Thoracic Aorta Remodeling after TEVAR: Monitoring Morphological Parameters to Predict Unfavorable Evolution

: Monitoring Morphological Parameters to Predict Unfavorable


Introduction
Thoracic Endovascular Aortic Repair (TEVAR) has been shown to be a safe and effective treatment for different aortic pathologies, outstripping open surgery as the primary approach [1].The post TEVAR aortic remodeling is due to the natural aging process, disease progression, and endoprosthesis radial forces and it has been confirmed as critical in determining treatment durability [2].Other investigators have extensively described the importance of the aortic anatomy (angulation, diameter, tortuosity) and their relationship with endoleaks in different aortic pathologies, but these studies mainly considered a short follow-up period [3][4][5].Several reports describing heterogeneous pathologic processes indicate that endoleaks are associated with anatomic factors, such as the diameter of the residual aneurysm, the radius of the aortic curve, and the tortuosity of the aorta [2,6,7].But maximal diameter, maximal diameter evolutions over time as well as endoleak apparition remain the main parameters to unfavorable aortic remodeling after TEVAR.The insertion of the endoprosthesis in an aneurysm sac may promote adverse aortic remodeling because the stent graft is less compliant than the normal aortic tissue [8,9].Not all patients will experience the same evolution of thoracic aorta remodeling and risk of endoprosthesis failure after TEVAR.Assessing remodeling progression should enable clinicians to better predict which patients are at higher risk of aortic complications, allowing them to provide a better and earlier patient-specific treatment [10].
The aim of this study was, 1) to describe a framework of medical image analysis to quantify geometrical thoracic aorta changes during the first three years after TEVAR 2) To assess the value of several geometrical parameters to predict unfavorable aortic remodeling earlier than reference parameters (i.e., diameter and diameter progression).

Materials and Methods
The study was conducted in accordance with the Declaration of Helsinki and RGPD Law.This restrospective study follows the MR004 rules and local agreement was obtained # PADS23-17 on 6 October 2021.

Study Design and Patients Sample
A retrospective analysis was conducted of twenty-five patients who were treated with thoracic stent-graft at a single center for thoracic aortic aneurysm, with the following inclusion criterions: availability of a preoperative computed tomography angiography (CTA) (T0) and 3 postoperative CTA performed 6 to 12 months (T6), 24 months (T24) and 36 months (T36) after surgery and availability of all clinical information for a follow up covering at least 36 months after surgery.Only patient with atherosclerotic aneurysm were included.Patients with a missing CTA (T0, T6, T24 or T36) or lost of view for medical follow-up or aneurysm of a non-atherosclerotic origin were excluded.Favorable A group (FAG) was define by the association of 2 parameters: patient without significant aortic diameter increase (maximal aortic diameter increase <10mm / 3 years) and patients who did not require an aortic reintervention during follow-up.On the other hand, patient who required aortic reinterventions as additional treatment related to the thoracic aorta or any direct complication of the initial TEVAR procedure were included in an unfavorable B group (UBG).All the TEVAR procedures were performed using the following stents-graft: GORE Conformable TAG (W.L. Gore & Associates, Flagstaff, Arizona), Cook (Cook Medical, Bloomington, IN, USA) and Medtronic (ValiantTM or the Valiant CAPTIVIA generation).The diameter of stent-graft was oversized by 15% to 20% according to pre intervention CTA measurements.The mean of the three diameter measurements for each proximal and distal landing zone was subtracted from the nominal device diameter and then divided by the mean diameter of the landing zone to calculate the endoprosthesis oversizing.The proximal and distal anchoring zone was recorded according to Ishimaru's classification modified by Criado [6,7].Proximal and distal sealing zones of at least 20 mm along the aortic centre line was selected in normal thoracic aorta, defined by an aortic wall with no evidence of thrombus, calcification or excessive angulation with a diameter lower than 40mm.The overlap between 2 stent graft was ≥ 3 cm if second device was one or two sizes larger than the first device.The overlap was ≥ 5 cm if second device was the same size.Prophylactic lumbar drainage and revascularization of the supraaortic trunk vessels was discussed during Multidisciplinary Consultation Meetings (MCMs) before surgery and according to international guidelines and multidisciplinary expertise.

Image Acquisition and 3D Geometric Analysis
CTA (see Supplemental Appendix 1 for details) was performed on a multi-detector 64-row scanner (REVO EVO, General Electric Healthcare, Buc, France) after contrast media injection with standard parameters.All CTAs (T0, T6, T24, T36) were transferred on a workstation equiped with a vascular imaging software (Endosize; Therenva, Rennes, France).The first step of image analysis was the manual extraction of a three dimensional (3D) arterial Lumen Centerline (CL) starting by a manual designation of the proximal and distal ends of the thoracic aorta from sinotubular junction to celiac trunk allowing the automatic creation of a 3D aortic CL (Figure 1A).Spatial coordinates (x,y,z) of CL points were exported every mm.The aorta was divided into five anatomic zones, from zone 0 to zone 4 according to Ishimaru's classification modified by Criado [6,7,11].Points of the CL that crosses limits between two successive zones were defined as follows: P0 for the first point at the sinotubular junction, P1 between Z0 and Z1, P2 between Z1 and Z2, P3 between Z2 and Z3, P4 between Z3 and Z4, and P5 at the end of Z4 (Figure 1B).

Figure 1.
Image A illustrates the centerline created from the sinotubular junction to the coeliac trunk.Image B shows the points (P0 to P5) used to define the cross-sections of the aortic lumen and length of the successive zones (Z0 to Z4).Image C shows an example of measurements of angles (α3).Image D shows an example of tortuosity measurement (TI) from Z0 to Z2.

Definition of the Geometrical Parameters
Centerline was used to define aortic length, angle, and tortuosity in the 5 predefined zones (Figure 1B).
Lengths: L0, L1, L2, L3 and L4 were defined respectively as the length of Z0, Z1, Z2, Z3, and Z4 along the CL.The length Li_j corresponded to the length from the beginning of zone Zi to the end of zone Zj.The sum of all lengths (L0+L1+L2+L3+L4) defined the length of the thoracic aorta (L_ATot).The lengths of proximal and distal neck (Lpn and Ldn respectively), as well as the length of the entire endoprothesis (L_EP), were measured (Figure 1C).Aortic Angulation: α0, α1, α2, α3, and α4 were the angles between planes perpendicular to the CL at the points marking the start (Pi) and end (Pi+1) of each zone.The angle αi_j corresponded to the angle from the beginning of zone Zi to the end of zone Zj.Angles between start and end of the proximal and distal neck of the aneurysm (αpn, and αdn respectively), the angulation of the entire endoprothesis (α_EP), and overall aortic angulation of the whole thoracic aorta (α_ATot) were also assessed.(Figure 1C) Tortuosity Index: TIi reflected the tortuosity of a Zi zone, defined by dividing the length of the zone Li by the spatial straight distance di ( ) between the start point (Pi) and the end point (Pi+1) of Zi.The overall tortuosity of the aortic arch (TI0_2) (Figure 1D) and of the descending aorta (TI3_4) were considered for statistical analysis.The tortuosity index of the entire endoprosthesis (TI_EP) was also assessed.Finally, overall tortuosity of the aorta (TI_ATot) was evaluated by dividing L_ ATot by spatial straight distance between proximal and distal ends of the whole CL ( ).
Diameters: Maximal aortic diameter was assessed perpendicular to the CL and including aortic thrombus and aortic wall.There were automatically computed by the post-processing tool and corrected, if necessary, by the reader.D0, D1, D2, D3 and D4, were the maximal aortic diameters at P0, P1, P2, P3, P4, respectively.Diameters of proximal and distal necks of the aneurysm (Dpn and Dpn respectively), and maximal aneurysm diameter, Daneurysm, were also measured.

Statistical Analysis
Values are expressed in mean and range.Bayesian Gaussian logistic regression and linear parametric approaches were therefore chosen for their ability to treat small populations (see Supplemental Appendix 2 for implementation details and references).The first model (Bayesian logistic regression) is performed to evaluate the associations between unfavorable outcomes and geometrical explanatory variables at preoperative (T0) and postoperative stages (T6, T24, and T36).When an odd ratio (OR) is higher than 1, the risk of poor outcome increases whereas an OR < 1 is predictive of good outcome.The results are significative if the 95% confidence interval (CI 95% ) does not include 1 value.
The second model (Bayesian linear) is performed to compare the evolution of each morphological and geometrical parameter between pre and each postoperative time in FAG and UBG.Mean temporal evolution for each group is estimated and the difference between UBG mean temporal evolution value and FAG mean temporal evolution value is reported (β 1 values).The 95% confidence interval (CI 95% ) is calculated for the value of group variable.If the confidence interval does not include the null value, we conclude that there is a statistically significant difference in the temporal evolution between the groups.
To compare the means between group and temporal evolution of the means between UBG and FAG groups, a two-way analysis of variance (ANOVA) was used with a significance level of 0.05.Anova was performed using Prism (GraphPad, Boston, USA).

Patient Cohort
Twenty-five subjects met the inclusion criteria for this retrospective study.Demographic data of the patients are presented in Table 1.There was no major perioperative morbidity, and no postoperative mortality.The location of the distal landing zone was on Z4 for all patients.A debranching procedure was performed in 13 cases (52%), with 100% transpositions of the left subclavian artery, 46% debranching of the left carotid artery, and 62% transpositions of the brachiocephalic trunk.Seventeen patients were included in FAG.Eight patients required an aortic reintervention during follow-up due to endoleaks (Ia n=1; Ib n=2; Ia +Ib n=1; III n=2; Ib +III n=2) and were included in UBG.All surgical intervention were endovascular with the addition of at least one stent graft.The secondary procedures were performed for one patient after 12 months, for one patient after 24 months and for 6 patients after 36 months following elective TEVAR.
was higher in UBG and predictive of poor outcome at T24 and T36.The vast majority of the other parameter did not showed and significance or significance at only one time point which is difficult to interpret and probably need more data.

Table 2:
Assessment of risk of a patient switching to unfavorable group at T0 and at each post-operative follow-up.

a. Temporal evolution of geometrical parameters
Angle α3_4 increases by a mean value of 23 ° and length L3_4 increases by a mean value of 22mm in UBG, whereas in FAG, the evolution is negligible (-1 ° and 0.01mm respectively).This analysis showed that the temporal evolution of several parameters were able to predict unfavourable evolution earlier that diameters and consistently over follow-up.The decrease of α2 over time and on the opposite side the increase of α3_4 are predictive of bad evolution and showed that the unfavorable aortic remodelling is highly dependent of the anatomy of the thoracic aorta.Interestingly evolution of the aorta length over time showed consistent result with a decrease of L2 and the increase of L3_L4 were predictive of poor outcome.The tortuosity of the distal part of the aorta showed as well interesting and early information to predict unfavourable evolution.(Table 3 and Figure 3).

Discussion
The main findings of the present study are: 1) The described method to assess geometrical parameter is feasible but time consuming.
2) Several geometrical parameters showed the ability to discriminate 6 months after TEVAR patients that will show bad aortic outcomes.
Most clinical studies consider a few parameters at one fixed point in the post-operative follow-up [12,13]; a short postoperative period and/or patients suffering from a variety of pathologies [14][15][16].Temporal evolution of aortic length differs significantly between the two groups once a comparative analysis between T0 and T6 is performed.These results are consistent with those of Spinella et al. [17] who showed that the aortic length along the centerline between the aortic root and celiac artery increased when 1-month and 1-year follow-up CTs were compared.A recent study performed by Chen et al. [18] on the lengthening of the thoracic aorta in heterogeneous pathologies showed a progressive increase after TEVAR, with lengthening from the innominate artery to the celiac artery at a mean rate of 1.7mm per year.L_Atot also shows a significantly different temporal evolution in the two groups between T0 and T24 and between T0 and T36.Aortic elongation in aneurysmal patients has already been noted in previous studies [12,16].The present study, based on long-term regular yearly follow-up, found an increase in centerline length from the subclavian artery to the coeliac trunk, particularly in UBG evolution.This could be due to progressive and continuous elongation, even in patients who will not develop endoleak.We believe that the interaction of the endoprosthesis with the aortic wall, together with wall aging, modifies the structure of the media, leading to slow and progressive elongation.The present study showed that the tortuosity of the descending aorta was associated with poor outcome.This result was in line with previous study.Chen et al. [19] demonstrated that high tortuosity of the thoracic aorta is associated with higher rates of endoleaks and stroke, and lower survival in patients undergoing TEVAR for atherosclerotic aneurysm, through a follow-up lasting 29±26 months.Higher tortuosity of the aorta is likely to lead to a higher rate of endoleaks because a tortuous aorta provides a poor fit for stent grafts, leaving a space between the endoprosthesis and the aortic wall.Aneurysm diameter is predictive of poor outcome at T24 and T36 but not at T6. On the contrary, the lengths and angles of the aortic arch (Z2) and of the descending aorta (Z3_Z4) are found to change significantly in both groups between T0 and T6.This tends to show that the diameter seems to be the latest parameter to be impacted by post TEVAR remodeling.Moreover, concerning the lengths and angles of the aortic arch (Z2) and of the descending aorta (Z3_Z4), most of the significant differences in evolution found between T0 and T6 remain valid when analyzing evolution between T0 and T24 or between T0 and T36.This shows that evolution of these key parameters over time follows a consistent pattern.
Adaptation and interaction of the vessel with the endoprosthesis in the first months should be closely monitored.Regardless of the native morphology of the aorta, choosing a device whose design accommodates a complex geometry might be of prime importance.The main limitation of the study regards the use of the semimanual methods to identify the external wall of the aneurysm which could be affected by inter-operator errors.Furthermore, the presented method is time consuming.Although the number of enrolled patients is small for that purpose bayesian statistical studies have been used.Finally, there is an inhomogeneity of the proximal landing zone in our study that might have introduce heterogeneity in data analysis.

Figure 2 .
Figure 2. Example of centerline evolution on two different patients: one from the FAG (left graph) and one from the UBG (right graph).a. Geometrical Parameter at Each Time Points (Table2)

Table 3 :
Temporal evolution of parameters between T0 and each post-operative follow-up and statistical analysis.Citation: De Masi M, Guivier-Curien C, Boucekine M, Barral PA, et al. (2023) Thoracic Aorta Remodeling after TEVAR: Monitoring Morphological Parameters to Predict Unfavorable Evolution.J Surg 8: 1840 DOI: 10.29011/2575-9760.0018407 Volume 08; Issue 12 J Surg, an open access journal ISSN: 2575-9760Finally, evolution of Daneurysm over time is predictive of bad outcomes since T24 wile several other parameter explained above showed earlier significance.

Figure 3 .
Figure 3. Graphs plotting the difference between T0 and successive time points, for the 9 morphological parameters of interest.Blue lines are FAG evolution, red lines are UBG evolution.

Table 1 :
Clinical and procedure characteristics of the entire population (n =25).