DILATATION AND ELONGATION OF THE DISTAL AORTA AFTER A

DILATATION AND ELONGATION OF THE DISTAL AORTA AFTER A PROXIMAL AORTIC REPLACEMENT FOR AORTIC ANEURYSM

Anne-Sofie De Crem Student number: 01406123

Marvin D’Hondt Student number: 01305225 Supervisor: Prof. Dr. Katrien François A dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of Master of Medicine in Medicine Academic year: 2017 – 2019

Deze pagina is niet beschikbaar omdat ze persoonsgegevens bevat.Universiteitsbibliotheek Gent, 2021.

This page is not available because it contains personal information.Ghent University, Library, 2021.

Deze pagina is niet beschikbaar omdat ze persoonsgegevens bevat.Universiteitsbibliotheek Gent, 2021.

This page is not available because it contains personal information.Ghent University, Library, 2021.

Dilatation and elongation of the distal aorta after a proximal aortic replacement for aortic aneurysm

Anne-Sofie De Crem & Marvin D’Hondt

Prologue This work is the Master’s thesis of Marvin D’Hondt and Anne-Sofie De Crem, in partial fulfilment

of the requirements for the degree of Master of Medicine at the University of Ghent. From all

the systems of the human body, we are both most intrigued by the heart which is not only the

motor of the body but also the powerful symbol of what drives people to live. In reality, the

heart and its vessels are the vital parts of the body that keep it alive physically and mentally.

A note of gratitude to Prof. Dr. Katrien François of the department of cardiovascular surgery

for the opportunity, her endless support and help and constructive annotations. We would also

like to thank Dr. Daniel Devos of the department of radiology for his passionate explaining on

the ins and outs of cardiothoracic radiology and it’s techniques, and the patience required to

make the scans ready for research. Furthermore, a note of appreciation to the workers at the

secretary of the cardiovascular surgery department for their welcome, administrative help, and

use of their facilities. To all, a great recognition for their accessibility and determination to steer

this work in the right direction.

There are no words to say how much appreciation we have for their believe in this work,

professional help and guidance.



Abbreviations

AA Aortic Aneurysm IQR Interquartile Range

AAA Abdominal Aortic Aneurysm KWT Kruskal-Wallis Test

AR Aortic Regurgitation IF Impact factor

ASA Aortic Surface Area L Length Segment

ASI Aortic Size Index LDS Loeys-Dietz Syndrome

AVR Aortic Valve Replacement LM Landmark

BAV Bicuspid Aortic Valve LSA Left Subclavian Artery

BCT Brachiocephalic Trunk MRI Magnetic Resonance Imaging

BP Blood Pressure MWUT Mann-Whitney U Test

BSA Body Surface Area PAA Proximal Aortic Aneurysm

CI Confidence Interval PACS Picture Archiving And Communication System

COPD Chronic Obstructive Pulmonary Disease

STJ Sinotubular Junction

CoZo Collaboratief Zorgplatform (Collaborative care platform)

TAA Thoracic Aortic Aneurysm

CT Computed Tomography TAAD Thoracic aortic aneurysms and dissections

CTD Connective Tissue Disease TAD Type A dissection

D/d Diameter (maximal/perpendicular) TBD Type B dissection

EPD Electronic Patient File (Dossier) TEVAR Thoracic Endovascular Aortic Repair

HCT Helical CT TTE Transthoracic Echocardiography

HDL-C High Density Lipoprotein – Cholesterol UHG University Hospital Ghent

IF Impact Factor SPSS Statistical Package for the Social Science

Dilatation and elongation of the distal aorta after a proximal aortic replacement for aortic aneurysm Anne-Sofie De Crem & Marvin D’Hondt

TABLE OF CONTENTS 0. ABSTRACT ____________________________________________________________ 1

1. INTRODUCTION _________________________________________________________ 3 1.1 RELEVANCE OF THE STUDY _________________________________________________________ 3

1.2 THE AORTA _____________________________________________________________________ 5

1.2.1 A brief summary of the anatomy ______________________________________________ 5 1.2.2 The size of the distal aorta ___________________________________________________ 5

1.2.2.1 Aortic diameters ______________________________________________________ 5 1.2.2.1.1 The physiological aorta ________________________________________________ 5

1.2.2.1.1.1 Dimensions ____________________________________________________ 6 1.2.2.1.1.2 Relation to gender, age and BSA ___________________________________ 6

1.2.2.1.2 The pathological aorta ________________________________________________ 8 1.2.2.1.2.1 Dimensions ____________________________________________________ 8 1.2.2.1.2.2 Pathological Influences __________________________________________ 10

1.2.2.2 Aortic length ________________________________________________________ 12 1.2.2.2.1 The physiological aorta _____________________________________________ 12

1.2.2.2.1.1 Dimensions ___________________________________________________ 12 1.2.2.2.1.2 Relation to gender, age and BSA __________________________________ 12

1.2.2.2.2 Pathological aorta __________________________________________________ 13 1.2.2.2.2.1 Dimensions ___________________________________________________ 13 1.2.2.2.2.2 Pathological influences __________________________________________ 13

1.2.2.3 Common evolution of diameter and length _________________________________ 14 1.2.3 The relation between the proximal and distal aorta ______________________________ 14

1.3 PROXIMAL REPAIR OF AN AORTIC ANEURYSM ___________________________________________ 14

1.3.1 Procedures for proximal aortic aneurysm _____________________________________ 15 1.3.1.1 David Procedure _____________________________________________________ 15 1.3.1.2 Bentall procedure ____________________________________________________ 15 1.3.1.3 Aortic valve replacement with separate tube _______________________________ 15

1.4 DISTAL FOLLOW-UP AFTER PROXIMAL REPAIR __________________________________________ 16

1.4.1 When and How ___________________________________________________________ 16 1.4.2 Imaging of the distal aorta __________________________________________________ 17

1.4.1.1 Measuring error between CT and MRI ____________________________________ 17 1.4.1.2 Measuring technique _________________________________________________ 18

1.4.1.2.1 Aortic landmarks and segments _______________________________________ 18 1.4.1.2.2 Measuring technique regarding the diameter _____________________________ 19 1.4.1.2.3 Measuring technique regarding the length _______________________________ 20

1.5 LITERTURE FINDINGS CONCERNING THE DISTAL AORTA AFTER PROXIMAL REPAIR _________________ 20

1.5.1 Reinterventions and indications _____________________________________________ 20 1.5.1.1 Marfan studies ______________________________________________________ 21 1.5.1.2 Dissection studies ____________________________________________________ 21

Dilatation and elongation of the distal aorta after a proximal aortic replacement for aortic aneurysm Anne-Sofie De Crem & Marvin D’Hondt

1.5.2 Influence of risk factors __________________________________________________ 22 1.5.3 Conclusion _____________________________________________________________ 22

2. METHOD ______________________________________________________________ 23 2.1 AIM AND PURPOSE OF THE STUDY ___________________________________________________ 23

2.2 DESIGN ______________________________________________________________________ 24

2.3 DATA SELECTION AND COLLECTION __________________________________________________ 25

2.3.1 Literature study: search strategy ____________________________________________ 25 2.3.2 Experimental study ______________________________________________________ 26

2.3.2.1 Patient selection _____________________________________________________ 26 2.3.2.2 Data collection ______________________________________________________ 27

2.4 VARIABLES AND TECHNIQUE _______________________________________________________ 28

2.4.1 Variables ______________________________________________________________ 28 2.4.2 Measuring technique ____________________________________________________ 30

2.4.2.1 Instruments _________________________________________________________ 30 2.4.2.2 Method ____________________________________________________________ 30 2.4.2.3 Frequency __________________________________________________________ 33 2.4.2.4 Standardization ______________________________________________________ 33 2.4.2.5 Validation __________________________________________________________ 33

2.5 STATISTICAL ANALYSIS ___________________________________________________________ 34

3. RESULTS _____________________________________________________________ 35 3.1 AORTIC DIMENSIONS AND INFLUENCES ________________________________________________ 35 3.2 TIME AND AORTIC GROWTH ________________________________________________________ 39 3.3 ELONGATION AND DILATATION OF THE AORTA __________________________________________ 40

4. DISCUSSION __________________________________________________________ 40 4.1 DOES THE DISTAL AORTA CHANGE AND WHAT ARE THE POSSIBLE CAUSES __________________ 40

4.1.1 Is there a significant difference between the preoperative and postoperative aorta in diameter and length at every landmark ______________________________________ 40

4.1.2 Is the ASA useful as parameter for aortic health assessment ___________________ 41 4.1.3 Do risk factors or patient characteristics influence the aorta ___________________ 41 4.1.4 Explanation of negative aortic evolutions ___________________________________ 44

4.2 SHOULD WE CONSIDER TIME AS A FACTOR _________________________________________ 44

4.3 DO ELONGATION AND DILATATION GO HAND IN HAND __________________________________ 45

5. STUDY LIMITATIONS ___________________________________________________ 46

6. CONCLUSION ___________________________________________________________ 47

REFERENCES _____________________________________________________________ 48

APPENDICES



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0. Abstract Objectives: Tis study aims to define the distal aortic changes after a proximal aortic aneurysm repair and to identify the corresponding higher risk population that needs closer follow-up. Furthermore, it aims to evaluate the influence of time on the aorta and to define the aortic length, aortic surface area and diameter as useful parameters to assess distal aortic elongation and dilatation. Finally, the purpose is to combine this into recommendations to optimize risk stratification and evaluation (e.g. treatment and follow-up) of these patients. Methods: The aorta was measured with specific aortic parameters (diameter, aortic surface area and length) at predefined aortic landmarks (LM) and segments (L) in perpendicular slices to the centerline on CT or MRI imaging. Each aorta (patient, n=30) was retrospectively compared with itself by measuring the aortic parameters on a well-defined preoperative and postoperative scan and conclusions were drawn from the differences between them. Statistical analysis was performed between subgroups of patients to assess these differences and the influence of time, patient characteristics (age, BSA and gender) and risk factors (hypertension, dyslipidemia, Marfan, connective tissue disease and statins) on the distal aorta. Results: DIMENSIONS. A significant dilatation of the complete distal aorta (except for the proximal aortic arch) was found, with a mean diameter increase of 1.033 mm (CI:0.24-1.83, p=0.012) and 1.57 mm (CI:0.42-2.71, p=0.009). The same landmarks were found to be significantly (p<0.05) dilated when calculating the aortic surface area. A significant elongation of the aortic arch length segment (p=0.026) was found and the thoracoabdominal aorta length segment (p=0.012) was elongated with a mean of 9.28 mm (CI:2.21-16.36). RISK FACTORS. The most significant (p<0.05) correlation between the age of the patients and the absolute diameter was found at the proximal aortic arch (r=0.716), the distal descending aorta (r=0.803) and proximal abdominal aorta (r=0.632). For absolute aortic lengths, age was mainly correlated to the descending aorta (r=0.620) and combined thoracoabdominal aorta (r=0.512). Marfan patients showed a significant (P<0.05) median diameter increase at the mid-aortic arch (1 mm), the distal descending aorta (4 mm) and the proximal abdominal aorta (1 mm). The presence of connective tissue diseases resulted in a significant (P<0.05) median diameter increase at the mid-aortic arch (2 mm) and the distal descending aorta (2.5 mm). Patients that underwent the David procedure had a significantly (p = 0.033) larger median dilatation (1 mm) at the proximal abdominal aorta comparing to those with a Bentall procedure. Also, patients without statins treatment had a significantly (p<0.05) larger median dilatation at the mid-aortic arch (1.5 mm), the mid-descending aorta (2 mm) and the distal descending aorta (2 mm). Also, Normotensive patients had a significantly (p<0.05) larger median dilatation at the mid-aortic arch (2.5 mm), the proximal descending aorta (2.25 mm) and the mid-descending aorta (2 mm).



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TIME. Time was only significantly (p<0.05) correlated to the elongation of the combined descending and proximal abdominal aorta length segment (r=0.584) and of the combined thoracoabdominal length segment (r=0.445), that had a median increase of 1.58 mm/year. The median aortic surface area had a yearly significant (p<0.05) increase at the mid-aortic arch (13.37mm²/year), at the mid-descending aorta (7.47mm²/year), at the distal descending aorta (8.57 mm²/year) and at the proximal abdominal aorta (8.13 mm²/year). ELONGATION AND DILATATION. A weak common evolution of the dilatation and elongation of the aorta was demonstrated between the elongation in the descending (r=0.420) or combined thoracoabdominal (r=0.379) aorta and the dilatation at the mid-descending aorta. The same results were found when correlating elongation to the corresponding evolution in ASA (respectively r=0.439 and r=0.364). Conclusions: Patients that underwent surgery for a proximal aortic aneurysm (without dissection) should undergo follow-up with standardized distal aortic imaging, since the distal aorta knows a certain dilatation and elongation after a proximal aortic repair. The elongation should not be used to replace the dilatation as an assessor of aneurysm risk, but as an additional tool if new criteria are defined. The ASA parameter however, could be used as an alternative due to its similarity in results. Special attention is advised for the age and gender of the patient and the presence of Marfan disease or other connective tissue diseases. Finally, statins should be considered as drugs with a protective effect on the aortic size. The predictive value (morbidity and mortality) and potential inclusion of the ASA and length parameters in risk or diagnostic scores, should be further analyzed in future studies. Longer studies with larger study populations are required to analyze the influence of risk factors or change in distal aortic dimensions on the morbidity and mortality.

Samenvatting Bij patiënten (n=30) die reeds een vervanging van de proximale aorta voor een aneurysma ondergingen, werden de distale veranderingen in de aorta nagegaan op CT of MR. Er werd vervolgens een antwoord geformuleerd op volgende onderzoeksvragen:

1. Is er distaal een verandering in de diameter, lengte en oppervlakte te zien? Kan de lengte en/of oppervlakte als een nuttig alternatief voor de opvolging beschouwd worden?

2. Welke risicofactoren (roken, hypertensie, dyslipidemie, bindweefselziekten en statines) en karakteristieken (leeftijd, geslacht en BSA) van de patiënt spelen een rol bij de distale veranderingen in de aorta?

3. Hoe evolueert de aorta in de tijd? 4. Volgt de elongatie eenzelfde trend als de dilatatie van de aorta? Is lengte bijgevolg een nuttige

bijkomende parameter voor opvolging, op dezelfde manier als de diameter dat reeds was? Deze resultaten werden gebundeld in een aantal aanbevelingen in verband met de risicostratificatie en aorta evaluatie (behandelingscriteria en opvolging) van deze patiënten.



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1. INTRODUCTION

1.1 Relevance of the study The main purpose of this study was to assess the possible changes in diameter and length of the

distal aorta, after a proximal aortic repair for aneurysm.

Aortic aneurysms (AA) are the second most frequent aortic disease after atherosclerosis [1]. AA

are defined as an abnormal swelling or dilatation of the aorta greater than 50% of the normal

diameter or as greater than a specific diameter, depending on the aortic segment [2]. They are

caused by the pressure the blood exerts on the weakened middle layer or tunica media of the

aortic wall. This weakening of the aortic wall i.e. loss of smooth muscle cells and elastic fibers,

can be engendered by atherosclerosis, hypertension, vasculitis, infection, smoking, trauma,

COPD, genetic diseases (eg. Marfan syndrome) and congenital heart diseases like a BAV [2,3].

In 1989, a study in England and Wales reported an incidence of thoracic aortic aneurysms (TAA)

of 10.4 per 100.000 person-years when standardized for age and gender. More recently, a

Swedish study published a combined incidence of TAA and thoracic aortic dissection (TAD) of

9.1 per 100.000/year for women and 16.3 per 100.000/year for men [4]. In general, an increase

in TAA and TAD was seen in 52% of the men and 28% of the women over 15 years, the biggest

contributing factors being the ageing of the general population and improvement of diagnostic

tools [4,5]. Abdominal aortic aneurysm (AAA) are also not uncommon with a reported prevalence

of 4.0-8.9% in men and 0.7-2.2% in women in Europe, depending on age, gender and

geographical location [6].

The greatest risk is the rupture of an aneurysm, which occurs in 5.6-17.5 per 100.000 person-

years in Western countries with an extremely high mortality rate of 80-90%. This high mortality

rate is due to the fact that patients often do not make it in time for an emergency operation, and

if they do, the operative mortality rate is still of 32-80% [6]. Thus stating the importance of early

detection by imaging and if needed, elective surgery before rupture.



4

The only well studied parameter for (re)intervention or diagnosis of an aneurysm, is the diameter

of the aorta. The length of the aorta and the aortic surface area (ASA) are less studied and not

yet included in any guidelines. Also, very little is known or proven about the distal aortic changes

after a proximal aneurysm repair and with this about the connection between proximal and distal

aortic pathology.

This lack of knowledge resulted in this study, where distal aortic measurements of preoperative

and postoperative scans were analyzed and compared to research the usefulness of the existing

and new parameters of aortic size, the aortic growth and the influences of physiological and

pathological factors on the aorta.



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1.2 The aorta

1.2.1 A brief summary of the anatomy The aorta consists of 5 segments (Fig. 1) [1,3]:

1. Aortic root: I. Aortic valve annulus

II. Aortic valve cusps

III. Sinuses of Valsalva

2. Ascending aorta: I. Starts at the sinotubular junction (STJ)

II. Ends at the root of the brachiocephalic

trunk (BCT)

3. Aortic arch I. Starts at the root of the BCT (start distal

aorta)

II. Ends at the left subclavian artery (LSA)

4. Descending aorta: I. Starts at the LSA

II. Ends at the diaphragm

5. Abdominal aorta The abdominal aorta runs from the diaphragm to the bifurcation into the iliac

arteries (end distal aorta). The renal arteries divide the abdominal aorta into the

suprarenal aorta and the infrarenal aorta.

1.2.2 The size of the distal aorta

1.2.2.1 Aortic diameters 1.2.2.1.1 The physiological aorta American and European guidelines depict that average aortic diameters should be reported by

gender, BSA, age, imaging modality and location, as these are the most relevant to the changing

aorta and clinical practices [1,3]. In addition, the measuring method should also be mentioned

[3,7,8].



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1.2.2.1.1.1 Dimensions The aortic diameters of healthy adults do not usually exceed 40 mm [1,9]. The mean diameter for

the descending thoracic aorta is 24 mm (+/- 3 mm) with a 30 mm upper limit [3,10]. In general,

the abdominal aorta is known to have a maximum of 29 mm measured with CT, irrespective of

age, gender or BSA [9]. Rogers et al. and Mensel et al. described average diameters at certain

landmarks, respectively with CT and MRI in 2.343 and 1.759 healthy participants (table 1) [11,12].

TABLE 1. The average diameters in men and women, using CT and MRI [11,12].

Men Women

CT (mm) MRI (mm) CT (mm) MRI (mm)

Ascending thoracic aorta 34.1 (+-3.9) 34.9 31.9 (+-3.5) 32.0

Aortic arch / 29.3 / 27.3

Descending thoracic aorta 25.8 (+-3.0) 26.3 23.1 (+-2.6) 23.4

Subphrenic aorta / 24.6 / 22.2

Suprarenal aorta / 23.4 / 20.7

Infrarenal abdominal aorta 19.3 (+-2.9) 19.7 16.7 (+-1.8) 17.5

Lower abdominal aorta 18.7 (+-2.7) / 16.0 (+-1.7) /

1.2.2.1.1.2 Relation to gender, age and BSA

1. Gender

Men typically have larger aortas than women, although this difference tends to fade away with

rising age and when correlating age to BSA. [1-3,9-11].

2. Age

The ageing aorta indicates the presence of a normal growth rate of the aorta with rising age [1-

3,8-11]. Aronberg et al. proposed a simplified model using CT, where 1 mm should be added to

the normal aortic size for each decade of life, whereas Erbel et al. proposed an expansion of 0.9

mm for men and 0.7 mm for women for each decade of life [1,13].



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3. BSA

Although guidelines and studies refer to BSA as a substantial factor contributing to the aortic

diameter [1,3,10-12], there are still doubts about the impact of BSA on aortic sizes. For example,

Krüger et al. found BSA to be partially insubstantial to the aortic size [8].

Rogers et al. from the Framingham Heart Study reported a more extensive study on the aortas’

mean diameters in relation to age (years), BSA and gender (male 0, female 1), using CT-modality

on 2.343 participants (table 2). Formulas (regressions) were defined, predicting the aortic

diameter [12]:

- 14.8 + 0.16(age) - 1.04(gender) + 5.34(BSA) = diameter ascending ao (mm)

- 8.86 + 0.16(age) - 1.79(gender) + 4.25(BSA) = diameter descending thoracic ao (mm)

- 8.60 + 0.10(age) - 2.03(gender) + 2.64(BSA) = diameter infrarenal abdominal ao (mm)

- 8.71 + 0.08(age) - 2.11(gender) + 2.78(BSA) = diameter lower abdominal ao (mm)

TABLE 2. Mean increase in diameter in relation to age, BSA and gender, using CT [12].

Age* BSA**

Men Women Men Women

Ascending aorta 0.20 0.16 5.8 4.14

Descending thoracic aorta 0.19 0.16 4.15 3.61

Infrarenal abdominal aorta 0.13 0.09 2.92 2.38

Lower abdominal aorta 0.12 0.07 2.90 3.11

* Increase in mean aortic diameter (mm) for every 1 year increase ** Increase in mean aortic diameter (mm) for every 0.1 m2 increase

Mensel et al. conducted a similar study using MRI-modality on 1.759 healthy participants [11].

Their findings concerning the BSA-adjusted diameters i.e. Aortic Size Index (ASI) were

summarized in the table below (table 3).



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TABLE 3. Median ASI* in men and women in relation to age, using MRI [11].

Women (cm/m²) Men (cm/m²)

Thoracic Ascending 1.230 + 0.011(age) 1.170 + 0.010(age)

Arch 1.209 + 0.006(age) 1.073 + 0.007(age)

Descending 0.852 + 0.009(age) 0.831 + 0.009(age)

Abdominal Subphrenic 0.797 + 0.009(age) 0.704 + 0.010(age)

Suprarenal 0.837 + 0.006(age) 0.766 + 0.007(age)

Infrarenal 0.746 + 0.005(age) 0.708 + 0.005(age)

*ASI= median aortic diameter (cm)/BSA(m2)

1.2.2.1.2 The pathological aorta

1.2.2.1.2.1 Dimensions 1. Thoracic aorta The pathological or aneurysmatic aorta is defined as an abnormal dilatation of the aorta with more

than 50% of the normal diameter or as greater than the maximal normal diameter [2]. The mean

growth rate for all thoracic aortic aneurysms is approximately 1 mm/y and that growth rate

increases with increasing aneurysm diameter. Growth rates also tend to be faster for aneurysms

involving the descending (3 mm/year) versus the ascending aorta (1 mm/year), in patients with

Marfan syndrome versus those without, and in patients with bicuspid versus tricuspid aortic valves

[1,3].

Surgery for a thoracic aortic aneurysm should be considered when the risk of rupture is greater

than the risk of surgical complications [1]. The risk of rupture increases rapidly when the

ascending aorta is 60 mm or more and the descending aorta is 70 mm or more [1]. Elective open

surgery or TEVAR (Thoracic Endovascular Aneurysm Repair) at specific aortic size thresholds is

recommended in the guidelines to prevent rupture (table 4) [1-3].



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TABLE 4. Aortic size thresholds for elective repair of the thoracic aorta [1-3].

Diameter Indications for elective surgery

>60 mm All asymptomatic patients and in the descending thoracic aorta, open surgery is recommended when TEVAR is not possible.

≥55 mm All asymptomatic patients with ascending and arch aneurysms, regardless of etiology [2] or with a growth rate of more than 5 mm/y [3]. In the descending aorta, TEVAR is possible [2].

≥50 mm Consider surgery for asymptomatic patients with the presence of genetically mediated disorders (Marfan, Turner, …), a growth rate of 3mm/year, a BAV with risk factors or other risk factors for dissection [2,3]. Also consider in case of concomitant repair of an adjacent aneurysm of the aorta.

≥45 mm Asymptomatic patients with concomitant aortic valve replacement or Marfan with risk factors, in the ascending aorta.

Any size Symptomatic patients, suggestive for expansion of an AA [3].

Further specific recommendations have been made for patients with risk factors, genetic or

congenital diseases and are to be found in full in the European and American guidelines [1-3].

Concerning the ASI, European guidelines recommend usage but do not specify specific cut-off

values [1]. Davies et al. reported that an increasing aortic size index was a significant predictor of

increasing rates of rupture, dissection or death in the thoracic and thoracoabdominal aorta.

Patients were stratified in 3 risk groups of rupture based on ASI (table 5) [14].

TABLE 5. Risk groups with respective ASI and incidence of rupture per year [14].

Risk ASI Incidence

Low <2.75 cm/m2 4%

Moderate 2.75-4.24 cm/m2 8%

High 4.25 cm/m2 20%

2. Abdominal aorta Pathological sizes for the abdominal aorta are defined as a diameter of ≥30 mm or a 50% increase

in diameter in comparison with the normal size [1,9]. A large and life-threatening AAA is preceded

by a long period of subclinical growth in diameter of the aneurysm (1-6 mm/year) that depends

on genetic and environmental factors (e.g. continued smoking increases the growth the most) [1].

Follow-up and indications for repair in patients with pre-AAA (25-29 mm), small AAA (30-55 mm)

and great AAA (>55 mm) are represented in table 6 [1].



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TABLE 6. Aortic size thresholds for follow-up and repair of AAA [1].

Size Follow-up

25-29 mm Every 4 years surveillance is recommended



>45 mm Every year surveillance is recommended

>55 mm Aneurysm repair

Any Aneurysm repair if growth rate is >10mm/year

1.2.2.1.2.2 Pathological Influences

1. Risk factors

Mainly the traditional atherosclerotic risk factors are known to influence the aortic diameter. The

influential risk factors on aneurysm incidence are stated in table 7 [1-3,9,10,15].

TABLE 7. Risk factors with an influence on the aortic diameters [1-3,9,10,15].

Risk factor Influence

Smoking It is the most important risk factor (OR=13.72, CI: 6.12-30.78) if comparing current smokers (≥20/d) with never-smokers. It is positively correlated with the aortic diameter in the descending thoracic aorta and the abdominal aorta (e.g. infrarenal abdominal aorta: 0.27 and 0.3 mm/year increase resp. for men and women)* [10,11,12.].

Hypertension It is positively correlated directly with the thoracic aortic dimensions, (OR= 1.54, CI:1.03-2.30) [10,15]. Mensel et al. and Rogers et al. reported a positive association of diastolic blood pressure, but also a negative association of systolic blood pressure with the descending thoracic aortic diameters [11,12]. Rogers et al. reported an increase of the mean ascending aortic diameter with 0.08mm for men, and of the descending thoracic aorta with 0.03mm [12].

Dyslipidemia Aorta diameters are positively correlated with hypercholesterolemia (OR=2.11 CI:1.23-3.64, comparing serum total cholesterol ≥7.55 mmol/L with <5.85 mmol/L) and low HDL-cholesterol (OR=3.25 CI: 1.68-6.27, comparing <1.25 mmol/L with ≥1.83 mmol/L) [15], but with a weaker risk of directly affecting the diameter. Contradictorily, Rogers et al. reported no association with the aortic diameter [12,15].

Atherosclerosis Positively correlated



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Already existing enlarged aorta

Positively correlated (with more effect if concomitant smoking), confirming the presence of tandem lesions (27%) [1].

Familial history of aneurysm

Positively correlated

Medication Positively correlated e.g. statins (OR=3.77 CI: 1.45-9.81)* [15].

Diabetes Positively correlated, only with the ascending aorta diameter [10].

*Examples are for AAA.

2. Genetic and congenital diseases An AA is often related to genetic and congenital diseases. It is therefore very important to notify

the higher risk and repercussions for the aorta of these diseases.

Turner Syndrome A sex-chromosomal disorder (45,X) in which a female is partly or completely missing an X

chromosome resulting in heart defects, diabetes and low thyroid hormone. An aortic dilatation

was observed in 33% of Turner patients [1,2].

Marfan Syndrome An autosomal dominant genetic disorder of the connective tissue that results in a typical

appearance (tall, thin, long extremities), flexible joints, scoliosis and heart and aortic diseases.

Marfan patients are often known with aortic enlargement (mean growth rate of 0.5-1mm/year);

after prophylactic repair of the ascending aorta, late-onset aneurysms and dissections of the distal

aorta were also reported [1,2,3,16]

Loeys-Dietz syndrome (LDS) An autosomal dominant genetic connective tissue disorder with a typical pathology-triad: bifid

uvula, hypertelorism and arterial tortuosity or aneurysm [1]. Patients with LDS can have a thoracic

aortic growth rate of >10mm/year, resulting in death at a mean age of 37 years and also develop

aneurysms of other vessels (53%) [1,3,16].



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Ehlers-Danlos syndrome type IV or vascular type This autosomal dominant rare connective tissue disorder mostly affects the skin, joints and blood

vessels, shortening the life span to a median of 48 years [1,3]. Higher prevalence’s of aortic

dilatation have been found and arteries can dissect without previous dilatations, making the

patient's status unpredictable [1,16].

Bicuspid aortic valve Bicuspid aortic valve (BAV) is an aortic valve that only has two leaflets instead of three through

embryonic fusion of 2 leaflets. This common congenital heart defect (0.5-2%) with a male

predominance (3:1) can be autosomal dominant and is associated with serious cardiovascular

complications [1,16]. It can lead to a premature onset of a proximal aortic aneurysm (PAA, rarely

the arch), with a higher rate of aortic growth (1.9mm vs 1.3mm/year for a tricuspid valve), even if

the patient is hemodynamically normal, thus requiring cardiovascular surgery in 27% within 20

years [1,3]. 50-70% of BAV patients have evidence of aortic dilatation and the risk of dissection

is 8 times higher, typically in the ascending aorta and aortic arch [16,17].

Other related syndromes Arterial tortuosity syndrome, aneurysm-osteoarthritis syndrome, non-syndromic familial TAAD,

aberrant right subclavian artery and coarctation of the aorta are also known to be related to aortic

aneurysms [1,3].

1.2.2.2 Aortic length 1.2.2.2.1 The physiological aorta

1.2.2.2.1.1 Dimensions Literature concerning the length of the aorta is scarce. Krüger et al. reported mean aortic lengths

for different segments in healthy adults; 92mm for the ascending aorta, 36mm for the aortic arch,

61mm for the proximal descending aorta and 128mm for the abdominal aorta [18].

1.2.2.2.1.2 Relation to gender, age and BSA

Literature seldom describes influences of age, BSA and gender on the length of the aorta and

only a small number of articles can be found, describing the age-, gender- and BSA-related

elongation of the aorta.



13

Adriaans et al. described a significantly longer thoracic aorta in men than in women for all

individual segments, although none of these differences persisted after adjustment for BSA. The

BSA-indexed length of the entire thoracic aorta was positively related to age and a relative lifelong

growth of 125% as from the age of 20 was calculated. The extent of elongation was different for

each segment with the greatest increase seen in the proximal part of the descending thoracic

aorta [19].

However, Sugawara et al. reported an increasing length of the ascending aorta with advancing

age whereas other parts of the aorta were not affected by age. Morrison et al. described an

average of 14% increase in the aortic arch length over a period of approximately 27 years, by

comparing sizes of younger patients (mean age 41 years) with different older patients (mean age

68 years) [20]. Krüger et al. showed a median length increment of 7 mm per life decade for the

aortic arch and only the distal arch length was found to be correlated with age [8]. The cause for

this proximal elongation, might be that the proximal aorta is more likely to experience material

fatigue due to its location closest to the left ventricle [21].

1.2.2.2.2 Pathological aorta

1.2.2.2.2.1 Dimensions In theory, aortic elongation can lead to the loss of longitudinal elasticity and the risk of intimal

rupture [7]. Recent studies from the TAIPAN Project in 2017 showed that the development of

Type B Dissection (TBD) and Type A Dissection (TAD) are associated with aortic arch elongation

[7,8]. In addition, the length of the healthy ascending aorta was 71 mm while in a pre-TAD and

TAD aorta, the same values were respectively 81 mm and 92 mm, respectively [22]. As a result,

the aortic arch elongation may be used as a risk assessment for TAD and TBD in the future

[8,18,22]. The use of the elongation in relation to the development of an aneurysm is still to be

researched.

1.2.2.2.2.2 Pathological influences

Krüger al. reported a positive correlation of hypertension to the distal aortic arch length. Notice

that patients having hypertension were generally older and that therefore both parameters could

interfere with each other [8].



14

1.2.2.3 Common evolution of diameter and length A possible explanation for the correlation between the diameter and length was given by

Michineau S. et al based on a rat model. They believed that length increases in correlation with

diameter during AAA formation and expansion as a consequence of extracellular matrix injury,

driven by matrix metalloproteinases that are activated by the plasmin pathway [23].

1.2.3 The relation between the proximal and distal aorta

It is important to note that the division into TAA and AAA is artificial because of the existence of

thoracoabdominal aneurysms and tandem lesions (27% of AA). This emphasizes the importance

of the assessment of the entire aorta in patients with aortic aneurysms, both at baseline and

during follow-up [1].

1.3 Proximal repair of an aortic aneurysm A proximal aortic aneurysm (PAA) is defined as an AA of the aortic root and/or ascending aorta.

Once diagnosed with a PAA, the patient will need a lifelong follow-up with regular ultrasound, CT

or MRI and especially young patients will go through genetic research to discover a possible

connective tissue disorder. Prophylactic aneurysm treatment consists of lifestyle advice,

medication and/or surgery. The choice of treatment is made case-by-case in a multidisciplinary

meeting by the cardiologist, heart surgeon and vascular surgeon.

Recommendations for lifestyle are the control of hypertension (<120 mmHg) and heart

rate(<60/min), lipid profile optimization, smoking cessation and atherosclerosis risk-reduction

measures (e.g. weight control, sport and healthy diet) [1,3].

Recommendations for pharmacological treatment are needed in most patients, as certain

medications have shown a protective effect by reducing the aortic aneurysm growth: beta-

blockers, ACE-inhibitors, angiotensin II receptor blockers (ARB), non-dihydropyridine calcium

channel-blocking agents (NDCCBA) and statins [1-3].



15

1.3.1 Procedures for proximal aortic aneurysm The purpose of the surgical procedure is to replace the swollen part of the ascending aorta and/or

root, with a prosthesis (with or without replacement of the malfunctioning aortic valve). The

surgical procedure should be chosen in function of the aortic valve anatomy (cusp characteristics)

and the extent of the aneurysm [1,24].

1.3.1.1 David Procedure The David procedure is used in case of an undamaged aortic valve (valve-sparing technique) to

stabilize the aortic annulus and therefore prevent further dilatation. It covers five different types of

reimplantation, from which the two most important are described here [25,26]:

David I: using a cylindrical tube graft (original).

David II: Yacoub remodeling.

The David procedure begins with an excision of the

aneurysmal portion of the ascending aorta and sinuses of

Valsalva, without the removal of the aortic valve leaflets

[27]. Afterwards, implantation of a prosthetic tube can be

performed as a David I procedure in which the graft is

proximally sutured to the annulus and the sinus remnant is sutured inside the aortic graft (Fig.2).

The David II (Yacoub) procedure is characterized by the suturing of a scalloped graft to the sinus

remnant around the attachment of the valve leaflets. Coronary ostia are reimplanted into the aortic

prosthesis during both procedures [25].

1.3.1.2 Bentall procedure This procedure consists of replacing the entire aortic root and aortic valve by a composite (tube

and valve) graft with reimplantation of the coronary ostia. Important to notice is that the aortic

valve is replaced by a mechanical or biological valve prosthesis [25, 28].

1.3.1.3 Aortic valve replacement with separate tube Separate valve and ascending aorta replacement are recommended in patients without significant

aortic root dilatation, in elderly patients and in young patients with minimal dilatation that have an

aortic valve disease [3].



16

Comparing these 3 procedures might be useful for assessing a possible effect on the diameter or

length of the distal aorta; only relevant differences are summarized in table 8 [25,29,30].

TABLE 8. Comparison of open surgery procedures for a proximal aortic aneurysm repair [25,29,30].

Procedure PRO CONTRA

David I No need for lifelong anticoagulation therapy. No prevention of risks related to prosthetic valves (thromboembolism and endocarditis)[31].

Potential risk of impending natural leaflet mobility in a rigid straight graft.

David II No need for lifelong anticoagulation therapy. No prevention of risks related to prosthetic valves. Mimics the natural sinus of Valsalva. Absence of sub-annular sutures preserves some distensibility within the deformation of the aortic root during cardiac-cycle. More natural leaflet motion or less cusp-closure stress (= durability of the valve).

Absence of sub-annular fixation can create a predisposition to postoperative annular dilation, resulting in recurrent aortic regurgitation. Valve-sparing operations are only feasible with (near) normal aortic leaflets.

Bentall - Lifelong anticoagulation in mechanical valves.

AVR + Tube - Higher complication rate for the remaining ascending aorta on long-term follow up when compared with the Bentall procedure. Lifelong anticoagulation.

1.4 Distal follow-up after proximal repair

1.4.1 When and How Suggested follow-up after aortic root or ascending aortic repair is a transthoracic

echocardiography (TTE) before discharge and at yearly interval, assuming the aneurysm is visible

with a TTE [3]. For new, small and stable distal aneurysms, an imaging frequency of every 2 to 3

years, especially in older patients, is currently reasonable, although the American and European

guidelines do not have a consensus on frequency of surveillance imaging [1,3,32]. This being

said, medical institutions typically use MRI as the first choice imaging modality for follow-up [3].

In addition to imaging, all visits should include medical care and clinical checks [32]. These clinical

checks should include blood pressure registration (>50% has resistant hypertension) and



17

questioning on new-onset hoarseness or dysphagia. Patients with aortic aneurysms are, even

after successful repair, at increased risk of cardiovascular events e.g. myocardial infarct (higher

than the risk of amputation or aortic rupture) [3]. That’s why secondary cardiovascular prevention

is recommended [1].

1.4.2 Imaging of the distal aorta Imaging should focus on surgery-related complications on the discharge scan but should also

evaluate disease progression in remote parts of the aorta [1,32]. Utilization of the same imaging

modality and method at the same institution is reasonable, so that similar images of matching

anatomic segments can be compared side by side [1,3]. CT and MRI are the recommended

modalities with a preference for MRI if the patient needs regular imaging due to the absence of

radiation; knowing that no imaging has perfect resolution (table 9) [1-3].

TABLE 9. Ranking of imaging modalities for the assessment of the aorta [1-3].

° Modality Motivation for ranking

1 MRI MR is a good diagnostic method for aortic disease with sensitivities and specificities that are equivalent to hose for CT. The main advantage over CT is the absence of radiation, which is recommended to be as low as possible [1,3]. MRI also gives the best representation of the aneurysm and therefore is recommended to use first [1].

2 CT Multidetector helical CT is a proven good screening method for aortic injuries of all kinds (sensitivities of up to 100% and specificities up to 99%). 3D reconstructions may augment interpretation and improve communication of the findings [1,3].

3 Ultrasound Regular echographic screenings are useful for patients with risk factors, especially for cases of Marfan syndrome and BAV [1]. Ultrasound was found impractical for visualizing the aortic arch and almost impossible for the descending aorta. Because of this, MRI and CT scans are more commonly used at follow-up than the recommended TTE [3].

4 Chest X-ray Chest X-ray is a poor screening test for the diagnosis of aortic dilatation [1,3].

1.4.1.1 Measuring error between CT and MRI Hager et al. researched the aortic diameters of 37 patients with both methods i.e. helical CT (HCT)

and MRI, reporting a high correlation. Nevertheless, a slight bias toward larger diameters in HCT

was reported, with a mean difference of 1.20 mm (± 2.58). This must be kept in mind when drawing

therapeutic conclusions from an alleged "progression" of the aortic diameter [33].



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1.4.1.2 Measuring technique 1.4.1.2.1 Aortic landmarks and segments To make a standardized evaluation of the aorta, it is recommended that the aorta be segmented

at anatomical landmarks as seen in the European and American guidelines (Fig.3) [1,3]. The

segmentation into landmarks (LM) was originally only used to assess the diameter of the aorta

although recently, slightly adapted guideline landmarks were also used by the TAIPAN project as

referral points for aortic length segments (table 10) [7,8,18,22].

A. Sinuses of Valsalva. B. Sinotubular junction. C. Mid ascending aorta. D. Proximal aortic arch (at the origin of the

brachiocephalic trunk). E. Mid aortic arch. F. Proximal descending thoracic aorta (2 cm

distal to the LSA). G. Mid descending aorta (level of the

pulmonary arteries). H. At diaphragm. I. At the coeliac axis origin. J. Right before aortic bifurcation.

Figure 3. Landmarks defined by the European guidelines [1].

TABLE 10. Length segments defined by the TAIPAN project [8,18,22].

N° Segment Description

1 Aortic root From the aortic valve annulus to the STJ

2 Ascending aorta From the STJ to the BCT

3 Aortic arch From the BCT to directly distal to the LSA (Differ from European guidelines: to 2 cm distal to the LSA)

4 Proximal descending aorta

From the LSA to the pulmonary arteries bifurcation

5 Distal descending aorta From the pulmonary arteries bifurcation to the celiac origin (Differ from European guidelines: to the diaphragm)

6 Abdominal aorta From the diaphragm to the aortic bifurcation



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1.4.1.2.2 Measuring technique regarding the diameter A standardized measuring technique helps minimize errant reports of significant aortic growth due

to variability in measuring [3]. Following techniques were found and agreed upon in the literature

or in the guidelines (table 11 and table 12).

TABLE 11. Measuring techniques found in the literature [7,8,34,35].

The diameter First, Lescan et al. among other articles, delineated the aortic perimeter at defined landmarks, and calculated the optimized aortic diameter [7,8]. Second, the creation of a centerline, from the aortic valve annulus to the most distal available portion of the aorta, was described. Subsequently, the thoracic aorta was divided into segments by planes perpendicular to the centerline (=landmarks). In those planes, only the maximum diameter was measured (using the DICOM program) and reported in literature [35]. The volume and ellipticity index

1. Volumetric measurements can be obtained in a semiautomated fashion preceded by manual aortic segmentation of the aortic wall’s outer surface in cross sections. After segmentation, the software automatically constructs a 3D model of its shape, which can be corrected manually if needed [34,35].

2. The ellipticity index, defined as maximum diameter divided by minimal diameter, can also be calculated for each plane.[34,35].

TABLE 12. Measuring techniques according to the European and American guidelines [1,3].

European guidelines [1] American guidelines [3]

Technique Similar determination of edges (inner-to-inner, leading-to-leading, outer-to-outer), even though no consensus on what is the best way. Changes >5 mm on CT are significant, smaller changes are difficult to interpret (Bland-Altman limits of agreement). No real consensus is met as new studies describe a change of the aortic diameter of >3mm as significant [33, 36].

For measurements taken by CT/MRI, the diameter should be measured perpendicular to the longitudinal or blood flow axis. Diameter measurements taken from axial images are inherently incorrect unless the artery being measured is perfectly aligned in cross section on the image.

Landmark Recommended that diameters be measured at pre-specified anatomical landmarks perpendicular to the longitudinal axis.

Measurements of aortic diameter should be taken at reproducible anatomic landmarks, perpendicular to the axis of blood flow, and reported in a clear and consistent format [2].

Abnormal It is recommended that all relevant aortic diameters and abnormalities be reported according to the aortic segmentation.

Abnormalities of aortic morphology should be recognized and reported separately even when aortic diameters are within normal limits e.g. when a prior examination is available, direct image to image comparison to determine if there has been any increase in diameter [2].

Indexing Aortic diameters may be indexed to the BSA, especially for the outliers in body size.

It can be useful to relate aortic diameter to the patient’s age and body size.



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1.4.1.2.3 Measuring technique regarding the length After post-processing (e.g. using OSIRIX MD), the length can be defined as the distance between

two landmarks at [7]:

1. The center line [22], defined as the centerline

distance between the previously-defined

planes [34,35]. A 3D modeling of the aorta with

a centerline tool results (Fig. 4) in reliable

measurements, measuring the length along

the centerline in the curved multiplanar

reformats (from the aortic valve annulus to the

aortic bifurcation) after identifying the

previously mentioned landmarks [7,8]. Additionally, the possibility exists of describing a

derived parameter; Tortuosity (T) is calculated as the ratio of the centerline length (Lc) of

the segment to the linear distance (d) between its 2 endpoints (Fig. 4).

2. The outer and inner longitudinal curvature of the aorta [22].

3. The direct distance in the frontal and sagittal planes [21,22].

1.5 Literature findings concerning the distal aorta after proximal repair

1.5.1 Reinterventions and indications The aim of follow-up and surveillance imaging is to detect early progression or new onset aortic

pathology that could lead to (re)interventions over time. Literature findings reported a 2.4%

reintervention rate over a 9-year period, after a proximal aneurysm repair [32]. In Raudikivi et al.,

aneurysmal disease in the ungrafted aorta was one of the causes for late deaths and for 33% of

reoperations [37]. The most common indication for reintervention is the metachronous

development of an aneurysm of the descending or thoracoabdominal aorta, as described by

Iribarne et al. in 10 patients (47.6%) in a group of 21 reinterventions, at a median interval of 3.4

years [32].



21

It is important to note that two recurring study subjects appear in literature. The first concerns

studies about Marfan patients and the other concerns proximal repair due to dissections apart

from dilatations. The difference in influence on the aorta, between dissection and dilatation, was

proven by Schoenhoff et al.; reinterventions on the distal aorta of Marfan patients were

significantly more frequent in patients with a history of dissection compared to those without (48%

vs. 11%) [38]. The following literature was divided according to those two trends.

1.5.1.1 Marfan studies Literature reports that the absence of aortic reoperation after 10 years is significantly lower for

Marfan patients (79.6% +-13.6%) than for the other patients (94.6% +-2.6%) [39]. According to

Gott et al., the absence of aortic reoperation after 20 years was 74% and 9.7% of Marfan patients

had a procedure for progressive disease and dissection of the aorta and 3% died of late rupture

or dissection of the residual aorta over a 24-year period [31]. Girdauskas et al. reported a 3.2%

distal reintervention for a (dissecting) aneurysm [40]; according to Kawamoto et al. 35% of 48

patients had a significant distal change (>3mm) with aneurysms in 71% and a reintervention rate

of 82% [36]. In another Marfan study, 53% (103 patients over 26 year) needed a repair for

subsequent aneurysms or dissections at other sites; the most common being a proximal

descending thoracic aneurysm surgery after an ascending aortic aneurysm repair [41]. This

confirms the importance of differentiating between Marfan (connective tissue disease) patients

and the other patients.

1.5.1.2 Dissection studies Most existing studies examine the distal aorta after a proximal dilatation combined with dissection.

Few studies exist on merely the effect on the distal aorta after proximal dilatation without

dissection. This made it difficult to distinct both study groups from each other in following studies.

In a study of 1.889 patients that underwent proximal aortic replacement, Idrees et al. described

an unplanned aortic reintervention of 3% (after 30 days), 25% (after 1 year), and 27% (after 4

years) after an isolated replacement (n=212) and 2% (30 days), 17% (1 year), and 19% (4 years)

after multicomponent (concomitant, n=1677) operations [42]. Crawford et al. also reported a total

replacement of the aorta in 53 patients, near total in 25, total thoracic aorta in 78 and total aorta

except the arch in 27, after 1193 proximal operations [43]. According to Pacini et al. 4% (11/274,

70.8% with aneurysm repair) required reintervention between 1978 and 2001, for an aneurysm



22

or dissection of the remaining aorta (4 Marfan patients among them, with aortic dissection in all

of them) [39].

Concurrent distal aneurysmal disease is present or developed in 37% of the patients having a

proximal aneurysm or dissection (mostly in patients with arch involvement) [43].

1.5.2 Influence of risk factors

The need for reinterventions after the David procedure is not significantly higher than after the

Bentall procedure [44]. The insignificant difference in reintervention between the David and the

Bentall procedure was also confirmed in Marfan patients [45]. According to Caynak et al., the type

of operation i.e. Bentall (n=54), David (n=27) or separate AVR with tube (n=18), was not found to

be an independent predictor of overall mortality in long-term follow-up after aortic root repair [46].

This was confirmed by Price et al.; no independent difference in long-term survival, freedom from

reoperation or freedom from endocarditis between the Bentall and David procedures was denoted

[47], although the ten-year survival in patients undergoing Bentall procedure was 90.5% but

96.3% in patients undergoing David. This apparently slight disadvantage for the Bentall procedure

was also reported by Hagl et al. (n=142), where surgery for distal aortic segments was only

performed in 4 patients after a Bentall procedure [48].

One of the risk factors for early and late aortic reintervention is a larger descending aortic diameter

[42]. The variables predicting Marfan patients that need second vascular surgeries are: presence

of acute or chronic dissection at the time of the first surgery, hypertension after the first surgery,

and a history of smoking [41]. In the study of Abdelkareem et al., no significant dilatation of the

aortic arch was observed after aortic root replacement in patients with BAV, compared to TAV,

up to 5 years after operation [49]. More influences of risk factors on the aorta were described

above.

1.5.3 Conclusion In this brief review of literature there is still little data and no consensus about the further changes

in the aorta at certain locations after an initial intervention for a PAA. Henceforth, this retrospective

study where more data was collected about the thoracic and abdominal aorta to describe the

evolution of these parts of the aorta.



23

2. METHOD

2.1 Aim and purpose of the study The coexistence of TAA and AAA, either synchronous or metachronous, either as a tandem lesion

(27%) or a thoracoabdominal aneurysm (20%), established a connection between the proximal

and distal aorta which is still unclear. [1]. Clarifying this connection could help prevent serious

cardiovascular complications and potentially save lives as urgent or even elective surgery is

correlated with major mortality rates.

This study focused on the thoracoabdominal connection by developing and using a unique

measuring technique to describe the evolution of the distal aorta at follow-up. To this day, the

diameter is the only broadly and thoroughly studied parameter for diagnosis, intervention and

follow-up of aneurysms. In this study, not only the existing parameter i.e. diameter was used, but

also two new parameters i.e. length and aortic surface area (ASA) were introduced and evaluated.

The evolution of the aorta over time and the influence of patients characteristics and risk factors

were also assessed to help anticipate distal aortic growth and future problems in risk populations.

The final goal was to anticipate distal aortic growth, aneurysms or ruptures and to identify a

possible risk population in which closer follow-up is needed.

Thus, this study intends to profile:

I. The change in diameter, length and aortic surface area and consequently define if length

and ASA are valuable alternatives for assessment of the distal aorta;

II. The influence of risk factors (smoking, hypertension, Marfan syndrome etc.) and patient

characteristics (age, gender, BSA) on the distal aorta;

III. The evolution of the distal aorta over time;

IV. The relation between dilatation and elongation of the aorta and consequently define if

length could be used as a parameter for distal aortic assessment;

and ideally intends to combine this into certain recommendations to optimize risk stratification and

evaluation (e.g. treatment and follow-up) of these patients.



24

2.2 Design The study ran from the summer of 2017 till the end of 2018 at the University Hospital of Ghent.

Patients that underwent proximal aortic repair (with or without valve surgery) for a proximal aortic

aneurysm (root or ascending aorta without aneurysm), in the period from 2000 until 2017, were

considered for this study. Further selection was based on the availability of a preoperative and

postoperative scan of the complete aorta with branches, either CT or MRI, and with the

preoperative scan being maximally 1 year before surgery and the postoperative scan being at

least 1 year after the surgery. Patients with aortic dissection at first presentation were excluded.

Measurements from the preoperative and postoperative CT’s or MRI’s were taken at predefined

diameter landmarks (LM) and length segments (L) of the aorta. The dimensions of the aorta were

standardized by making consistent use of a unique measuring technique, based on the American

and European guidelines and the TAIPAN project [1-3,7]. These measurements and the

anthropometric data i.e. patient characteristics and risk factors (sex, age, hypertension,

medication, etc.) of the patients were combined in a database. Statistical analysis was performed

on the database to evaluate the aortic dilatation and elongation. In addition, the time interval,

patient characteristics and risk factors were analyzed for their influence on the aorta.

This study was an experimental, clinical based, observational, retrospective cohort study with an

additional literature study, using the already existing guidelines [1-3,9,24] and the recent literature

[7,8,18,19] as reference. The ethical committee approved the set-up of the study and an informed

consent was not waived due to the observational and retrospective design of the study (Belgian

registration number B670201733234).

The study sample consisted of patients linked to the “multidisciplinary aortic centrum” of the

University Hospital of Ghent (UHG, from Belgium) from 2000 until 2017, forming a database with

a total of 302 patients. The experimental data collection consisted of 2 aspects:

I. Anthropometric data collection of the patients in the EPD (electronic patient dossier) of the

department of Cardiothoracic Surgery of the UHG (under the supervision of Prof. Dr.

Katrien François).

II. Measurements of the aorta on CT and MRI at the department of Radiology, making use

of the PACS screens (under the supervision of Dr. Daniel Devos).

.



25

2.3 Data selection and collection

2.3.1 Literature study: search strategy For the literature search in this study, the following sources were used: the World Wide Web (e.g.

Mayo Clinic website), Google Scholar, Embase, PubMed and Web of Science (Journal Citation

Manager); in English, Dutch and French.

After a thorough selection of guidelines, reviews and articles (chronologically), using all possible

keywords in every possible way (through ‘similar articles’, ‘title matching your search’, ‘sort by

best match’ or ‘sort by most recent’), only those in the references were included. The literature

was further chosen based on the year of publishing (more recent), the journals’ impact factor and

rank, the design of the study and most importantly the study focus and quality. For an in-depth

elaboration of the search strategy (including impact factor and rank of the journals), see Appendix

1.

Underlying subjects were searched for in the literature with the respective keywords and led to

the articles, detailed in the references.

I. Background information about aortic aneurysms [4-6,25-28,30]. I. Search terms in PubMed: aortic aneurysm, thoracic aorta, proximal aortic repair,

aorta replacement, aortic valve sparing David, valve sparing aortic replacement,

Bentall procedure or replacement, ascending aorta replacement, ascending aorta

Bentall, comparison surgical methods aortic root [25,46], follow-up Bentall [29].

II. Mesh Terms in PubMed: Aortic Aneurysm/surgery, Aortic Valve/surgery, Sinus of

Valsalva/surgery, Treatment Outcome, Blood Vessel Prosthesis

Implantation/methods.

II. Guidelines. I. Europe, in 2014 [1] and in 2017 [24],

II. USA in 2006 [9], 2010 [3] and 2017 [2].

III. Measuring techniques for dilatation and elongation. I. Descending aorta geometry [19,34,35]

II. Aortic elongation thoracic aneurysm [7,8,18,20,22]

III. Aortic elongation age [21]

IV. Aortic length expansion aneurysm [23].



26

IV. Imaging and the CT-MRI error. I. MRI CT compare aorta [33]

V. The distal follow-up after a proximal aortic aneurysm repair. I. Distal aortic reinterventions after root surgery [31,32,36-39,41-45,49]

II. Follow up Bentall [47,48]

III. Bentall distal dilatation [40]

VI. The influence of patient characteristics and risk factors. I. Risk factors aortic diameter [10-15]

II. Aortic disease genetic syndromes connective tissue familial [16,17]

2.3.2 Experimental study

2.3.2.1 Patient selection The inclusion criteria for the selection of the patients were the following: all patients between 2000

and 2017 within the UHG database, that underwent proximal aortic surgery for aortic aneurysm,

without dissection, with preoperative and postoperative scans of the complete aorta with branches

until at least the coeliac trunk, either both CT scans or both MRI scans, with the preoperative scan

being maximally 1 year before surgery and the postoperative scan being at least 1 year after the

surgery.

For imaging made in the UHG itself, the CT’s and MRI’s were directly accessible through the

PACS-network, where all intra-hospital imaging is kept. For imaging made in other hospitals, CT’s

and MRI’s were downloaded from the CoZo-platform. This is a platform where certain data

(imaging, letters, lab findings etc.) of the patients of almost every Flemish hospital are accessible

to the treating doctors (if their informed consent was given). If the scans were not immediately

accessible on CoZo, the hospital was contacted to send them. These images were then uploaded

via the WEBPACS-network onto the PACS-network. “Syngo.via” is the post-processing program

installed on the ‘PACS-screens’ in the radiology department and was used for exact

measurements and special imaging (3D imaging and 2D multiplanar etc).



27

A total of 302 patients were available from the UHG database. After exclusion, 30 patients were

included in the study (Fig.5).

Figure 5. Flowdiagram

2.3.2.2 Data collection For those 30 selected patients, medical information (patient characteristics and risk factors) was

collected from their health registers and patient files, available in the Electronic Patient Dossier

(EPD) of the department of cardiothoracic surgery of the UHG (Appendix 2, table 2.A). The non-

fluctuating patient information was retrieved at a certain point in their lifetime, whilst the fluctuating

was measured at “follow-up”, meaning the time in between both scans (table 13). The data

collection concerning measurements was depicted in ‘variables and technique’.

TABLE 13. Time of measurement. Patient information Time indication

Medication At dismissal and follow-up Weight and height At follow-up Blood pressure At follow-up, status under medication (if present) Smoking At follow-up, only if current not if ex-smoker Dyslipidemia At follow-up Diabetes If DMI unspecified, if DMII at follow-up



28

2.4 Variables and technique

2.4.1 Variables The descriptive, predicting and confounding variables of the patients with the respective codes,

were listed in Appendix 3 (table 3.A). The outcome variables for diameters and lengths of the

aorta were listed in Appendix 4 (table 4.A) and the derivative variables (BSA, ASA) in Appendix

5 (table 5.A).

Concerning the diameter and length of the aorta, different sites of measurements (landmarks and

segments) were defined. As the guidelines by Erbel et al., Hiratzka et al., Baumgartner et al. and

Mokashi et al. [1-3,24] only depicted anatomical landmarks referring to the diameter of the aorta,

and as the TAIPAN project [7,8,18,22] used slightly different landmarks in comparison with the

guidelines (better adapted to measuring the aortic length), both were used in this study.

The final landmarks were chosen by combining the different methods described above and by

adapting them to the necessity and feasibility of this study (Fig.6 and Appendix 4). At every

landmark (LM), 2 measurements were taken; the maximal diameter (D) and the diameter

perpendicular (d) to the maximal diameter. This made it possible to create the derivative variable

aortic surface area (ASA) or elliptic surface area of the aorta at a certain landmark (Appendix 5,

table 5.A). Every length segment (L) was measured at the centerline. Some length segments

were also analyzed as combined length segments i.e. L3+L4 as the combination of the

descending aortic length segment (L3) and proximal abdominal length segment (L4), and

L2+L3+L4 as the combination of the arch (L2), descending aorta (L3) and proximal abdominal

aorta, further referenced to as the thoracoabdominal aorta.



29

Figure 6. The centerline and the defined landmarks. From cranial (yellow transversal plane) to caudal: LM1 (sinotubular junction), LM2 (proximal aortic arch), LM3 (mid-aortic arch), LM4 (proximal descending aorta), LM5 (mid-descending aorta), LM6 (distal descending aorta), LM7 (proximal abdominal aorta) and LM8 (distal abdominal aorta). The length segments were measured between those defined landmarks (Appendix 4).



30

2.4.2 Measuring technique

2.4.2.1 Instruments

I. IMPAX 6.5.3.1005 program, available on the PACS screens with access to the PACS and

WEBPACS system and thus forth the medical imaging.

II. Post-processing program “Syngo.via” from Siemens, also available on the PACS screens

at the radiology department of the UHG. It’s the standard post-processing program to

assess CT’s and MRI’s at the UHG.

2.4.2.2 Method The preoperative and postoperative image of every patient was opened individually in

“Syngo.via”. This program gives a detailed representation of the aorta with a wider range of editing

tools, using certain preprogrammed “workflows” specifically for arteries: “CT Vascular” and “MR-

angio” with either “Single Station” or “Multi Station”.

1. Measuring technique for CT (Fig.7)

1. The centerline of the aorta was drawn, either automatically using the ‘Define Centerline’

and ‘Multiple Clicks Vessel Tracing’ tool or manually, in case automatic drawing fails

(mostly due to non-contrast images), using the ‘Define Centerline’ and ‘Manual Vessel

Tracing’ tool. This manual drawing is done with the ‘eye-balling’ method; performed by

aligning the frontal, sagittal and transverse planes, using the transversal plane to measure

the aorta. When the automatically-drawn centerline would show incoherence with the

shape of the aorta, manual modifications would be conducted using the ‘Freeline Edit’

function. The beginning of the centerline was consistently set at the sinotubular junction

whereas the end was mostly set at the coeliac trunk because the bifurcation into the iliac

arteries wasn’t always part of the imaging.

2. The predefined anatomical landmarks were searched using the anatomical references

(Appendix 4, table 4.A) and were marked with the ‘Marker’ tool on the corresponding

transversal plane, perpendicular to the centerline in that point.

3. In those planes, the maximal diameter was measured automatically by the ‘Vessel

Diameter Measurement’ function. This function draws the perimeter of the aorta and

calculates the maximal and second maximal diameter automatically. The minimal

diameter, perpendicular to the maximal diameter, was measured with the ‘eye-balling’



31

method using the ‘Distance Line’ tool. If the maximal diameter couldn’t be measured

automatically, the same method was used as for the perpendicular diameter, using

alignment of the planes to get a plane perpendicular to the centerline and self-draw the

line.

4. The length of the aorta was measured between the predefined landmarks, as predefined

segments on the centerline, using the ‘Vessel Length Measurement’ function with the ‘eye-

balling’ method. This was done on the 3D model of the aorta or on the curved multiplanar

reconstruction.

Figure 7. CT-method. Left: centerline in yellow from the STJ to the iliac bifurcation on 3D imaging; measurement of the descending aortic length segment in blue (also seen in the curved multiplanar reformat right). Right: transversal plane perpendicular to the centerline in which the perimeter and 2 diameters were drawn automatically.



32

2. Measuring technique for MRI (Fig. 8)

In contradiction to the measurements on CT, Syngo.via did not provide automaticity of any kind

regarding MRI. Consequently, every measuring was aligned with the “eye-balling method”.

1. Anatomical landmarks were searched and marked with the ‘Marker’ tool.

2. To assure a standardized approach, every landmark was aligned by moving the

‘Reference Lines’ from the sagittal, frontal and transversal plane to intersect the aorta in

a perpendicular way. In that way, a plane was created perpendicular to the (imaginary)

centerline, in which the measurements were taken.

3. In those planes, the maximal diameter and the diameter perpendicular to the maximal

diameter were measured, using the ‘Distance Line’ function, at every landmark.

4. The length was measured by use of a self-drawn centerline, drawn by connecting the

intersections of the diameters after aligning, using the ‘Distance Polyline’ function.

Figure 8. MRI-method. Left: 3 planes (sagittal, frontal and transversal) in which the reference lines needed to be aligned to assure correct measurements in MRI scans. Right: Overview of the complete aorta on MRI.



33

2.4.2.3 Frequency As most of the literature reports aortic growth per year and a reintervention after proximal aortic

surgery is most common 3 years after the surgery, a one-year interval between surgery and

postoperative imaging was set as a minimum. The same one-year interval was set as a maximum

between preoperative imaging and surgery, as longer periods could influence the normal aortic

growth. [32].

2.4.2.4 Standardization To standardize the patient characteristics and risk factors, outcomes were reported conform

literature with attention for the confounding variables sex, age and BSA. Guidelines were used as

a reference to work in an evidence based and standardized way. In accordance with the existing

literature and guidelines, the centerline method was consistently used [1-3,24]; concerning the

diameter of the aorta, both the maximal diameter and the diameter perpendicular to it, were

measured in the plane perpendicular to the centerline of the aorta.

2.4.2.5 Validation

Measurements of the aorta were performed by Anne-Sofie De Crem and Marvin D’Hondt.

Precision in taking the measurements was threatened by interobserver and intraobserver

variability, the lowest level of variability. There was an interobserver variability, meaning the

possibility of a difference in measurements if remeasured by another observer than the original

one. Although both preoperative and postoperative scans from the same patient were measured

by only one student in one day, slight interobserver variability was not avoidable. There was also

an intra-observer variability, meaning the possibility of a difference in measurement if remeasured

by the same observer. Although with every scan a standardized measuring technique was

followed while using a program with automatic measurements (CT).

The accuracy of the measurements depended on the thickness and pixels of the scan, on the

outer-to-outer edge measurements and on the CT-MRI error. First of all, the slice thickness of

every scan needed to be 3mm or less, which drastically reduced the chance of missing a

dilatation. Secondly, CT to MRI comparison was explicitly avoided because of the big difference

in displaying and in measuring the scans of these two modalities. Furthermore, due to the lack of

scans with a high resolution, high enough to differentiate the inner from the outer aortic wall in

non-enlarged aortic walls, the outer wall was consistently used to measure the aortic diameter.



34

2.5 Statistical Analysis Statistical analyses were performed with IBM® SPSS® Statistics 25.0 (Armonk, NY: IBM Corp.).

Data-cleaning was conducted by going over the correct input of data, the validity of the inclusion

criteria and by producing baseline characteristics. Continuous variables were presented as

mean(CI) or as median(IQR) in the presence of skewness. Categorical variables were expressed

as frequencies (%). Measurements at the sinotubular junction (LM1, L1) were left out due to the

implications of the surgery and also the measurements of the distal abdominal aorta (LM8, L5)

were not statistically analyzed due to insufficient data. Variables with small subgroups (<5) in this

sample of 30 patients (n=30) were excluded or if possible, besides the original grouping,

conjoined and dichotomized i.e. patients with a congenital disease or genetic disease were

conjoined as patients with a connective tissue disease (CTD) and dichotomized in with or without

this CTD. All p-values were tested two sided and considered significant if alpha <0.05.

To test for normality, the Shapiro-Wilk test (small sample n =30), QQ-plots and assessment of

skewness and kurtosis were. The influence of age, time and BSA on the aortic dimensions and the coherence in dilatation and elongation per segment were calculated and tested with

the Pearson (normal) and Spearman (non-normal) correlation and assessment of linearity was

shown on scatterplots by use of a linear regression.

The absolute elongations and dilatations (continuous, paired variables) were tested with the

paired Student’s t-test (normal), the Wilcoxon matched-pairs signed rank test (non-normal,

symmetrical) and the Sign test (non-normal, non-symmetrical). The influence of risk factors, besides BSA, on the aortic dimensions (Continuous, unpaired variables) were tested with the

Independent samples t-test (normal, 2 groups), One-way ANOVA (normal, >2 groups), Mann-

Whitney U test (MWUT) (non-normal, 2 groups) or Kruskal Wallis test (KWT) (non-normal, >2

groups) . The 2 specific conditions for normal distributions were checked, i.e. the normality of

residues (Shapiro-Wilk test, QQ-plots) and homogeneity of variances (Levene’s test). If the 2nd

condition was not met the Brown or Welsh-Forsythe was analyzed. Post-Hoc tests for a significant

One-way ANOVA were Tukey and/or Scheffe, whilst a 2-on-2 MWUT was used after a significant

KWT, both with consideration of the Bonferroni correction. Normally distributed variables were

also tested with the MWUT and KWT to make the results more comparable.

Elongation, dilatation (both absolute and per year) and the usefulness of the ASA parameter were tested with the One-Sample Wilcoxon signed rank test to check for a zero

difference. (A full overview of the statistical analysis can be found in Appendix 6)



35

3 RESULTS

3.1 Aortic dimensions and influences The theory of aortic expansion is a well-studied phenomenon for the aortic diameters, but not as

much for the aortic lengths. Assessment of the absolute expansion in diameter, length and aortic

surface area was needed before making a statement about which factors (risk factors or patient

characteristics) influence the aortic dimensions.

Certain Landmarks (LM) and Length segments (L) were tested but not found relevant:

o The sinotubular junction landmark (LM1) and ascending aorta length segment (L1) were

unreliable because of the preoperative aneurysmatic diameter and length and the

postoperative diameter and length of the prosthesis that do not change over time.

o The distal abdominal aorta landmark (LM8) and corresponding length segment (L5) were

also unreliable in this study because of the incomplete aortic imaging at the aortic

bifurcation in several patients (4 preoperative and 7 postoperative scans).

The scans did elicit a statistically significant dilatation of the aorta in postoperative patients

compared to preoperative patients at every landmark (LM3, LM4, LM5, LM6 and LM7) except for

the aortic arch (LM2), with a mean dilatation between 1.03 mm (CI:0.24-1.83, p=0.012) and 1.57

mm (CI:0.42-2.71, p=0.009). A statistically significant elongation of the aortic arch (L2, p=0.026)

and the thoracoabdominal aorta (L2+L3+L4, p=0.012) with a mean elongation in this length

segment of 9.28 mm (CI:2.21-16.36) was found. Median elongations and dilatations could be

computed for each landmark e.g. the median length for L2 was 59mm (IQR 55.5-64) in the

preoperative scan and 61mm (IQR 57-68.75) in the postoperative scan, thus indicating a slight

but significant difference (Z=-2.226, p=0.026). For more details, see boxplots in Appendix 7 and

table 8.A and 8.B in Appendix 8.

The aortic surface area (ASA) at a certain landmark could be a more precise way of measuring

the aortic growth due to its double check function. Moreover, the ASA eliminates the bias by

squeezed aorta’s. A significant difference in aortic surface area between both scans was found

for all landmarks (p<0.05) except for the aortic arch (table 8.D in Appendix 8). These results are

the same as those describing the diameters (table 8.C in Appendix 8).



36

1. AGE AND BSA The aortic dimensions know a physiological increase for increasing age, BSA and the male

gender. In this study, every patient’s aorta was compared to itself i.e. as paired samples, thus no

correction was needed for BSA and gender, as those remained the same over time, and only age

was assessed with a median difference of 4 years between both scans.

A significant correlation (p<0.05) was found between the age of the patients and the absolute

diameters at the aortic arch (proximal and mid resp. LM2:r=0.716 and LM3:r=0.683), the

descending aorta (proximal, mid and distal resp. LM4:r=0.571, LM5:r=0.755 and LM6:r=0.803)

and proximal abdominal aorta (LM7:r=0.632). For aortic lengths, only the preoperative age was

correlated to the preoperative lengths of the arch (L2,r=0.379), the descending (L3,r=620), the

combined descending and proximal abdominal (L3+L4,r=0.463) and the thoracoabdominal aorta

(L2+L3+L4,r=0.512) (Fig.9). In contrast, the postoperative age did not evolve with most of the

postoperative lengths, correlations are represented in table 8.E in Appendix 8.

Figure 9. Scatterplots illustrating the relation between age and aortic dimensions



37

The BSA was not found having any influence on the evolutions in diameter, ASA (dilatation) and

length (elongation) at every landmark.

2. RISK FACTORS A multitude of studies and guidelines describe effects of certain medications, diabetes mellitus,

genetic disorders and other possible risk factors or patient characteristics on the aortic diameter.

To our knowledge, none of these studies describe an influence on both the diameter and length,

and none of these use the increase in length as a collateral parameter of aortic health

assessment.

Certain risk factors couldn’t be tested due to:

I. Very small subgroups (<5 patients) i.e. diabetes mellitus (n=2), smoking (n=4), genetic

disease i.e. Turner (n=1) or Loeys-Dietz (n=1), BAV and coarctation (n=1), other

congenital diseases (n=2), AVR + tube procedure (n=3), proximal (n=1) and distal (n=1)

reintervention, descending aneurysm (n=1) and other (n=1) indication for reintervention,

beta-blocker (n=4), ace-inhibitor (n=3), angiotensin II receptor blocker (n=4) and non-

dihydropyridine calcium channel-blockers (n=1). To make more representative results, the

connective tissue diseases were tested together, consisting of patients with Marfan,

Turner, Loeys-Dietz, BAV, coarctation or other congenital diseases (n=20), to compare

them to the other patients (n=10).

II. The fact that the assumption of homogeneity wasn’t fulfilled for angiotensin II receptor

blockers and “other” medication.

III. The type of imaging modality that was chosen randomly when assessing a patient for an

aneurysm, therefore the difference in dilatation or elongation between the MRI and CT

group was random and testing this was of no relevance.

Overall, no significant influence of the risk factors on length was found. Nevertheless, following

risk factors were found influencing the aortic diameters, illustrated by the median differences

between the subgroups (see table 8.F and 8.G in Appendix 8 for more details):



38

Marfan At the mid-aortic arch (LM3, p=0.042), the distal descending aorta (LM6, p=0.010) and

the proximal abdominal aorta (LM7, p=0.027), the aorta was resp. 1 mm, 4 mm and 1 mm

more dilated in patients with Marfan.

Connective tissue disease At the mid-aortic arch (LM3, p=0.032) and the distal descending aorta (LM6, p=0.020),

the aorta was resp. 2 mm and 2.5 mm more dilated in patients with connective tissue

diseases.

Surgical procedure And at the proximal abdominal aorta (LM7, p=0.033), the aorta was 1 mm more dilated in

patients with David than those with Bentall.

Statins At the mid-aortic arch (LM3, p=0.003)), the mid-descending aorta (LM5, p=0.013) and the

distal descending aorta (LM6, p=0.032), the aorta was resp. 1.5 mm, 2 mm and 2 mm

more dilated in patients without statins than those with statins.

Blood pressure At the mid-aortic arch (LM3, p=0.005), the proximal descending aorta (LM4, p=0.043) and

the mid-descending aorta (LM5, p=0.024), the aorta was resp. 2.5 mm, 2.25 mm and 1.5

mm more dilated in normotensive patients.

Dyslipidemia At the distal descending aorta (LM6, p=0.016), the aorta was 2 mm more dilated in

patients without dyslipidemia.



39

3.2 Time and aortic growth

Results on the time interval between

both scans and the increase in

diameter or length were inconclusive.

(table 8.H in Appendix 8). Nothing

significant was found for the influence

on time on the aortic diameters. Only

for the combined length segment of

the descending and proximal

abdominal aorta (L3+L4, p<0.01) and

the thoracoabdominal aorta

(L2+L3+L4, p<0.05), a significant

correlation was found with the time

interval. This correlation was

described more clearly with

scatterplots (Fig.10) and a function

representing the linear regression

(scatterplot). For L3+L4 (r=0.584),

determination coefficient R2 was 0.19

and the linear function y= -6.06 +

2.37x, meaning that 19% could be

explained by this function. For

L2+L3+L4 (r=0.445), R2 was 0.20 and

the linear function y=-4.46 +2.84x, meaning that approximately 20% could be explained by this

function. Only the thoracoabdominal length segment (L2+L3+L4), increased significantly

(p=0.035) with a median increase of 1.58 mm/year.

An increase of the ASA per year was described for some landmarks. The aortic surface area of

the mid-aortic arch (LM3, p=0.009), the mid-descending aorta (LM5, p=0.018), the distal

descending aorta (LM6, p=0.046) and proximal abdominal aorta (LM7, p=0.032) increased

significantly every year with medians of resp. 13.37 mm²/year, 7.47 mm²/year, 8.57 mm²/year and

8.13 mm²/year. Important to note is that no significant correlation was found between time and

increase in aortic surface area (same results as for increase in diameters)

Figure 10. Scatterplots illustrating the relation between elongation and aortic growth



40

3.3 Elongation and dilatation of the aorta

If the elongation is correlated with the dilatation of the aorta, the length could be used as another

parameter for assessing growth of an aortic aneurysm.

No common evolution of the dilatation and elongation of the aorta was demonstrated for most

landmarks, except for the weak correlation between the elongation in the descending aorta

(L3,r=0.420) or the elongation in the thoracoabdominal aorta (L2+L3+L4,r=0.379) and the

dilatation at the mid-descending aorta (LM5). The same results were found when correlating the

elongation to the corresponding evolution in ASA with only a significant correlation of L3 (r=0.439)

and L2+L3+L4 (r=0.364) with LM5.

4 DISCUSSION

4.1 Does the distal aorta change and what are the possible causes

4.1.1 Is there a significant difference between the preoperative and postoperative aorta in diameter and length at every landmark

There was a slight but true difference between preoperative and postoperative measurements at

all diameter landmarks and length segments, thus confirming that there was a significant and

positive evolution of the aortic diameters and/or lengths in the distal aorta after proximal repair,

except for:

o The proximal aortic arch (LM2) did not change significantly over time, which may be due

to the fact that this part of the aorta is very well fixed by the 3 large aortic branches (BCT,

LCA, LSA). This landmark is also very close to the suture place of the proximal aortic

prosthesis or even included in the repair (hemi-arch repair), making it less likely to change

in diameters.

o The descending and proximal abdominal aortic lengths, did change but not significantly

(with a median difference of resp. 7 mm, 4.5 mm and both lengths together 6 mm). The

thoracoabdominal length (L2+L3+L4) did change significantly, thus indicating that the

separate aortic segments are lesser indicators of aortic change than the combined distal

aorta.



41

This confirms that the increase in postoperative diameters and lengths was not only seen in

dissections, as reported in the studies of the Taipan project, thus stating that the length

measurements after proximal aortic aneurysm repair could also be useful as an additional

parameter for follow-up (as already proven for dissection by the Taipan project) [7,8,18,22].

4.1.2 Is the ASA useful as parameter for aortic health assessment The aortic surface area (ASA) was deemed a valuable alternative to the aortic diameter for the

distal aortic assessment, due to identical results but with the advantage of double checking and

eliminating the bias of automatically drawn maximal diameters in squeezed aortas. There was no

common evolution of ASA and the time interval, suggesting that time didn’t have an influence on

the dilatation. If time didn’t have an influence, other risk factors may have had and from the results

on the dilatations in diameter and elongations we can assume that some had an influence. A

pathological influence could thus be thought of as one of the reasons for enlargement. This

parameter could be used for physiological aortas, thus making ASA a possible general way of

measuring the dimensions of the aorta. Although the ASA is too time consuming to do manually

for a radiologist, if better post-processing and automatization of this function would exist, it could

be a more efficient and specific way of assessment. Further elaboration of the ASA as a useful

parameter should be performed by setting up a study in which the ASA and diameter parameter

are compared.

4.1.3 Do risk factors or patient characteristics influence the aorta

1. AGE

A common evolution of the age with the absolute diameter and/or length at most of the landmarks

was found. This confirmed that the distal aorta evolves with the ageing patient, reaffirming the

findings of Rogers et al., Mensel et al. and Wolak et al. [10-12].

For those landmarks that were not found significant, the following interpretations were given:

I. The proximal abdominal aorta length segment (L4) depends on the position of the

diaphragm which depends on the respiration of the patients at the moment that the scan

was taken. Because of this fluctuation in diaphragm position, the length at this segment is

not reliable and has to be further evaluated by adding this length to the descending aorta



42

length segment (L3). In that way the respiration has no influence anymore on the length

of the segments.

II. The fact that there is no correlation between the age and most postoperative length

segments (L2,L3,L3+L4 and L2+L3+L4), could indicate that these postoperative lengths

deviate from the physiological growth of the aorta with age.

2. BSA

The influence of BSA on the aortic elongations and dilatations was assessed and resulted in no

significant correlation for any landmark, meaning that this typical confounding factor didn’t have

any influence on the aortic growth in this sample. This contradicts the literature in which the aortic

diameter increases with every 0.1 m² BSA increase (BSA-adjusted diameters) [11,12].

3. RISK FACTORS

Marfan and connective tissue diseases Marfan disease had an influence on the distal aorta, more precisely at the mid-aortic arch

(LM3), the distal descending aorta (LM6) and the proximal abdominal aorta (LM7). Also,

patients with a connective tissue disease had more dilated distal aortas at the mid-aortic

arch (LM3) and the distal descending aorta (LM6). These findings are in accordance with

the findings in literature for Marfan patients on the distal aorta e.g. 9.7% of patients have

progressive disease and dissection, 3.2% have a (dissecting) aneurysm and 35% have a

significant change in aortic diameters (>3 mm) with a 29% reintervention rate [21,36,40].

In some studies [41] up to 53% needed repair for subsequent aneurysms or dissections

at other sites and the freedom from aortic reoperation at 10 years, was significantly lower

(p=0.008) for Marfan patients (79.6% +-13.6%) than for the remaining patients (94.6% +-

2.6%) [39]. The results of this study and the literature suggest that CTD such as Marfan

have an influence on the entire aorta. A pathological influence is sooner noticeable

proximally due to the influence on the aortic valve, but is also certainly present distally,

even after a proximal surgery.

Surgical procedure A slightly greater but significant dilation was seen in the proximal abdominal aorta (LM7)

in patients with David than those with Bentall. No logical explanation for this phenomenon

could be found and literature states no significant difference in reintervention rates



43

between the David and Bentall [44,45l]. Furthermore, Caynak et al. reported that the type

of operation i.e. Bentall (n=54), David (n=27) or separate AVR with tube (n=18) was not

found to be an independent predictor of overall mortality in long-term follow-up after aortic

root repair [46].

Statins Patients taking statins were less dilated at the mid-aortic arch (LM3), the mid-descending

aorta (LM5) and the distal descending aorta (LM6). This confirms the protective influence

of statins on the aortic aneurysm growth as seen in the literature [1,3]. Some studies

however reported a positive correlation with statins (OR =3.77). This correlation could be

biased by the already existing higher cardiovascular risk of patients that use statins [15].

Dyslipidemia Overall, the results of this study showed that dyslipidemia doesn’t influence the aortic

dimensions as such. Only at the distal descending aorta (LM6), a lesser dilatation was

found for patients with dyslipidemia. This could perhaps be explained by plaque formation

in the aortic wall in patients with dyslipidemia, which stiffens the aorta and restricts

expansion or by intake of statins. Rogers et al. reported no association with the aortic

diameter unlike the study of Forsdahl et al. that contradicts these findings with a positive

correlation for hypercholesterolemia (OR=2.11) and low HDL-cholesterol (OR=3.25).

[12,15]. Notice that in this study 7 of the 8 patients with dyslipidemia took combined

antihypertensive drugs, which may again influence the outcomes.

Blood pressure In this study, the normotensive patients had a more dilated mid-aortic arch (LM3),

proximal descending aorta (LM4) and mid-descending aorta (LM5) compared to the

hypertensive patients. Mensel et al. and Rogers et al. described a similar negative

association of systolic blood pressure for the descending thoracic aortic diameters, but a

positive association of diastolic blood pressure [11,12]. Other studies reported a positive

correlation with hypertension and thoracic aortic dimensions [10], OR=1.54 (1.03-2.30)

[15]. The literature does not agree upon this risk factor. The larger dilatation of

normotensive patients (also including the patients with a controlled hypertension taking

antihypertensive drugs), could thus not be explained. However, one could argue that the



44

controlled hypertension of some patients may be the cause of this influence on the aorta

in comparison to normotensive patients. Controlled hypertensive patients could have

undergone earlier preoperative dilatation and a greater postoperative dilatation, even

under antihypertensive drugs.

4.1.4 Explanation of negative aortic evolutions Although a median/mean increase in aortic diameter and length was observed in

segments of the aorta, sometimes postoperative measurements of the same patient were

slightly smaller for those segments. These smaller measurements could be explained by

several factors:

o Possible problems with the aortic dimensions assessment (as described in

the limitations).

o Better follow-up, medication and the influence of the surgery affected the

postoperative aorta in a cardiovascular risk reducing way.

o Intra- and inter-operator variability with influence on the internal validity.

4.2 Should we consider time as a factor Only for the combined length segments of the descending and proximal abdominal aorta (L3+L4,

r=0.584)) and the thoracoabdominal length (L2+L3+L4, r=0.445), a common evolution was found

between elongation and time (table 8.H, Appendix 8). Time could thus be a confounding factor

for the total aortic elongation from the arch to the proximal abdominal aorta. The linear function

of the elongation in L3+L4 over time (that accounts for only 19%) estimated an elongation of 17.64

mm over 10 years (Fig.10). The same function of the elongation in L2+L3+L4 over time (that

accounts for only 20%) estimated an elongation of 23.94 mm over 10 years (Fig.10). No exact

data were found in the literature to compare these elongation rates. An explanation for having a

decrease of a few millimeters in the first year(s) after proximal repair of an aneurysm could be

because of the shorter prosthesis that replaced the previously longer aneurysm. Those results

only confirm that after some time (at least 2-3 years), an elongation of the aorta was seen, only

in the total length between the celiac trunk on the one hand and the left subclavian artery (L3+L4)

or the brachiocephalic trunk (L2+L3+L4) on the other hand. This means that for most individual

landmarks and length segments, time does not have a sufficient influence on aortic growth, but in

total the aorta does undergo a significant elongation over time. These results are different from



45

literature, as they add an extra parameter and do not conclude that time has an important

influence on the diameter [11,12]. The results from this study would probably have matched those

of literature concerning the influence of time on dilatation if the sample had been bigger and the

time interval longer, as correlations could be guessed out of plots, but not statistically proven.

As the increases in aortic surface area and total elongation per year were proven to be significant,

we deem appropriate to say that the aorta knows a yearly growth rate both in length (1.6 mm/year)

and ASA (7.5 - 13.4 mm²/year).

For the dilatation (diameter and ASA), although a significant increase per year was noted, no

correlation with the time interval could be found, thus suggesting that other (risk) factors play a

role in the yearly growth of the aorta. Therefore, the time influence on the aorta (as reported in

literature) was not taken into account. For the elongation, the results show that time had an

influence on the combined aortic length from the arch or descending aorta to the proximal

abdominal aorta ( L2+L3+L4 or L3+L4).

To conclude, time should be considered as an influential variable on both dilatation (literature)

and elongation (this study).

4.3 Do elongation and dilatation go hand in hand As almost no common evolution was demonstrated between dilatation and elongation for most

landmarks, the same diagnostic values cannot be used for elongation as they do for dilatation.

Thus, the length cannot be used to replace the diameter as a defining parameter for aneurysm

repair because the evolution in length is not similar to the evolution in diameter in this sample.

The elongation will need its own criteria for aortic assessment and more research is needed to

test this correlation again in a larger population, over a longer time interval.



46

5 STUDY LIMITATIONS Limitations of this retrospective analysis are reported in the table below (table 14).

TABLE 14. Study limitations

Imaging Technique

o Only inclusion of preoperative and postoperative scans of the same imaging modality due to the difficulty of CT-MRI error implementation.

o Imaging in different hospitals with other standardization on the techniques.

o Imaging without inclusion of the aortic bifurcation.

o Imaging without contrast or of poor quality.

o No other choice but to measure the perpendicular diameter, instead of the smallest to calculate the aortic ellipse function.

o Round off to 1 mm although most of the studies go as low as 0.01mm.

o Use of the eyeballing method due to program restrictions for MRI and CT without contrast.

o Arbitrary choice of outer-to-outer wall measurements, although the quality of the scans did not allow for a differentiation between the inner and outer wall.

o Non-experienced researchers with unavoidable intra- and inter-operator variability, even if each patient was assessed by one observer in one day.

Design Analysis and Results

o Scarce literature and data on aneurysms without dissections, as they are often combined.

o Only 10% inclusion of the initial study population (30 patients), thus with more chance of random findings.

o Missing literature to evaluate the results on physiological and pathological elongation.

o Probability of selection bias as patients with higher risk know a closer follow-up (scans).

o Relatively short duration of follow-up given the lifetime risk of metachronous aortic pathology.

o Negative values for some aortic evolutions even though the mean/median was always positive.

o Possible problems for dimension assessment: o Systolic/diastolic pulsations in the

aorta. o Surgery-related: hemi-arch repair with

influence on aortic arch evolution (explaining results for LM2).

o Blood volume and medication intake. o Changing measuring point at the diaphragm

depending on inspiration or expiration. o No account taken for the >3mm significance

limit described in literature o Missing subgroups with at least 5

observations for analysis of some risk factors.



47

6. CONCLUSION Patients that underwent surgery for a proximal aortic aneurysm (without dissection) should

undergo distal aortic imaging at follow-up since the distal aorta knows a certain dilatation and

elongation after a proximal aortic repair. Consideration for the time-interval after surgery should

be kept in mind and the length parameter should be assessed for the combined distal aorta (not

in segments) but should not be used to replace the diameter as a defining parameter for aneurysm

assessment. Instead, new criteria on aortic follow-up are needed for the elongation of the distal

aorta after proximal aortic repair. To continue, the ASA parameter could be used as an alternative

for the diameter if automatization of this function would exist (i.e. easier to use) and the

parameters diameter, length and ASA should be measured at predefined and standardized

landmarks for the distal follow-up. Furthermore, special attention is advised for the age and

gender of the patient and the presence of Marfan disease or other connective tissue diseases.

Finally, statins should be considered as drugs with a protective effect on the aortic size.

This study evoked more research questions and future possibilities of research concerning the

distal aortic follow-up, of which some examples are discussed in the following. Future studies

should address the standardization of postoperative follow-up on both time (e.g. after 1 year, 3

years, 5 years, ...) and imaging (e.g. always a MR until the aortic bifurcation). The predictive value

(morbidity and mortality) and potential inclusion in risk or diagnostic scores of the parameters

ASA and length still needs in depth evaluation with an additional re-consideration of the

correlation between the elongation and the dilatation. Longer studies with larger study populations

are required to analyze the influence of risk factors or changes in the aortic dimensions on the

hard endpoints i.e. need for reintervention and mortality.



48

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_____________________________________________________________________________

Appendices

Table of Contents

1. Appendix 1: Full literature search strategy 2. Appendix 2: Baseline characteristics

3. Appendix 3: Descriptive, predicting and confounding variables

4. Appendix 4: Outcome variables for length, diameter and ASA

5. Appendix 5: Derivative variables

6. Appendix 6: Full Statistical analysis

7. Appendix 7: Boxplots for diameters and lengths

8. Appendix 8: Table reports of the results

Appendix 1

Elaboration of the literature search: search strategy

The literature research started with a comparison of the guidelines from both Europe, in 2014

[1] and in 2017 [24], and the USA in 2006 [9], 2010 [3] and 2017 [2], found in Google Scholar

with the search terms “guidelines thoracic aorta”.

I. Background information about aortic aneurysms [4-6,25-28,30]. I. Search terms in PubMed: aortic aneurysm, thoracic aorta, proximal aortic

repair, aorta replacement, aortic valve sparing David, valve sparing aortic

replacement, Bentall procedure or replacement, ascending aorta replacement,

ascending aorta Bentall, comparison surgical methods aortic root [25,46],

follow-up Bentall [29].

II. Mesh Terms in PubMed: Aortic Aneurysm/surgery, Aortic Valve/surgery, Sinus

of Valsalva/surgery, Treatment Outcome, Blood Vessel Prosthesis

Implantation/methods.

Articles, about the 3 different types of open proximal aortic repair, were found with the following

search terms in PubMed:

• “aortic valve sparing david”, “valve sparing aortic replacement”, “Bentall procedure”,

“Bentall replacement”, “ascending aorta replacement”, “ascending aorta Bentall”,

… and Mesh Terms: “Aortic Aneurysm/surgery”, “Aortic Valve/surgery”, “Sinus of

Valsalva/surgery”, “Treatment Outcome”, “Blood Vessel Prosthesis

Implantation/methods”, … [4-6,25-28,30].

• “comparison surgical methods aortic root” via “see 1 citation found by title matching

your search”, via similar articles of “Comparison of three different surgical methods in

aortic root aneurysms: long-term results” by Caynak B. et al, another article about

valve-sparing replacement was found [25,46].

• “follow-up bentall”. Via similar articles of “Peri-aortic fluid after surgery on the ascending

aorta: Worrisome indicator of complications or innocent postoperative finding?” and

further via similar articles of “Clinical outcomes after separate and composite

replacement of the aortic valve and ascending aorta.” An article about long-term results

of the Bentall procedure were found [29].

II. Measuring techniques for dilatation and elongation. I. Descending aorta geometry [19,34,35]

II. Aortic elongation thoracic aneurysm [7,8,18,20,22]

III. Aortic elongation age [21]

IV. Aortic length expansion aneurysm [23].

A standardized measuring technique to measure the diameters and lengths of different aortic

segments, was constructed in different articles with the following search terms:

• “Descending aorta geometry”, the first article of the 278 results was used [34], because

it is crucial for this study and was published in the “Journal of the american college of

cardiology”. Further investigation via “see all similar articles”, if “sort by: best match”,

resulted in two more articles, used in this study. Firstly, the second article in line: “aortic

elongation part I: the normal aortic ageing process” which was recently published in

March 2018 in “Heart” by Adriaans et al. Secondly , another article by Rylski B. et al,

published in August 2018 in the “European Journal of Cardio-Thoracic Surgery”, was

found in the “similar articles” of lastnamed article [35].

• The search: “Aortic elongation thoracic aneurysm”, led to two interesting articles from

the TAIPAN project. The first one by Lescan M. et al, published in Augustus 2017 in

the “European Journal of vascular and endovascular surgery” and the second,

by Krüger et al, published in June 2017 in “European Journal of Cardio-thoracic

Surgery”. Via “similar articles” of Krüger et al, two other articles of Krüger were

published in the “European Journal of Cardio-thoracic Surgery” was included

[7,8,18,22]. From the reference list of Lescan et al., the study of Morrison et al. about

the circumferential and longitudinal strain of the aorta, was included [20].

• “Aortic elongation age”, gave 75 articles, the fifth on the list, concerning the age-

associated elongation, was included [21]

• To better understand the correlation between the dilatation and elongation of the aorta,

other search terms were used e.g. “aortic length expansion aneurysm”. The second

article (of the 95 results given in PubMed), by Michineau et al. and published in the

“European Journal of Vascular and Endovascular Surgery”, was included. Although this

article is from 2010, it’s still of great importance to demonstrate the correlation.

III. Imaging and the CT-MRI error. I. MRI CT compare aorta [33]

As both CT and MRI were used in this study, it was necessary to compare these two methods

and find the possible divergence between their measurements. Searching PubMed with “MRI

CT compare aorta”, led to the 4th of the 24 given articles. An interesting article was published

in “Chest” in 2004 and pointed out the differences in measurements between Helical CT and

MRI, the so called “CT-MRI error”. This could theoretically make it possible to compare the

results obtained by both imaging modalities.

IV. The distal follow-up after a proximal aortic aneurysm repair. I. Distal aortic reinterventions after root surgery [31,32,36-39,41-45,49]

II. Follow up Bentall [47,48]

III. Bentall distal dilatation [40]

At last, the core of this study, scilicet the distal findings after a proximal aorta aneurysm repair,

was searched in the literature. Very different articles were found with very different keywords

and search terms:

• “distal aortic reinterventions after root surgery” resulted in 12 articles. An article by

Iribarne et al, published in “The Annals of Thoracic Surgery in 2017 and by Idrees et

al. in 2016, were found to be interesting, as it focuses on the distal aorta after proximal

repair. In the reference list of previous article, other important articles were found:

studies by Abdulkareem et al., Gott et al., Pacini et al., Raudikivi et al., Schoenhoff et

al., Schoenhoff et al., Price et al., Flynn et al., Finkbohner et al., Kawamoto et al.. and

Crawford et al [31,32,36-39,41-45,49].

• “Follow up bentall” resulted in, when sorted by “most recent”, an article about the

postoperative findings i.e. the study of Boccalini et al. In its “similar articles” Houël et

al. was found again. The first “similar article” of this article was from Hagl et al. and was

included, due to the essential information about event-free survival after Bentall [47,48].

This too was published in the renowned “The Annals of Thoracic Surgery”.

• “bentall distal dilatation”, resulted in an article by Luciani et al, in its “similar articles”

another relevant article, published by Girdauskas et al in “The Annals of Thoracic

Surgery”, about reinterventions after root surgery, was found and included [40]. Other

articles already found by previous search results (explained above) [46].

V. The influence of patient characteristics and risk factors. I. Risk factors aortic diameter [10-15]

II. Aortic disease genetic syndromes connective tissue familial [16,17].

To define the correlation between certain risk factors and the measurements of the aorta,

articles were included, using the following keywords in PubMed:

• “risk factors aortic diameter”, sorted by “best match”. The article by Mensel et al (2016),

published in the “European Radiology”, was used to correctly demonstrate the

correlation [11]. Three other studies were found in the “similar articles” of Mensel et al.

The first stating the distributions of the aortic diameters, published in 2013 in “The

American Journal of Cardiology” and the second from the reference list of Mensel et

al., stating the influences of risk factors by Forsdahl et al. in Circulation [13,15]. Thirdly

an article concerning the normal limits by age, gender and BSA of the aortic size,

published in 2008 in the “JACC, Cardiovascular Imaging” [10]. In Wolak et al. another

useful article was spotted in their references about the influence of age on the aorta.

This study by Aronberg et al. from 1984 is still referenced by many studies today [11].

• “Aortic disease genetic syndromes connective tissue familial” led to the study of Cury

et al. and Cikach et al. about the aortic diseases influencing the diameter [16,17].

TABLE 1.A. Journals used in the search strategy with their corresponding impact factor (IF) and ranking in their field of medicine.

Journal IF Ranking in their field

BMJ [5] 23.562 4/155 medicine, general and internal

Journal of the American college of cardiology [34] 19.896 2/126 cardiology

Circulation [4,15,41] 18.881 2/128 cardiovascular

JACC, Cardiovascular Imaging [10,21] 10.189 1/127 radiology

Radiology [36] 7.469 4/129 radiology

Chest [33] 6.147 7/59 respiratory

Heart [19] 6.059 17/126 cardiology

Journal of thoracic and cardiovascular surgery [37,43,47]

4.880 28/128 cardiovascular

9/200 surgery

European Journal of vascular and endovascular surgery [6,7,23]

4.061 15/127 surgery

European Radiology [11] 3.967 16/127 radiology

European Journal of Cardio-Thoracic Surgery [8,18,22,35,38,44]

3.759 24/127 surgery

Annals of Thoracic Surgery [31,32,39,40,45,48,49] 3.7 27/197 surgery

American Journal of Cardiology [12] 3.398 47/126 cardiology

Journal of Vascular Surgery [20] 3.294 34/200 surgery

International journal of vascular medicine [16] 1.210 57/65 pheripheral vascular disease

Cleveland clinic journal of medicine [17] 1.783 67/155 medicine, general and

internal

TABLE 2.A. Baseline characteristics Characteristics Patients (n=30)

Median (Q1-Q3) Mean (SD) Age

Pre-op 47.5 (37.5-65.3) 49.80 (17.1) Surgery 48.0 (37.5-65.3) 49.97 (17.1) Post-op 53.0 (42.0-69.0) 54.43 (15.9)

BSA (m2) 1.97 (1.88-2.17) 1.99 (0.21) Height (cm) 177.5 (168.5-185.3) 176.5 (12.6) Weight (kg) 81.5 (70-90.5) 80.7 (13.2)

N (%) Gender

Male 21 (70.0) Female 9 (30.0)

Blood pressure Normotension 20 (66.7) Hypertension 10 (33.3)

Diabetes Mellitus 2 (6.7) Dyslipidemia 8 (26.7) Current smoking 4 (13.3) Connective tissue diseases 20 (66.7) Genetic disease

None 21 (70.0) Marfan 7 (23.3) Turner 1 (3.3)

Loeys-Dietz 1 (3.3) Ehlers-Danlos 0 (0.0)

Congenital disease None 17 (56.7) BAV 10 (33.3)

Coarctatio 0 (0.0) BAV + Coarctatio 1 (3.3)

Other 2 (6.7) Medication

Beta-blocker 26 (86.7) ACE-inhibitor 3 (10)

Angiotensin II RB* 4 (13.3) NDCCB** 1 (3.3)

Statins 6 (20.0) Other 5 (16.7)

Procedure David I or II 14 (46.7)

Bentall 13 (43.3) AVR + tube 3 (10)

Re-intervention None 28 (93.3)

Proximal 1 (3.3) Distal 1 (3.3)

Indication for reintervention Descending or

thoracoabdominal aneurysm 1 (3.3)

Other 1 (3.3) Imaging modality

MRI 10 (33.3) CT 20 (66.7)

*RB = receptor blocker, **NDCCB = non-dihydropyridine calcium channel blocker

Appendix 2

Appendix 3

TABLE 3.A. Descriptive, predicting and confounding variables with respective explanations and codes.

Variable

Explanation

Code

id Patient number /

nm Name / sx Gender 1 = male, 2 = female

agepre ageop agepos

Age (years) /

bsa Body surface area (m2) / w Weight (kg) / h Height (cm) / bb Beta-blocker 0 = no, 1 = yes ai Ace-inhibitor 0 = no, 1 = yes

atrb Angiotensin II receptor blocker 0 = no, 1 = yes

ndccb Non-dihydropyridine calcium channel-blocking agent 0 = no, 1 = yes

stt Statin 0 = no, 1 = yes oth Other medication 0 = no, 1 = yes

bp Blood pressure

0 = normotension (including under treatment)

1 = hypertension (including under treatment) 2 = hypotension

smo Current smoking 0 = no, 1 = yes

gen Genetic disease 0 = none, 1 = Marfan,

2 = Turner, 3 = Loeys-Dietz, 4 = Ehlers-Danlos

con Congenital disease

0 = none, 1 = BAV, 2 = coarctation,

3 = BAV + coarctation, 4 = other

ctd Connective tissue disorder 0=none, 1 = all genetic and congenital diseases

lip Dyslipidemia 0 = no, 1 = yes dm Diabetes Mellitus 0 = no, 1 = yes

pro Surgical procedure 1 = David I or II, 2 = Bentall, 3 = AVR + tube

rei Reintervention 0 = no , 1 = proximal, 2 = distal

irei Indication for reintervention

0 = none, 1 = descending and/or

thoracoabdominal aneurysm, 2 = other

dpre Date preoperative imaging / dop Date surgery / dpos Date postoperative imaging / ima Imaging modality 1 = MRI, 2 = CT

Appendix 4

TABLE 4.A. Outcome variables for lengths, diameters and aortic surface area.

Variable Anatomical location Exact point of measurement

LM1 D1/d1/asa1 Sinotubular junction (mm) Right above the aortic valves

LM2 D2/d2/asa2 Proximal aortic arch (mm) At the origin of the BCT

LM3 D3/d3/asa3 Mid-aortic arch (mm) At the origin of the left LSA

LM4 D4/d4/asa4 Proximal descending aorta (mm) Approximately 2 cm distal to

LSA LM5

D5/d5/asa5 Mid-descending aorta (mm) Level of the pulmonary artery bifurcation

LM6 D6/d6/asa6 Distal descending aorta(mm) At the diaphragm. CT: in frontal

plane, MRI: in sagittal plane LM7

D7/d7/asa7 Proximal abdominal aorta (mm) Just above the celiac origin

LM8 D8/d8/asa8 Distal abdominal aorta (mm) Just above the aortic bifurcation

L1 Ascending aorta (mm) LM1-LM2

L2 Aortic arch (mm) LM2-LM4

L3 Descending aorta (mm) LM4-LM6

L4 Proximal abdominal aorta (mm) LM6-LM7

L5 Distal abdominal aorta (mm) LM7-LM8

LM = landmark, for diameter (D/d, maximal/perpendicular) and aortic surface area (ASA).

Appendix 5

TABLE 5.A. Derivative variables with respective explanations and codes.

Variable Explanation Code

BSA Body surface area (m2) Mosteller = ((W*H)/3600)/2

ASA Aortic surface area (mm2) Ellipse surface area = (maximal

diameter/2)*(perpendicular diameter/2)*𝜋

Appendix 6

STATISTICAL ANALYSIS Statistical analysis of the measurements and the anthropometric data of the patients (sex, age,

hypertension, medication, etc.) was done with IBM® SPSS® Statistics 25.0 (Armonk, NY: IBM

Corp.). To minimize non-sampling errors, a thorough and general datacleaning was conducted.

General data-cleaning and Baseline Characteristics. First, correct input of data was checked manually by going over the different columns and

rows of the DATA-file to look for inconsistencies. Second, two new variables were computed

to check the inclusion criteria: tpre (dop-dpre/31557600s) and tpos (dpos-dop/31557600s)

namely the time between surgery and respectively, the preoperative and postoperative scan.

Third, the BSA (bsa) of every patient in the DATASET was calculated and computed, based

on the weight (w) and height (h) of the patient. Fourth, all of the variables were attributed a

correct ‘Type’, ‘Width’, ‘Decimals’, ‘Label’, ‘Values’ and ‘Measure’ by use of the FORMATS-,

VARIABLE LABELS-, VALUE LABELS- and VARIABLE LEVEL-functions. Before starting with

the statistical testing, the ‘Frequency tables’ (FREQUENCIES), the ‘Codebook’ (CODEBOOK)

and the ‘Case summaries’ (SUMMARIZE) were used to detect any ‘Missing values’, ‘Outliers’

and incorrect or deviated input. Additionally, the same functions were used to produce

baseline characteristics of the sample (see table baseline and boxplots).

Statistical testing Inductive statistics were utilized to make assumptions on the population (N), based on our

sample of 30 patients (n=30). All p-values were tested two sided and considered significant if

alpha < 0.05. To test for normality, the Shapiro-Wilk test and QQ-plots were used

consistently, as these ones are the most reliable for small samples (n=30).

1. Aortic ageing: does the aorta change with increasing age? First, four continuous variables were computed: L34pre (L3pre+L4pre), L34pos

(L3pos+L4pos), L234pre (L2pre+L3pre+L4pre) and L234pos (L2pos+L3pos+L4pos) to

eliminate the need for the D6/d6 landmark, as this one is the most prone to fluctuation due to

its location (at the diaphragm, depending on respiration). Second, these new continuous

variables were computed (COMPUTE VARIABLE) for every landmark using this formulas:

Dxdiff = Dxpos - Dxpre dxdiff = dxpos - dxpre with x = [1,7], ∈N and y = 1, 2, 3, 4, 34, 234 Lydiff = Lypos - Lypre

Dxdiff, dxdiff, and Lydiff represent the difference in diameter and length between preoperative

and postoperative aortas i.e. the dilatation and elongation. Note that the landmark D8/d8 and

the segment L5 were not included in the formula, as only one patient had both a preoperative

and postoperative scan. Third, the variable tdiff (dpos-dpre/31557600) was created to calculate

the exact time between the preoperative and postoperative scan.

To continue, every variable (Dxpre, Dxpos, dxpre, dxpos, Lypre, Lypos, Dxdiff, dxdiff, Lydiff)

was assessed for normality of distribution by means of the Shapiro-Wilk test (DESCRIPTIVE

STATISTICS - EXPLORE). Results of these can be found in full in table 6.A. To answer the

research question, the Pearson and Spearman Correlations (CORRELATE) (respectively

for normally and non-normally distributed parameters), were calculated and tested (two-sided,

alpha = 0.05). Results for the Pearson or Spearman correlation (r e [-1,1]), with r=0 standing

for no linear correlation, r=1 for a perfect linear correlation and r = -1 for a perfect inverse linear

correlation are to be found in table x in appendix E. If possible, the linear regression was drawn

and shown on scatterplots (CHART BUILDER - CHART EDITOR). The following 2 research

questions were tested (two sided, alpha = 0.05): Question 1: Are age and diameter significantly correlated? Using:

o Preoperative age (agepre) and preoperative diameters and lengths (Dxpre, dxpre, Lypre).

o Postoperative age (agepos) and postoperative diameters and lengths (Dxpos, dxpos, Lypos).

Question 2: Are time and dilatation and/or elongation significantly correlated? Using:

o Time between scans (tdiff) and the diameter/length differences (Dxdiff, dxdiff, Lydiff).

2. Aortic dimensions

2.1 Is there a significant difference between the preoperative and postoperative aorta in diameter and length at every landmark?

The variables used to answer this research question were all continuous and paired (Dxpre,

Dxpos, dxpre, dxpos, Lypre, Lypos). Henceforth, the paired Student’s t-test (COMPARE

MEANS - PAIRED-SAMPLES T TEST) was performed for normally distributed variables (table 6.A), to test the null hypothesis that the mean aortic dilatation and elongation equals

zero (two sided, alpha=0.05). The specific condition for carrying out this test was the normal

distribution of the difference variables (Dxdiff, dxdiff, Lydiff) over the paired preoperative and

postoperative population and was assessed earlier (table 6.A).

For the non-normally distributed variables, the Wilcoxon matched-pairs signed-rank test (NONPARAMETRIC TESTS) was used if the distribution of differences between preoperative

and postoperative aortas was symmetrical (demonstrated by boxplots (GRAPHS -

CHARTBUILDER)), and the Sign test (NONPARAMETRIC TESTS) if this distribution of

differences was not symmetrical. The Wilcoxon matched-pairs signed-rank test assumed a null

hypothesis dictating that the median aortic dilatation or elongation equals zero (two sided,

alpha = 0.05), whilst the null hypothesis of the Sign test was the assumption of equal positive

and negative differences in diameters and lengths. Due to the asymmetrical aspect of the

tested groups using the Sign test, median differences should not be reported.

2.2 Do elongation and dilatation of the aorta go hand in hand for every landmark?

To begin with, new continuous variables were computed for every maximal and

perpendicular diameter of a landmark: meanDLydiff and meandLydiff were defined as being

the mean maximal and perpendicular dilatation for the corresponding aortic length segment.

meanDLydiff with y = 1, 2, 3, 4, 34, 234 meandLydiff

This was calculated by making the sum of the diameter difference variables of the landmarks

situated in the corresponding length segment and dividing them by the number of landmarks

in that length segment (see table x). Notice that again the variables meanDL5diff and

meandL5diff do not exist, because of the small number of observations for this segment.

To continue, the elongations (Lydiff) were correlated with their corresponding dilatation both in

diameters (Dxdiff, dxdiff) and ASA (asaxdiff, see lower) and again the landmark D8/d8 and

segment L5 were left out due to insufficient observations. By means of the Shapiro-Wilk test

(DESCRIPTIVE STATISTICS- EXPLORE), normality was assessed for the newly created

variables meanDLydiff and meandLydiff. P-values, skewness and kurtosis for the non-normally

distributed variables are shown in table 6.A. To answer the research question i.e. the presence

of a correlation between dilatation and elongation of the aorta, the Pearson and Spearman Correlations (CORRELATE) were calculated and tested (two sided, alpha = 0.05):

o Elongation per segment (Lydiff) with the corresponding maximal (Dxdiff) and

perpendicular (dxdiff) dilatation.

o Elongation per segment (Lydiff) with the corresponding ASA dilatation (asaxdiff).

o Elongation per segment (Lydiff) with the corresponding mean maximal (meanLydiff)

and perpendicular (meanpLydiff) dilatation per segment.

2.3 Do risk factors or patient characteristics influence the aortic dimensions?

The possible influence of risk factors or patient characteristics on the previously reported

landmarks were assessed, using unpaired continuous tests for following variables:

o Gender (sx), Blood pressure (bp), Diabetes mellitus (dm), Dyslipidemia (lip), Smoking

(smo), Genetic disease (gen), Congenital disease (con), Procedure (pro),

Reintervention (rei), Indication for reintervention (irei), Imaging modality (ima), Beta-

Blocker (bb), Ace-Inhibitor (ai), Angiotensine-II receptor blocker (atrb), Non-

dihydropiridine calcium channel blocking agent (ndccb), Statins (stt), Others (oth).

o Only the landmarks in which a significant dilatation or elongation was reported were

examined for external influences i.e. D1diff, d1diff, D3diff, d3diff, D4diff, d4diff, D5diff,

d5diff, D6diff, d6diff, D7diff,d7diff, L234diff.

To make better assumptions for small groups in this sample of 30 patients (n=30), the

congenital diseases (con) and genetic diseases (gen) were also, besides the normal grouping,

dichotomised in with or without having a connective tissue disease by transforming both

variables in a new one nl connective tissue disease (cnv) (TRANSFORM - RECODE)

For normally distributed variables, the Independent samples T-test (2 groups) or the One-way ANOVA (>2 groups) (ANALYZE - COMPARE MEANS) was executed, taking in to account

that groups had to have at least 5 individuals. The 2 specific conditions, i.e. the normality of

residues and homogeneity of variances, were checked. The first condition was tested by

computing the residual values (ANALYZE - GENERAL LINEAR MODEL - UNIVARIATE) and

testing them on normality using the Shapiro-Wilk test, QQ-plots (DESCRIPTIVE STATISTICS

- EXPLORE) and histograms (CHART BUILDER). The second condition was tested using the

Levene’s test with the null hypothesis stating that the variances are equal (2-sides, alpha =

0.05). If the null hypothesis wasn’t rejected, the independent samples T-test or ONE-way

ANOVA test was executed to test the null hypothesis that the mean of the elongation or

dilatation, was equal for every group of a specific descriptive statistic e.g. gender, with an equal

mean for male and female patients (2-sided, alpha = 0.05). For a significant result after a ONE-

way ANOVA, the Post-Hoc tests Tukey and/or Scheffe were performed, with consideration of

the bonferroni correction. For the continuous variables who were found to have normality of

residuals but didn’t meet the assumption of homogeneity of variances (significant Levene’s

test), the Brown or Welsh-Forsythe was analysed to test the same null hypothesis as for the

ONE-way ANOVA.

For non-normally distributed variables, the Mann-Whitney U test (MWUT) (2 groups) or the

Kruskal Wallis test (KWT) (>2 groups) was used (NONPARAMETRIC TESTS). The most

important assumption for using the KWT or MWUT was the presence of at least 5 samples in

each group. Box plots and histograms were drawn to assess identical and symmetrical shapes

of the distributions of dilatations and elongations in each group. Depending on the shape, the

null hypothesis, in general stating that both groups are from the same population, differ slightly

(2-sided, alpha = 0.05):

o Symmetric and identical shape: the mean of every group is equal.

o Not symmetric, but identical shape: the median of every group is equal.

o Neither symmetric, nor identical shape: the different groups are samples of the same

population (the medians should not be reported, only the significance of the test).

Post-hoc testing with the Mann-Whitney U test was performed to assess the 2 on 2 differences,

with the same null hypothesis as stated above and with consideration of the Bonferroni

correction. Not only the non-normally distributed variables but also the normally distributed

variables were tested with the MWUT and KWT to make the results more comparable.

The influence of BSA (bsa) on the ASA, aortic elongations and dilatations (both in diameters

and ASA), was assessed by use of a correlation, because BSA (bsa) is a continuous variable.

The variable was found to be normally distributed within the population (p = 0.380) by use of

the Shapiro-Wilk test and QQ-plots (DESCRIPTIVE STATISTICS- EXPLORE). Thus the

Pearson correlation and Spearman correlation (CORRELATE) were tested and calculated

respectively for normally and non-normally distributed dilatations and elongations (2-sided,

alpha = 0.05).

2.4 Does the aorta have a significant growth per year? To answer this research question, new variables were computed (COMPUTE VARIABLE)

asaxdifftime and Lydifftime, representing the dilatation in ASA and elongation per year, using

next formulas: asaxdifftime = asaxdiff / tdiff with x = 1,3,4,5,6,7 and y = 1,2,234 Lydifftime = Lydiff / tdiff

The new variables asaxdifftime and Lydifftime were only computed for elongations and

dilatations known to be significantly different from 0 and tested for normality by means of the

Shapiro-Wilk test and QQ-plots ((DESCRIPTIVE STATISTICS- EXPLORE). All new variables

were found to be non-normally distributed and thus the One-Sample Wilcoxon signed rank test (NONPARAMETRIC TESTS) was used to test the null hypothesis that the median

elongation and/or dilatation was equal to zero (two-sided, alpha = 0.05).

3. Is the aortic surface area a useful parameter to describe the aortic growth?

First, the new variables asaxpre, asaxpos and asaxdiff were computed (COMPUTE

VARIABLE), using the formula for the surface area of an ellipse (in mm²):

asaxpre = (Dxpre/2) * (dxpre/2) * 𝜋 asaxpos = (Dxpos/2) * (dxpos/2) * 𝜋 with x = [1,7], ∈ N and 𝜋 = 3.1415 asaxdiff = asaxpos - asaxpre

The variables asaxpre and asaxpos represent the aortic surface area at each landmark,

respectively preoperative and postoperative. Asaxdiff stands for the difference in aortic surface

area at landmark ‘x’. Notice that landmark D8/d8 was not taken into account, because neither

D8diff nor d8diff exist. Only asa3diff and asa7diff were found to be normally distributed, by

means of QQ-plots and the Shapiro-Wilk test (DESCRIPTIVE STATISTICS- EXPLORE) (table

6.A). To make all landmarks more comparable, a non-parametric test was used for all

variables. Thus the non-parametric One-Sample Wilcoxon Signed Rank Test (NONPARAMETRIC TESTS) was used to test the null hypothesis that the median of the

difference in aortic surface area (asaxdiff), equals zero, at a certain landmark (2-sided, alpha

= 0.05).

To test and confirm significant elongation or dilatation a third time, the Dxdiff, dxdiff and Lxdiff

were tested in another way, using the One-Sample Wilcoxon signed rank test (NONPARAMETRIC TESTS) with a null hypothesis dictating that the median of the difference

in diameter or length at a certain landmark equals zero (see table x). At last, the spearman correlation (CORRELATE) between asaxdiff and agediff was calculated and tested, to

research the influence of time on the aorta in another way.

TABLE 6.A. Significant values for the Shapiro-Wilk test.

Variable* Significance (p) Skewness (s) Kurtosis (k)

D1pre 0.048 1.016 1.721

D5pre 0.001 1.885 6.361

d5pre 0.001 1.727 5.225

D5pos < 0.001 2.995 12.361

d5pos < 0.001 3.331 14.574

L1pos 0.023 -0.939 2.593

L2pos 0.005 1.039 4.155

L4pos 0.017 0.945 0.920

L5pre 0.032 1.853 3.441

D1diff 0.026 -1.066 1.502

D2diff < 0.001 -2.118 6.899

d2diff < 0.001 -1.550 2.696

D5diff < 0.001 2.192 8.287

d5diff < 0.001 3.169 14.055

d6diff 0.001 0.109 3.845

D7diff 0.001 1.665 5.496

d7diff 0.039 0.497 2.305

L3diff 0.001 0.782 4.641

L34diff 0.002 1.510 2.823

MeanDL1diff 0.013 -1.315 3.096

MeanDL3diff 0.028 0.618 2.154

MeandL3diff 0.004 1.286 1.688

MeanDL4diff 0.031 1.115 2.023

MeanDL34diff 0.040 0.693 1.398

MeandL34diff 0.001 1.381 1.746

asa1diff 0.004 -1.474 2.728

asa2diff < 0.001 -1.974 5.127

asa4diff 0.036 1.094 1.515

asa5diff < 0.001 4.646 23.863

asa6diff 0.005 1.237 2.840

asa1pre 0.006 1.438 2.726

asa5pre < 0.001 2.856 11.310

asa6pre 0.005 1.502 3.292

asa3pos 0.005 0.926 0.923

asa4pos 0.039 0.912 0.362

asa5pos < 0.001 4.382 21.754

asa6pos 0.002 1.635 4.193

*Not shown variables had non-significant results and were thus found to be normally distributed. In these variables the non-parametric tests and spearman correlation were used.

Appendix 7

c Figure 7.A. Boxplots for lengths

Figure 7.B. Boxplots for diameters

TABLE 8.A. Outcomes of the parametric distributed variables to test the absolute mean dilatation or elongation.

Variables Mean difference (mm)

CI lower*

CI upper* P-value

Sinotubular junction (d1) -11.733 -16.049 -7.418 <0.001

Mid-arch (D3) 1.033 0.240 1.827 0.012

Mid-arch (d3) 1.400 0.564 2.236 0.002

Proximal descending (D4) 1.567 0.424 2.709 0.009

Proximal descending (d4) 1.433 0.145 2.722 0.030

Distal descending (D6) 1.500 0.418 2.582 0.008

Thoracoabdominal (L2+L3+L4) 9.283 2.210 16.356 0.012

The paired Student’s t-test was used in parametric distributed variables with a normal distribution of the difference variable. *CI = 95% Confidence Interval. Significant correlations (p<0.05) are marked. D= maximal diameter, d=minimal/perpendicular diameter and L=length.

Appendix 8

TABLE 8.B. Outcomes of the non-parametric distributed variables to test the absolute median dilatation or elongation.

Variables Median pre-op (mm)

Median post-op (mm) Z-value P-value

Sinotubular junction(D1) 49.00 36.50 -4.095 <0.001

Proximal arch (D2)S 37.00 37.00 -0.385 0.700

Proximal arch (d2)S 35.00 34.50 - 1.000b

Mid-descending (D5) 27.00 28.00 -2.552 0.011

Mid-descending (d5) 25.00 26.00 -2.633 0.008

Distal descending (d6)S 22.00 23.50 - 0.007b

Proximal abdominal (D7) 25.00 26.00 -3.047 0.002

Proximal abdominal (d7)S 22.50 22.50 - 0.043

Ascending aorta (L1) 70.00 56.00 -3.331 0.001

Aortic arch (L2) 59.00 61.00 -2.226 0.026

Descending aorta (L3) 197.50 204.50 -0.800 0.423

Proximal abdominal aorta (L4) 27.00 31.50 -0.165 0.869

Descending + Proximal abdominal aorta (L3+L4)

229.00 235.00 -1.375 0.169

The Wilcoxon matched-pairs signed-rank test was used in non-parametric distributed variables, if symmetric assumption was met. If not, the sign test was performed. S Signed test was used, medians not reportable due to not comparable. b binominal because <25 cases (ties excluded). Significant correlations (p<0.05) are marked. D= maximal diameter, d=minimal/perpendicular diameter and L=length.

TABLE 8.C. Outcomes of the Wilcoxon signed-rank test to test the absolute median difference in diameter (D/d) and length (L) over time.

Variable D1 D2 D3 D4 D5 D6 D7

Significance (p) <0.001 0.847 0.016 0.021 0.015 0.010 0.002

Variable d1 d2 d3 d4 d5 d6 d7

Significance (p) <0.001 0.313 0.003 0.022 0.006 0.010 0.022

Variable L1 L2 L3 L4 L5 L34d L234

Significance (p) 0.001 0.026 0.423 0.869 0.317 0.169 0.013

Wilcoxon signed-rank test, to test whether the median of the difference between preoperative and postoperative diameter and length, equals zero, at a certain landmark (asymp.sign. alfa=0.05). D= maximal diameter, d=perpendicular diameter, L=length segment.

TABLE 8.D. Outcomes of the Wilcoxon signed-rank test, to test the absolute median difference in aortic surface area (ASA) over time.

Variable asa1 asa2 asa3 asa4 asa5 asa6 asa7

Significance (p) <0.001 0.472 0.001 0.021 0.005 0.019 0.006

Wilcoxon signed rank test, to test whether the median of the difference between preoperative and postoperative aortic surface area, equals zero, at a certain landmark (asymp. Sign. alfa=0.05). asax = aortic surface area of landmark x. Significant correlations (p<0.05) are marked.

TABLE 8.E. Reporting the outcomes of the correlation (r) between age (agepre and agepos) and diameter or length.

D1pre* d1pre D2pre d2pre D3pre d3pre D4pre d4pre D5pre* d5pre* D6pre d6pre D7pre d7pre D8pre d8pre

agepre 0.066 0.003 0.676 0.765 0.682 0.660 0.571 0.440 0.753 0.755 0.754 0.803 0.632 0.584 0.971 0.873

L1pre L2pre L3pre L4pre L5pre* L34pre L234pre

agepre 0.163 0.379 0.620 -0.237 0.316 0.463 0.512

D1pos d1pos D2pos d2pos D3pos d3pos D4pos d4pos D5pos* d5pos* D6pos d6pos D7pos d7pos D8pos d8pos

agepos 0.171 -0.034 0.716 0.665 0.598 0.542 0.556 0.477 0.561 0.571 0.492 0.523 0.402 0.511 0.037 -0.409

L1pos L2pos* L3pos L4pos* L5pos L34pos L234pos

agepos -0.275 0.164 0.232 0.121 -0.421 0.338 0.349

* Spearman correlations, all others are Pearson correlations. agepre = preoperative age, agepos = postoperative age, L=length segment, D=maximal diameter and d=perpendicular diameter of a landmark. The significant correlations (p<0.05) are marked.

TABLE 8.F. The p-values of the Mann-Whitney-U test for non-parametric variables, demonstrating the influence of risk factors on the aortic dilatation.

Variables

P-values (median increase in dilatation, mm)

Name Code LM3 LM5 LM6 LM7 D3 d3 D5 d5 D6 d6 D7

Blood Pressure Normotension (20) Hypertension (10)

0.005 (Normo+

2.5)

0.024 (Normo +

1.5)

Dyslipidemia Yes (22) No (8)

0.049 (No + 2)

Smoking Yes (4) No (26)

0.037 (No + 1.5)

Genetic disease None (21) Marfan (7)

0.042 (Marfan +

1)

0.010 (Marfan +

4)

0.027 (Marfan + 1)

Connective tissue disease

Yes (20) No (10)

0.032 (Yes + 2)

0.020 (Yes + 2.5)

Procedure David (14) Bentall (13)

0.033 (David + 1)

Statins Yes (6) No (24)

0.003 (No + 1.5)

0.013 (No + 2)

0.032 (No + 2)

0.032 (No + 2)

Normo = normotensive patients.

Table 8.G. The p-values of the independent samples T-test for parametric variables, demonstrating the influence of risk factors on the aortic dilatation.

Variables P-values (mean increase in dilatation, CI)

Name Code LM3 LM4 LM6 D3 d3 d4 D6

Blood Pressure Normotension (20) Hypertension (10)

0.007 (Norm + 2.15

CI: 0.65 - 3.65)

0.043 (Norm + 2.25

CI: 0.08 – 4.42)

Dyslipidemia Yes (22) No (8)

*0.016 (No + 2.05

CI: 0.42 – 3.67) Genetic disease None (21)

Marfan (7)

0.035 (Marfan + 1.86 CI: 0.14 - 3.57)

0.002 (Marfan + 3.71 CI: 1.46 - 5.95)

Connective tissue disease

Yes (20) No (10)

0.020 (Yes + 2.5

CI: 0.43 - 4.67) Procedure David (14)

Bentall (13)

Statins Yes (6) No (24)

0.02 (No + 3

CI: 1.22 - 4.79)

*0.010 (No + 2.08

CI: 0.55 - 3.62) All had normality of residu. Only the significant data was reported. *equal variance is not assumed (Levene is significant and therefore the Brown or Welsh-Forsythe was used to test the same null hypothesis).

TABLE 8.H. Reporting the outcomes of the correlation (r) between time interval and dilatation or elongation of the aorta.

tdiff tdiff

D1diff* 0.092 D6diff 0.069

d1diff 0.158 d6diff* -0.018

D2diff* -0.109 D7diff* 0.201

d2diff* 0.193 d7diff* 0.186

D3diff 0.098 L1diff 0.085

d3diff 0.354 L2diff 0.135

D4diff 0.146 L3diff* 0.337

d4diff 0.031 L4diff -0.780

D5diff* 0.176 L34diff* 0.584

d5diff* 0.181 L234diff 0.445

Significant correlations (p<0.05) are marked. * Spearman correlation, all others Pearson correlation. Dxdiff = difference in maximal diameter in landmark x, dxdiff= difference in perpendicular diameter in landmark x, Lxdiff= difference in length in landmark x, tdiff = time interval between both scans.

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DILATATION AND ELONGATION OF THE DISTAL AORTA AFTER A