The role of ascending aortic size in outcomes of patients with uncomplicated acute type B aortic dissection

From the Western Vascular Society

The role of ascending aortic size in outcomes of patients with uncomplicated acute type B aortic dissection Hunter M. Ray, MD,a Joseph M. Besho, MD,a Jason Au, MD,b Kristofer M. Charlton-Ouw, MD,a Anthony L. Estrera, MD,a Charles C. Miller III, PhD,a Hazim J. Safi, MD,a and Ali Azizzadeh, MD, FACS,c Houston, Tex; and Los Angeles, Calif

ABSTRACT Objective: Recent studies demonstrate that uncomplicated acute type B aortic dissection (uATBAD) patients with enlarged descending thoracic aortic diameters are at high risk for development of complications. This study aimed to determine the association of maximum ascending aortic diameter and area and outcomes in patients with uATBAD. Methods: All patients admitted with uATBAD from June 2000 to January 2015 were reviewed, and those with available imaging were included. All measurements were obtained by a specialized cardiovascular radiologist, including the maximum ascending aortic diameter and area. Outcomes, including the need for intervention and mortality, were tracked over time. Data were analyzed by stratified Kaplan-Meier and multiple Cox regression analyses using SAS 9.4 software (SAS Institute, Cary, NC). Results: During the study period, 298 patients with uATBAD were admitted, with 238 having available computed tomography and 131 having computed tomography angiography imaging and adequate follow-up available for analysis. The cohort had an average age of 60.96 6 13.4 years (60% male, 53% white). Ascending aortic area >12.1 cm2 and ascending aortic diameter >40.8 mm were associated with subsequent arch and proximal progression necessitating open ascending aortic repair (P < .027 and P < .033, respectively). Ascending diameter >40.8 mm predicted lower intervention-free survival (P ¼ .01). However, it failed to predict overall survival (P ¼ .12). Ascending aortic area >12.1 cm2 predicted lower intervention-free survival (P ¼ .005). However, this was not predictive of mortality (P ¼ .08). Maximum aortic diameter along the length of the aorta >44 mm persisted as a risk factor for mortality (P < .001). Neither maximum ascending aortic diameter >40.8 mm (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.42-2.83; P ¼ .85) nor area >12.1 cm2 (HR, 0.992; 95% CI, 0.38-2.61; P ¼ .99) significantly predicted mortality when controlling for maximum aortic diameter along the length of the aorta >44 mm (HR, 7.34; 95% CI, 2.3-23.41; P < .001), diabetes mellitus (HR, 6.4; 95% CI, 2.17-18.93; P < .001), age (HR, 1.06/y; 95% CI, 1.03-1.10; P < .001), history of stroke (HR, 5.03; 95% CI, 1.52-16.63; P ¼ .008), and syncope on admission (HR, 21.11; 95% CI, 2.3-193.84; P ¼ .007). Ascending aortic diameter >40.8 mm (HR, 2.01; 95% CI, 1.033.95; P ¼ .04) and maximum ascending aortic area >12.1 cm2 (HR, 1.988; 95% CI, 1.02-3.87; P ¼ .04) on admission persisted as predictors of decreased intervention-free survival after controlling for maximum aortic diameter along the length of the aorta >44 mm (HR, 3.142; 95% CI, 1.47-6.83; P < .004), syncope on admission (HR, 26.3; 95% CI, 2.81-246; P < .004), and pleural effusion on admission (HR, 3.02; 95% CI, 1.58-5.77; P < .001). Conclusions: uATBAD patients with ascending aortic area >12.1 cm2 or maximum ascending aortic diameter >40.8 mm are at high risk for development of subsequent arch and proximal progression and may require closer follow-up or earlier intervention. Ascending aortic size (diameter and area) is predictive of decreased intervention-free survival in patients with uATBAD. (J Vasc Surg 2018;-:1-10.) Keywords: Acute type B aortic dissection; Predictors; Uncomplicated

Aortic dissection is an uncommon but highly lethal event with an incidence of 2.9 to 3.5 per 100,000 person-years.1-4 Despite improvements in both medical and surgical therapies, overall mortality associated with acute dissection remains significant. Patients with

uncomplicated acute type B aortic dissection (uATBAD) have historically been treated medically, with strict heart rate and blood pressure control, also known as impulse control. Despite optimal medical therapy, 30% to 42% of patients who initially presented with uncomplicated

From the Department of Cardiothoracic and Vascular Surgerya and Depart-

Correspondence: Ali Azizzadeh, MD, FACS, Professor & Director, Division of

ment of Diagnostic and Interventional Imaging,b McGovern Medical

Vascular Surgery, Vice Chair, Department of Surgery, Associate Director, Heart

School at The University of Texas Health Science Center at Houston

Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Ste A3100, Los

(UTHealth) and Memorial Hermann Hospital, Houston; and the Division of Vascular Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles.c Author conflict of interest: A.A. and K.M.C.O. are consultants for W. L. Gore and Medtronic. A.L.E. is a consultant for W. L. Gore. Presented at the Thirty-second Annual Meeting of the Western Vascular Society, Blaine, Wash, September 23-26, 2017.

Angeles, CA (e-mail: [email protected]). 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 any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2018 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvs.2018.07.048

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acute (within 14 days of initial tear) type B aortic dissection are subsequently redefined as complicated, given hemodynamic instability, rupture, aortic expansion, retrograde dissection, or malperfusiondall of which can be deadly and are indications for surgical repair.5-7 In 1965, Wheat et al8 initially proposed medical management of uATBAD, with surgery reserved for those deemed to be a complicated dissection, given the high mortality with surgical intervention and favorable results with impulse control. Whereas contemporary evidence has demonstrated that earlier intervention may be indicated in certain cases of uATBAD, to date, no general consensus has been reached with respect to timing or definitive indications for endovascular treatment owing to the lack of prospective randomized data comparing immediate and delayed intervention in various clinical and anatomic constellations.9 In a meta-analysis by van Bogerijen et al,5 several predictors were identified among uATBAD patients at high risk of growth during follow-up, with nearly half the studies examined revealing a maximum aortic diameter $40 mm in the acute phase to be a predictor of aortic growth, whereas a diameter of <40 mm was a negative predictor.5,10-16 We previously published data demonstrating that maximum aortic diameter along the length of the aorta >44 mm is predictive of mortality and need for intervention.17 The substantial mortality rate in patients with ATBAD underscores the importance of early diagnosis and initiation of optimal medical therapy. In this study, we aimed to investigate the role of ascending aortic size, including ascending aortic diameter and cross-sectional area, to determine whether these parameters have any association with outcomes of patients with uATBAD.

METHODS Cohort. This study was approved by the local Institutional Review Board with a waiver of informed consent. All patients admitted between June 2000 and January 2015 with uATBAD and initially managed with optimal medical therapy were reviewed, and only those with initial contrast-enhanced computed tomography angiography (CTA) imaging on admission were included in the cohort. All images were loaded into advanced imaging software (TeraRecon, Foster City, Calif) to allow multiplanar reconstruction of the source imaging data. The multiplanar reconstruction allowed double orthogonal oblique measurements to be taken of the maximum ascending aortic diameter and maximum ascending aortic area (crosssectional area). All measurements were obtained by a specialized cardiovascular radiologist and were performed using the initial admission scan. Initial admission imaging was defined as the earliest contrast-enhanced computed tomography (CT) scan that demonstrated an ATBAD. Outcomes, including the need for intervention and mortality, were tracked over time. Follow-up methods

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ARTICLE HIGHLIGHTS d

d

d

Type of Research: Retrospective analysis of singlecenter cohort data Take Home Message: Computed tomography angiography imaging from 131 patients with acute uncomplicated type B aortic dissection demonstrated that an ascending aortic diameter >40.8 mm or ascending aortic area >12.1 cm2 on admission was associated with decreased intervention-free survival because of the need for subsequent open ascending aorta and aortic arch repairs. Recommendation: This study suggests that ascending aortic morphology at the time of an uncomplicated type B aortic dissection is predictive of subsequent ascending aorta and arch intervention.

included medical records, imaging, telephone interview, clinic visit, and Social Security Death Index. Our typical imaging follow-up consists of an admission and a predischarge or “graduation” CT scan during the initial hospitalization for all patients. These CT scans are then followed by repeated scans at 1 month, 6 months, 12 months, and yearly thereafter. Definitions. As noted in our previous work, acute aortic dissection was defined as presentation <2 weeks from initial onset of symptoms. Type B aortic dissection was defined as not involving the ascending aorta. Uncomplicated was defined as patients without clinical malperfusion or rupture who had successful optimal medical therapy. Optimal medical therapy included the use of anti-impulse therapy by way of beta blockade, calcium channel blockers, nitroglycerin, or nitroprusside with goal systolic blood pressure <120 mm Hg, heart rate <60 beats/min, and pain medications as needed for control of pain. All patients were admitted to the cardiovascular intensive care unit with placement of monitoring lines, including a central line, arterial line, and Foley catheter to accurately monitor urine output. Continuous reassessment of the patient’s blood pressure, pain control, and urine output was performed, and adjustments were made as needed. Those patients who failed to respond to medical management became classified as complicated type B aortic dissections, with percutaneous or surgical intervention undertaken for rupture, malperfusion, acute expansion (aortic growth of 5 mm at 6 months or 1 cm at 1 year), or refractory symptoms, including pain and poorly controlled hypertension. Only those with classic type B dissection were included in the analysis. Patients with isolated intramural hematoma and penetrating atherosclerotic ulcer were excluded. Mortality was reported in terms of all-cause mortality. Need for intervention was defined

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Table I. Patients’ demographics: 298 total patients with uncomplicated acute type B aortic dissection (uATBAD) who are split into those with admission computed tomography angiography (CTA) available for review and those with uATBAD with either noncontrast-enhanced computed tomography (CT) or no available scan for review Imaging

No. of patients

CTA

Noncontrast-enhanced CT or not available

131

167

P value

60.96 6 13.4

61.79 6 13.3

Diabetes mellitus

16.28

15.53

.86

History of stroke (cerebrovascular accident)

6.20

11.04

.15

Connective tissue disorder

4.65

3.09

.36

Syncope on admission

0.77

4.85

.08

History of renal dysfunction

4.69

9.94

.09

Pleural effusion on admission

26.92

21.82

.31

Age, years

.6

Categorical variables are presented as percentage. Continuous variables are presented as mean 6 standard deviation.

as need for future aortic intervention after initial optimal medical therapy for uATBAD and is reported in terms of intervention-free survival where deaths are reported as failures to account for death as a competing risk. Statistical analysis. Univariate data analyses were conducted using contingency table methods for shortterm categorical outcomes, and unpaired t-tests, Wilcoxon rank sum, or linear regression analyses were used for continuous variables, depending on the distribution of the data. Long-term survival data were analyzed by stratified Kaplan-Meier analysis. Multivariable analyses were conducted with logistic regression and multiple Cox regression analysis. For all stratified analyses, aortic measurements were divided into quartiles and were assessed in contingency tables for short-term outcomes and Kaplan-Meier plots for long-term outcomes. Logistic regression was used, when appropriate, to develop receiver operating characteristic curves to identify optimal cut points from continuous data. Ultimately, cut points are identified on the basis of the data and the literature, when possible, with the intent of developing the most generalizable rather than the best-fitting models. Model selection was performed using Spearman rank correlation variable screening and results from univariate analyses. Variables were included for multivariable model selection when they met reasonable scientific plausibility criteria (eg, were not associated by reverse causality, would have been unknowable before surgery for preoperative risk models) and were significant at a nominal a of .05 or thereabouts. We did not reach further to .10, or other more lax criteria, because of the potential for a inflation. Automated (stepwise) variable selection was followed by purposeful selection. Model terms were required to be significant at P < .05, although some models were constructed using all significant variables with specific prespecified

variables (eg, ascending diameter) forced in to assess adjusted effects. All computations were performed using SAS 9.4 software (SAS Institute, Cary, NC).

RESULTS During the 15-year study period from 2000 to 2015, there were 298 patients with uATBAD who were admitted to our cardiovascular intensive care unit, with 238 having available CT scans (CTA or noncontrastenhanced scans) and 131 having admission CTA imaging with adequate follow-up available for analysis. The cohort had an average age of 60.9 6 13.4 years, with 60% male and 53% white patients, and median followup time of 6.9 years. The baseline characteristics of the patients are represented in Table I, which is split into two groupsdthose who had CTA imaging on admission and thus underwent complete analysis; and all others in the group, which includes those with no admission imaging available for review at the time of analysis and those with only noncontrast-enhanced CT at the time of review. Overall, 23 patients who initially presented with uATBAD eventually required aortic intervention. Details and timing are listed in Table II. Mortality and intervention-free survival Ascending aortic area. On analysis of the cohort’s data, maximum ascending aortic area was split into quartiles of <7.9, 7.95 to 9.98, 9.99 to 12.1, and >12.1 cm2, but this failed to reach significance in terms of mortality (P ¼ .34). However, there was a significantly decreased intervention-free survival across the quartiles of maximum ascending aortic area as area increased (P ¼ .05; Fig 1). When ascending aortic area was analyzed, it was determined that when split into two groups based on maximum ascending aortic area >12.1 cm2 and #12.1 cm2, ascending aortic area >12.1 cm2 predicted lower intervention-free survival (P ¼ .005; Fig 2) with a sensitivity of 34% and a specificity of 81%. Ascending

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Table II. Timing and indication for aortic intervention after uncomplicated acute type B aortic dissection (uATBAD) Patient

Time from uATBAD diagnosis to aortic intervention, days

Description of aortic intervention

Indication for intervention

1

415

Repair of DTA dissection (outside hospital)

DTA aneurysm (performed at outside hospital)

2

39

DTA extent A repair

DTA aneurysm

3

358

DTA extent A repair

DTA aneurysm

4

134

DTA extent A repair

DTA aneurysm

5

89

TAAA extent I repair

Extent I TAAA

6

608

DTA extent C repair

DTA aneurysm

7

742

Acute type A IMH repair

Acute type A IMH

8

49

DTA extent C repair

DTA aneurysm

9

587

DTA extent C repair

DTA aneurysm

10

575

DTA extent C repair

DTA aneurysm

11

1414

DTA extent C repair

DTA aneurysm

12

3504

Acute type A dissection repair

Acute type A dissection

13

64

14

124

DTA extent C repair

DTA aneurysm

Ascending aorta and arch repair

Ascending aorta and arch aneurysm

15 16

1553

TAAA extent II repair

Extent II TAAA

421

TAAA extent I repair

17

1380

Extent I TAAA

Endovascular repair of TAAA (outside hospital)

TAAA (performed at outside hospital)

18

16

DTA extent A repair

DTA aneurysm

19

26

Acute type A dissection repair

Acute type A dissection

20

23

Acute type A dissection repair

Acute type A dissection

21 22 23

623 650; 1876 196

DTA extent C repair

DTA aneurysm

DTA extent A repair (initial) and acute type A dissection repair (subsequent)

DTA aneurysm (initial) and acute type A dissection (subsequent)

TAAA extent II repair

Extent II TAAA

DTA, Descending thoracic aorta; IMH, intramural hematoma; TAAA, thoracoabdominal aortic aneurysm.

aortic area, however, was not a predictor of mortality (P ¼ .08). Maximum ascending aortic area >12.1 cm2 was associated with subsequent arch or proximal progression necessitating open ascending aortic repair (P < .027; Fig 3) with a sensitivity of 66.7% and specificity of 78.4%. Ascending aortic area >12.1 cm2 represents the 75th percentile of maximum ascending aortic area in our cohort, and this value was reached empirically, noting that ascending aortic area of this size or larger significantly predicted decreased intervention-free survival. Ascending aortic diameter. Maximum diameter of the ascending aorta was measured in each patient on admission. After analysis of the measurements, it was determined that when split into two groups based on maximum ascending aortic diameter >40.8 mm and #40.8 mm, ascending aortic diameter >40.8 mm significantly predicted decreased intervention-free survival (P ¼ .01; Fig 4) with a sensitivity of 34.1% and specificity of 80%. However, this failed to predict mortality (P ¼ .12). Further separation of maximum ascending aortic diameter into quartiles of <33.6, 33.7 to 37.8, 37.9 to 40.8, and >40.8 mm failed to predict mortality (P ¼ .5) as well as

intervention-free survival (P ¼ .15). Maximum ascending aortic diameter >40.8 mm was associated with subsequent arch or proximal progression necessitating open ascending aortic repair (P < .033; Fig 5) with sensitivity of 66.7% and specificity of 77.6%. Maximum ascending aortic diameter >40.8 mm represents the 75th percentile of maximum ascending aortic diameter in our cohort and the value was reached empirically, noting that ascending aortic diameter of this size or larger significantly predicted decreased intervention-free survival. Adjusted analysis Multivariable analysis demonstrated that maximum ascending aortic diameter >40.8 mm is not a significant predictor of mortality (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.42-2.83; P ¼ .85) when controlling for other significant predictors of mortality, including maximum aortic diameter along the length of the aorta >44 mm (HR, 7.34; 95% CI, 2.3-23.41; P < .001), diabetes mellitus (HR, 6.4; 95% CI, 2.17-18.93; P < .001), age (HR, 1.06/y; 95% CI, 1.03-1.10; P < .001), history of stroke (HR, 5.03; 95% CI, 1.52-16.63; P ¼ .008), and syncope on admission

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Fig 1. Kaplan-Meier curve for intervention-free survival of 131 patients with uncomplicated acute type B aortic dissection (uATBAD): Maximum ascending aortic area by quartiles.

Fig 3. Need for proximal aortic replacement after uncomplicated acute type B aortic dissection (uATBAD) as predicted by maximum ascending aortic area: Five patients progressed to type A dissection and one patient experienced proximal aortic dilation necessitating ascending aortic replacement.

Fig 2. Kaplan-Meier curve for intervention-free survival of 131 patients with uncomplicated acute type B aortic dissection (uATBAD): Maximum ascending aortic area #12.1 cm2 vs >12.1 cm2.

Fig 4. Kaplan-Meier curve for intervention-free survival of 131 patients with uncomplicated acute type B aortic dissection (uATBAD): Maximum ascending aortic diameter #40.8 mm vs >40 mm.

(HR, 21.11; 95% CI, 2.3-193.84; P ¼ .007). However, multivariable analysis showed that ascending aortic diameter >40.8 mm (HR, 2.01; 95% CI, 1.03-3.95; P ¼ .04) on admission persists as a predictor of decreased intervention-free survival after controlling for known predictors of decreased intervention-free survival, including maximum aortic diameter along the length of the aorta >44 mm (HR, 3.142; 95% CI, 1.47-6.83; P < .004), syncope on admission (HR, 26.3; 95% CI, 2.81-246; P ¼ .004), and pleural effusion on admission (HR, 3.02; 95% CI, 1.58-5.77; P < .001). Multivariable analysis was also performed in regard to maximum ascending aortic area. It was determined that maximum ascending aortic area >12.1 cm2 is not a significant predictor of mortality (HR, 0.992; 95% CI, 0.38-2.61; P ¼ .99) when controlling for maximum aortic diameter along the length of the aorta >44 mm

(HR, 7.49; 95% CI, 2.34-23.92; P < .001), diabetes mellitus (HR, 6.34; 2.15-18.71; P < .001), age (HR, 1.064; 95% CI, 1.031.10; P < .001), history of stroke (HR, 5.07; 95% CI, 1.5316.75; P < .008), and syncope on admission (HR, 20.49; 95% CI, 2.26-185.97; P ¼ .007). However, multivariable analysis demonstrated that maximum ascending aortic area >12.1 cm2 (HR, 1.99; 95% CI, 1.02-3.87; P ¼ .04) persists as a predictor of decreased intervention-free survival after controlling for other statistically significant predictors of decreased intervention-free survival, including maximum aortic diameter along the length of the aorta >44 mm (HR, 3.22; 95% CI, 1.48-6.99; P < .004), pleural effusion on admission (HR, 2.67; 95% CI, 1.41-5.07; P < .003), and syncope on admission (HR, 28.5; 95% CI, 3.01-270; P < .004). Variance inflation factors were <1.05 for all multivariable model terms in the intervention-free survival models.

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Fig 5. Need for proximal aortic replacement after uncomplicated acute type B aortic dissection (uATBAD) as predicted by maximum ascending aortic diameter: Five patients progressed to type A dissection and one patient experienced proximal aortic dilation necessitating ascending aortic replacement.

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Fig 7. Kaplan-Meier curve for intervention-free survival of patients with uncomplicated acute type B aortic dissection (uATBAD): Cohort with computed tomography angiography (CTA) imaging vs those with noncontrastenhanced computed tomography (CT) or no available imaging for analysis.

admission imaging for analysis, we compared the baseline characteristics of the two groups, one group composed of those with admission CTA (131 patients) and the other representing the 167 patients with uATBAD (Table I), which demonstrated no significant differences. Kaplan-Meier analysis was then performed comparing these two groups (Fig 7), demonstrating no difference in intervention-free survival (P ¼ .19).

DISCUSSION

Fig 6. Kaplan-Meier curve for overall survival of 131 patients with uncomplicated acute type B aortic dissection (uATBAD): Maximum aortic diameter along the length of the aorta #44 mm vs >44 mm.

The thresholds for maximum ascending aortic area >12.1 cm2 and diameter >40.8 mm were arrived at empirically. Both of these measures represent the 75th percentile of size distribution in our cohort. We analyzed the measurements by quartiles of size, with the 75th percentile of size found to be most predictive, and we thought that this was more generalizable than drilling down to the millimeter with receiver operating characteristic curve analysis. Testing of patients with these measurements or greater demonstrated a significantly decreased intervention-free survival. As previously demonstrated by our group, maximum aortic diameter along the length of the aorta >44 mm persisted as a risk factor for mortality (P < .001; Fig 6) and decreased intervention-free survival (P < .004) with sensitivity of 22% but specificity of 93%. To ensure that selection bias had not altered our results, given that only 131 of 298 patients had adequate

Acute aortic dissection continues to be the most common aortic emergency, with an incidence ranging from 2.9 to 3.5 per 100,000 person-years.1-4 All patients with diagnosis of acute aortic dissection were admitted to our cardiovascular intensive care unit, with appropriate monitoring lines placed and medical management initiated with intravenous antihypertensive agents with the goal of lowering the heart rate and blood pressure for impulse control. The details of our aortic dissection protocol have been previously published.7 Medical therapy aimed at lowering blood pressure and heart rate has shown favorable shortterm survival over open surgical repair and remains the standard of care for uATBAD.7,16,18-20 The study period spans the year 2000 to the start of 2015, which is important, given the introduction during this period of thoracic endovascular aortic repair (TEVAR), which first received approval by the U.S. Food and Drug Administration in 2005. It was not until later in the 2000s that TEVAR was adopted as a treatment modality for patients with complicated dissection and high-risk uncomplicated presentation, including poorly controlled hypertension and pain. In the acute phase, TEVAR has been shown to abrogate impending rupture and to relieve dynamic malperfusion. Studies have demonstrated that TEVAR in complicated ATBAD has a low early mortality and an acceptable rate

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of neurologic complications, emphasizing the benefits of such therapy.21 The delayed benefit of TEVAR appears to be false lumen thrombosis, which mitigates the risk of aneurysmal dilation and subsequent rupture.22 The Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial showed aortic remodeling (defined as true lumen recovery and false lumen thrombosis) to occur in 91.3% of patients treated with TEVAR and in only 19.4% of patients with medical treatment alone (P < .001).23 Chest CTA was the imaging modality of choice in this study, given availability as well as sensitivity between 83% and 95% and specificity of 87% and 100% in the acute setting.24-26 With the assistance of a cardiovascular radiologist, we used three-dimensional reconstruction images for precise aortic measurements. Contrastenhanced CTA was the imaging modality employed in our study, with measurements derived only from the initial admission CT scan that demonstrated ATBAD. The maximal aortic diameter and area were measured at cross-sectional images perpendicular to the direction of blood flow in the ascending aorta, with all measurements made in a double orthogonal oblique manner with the aid of advanced imaging software allowing multiplanar reconstruction. The use of double orthogonal oblique measurements allows accurate measurements of the lumen, given that the measurements can be made perpendicular to the direction of flow, eliminating overestimation or underestimation of the lumen size.27 Multiple previous studies have looked at predictors of poor outcomes in uATBAD, including a study at our institution, noting decreased intervention-free survival and increased mortality in those patients presenting with maximum aortic diameter >44 mm along the length of the aorta.17 In this study, we specifically investigated the association between ascending aortic size, including maximum ascending aortic diameter and area, and outcomes in patients with uATBAD. Our data demonstrate that patients with maximum ascending aortic area >12.1 cm2 experienced decreased intervention-free survival (P ¼ .005), with maximum ascending aortic area >12.1 cm2 representing the 75th percentile of maximum ascending aortic areas in our cohort (Fig 2). On further stratification based on quartiles of ascending aortic area, we also noted that across the quartiles of increasing size, there was a decreased intervention-free survival (P ¼ .05; Fig 1). Multivariable analysis demonstrated decreased intervention-free survival for maximum ascending aortic diameter >12.1 cm2 after controlling for other statistically significant predictors of decreased intervention-free survival with an HR of 1.99 (95% CI, 1.02-3.87) and P ¼ .04. These data suggest that those patients who present with increased aortic area on admission may warrant closer follow-up or more frequent surveillance imaging as they represent an elevated-risk group, especially those in the largest (>12.1 cm2) quartile.

On examining maximum ascending aortic diameter, it was noted that those patients who presented with maximum ascending aortic diameter >40.8 mm on admission experienced decreased intervention-free survival (P ¼ .01). However, when further stratified into quartiles of diameter, there were no significant findings (P ¼ .15). Multivariable analysis demonstrated that ascending aortic diameter >40.8 mm remained predictive of decreased intervention-free survival when controlling for identified predictors of decreased intervention-free survival with HR of 2.01 (95% CI, 1.03-3.95) and P ¼ .04. Again, these data suggest that closer follow-up or more frequent surveillance imaging may be indicated in those patients with admission ascending aortic diameter >40.8 mm, given that these patients represent an elevated-risk group. It was noted that neither maximum ascending aortic area >12.1 cm2 (P ¼ .08) nor maximum ascending aortic diameter >40.8 mm (P ¼ .12) was predictive of mortality. This held true after statistical adjustment with P values of .99 and .85, respectively. The most profound conclusion from this study was the association noted with maximum ascending aortic area >12.1 cm2 (P < .027) and maximum ascending aortic diameter >40.8 mm (P < .033) on initial admission and proximal aortic or arch progression, with both found as significant predictors of need for future ascending aortic replacement. In total, there were six patients who subsequently underwent proximal aortic replacement, with the indication for five of these patients being type A dissection. That includes four classic type A dissections and one type A intramural hematoma; the remaining operation was performed for progressively enlarging ascending aortic measurements (Table III). The relationship between increasing aortic size as a risk factor for acute aortic dissection and rupture has been investigated in several previous studies. However, they did not focus on the association between ascending aortic size and outcomes of patients with uATBAD.28-31 International Registry of Acute Aortic Dissection data have been used to demonstrate that approximately 20% of ATBADs (including complicated and uncomplicated) occurs in patients without aortic enlargement.28 Booher et al32 previously investigated ascending aortic diameter as part of the International Registry of Acute Aortic Dissection, and they also observed that there is no increased risk in mortality when the maximum diameter of the ascending aorta in ATBAD is increased. However, the study of Booher et al neither stratified on the basis of uATBAD nor standardized to a single imaging modality. Instead, it used transesophageal echocardiography, CT, magnetic resonance imaging, or aortography and used the largest measurement if all were available while also not examining whether any association existed between mortality and ascending aortic area. In a study by Kato et al,11 the predominant predictor for aortic enlargement in the chronic phase

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Table III. Timing and indication for proximal aortic intervention after uncomplicated acute type B aortic dissection (uATBAD) Patient

Time from uATBAD diagnosis to aortic intervention, days

1

742

2

3504

3 4

Description of aortic intervention

Indication for intervention

Acute type A IMH repair

Acute type A IMH

Acute type A dissection repair

Acute type A dissection

124

Ascending aorta and arch repair

Ascending aorta and arch aneurysm

26

Acute type A dissection repair

Acute type A dissection

5

23

Acute type A dissection repair

Acute type A dissection

6

650; 1876

DTA extent A repair (initial) and acute type A dissection repair (subsequent)

DTA aneurysm (initial) and acute type A dissection (subsequent)

DTA, Descending thoracic aorta; IMH, intramural hematoma.

was found to be a maximum aortic diameter >40 mm during the acute phase. They showed that at 5 years, patients with an aortic diameter of <40 mm could be expected to be free from aortic enlargement, whereas this applied to only 35% of patients with an aortic diameter of >40 mm acutely. Durham et al33 at Massachusetts General Hospital reported an aortic diameter >3.5 cm at index presentation to be a significant risk factor for future aortic growth, citing a mean aortic growth rate of 12.3 mm/y for the total aortic diameter, 3.8 mm/y for the true lumen diameter, and 8.6 mm/y for the false lumen diameter. They concluded that a significant number of patients who are initially managed medically with uATBAD eventually require intervention, with a reported 6-year intervention-free survival of 41% in uATBAD. They further demonstrated that those patients with uATBAD who were initially medically managed but subsequently underwent intervention fared better in terms of mortality than those who remained medically managed during a 6-year period (P ¼ .018). The reported long-term survival rate with optimal medical therapy alone varies between 60% and 80% at 4 to 5 years and is around 40% to 45% at 10 years,1,19 with our most recent data demonstrating 5-year survival of 76.6% in uATBAD.34 Whereas TEVAR is not without complications, including aortic rupture, retrograde dissection, and stent graftrelated complications, such as endoleak,23,35,36 freedom from aorta-related death using TEVAR in the treatment of thoracic aneurysms has been reported between 94% and 97% at 5-year follow-up.37 The INSTEAD trial with extended follow-up (INSTEAD-XL) has demonstrated 5-year mortality to be significantly lower in patients treated with TEVAR than with optimal medical therapy alone (6.9% TEVAR vs 19.3% medical; P ¼ .04) in terms of aorta-related mortality in uATBAD, with the caveat that the INSTEAD-XL trial did not implement TEVAR in the acute setting. However, it must be noted that the INSTEAD-XL trial failed to demonstrate a significant decrease in mortality with TEVAR at 5 years (11.1% TEVAR vs 19.3% medical; P ¼ .13).38 Although there are no long-term data at this time, the initial results of the Acute Dissection Stent Grafting or Best Medical Treatment (ADSORB) trial indicated that uATBAD can be

safely treated with TEVAR, with notable thrombosis as well as reduction in false lumen size.39 With the available data as well as the data from this study, it appears that TEVAR may be indicated in certain high-risk patients with uATBAD. At this time, the uATBAD patients at highest riskd and thus the most likely to benefit from earlier treatment with TEVARdinclude those patients with maximum aortic diameter along the length on admission >44 mm, false lumen >22 mm, maximum ascending aortic diameter >40.8 mm, or maximum ascending aortic area >12.1 cm2.17 Limitations of this study include its retrospective nature and the lack of available admission CT imaging for a large portion of the cohort, given that the images were no longer available in the hospital’s picture archiving and communication system. Potential issues with interrater reliability with measurements of the aorta were controlled by using a single specialized cardiovascular radiologist to perform the measurements. Whereas its single-institution design may constitute a potential for bias, we believe that the single-institution design allows more complete data abstraction and analysis and, overall, is advantageous.

CONCLUSIONS The uATBAD patients presenting with concomitant ascending aortic area >12.1 cm2 or maximum ascending aortic diameter >40.8 mm on initial admission imaging are at elevated risk for development of subsequent arch or proximal progression (P < .03 and P ¼ .03, respectively) with need for open ascending aortic repair. Ascending aortic size (diameter and area) is predictive of decreased intervention-free survival (HR, 2.01 [95% CI, 1.03-3.95] and 1.99 [95% CI, 1.02-3.87], respectively, with P ¼ .04 for both) in patients with uATBADdeven after controlling for known predictors of decreased intervention-free survival. Patients with any of these elevated-risk characteristics on admission may benefit from closer follow-up or earlier intervention.

AUTHOR CONTRIBUTIONS Conception and design: HR, JA, KCO, AE, CM, HS, AA Analysis and interpretation: HR, KCO, AE, CM, HS, AA

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Data collection: HR, JB, JA, KCO, AE, HS, AA Writing the article: HR, AA Critical revision of the article: HR, JB, JA, KCO, AE, CM, HS, AA Final approval of the article: HR, JB, JA, KCO, AE, CM, HS, AA Statistical analysis: CM Obtained funding: Not applicable Overall responsibility: HR

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Submitted Oct 26, 2017; accepted Jul 14, 2018.