versus angiography first. The images of the secondstudy would then have to be reviewed prior to perfor-mance of the third study. From a procedural standpoint,however, such a study would be somewhat cumbersometo carry out. Another limitation is the lack of pathologicdiagnosis, as 24 of the 25 patients did not have an opensurgical exploration.

CONCLUSIONS

CTA is useful as a screening test in patients suspected ofhaving TAI. When additional imaging is required after anequivocal reading for CTA, IVUS is better than angiogra-phy. If angiography had been used as the gold standard inthis study, three TAIs would have been missed. Therefore,we advocate the use of IVUS in potential TAI patients inwhom angiography is being considered.

The authors would like to thank G. Ken Goodrick forediting, Chris Akers for illustrations, and Edmundo Dipa-

supil for trauma registry.

UTHOR CONTRIBUTIONS

onception and design: AA, JV, CM, AE, KCO, SCnalysis and interpretation: AA, CM, LNata collection: AA, JV, KCO, SCriting the article: AA, CMritical revision of the article: AE, LN, KCO, SC, JH, HSinal approval of the article: AA, HStatistical analysis: CM, LNbtained funding: Not applicableverall responsibility: AA

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ubmitted Jun 10, 2010; accepted Sep 25, 2010.