Aortic Dissection in Patients With Genetically Mediated Aneurysms: Incidence and Predictors in the GenTAC Registry

Abstract

Background: Aortic dissection (AoD) is a serious complication of thoracic aortic aneurysm (TAA). Relative risk for AoD in relation to TAA etiology, incidence, and pattern after prophylactic TAA surgery are poorly understood.

Objectives: This study sought to determine the incidence, pattern, and relative risk for AoD among patients with genetically associated TAA.

Methods: The population included adult GenTAC participants without AoD at baseline. Standardized core laboratory tests classified TAA etiology and measured aortic size. Follow-up was performed for AoD.

Results: Bicuspid aortic valve (BAV) (39%) and Marfan syndrome (MFS) (22%) were the leading diagnoses in the studied GenTAC participants (n = 1,991). AoD occurred in 1.6% over 3.6 ± 2.0 years; 61% of AoD occurred in patients with MFS. Cumulative AoD incidence was 6-fold higher among patients with MFS (4.5%) versus others (0.7%; p < 0.001). MFS event rates were similarly elevated versus those in patients with BAV (0.3%; p < 0.001). AoD originated in the distal arch or descending aorta in 71%; 52% of affected patients, including 68% with MFS, had previously undergone aortic grafting. In patients with proximal aortic surgery, distal aortic size (descending thoracic, abdominal aorta) was larger among patients with AoD versus those without AoD (both p < 0.05), whereas the ascending aorta size was similar. Conversely, in patients without previous surgery, aortic root size was greater in patients with subsequent AoD (p < 0.05), whereas distal aortic segments were of similar size. MFS (odds ratio: 7.42; 95% confidence interval: 3.43 to 16.82; p < 0.001) and maximal aortic size (1.86 per cm; 95% confidence interval: 1.26 to 2.67; p = 0.001) were independently associated with AoD. Only 4 of 31 (13%) patients with AoD had pre-dissection images that fulfilled size criteria for prophylactic TAA surgery at a subsequent AoD site.

Conclusions: Among patients with genetically associated TAA, MFS augments risk for AoD even after TAA grafting. Although increased aortic size is a risk factor for subsequent AoD, events typically occur below established thresholds for prophylactic TAA repair.

Keywords: Marfan syndrome; aortic aneurysm; aortic dissection; bicuspid aortic valve.

Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Anatomic Locations of Aortic Segments

The locations of segments assessed for quantification of aortic size are shown. In each segment, aortic size was quantified based on maximal linear dimension perpendicular to the long axis of the vessel wall.

FIGURE 2. AoD Rates in Relation to Diagnostic Etiology of TAA

Among GenTAC participants, those with Marfan syndrome (MFS) (orange line) demonstrated increased incidence of aortic dissection (AoD) compared with those with bicuspid aortic valve (BAV) (gray line), and the remainder of the adult GenTAC registry (blue line) (both p < 0.001).

FIGURE 3. Pre- and Post-Dissection Imaging

(A) Pre-AoD (left): chest computed tomography (CT) performed 2 years before AoD in a 47-year-old woman with MFS displays a surgical graft in the ascending aorta (asterisk) and minimal dilation of the descending thoracic aorta (3.0 cm measured at line). Post-AoD (right), note dissection flap (arrow) originates in the descending thoracic aorta, distal to aortic graft. (B) Pre-AoD (left): chest CT performed 1 year before AoD in a 53-year-old woman with MFS demonstrates mild aortic arch dilation (3.1 cm measured at line). Post-AoD (right), note dissection flap originates in the distal aortic arch (arrow), extending throughout the descending thoracic aorta. Abbreviations as in Figure 2.

CENTRAL ILLUSTRATION. Aortic Dissection With Genetic Aortic Aneurysm

Longitudinal data from the multicenter GenTAC registry demonstrated that patients with genetically associated thoracic aortic aneurysm (TAA) remained at high risk for aortic dissection (AoD) in the current era, and that risk for AoD persisted even after prophylactic surgical repair of TAA. Although increased aortic size is a risk factor for subsequent AoD, events can occur below established thresholds for prophylactic TAA repair. Marfan syndrome (MFS) conferred increased risk for AoD even after controlling for maximal aortic size.