Risk Factors, Incidence, and Clinical Impact of Intraluminal Thrombosis Following the FRozen ElephAnt Trunk (FET) ProCedure and Thoracic Endovascular Repair (TEVAR): A Multicenter rEtrospective Cohort Study
Conditions: Intraluminal Thrombosis, Tevar, FET
Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                            - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Risk Factors, Incidence, and Clinical Impact of
Intraluminal Thrombosis Following the FRozen ElephAnt
Trunk (FET) ProCedure and Thoracic Endovascular
Repair (TEVAR): A multicenter rEtrospective cohort study
(Fattori di rischio, incidenza e impatto clinico della trombosi intraluminale dopo le procedure di
Frozen Elephant Trunk (FET) e Riparazione Endovascolare Aortica Toracica (TEVAR): uno studio
di coorte retrospettivo multicentrico)
Acronym: TRACE
Promoter: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 
 Via Sforza 28, 20122 Milano, Italia
Coordinating center: SC Chirurgia Vascolare
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 
Via Francesco Sforza 35, 20122 Milano, Italia
Principal Investigator: Prof. Santi Trimarchi
 
                      Signature___________________ 
Document type: non-interventional study protocol
Version number: v.1.0
Date: 15/09/2025
PRIVACY STATEMENT
All information presented in this document will be considered confidential and will remain the exclusive property of 
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The use of such confidential information must be 
limited to the recipient for the agreed purpose and must not be disclosed, published or otherwise communicated to 
unauthorized persons, for any reason, in any form without the prior written consent of Fondazione IRCCS Ca' Granda 
Ospedale Maggiore Policlinico.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
TABLE OF CONTENTS 
1. Title page
2. List of abbreviations 
3. Responsibilities (role of the promoter and collaborators)
4. Amendments and other changes to the Protocol
5. Timelines 
6. Rationale e background
7. Research question and objectives
8. Methods
8.1.  Study design
8.1.1. Primary endpoint 
8.1.2. Secondary endpoint 
8.2.  Setting
8.2.1. Study population
8.2.2. Inclusion criteria
8.2.3. Exclusion criteria
8.3. Variables
8.4.  Source documents
8.5.  Sample size 
8.6.  Data management
8.7.  Data analysis
8.7.1. Primary endpoitn: analysis
8.7.2. Secondary endpoitn: analysis
8.8. Quality control
8.9.  Study limitations
9. Protection of the subject enrolled
9.1. Information note to the subject and consent form for the processing of personal data 
9.2. Insurance Coverage 
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
10. Dissemination and communication plan for study results
11. Publications and Intellectual Property Rights on the Results of the Study
12. Financing
13. Bibliography
Annex 1. Abstract
2. List of abbreviations
ILT – Intraluminal Thrombosis
FET – Frozen Elephant Trunk
TEVAR – Thoracic Endovascular Aortic Repair
CT – Computed Tomography
NYHA Classification – New York Heart Association Classification
COPD – Chronich Obstructive Pulmonary disease
3. Responsibilities (role of the promoter and collaborators)
The promoter of this clinical study is Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico.
The Principal Investigator (PI) of the study is Prof. Santi Trimarchi,  SC Chirurgia Vascolare
director, which is responsible of the clinical coordination of the study
At the same SC Chirurgia Vascolare belong different collaborators, which play various functions:
- : investigator, patient screening and enrollment
- : investigator, patient screening and enrollment, data and imaging verification
- : investigator, data and imaging verification
- : data analysis
- i: study coordinator, eCRF RedCap desing, input and data verification
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
External collaborations 
Institution
Unit
Name
Role  and  functions  in
the study
Università degli Studi
di Milano
Dipartimento di Scienze
Cliniche e di Comunità
Protocol
 
review,
statistical
 
analysis,
manuscript review
Università degli Studi
di Milano
Dipartimento di Scienze
Cliniche e di Comunità
Protocol
 
review,
statistical
 
analysis,
manuscript review
4. Amendments and other changes to the protocol
NA 
5. Timelines
Study status
Planning
Start of the study and data collection
October 2025
End of the study and data collection
March 2026
Final report
May 2026
6. Rational and background 
Intraluminal  thrombosis  (ILT)  is  a  significant  but  underexplored  complication  in  aortic
interventions. It is defined as the formation of thrombosis, partially or totally obstructing the lumen,
in the surgically treated, stented, or native aorta. In cases of Frozen Elephant Trunk interventions
for which are performed regulary for type A dissections, or pathologies such as penetrating aorting
ulcers or aneurysm of the distal arch or proximal descending, an ILT can occur early in the
postoperative traject and have severe consequences. A recent systematic review and meta-analysis
from our group (abstract attached as Annex 1; manuscript pending) analyzed data from 825 patients
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
and estimated a pooled incidence of ILT of 8.6% [95% CI: 5.7-12.9]. The included studies reported
ILT rates ranging from 6.2% to 16.8% (1-4). Patients with ILT had significantly higher risks of
dialysis (43% vs. 16%) and mortality (25% vs. 8%). Risk factors included female gender, older age,
and concomitant aortic valve replacement. Despite these findings, the underlying pathophysiology
and management strategies for ILT in FET remain poorly defined
Intraluminal  thrombosis  (ILT)  is  a  recognized  but  poorly  studied  complication  following
endovascular  thoracic  aortic  repair  (TEVAR).  Case  reports  have  described  its  occurrence,
particularly in patients with blunt aortic trauma (5-14), and one study suggested a higher risk of
intraluminal narrowing among female patients, associated with increased reoperation rates (15).
However, no reliable data exist regarding the overall incidence, risk factors, or clinical outcomes of
ILT following TEVAR.
A recent systematic review conducted by our group (abstract attached as Annex 2; manuscript
pending) identified 10 case reports and three retrospective studies reporting highly variable ILT rates
(5-14, 16-18). A study, focusing on blunt aortic trauma patients, found an ILT incidence of 20.6% in
a cohort of 34 patients, while another study observed 2 cases in 97 patients (2.06%), and a third
study reported 0 cases in 11 patients (0%). The lack of consistent epidemiological data highlights the
necessity of a multicenter cohort study to establish a reliable incidence estimate and investigate
potential risk factors and clinical outcomes.
This study aims to fill the knowledge gap through a multicenter analysis involving patients treated
with FET and TEVAR. By identifying risk factors for ILT, describing related outcomes, and
evaluating management strategies, the ultimate goal is to improve clinical care and outcomes for
patients undergoing these procedures.
7. Research question and objectives
Question 1 – What is the incidence of ILT in patients undergoing FET or TEVAR?
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Question 2 – What are the risk factors for the onset of ILT after FET or TEVAR?
Question 3 – How does ILT modify the outcome of FET or TEVAR?
Primary objective: evaluate the incidence of ILT in patients undergoing FET or TEVAR.
Secondary objective: 
1 – search for any preoperative or perioperative risk factors, for the onset of postoperative ILT in
patients undergoing FET or TEVAR
2  –  evaluation  of  outcomes (mortality,  renal  complication,  organs  and  limbs  malperfusion,
prolonged hospitalization and ICU lenght of stay) in patients with or without postoperative ILT
after receiving FET or TEVAR
8. Methods
8.1 Study design
International, multicenter, non pharmacological, retrospective, observational, cohort clinical study.
8.1.1 Primary endpoint 
Incidence (percentage on total case) of postoperative ILT in patients undergoing FET or TEVAR
8.1.2 Secondary endpoint
1 – calculation of the possible correlation (pvalue, t-test and chi-test for risk factors) between
perioperative factors and the occurrence of postoperative ILT in patients undergoing FET or TEVAR
2 – calculation of the possible correlation (pvalue, t-test and chi-test for risk factors) between
postoperative ILT in patients undergoing FET or TEVAR, and postoperative complications
8.2 Setting 
The patients examined will be those who have undergone FET or TEVAR procedures in the
enrolling centers from January 2010 to June 2025. No further investigations will be performed other
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
than those that are commonly performed, particularly during the postoperative follow-up (CT
angiography).
8.2.1 Study population 
Adult patients undergoing elective and emergency FET and TEVAR procedures between Jan 2010
and June 2025.
8.2.2 Inclusion criteria
Patients who simultaneously meet the following criteria will be included:
- age ≥18 years
- males and females
- presence of pre- and post-operative CT imaging
8.2.3 Exclusion criteria 
Patients will be excluded if they meet at least one of the following criteria:
- Patients previously treated with TEVAR or FET
8.3 Variables
Demographic variables: age, sex, BMI,
Anamnestic clinical variables: comorbidities (hypertension, diabetes, hypercolesterlomia, hystory
of stroke, NYHA Classification, atrial fibrillation, previous coronary disease, peripheral artery
disease, COPD, liver disfunction, connective tissue disease, histroy of venous thrombosis, renal
impairement, dialysis dependant, previous open or endovascular surgery)
Preoperative imaging correlated variables: type of aortic pathology, maximum aortic diameter
Perioperative  and  postoperative  variables:  type  of  prosthesis  (diameter,  length,  type),
intraoperative complications, number of transfusions, mortality, renal failure requiring dialysis,
visceral ischemia, stroke, spinal cord injury, reoperations, aorto-related complications, prosthesis-
related  complications,  ICU  lenght  of  stay,  total  lenght  of  hospitalization,  postoperative
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
antithrombotic therapy,
Post operative imaging correlated variables: days form intervention, aortic diameter, presence of
ILT, location of ILT, presence of endoleak
-Variables for primary endpoint: presence of ILT at postoperative CT angiography
-Variables for secondary endpoint 1 – age, sex, comorbidities, type of aortic pathology, type of
prosthesis (diameter, length, type), intraoperative complications, number of transfusions
-  Variables  for  secondary  endpoint  2  –  mortality,  renal  failure  requiring  dialysis,  visceral
ischemia, stroke, spinal cord injury, reoperations, aorto-related complications, prosthesis-related
complications
8.4 Source documents
Eletronic Medical Records, CT scan imaging both stored according to clinical practice in the
departments/archives
8.5 Sample size
For  patients  treated  with  FET,  an  estimated  incidence  of  8.6%  requires  a  sample  size  of
approximately 400 patients to reach a 95% confidence interval with a margin of error of ±3%.
For patients treated with TEVAR, no reliable incidence data for ILT exist. Our systematic review
identified small retrospective studies with highly variable ILT rates in heterogenic cohorts, which
did not allow the pooling of data. The largest study, including 97 patients, reported an incidence of
2.06%, while another study with 11 patients found 0 ILT cases. A separate study found 20.6% ILT,
but this was in blunt aortic trauma patients, a highly specific subgroup that is not representative of
the broader TEVAR population. Therefore, this cohort was excluded from sample size estimation.
Based on the 2.06% incidence, approximately 87 patients would be required to achieve a 95%
confidence interval with a margin of error of ±3%. However, given the small sample sizes and
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
uncertainty surrounding the true incidence, a conservative target of 300-400 patients is proposed to
ensure sufficient statistical power. A post-hoc power analysis will be conducted once enough data
have been collected.
8.6 Data Management
Each participant, at the time of enrollment, will be assigned a unique code. The de-identification of
the data will be done in such a way that people accessing the database will not be able to trace the
identity of the subjects in any way. Only local investigators will be able to trace the identity of the
enrolled subjects.
The data necessary for the study will be recorded in a specific eCRF in a Data Management System
validated according to national regulations, provided by the Scientific Direction of the Foundation.
The platform used will be RedCap (Research Electronic Data Capture).
The  REDCap  Consortium  is  composed  of  >1000  institutional  partners  worldwide  (research
institutions,  universities,  ministries,  etc.).  The  consortium  supports  a  secure  web  application
(REDCap)  designed  exclusively  to  support  the  acquisition  of  data  for  research  studies.  The
REDCap application allows users to create and manage online databases quickly and securely, and
is currently in use for more than 110,000 projects with approximately 150,000 users covering
numerous areas of research interest across the consortium.
Through REDCap, for this study the following will be implemented: a) user-level identification,
with specific restrictions based on role in the study b) real-time data validation and integrity control
c) patient de-identification prior to data export d) centralized data storage with daily backup, a
secure server within the Foundation's IT structure.
The Study Manager guarantees that the data of patients enrolled during the study will be stored,
archived and processed in full compliance with the privacy regulations pursuant to art. 13 of
Regulation  no. 2016/679/EU  and  the  current  national  privacy legislation,  the  Code  of Ethics
regarding the processing of data for statistical-scientific purposes and the "Guidelines  for the
processing of personal data in the context of clinical trials of medicinal products" published in the
Official Journal no. 190 of 14 August 2008.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Patient data will be collected in pseudonymized form and will be accessible only to internal and
external personnel specifically appointed and bound by an obligation of confidentiality in relation to
any information learned during the study.
The Study Manager also guarantees that he has implemented the minimum security measures
prescribed by the aforementioned legislation for the processing of data using electronic and non-
electronic tools, in order to avoid unlawful data processing.
8.7 Data analysis
Continuous variables will be expressed as mean with standard deviation or median with a range.
Categorical variables will be presented as frequencies and percentages. Comparative univariate
analyses will use Chi-square or Fisher exact tests for categorical variables and Mann-Whitney U
test or t-tests for continuous variables to analyze any correlations between groups with versus
without postoperative ILT.
8.7.1 Primary endpoint - analysis 
The primary endpoints for analysis are the incidences of ILT following FET and TEVAR. For the
primary outcome no statistical analysis will be performed, the incidence will be reported as a
percentage of the total cohort in a descriptive manner.
8.7.2 Secondary endpoint - analysis
A secondary endpoint for analysis is to identify risk-factors for ILT formation after FET and
TEVAR. For this purpose demographic and intraoperative variables will be compared between
patients who developed an ILT and those wo did not. For continious data the Shapiro-Wilk test will
be used to assess the distribution of. Depending on the normality of distribution either the t-test
(normal  distribution)  or  Mann  Whitney  U  test  (non-normal  distribution)  will  be  used.  For
categorical variables either the Chi-square test or the Fisher’s exact test. The Chi-square test will be
applied when all expected cell counts in the contingency table are ≥ 5. However, if one or more
expected cell counts are < 5, Fisher’s exact test will be used instead. A p-value below 0.05 will be
considered  statistically significant. Outcomes in terms of complications and mortality between
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
patients devoloping ILT and those who do not, both in FET and TEVAR patients will be compared
in the same manner.
8.8 Quality control
To ensure adequate quality control of the study, the investigator will, if requested, allow direct
access to all relevant documentation and dedicate part of his/her time to discuss the results of the
study. In addition, Regulatory Authorities may carry out inspections. In this case, the investigator
must allow the inspector direct access to all relevant documentation, and dedicate part of his/her
time and personnel to the inspector to discuss the monitoring results and any other aspects of the
study. If applicable, all manual data entry must be performed by two operators to avoid any errors.
8.9 Study limitations

The retrospective nature of the study could represent a structural bias.

Since ILT is a relatively rare complication after FET or TEVAR, the data at our disposal
may not reach a statistically significant measure.
9. Protection of the subjects enrolled
The study will be conducted in accordance with the Rules of Good Clinical Practice, the ethical
principles deriving from the Declaration of Helsinki and the current regulations on observational
studies.
The observational study and the related documentation will be submitted to the competent Ethics
Committee of each center. The study will only begin after receiving the required authorizations
according to the institution's internal procedures. The Ethics Committee must also approve any
modification to the protocol and the advertising used to recruit subjects for the study, according to
local regulations.
9.1 Information note to the subject and consent form for the processing of personal data
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Given the nature of Scientific Hospitalization and Treatment Institutes of the Policlinico, promoter
of the study, in compliance with the current legislation on the protection of personal data (EU
Regulation 679/2016) and Legislative Decree 196/2003 (Privacy Code) as amended by Legislative
Decree 101/2018, for the data collected and processed within the scope of the study it will not be
mandatory to ask participants for consent to the use of their personal data for the conduct of the
study itself.
In compliance with the provisions of art. 110 bis paragraph IV of the amended Legislative Decree
196/2003, due to the instrumental nature that the healthcare activity assumes with respect to
research at the Scientific Hospitalization and Treatment Institutes, the processing, for research
purposes, of personal data already collected for clinical activity, including the anonymization of the
same, does not constitute further processing.
As provided by the Authority for the protection of personal data, the aforementioned provision
applies to any type of medical research (prospective and retrospective) promoted by IRCCS, even
of a multi-center nature that involves the participation of entities that do not have the same nature.
Therefore, the aforementioned legal basis also extends to all other centers participating in the study
that do not have the nature of IRCCS.
The IRCCS, as the Study Promoter, will be responsible for drafting an Impact Assessment to be
published on its website and communicated to the Authority for the protection of personal data.
9.2 Insurance Coverage
Given  the  observational  nature  of the  proposed  studies,  no additional  insurance  policies  are
necessary other than those already provided for normal clinical practice.
10. Dissemination and communication plan for study results
The scientific director of the study will undertake to draft a final report and to make the results
public at the end of the study. The data will be made public anonymously and presented in
aggregate form as requested.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
11. Publications and Intellectual Property Rights on the Results of the Study 
Pubblications:
The Foundation, as Promoter, will guarantee the dissemination and publication of the study results,
even in the event of negative results, without any constraints and guaranteeing the collaborating
center visibility proportional to the actual participation.
Each scientific journal or publication containing the results and data of the study must indicate the
role and participation of the Centers and the Foundation, in a manner proportional to the actual
contribution made to the study and the role covered by each party. The data will be published in
aggregate form or in any case anonymized, so as not to allow in any way the identification of the
interested party to whom the data refers.
Intellectual property rights:
The Parties acknowledge that for the conduct of the collaboration within the scope of the study,
data, information, know-how, inventions (patentable or not) owned by each party may be used and
shared, which remains the exclusive owner even if it grants the other a right of access and use, non-
exclusive and free of charge, for the sole purpose of carrying out the activities covered by the study
and limited to the duration of the study. It is understood that this right of use does not include the
right to sublicense to third parties.
In accordance with current legislation, the data and results generated within the scope of the Study
will be owned by the Promoter, except for specific agreements between the Promoter and the
Centers.
12. Financing
NA
13. Bibliography
1. Walter T, Berger T, Kondov S, et al. Postoperative in-stent thrombus formation following 
frozen elephant trunk total arch repair. Front Cardiovasc Med. 2022;9:921479. 
doi:10.3389/fcvm.2022.921479.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
2. Misfeld M, Marin-Cuartas M, Ramirez P, et al. Early intraluminal frozen elephant trunk 
stent graft thrombosis after aortic arch surgery. Ann Thorac Surg. 2023;116(2):450-457. 
doi:10.1016/j.athoracsur.2022.12.030.
3. Ibrahim M, Chung JC, Ascaso M, et al. In-hospital thromboembolic complications after 
frozen elephant trunk aortic arch repair. J Thorac Cardiovasc Surg. 2024;167(4):1217-1226. 
doi:10.1016/j.jtcvs.2022.08.005.
4. Martens A, Beckmann E, Kaufeld T, et al. Features and risk factors of early intraluminal 
thrombus formation within the frozen elephant trunk stent graft. J Thorac Cardiovasc Surg. 
2024;168(3):477-487.e9. doi:10.1016/j.jtcvs.2023.01.014.
5. Alvarez B., Constenla I., Maeso J., Matas M. Late thrombosis of a thoracic aorta stent graft: 
therapeutic management. J Vasc Surg. 2009;49:774–777. doi: 10.1016/j.jvs.2008.11.023.
6. Marone E.M., Kahlberg A., Tshomba Y., Logaldo D., Chiesa R. Surgical conversion for 
intragraft thrombosis following endovascular repair of traumatic aortic injury. J Vasc Surg. 
2012;55:538–541. doi: 10.1016/j.jvs.2011.07.075.
7. Reich H.J., Margulies D.R., Khoynezhad A. Catastrophic outcome of de novo aortic 
thrombus after stent grafting for blunt thoracic aortic injury. Ann Thorac Surg. 
2014;98:e139–e141. doi: 10.1016/j.athoracsur.2014.07.093.
8. Marino M., Kasemi H., Martinelli O., Bresadola L., Salvatori F.M., Irace L. Re-TEVAR for 
complications after blunt aortic traumatic injury stenting. Cardiovasc Intervent Radiol. 
2014;37:519–522. doi: 10.1007/s00270-013-0655-6.
9. Abdoli S., Ham S.W., Wilcox A.G., Fleischman F., Lam L. Symptomatic intragraft 
thrombus following endovascular repair of blunt thoracic aortic injury. Ann Vasc Surg. 
2017;42:305. doi: 10.1016/j.avsg.2016.12.007.
10. García Reyes M.E., Martins G.G., Valenzuela V.F., González J.M.D., Lebrun J.M., 
Montoya S.B. Long-term outcomes of thoracic endovascular aortic repair focused on bird 
beak and oversizing in blunt traumatic thoracic aortic injury. Ann Vasc Surg. 2018;50:140–
147. doi: 10.1016/j.avsg.2018.02.001.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
11. Liesdek O.C.D., Jacob K.A., Vink A., Vermeulen M.A., Hazenberg C.E.V.B., Suyker 
W.J.L. Surgical treatment of acute thoracic stent graft occlusion. Ann Thorac Surg. 
2019;107:e127–e129. doi: 10.1016/j.athoracsur.2018.05.099.
12. Hostalrich A., Canaud L., Ozdemir B.A., Chaufour X. Severe thoracic aorta stenosis after 
endovascular treatment of blunt thoracic aortic injury. Semin Thorac Cardiovasc Surg. 
2019;31:227–229. doi: 10.1053/j.semtcvs.2019.01.014.
13. Martinelli O., Malaj A., Faccenna F., Ruberto F., Alunno A., Totaro M., et al. Open 
conversion for recurrent endograft occlusion after endovascular treatment of blunt traumatic 
aortic injury: a peculiar case report. Ann Vasc Surg. 2020;67:568. doi: 
10.1016/j.avsg.2020.03.027.
14. Beijer E, Scholtes VPW, Truijers M, Nederhoed JH, Yeung KK, Blankensteijn JD. 
Intragraft Obstructive Thrombus Two Years After Endovascular Repair of Traumatic Aortic
Injury: A Case Report and Review of the Literature. EJVES Vasc Forum. 2021 Nov 
9;53:36-41. doi: 10.1016/j.ejvsvf.2021.10.018.
15. Kuo MC, Meena RA, Ramos CR, Benarroch-Gampel J, Leshnower BG, Duwayri Y, Jordan 
WD Jr, Rajani RR. Female gender is associated with increased late luminal narrowing 
within the stent graft after thoracic endovascular aortic repair. J Vasc Surg. 2022 
Jan;75(1):67-73. doi: 10.1016/j.jvs.2021.07.226. Epub 2021 Aug 25. PMID: 34450242.
16. García Reyes ME, Gonçalves Martins G, Fernández Valenzuela V, et al. Long-Term 
Outcomes of Thoracic Endovascular Aortic Repair Focused on Bird Beak and Oversizing in 
Blunt Traumatic Thoracic Aortic Injury. Ann Vasc Surg. 2018 Jul;50:140-147. doi: 
10.1016/j.avsg.2018.02.001.
17. Rockley M, Rommens KL, McClure RS, Herget EJ, Smith HN, Moore RD. Aortic arch 
endovascular branch and fenestrated repair: Initial Canadian experience with novel 
technology. J Vasc Surg Cases Innov Tech. 2023 Jul 27;9(4):101274. doi: 
10.1016/j.jvscit.2023.101274.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
18. Deniz G, Kasımzade F, Ozcınar E, Yazicioglu L, Eryılmaz S. Long-term outcomes of 
TEVAR for thoracic aortic diseases: a retrospective single-center study. J Cardiothorac 
Surg. 2024 Jun 29;19(1):405. doi: 10.1186/s13019-024-02886-6.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Annex 1. Abstract
Incidence and Clinical Importance of Intraluminal Thrombosis Following Frozen Elephant 
Trunk: A Systematic Review 
Nesar A. Hasami1,2,3, Michiel Been1, Jasper F. de Kort1,3, Guillaume S.C. Geuzebroek2, Guido 
Gelpi4, Carlo de Vincentiis5, Himanshu J. Patel6, Martin Czerny7,8, Robin H. Heijmen2, Joost A. van 
Herwaarden3, Santi Trimarchi1,9
1 Department of Vascular Surgery, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, 
Milan, Italy
2 Department of Cardiothoracic Surgery, Radboud University Medical Centre, Nijmegen, The 
Netherlands
3 Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
4 Department of Cardiac Surgery, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, 
Milan, Italy
5 Department of Cardiac Surgery, Policlinico San Donato IRCCS, Milan, Italy
6 Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan
7 Department of Cardiovascular Surgery, University Heart Centre Freiburg, Freiburg, Germany
8 Faculty of Medicine, Albert Ludwigs University Freiburg, Freiburg, Germany
9 Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, 
Italy
Abstract
Objectives
The frozen elephant trunk procedure can treat aneurysms of both the arch and descending aorta. 
Although being a single stage treatment, it is associated with certain deleterious complications. 
Among these, intraluminal thrombosis is a relatively underrecognized but clinically significant 
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
complication. This systematic review and meta-analysis aimed to determine the incidence and 
clinical impact of intraluminal thrombosis.
Methods
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 
guidelines. PubMed, Web of Science, and SCOPUS databases were searched for relevant studies.
Quality was assessed using the Risk of Bias in Non-Randomized Studies of Interventions tool. 
Evidence certainty was evaluated with Grading of Recommendations Assessment, Development, 
and Evaluation analysis. The primary outcome was the incidence of intraluminal thrombus (both 
partial and total). Meta-analysis was performed to calculate pooled proportions and weighted 
means with 95% confidence intervals. Additionally, patients with and without intraluminal 
thrombosis were compared to identify differences in clinical characteristics and outcomes.
Results
Four studies with 825 patients were included. The pooled incidence of intraluminal thrombosis was 
8.6% [95% confidence interval: 5.7–12.9]. Patients with intraluminal thrombosis were older, more 
often female, and more likely to present with an aneurysm than a dissection. They also had higher 
rates of dialysis (43% versus 16%) and mortality (25% versus 8%) compared to patients without 
intraluminal thrombosis.
Conclusion
Intraluminal thrombosis after frozen elephant trunk procedure is not uncommon and is associated 
with increased mortality. These findings highlight the need for awareness, further research on risk 
factors, and development of preventive strategies.
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
Annex 2. Abstract
Incidence and Clinical Importance of Intraluminal Thrombosis Following Frozen Elephant 
Trunk: A Systematic Review 
Nesar A. Hasami1,2,3, Jasper F. de Kort1,3, Guillaume S.C. Geuzebroek2, Constantijn E.V.B. 
Hazenberg3, Robin H. Heijmen2, Joost A. van Herwaarden3, Santi Trimarchi1,4
1 Department of Vascular Surgery, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, 
Milan, Italy
2 Department of Cardiothoracic Surgery, Radboud University Medical Centre, Nijmegen, The 
Netherlands
3 Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
4 Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, 
Italy
Abstract
Objectives
Thoracic endovascular aortic repair has expanded as a treatment for various aortic 
diseases, but complications such as intraluminal thrombosis remain poorly understood. This 
systematic review evaluates the available literature on intraluminal thrombosis after thoracic 
endovascular aortic repair, its incidence, and management strategies.
Methods
A systematic search of PubMed, Web of Science, and SCOPUS identified studies reporting 
intraluminal thrombosis following thoracic endovascular aortic repair. Retrospective cohort studies 
and case reports were included. Risk of bias was assessed using the Risk of Bias in Non-
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Dipartimento Cardio-Toraco-Vascolare
SC Chirurgia Vascolare                                                - Direttore: Prof. Santi Trimarchi
Tel. 02 5503.2438 
E-mail: chirurgiavascolare@policlinico.mi.it 
randomized Studies of Interventions tool for cohort studies and the Joanna Briggs Institute 
checklist for case reports. Due to study heterogeneity, findings were synthesized narratively.
Results
A total of three retrospective cohort studies and ten case reports were included. The overall 
incidence of intraluminal thrombosis remains unclear but appears low, except in blunt aortic 
trauma, where one study reported an incidence of 20.6%. Quality assessment showed a critical 
risk of bias in all retrospective studies, primarily due to confounding. Case reports were of 
moderate to good quality. In nine out of ten case reports, intervention was required, with seven 
patients undergoing open surgical repair. Thrombus recurrence occurred after endovascular 
relining in one case.
Conclusion
The literature on intraluminal thrombosis after thoracic endovascular aortic repair is scarce 
and of limited quality. Although the overall incidence appears low, patients treated for blunt aortic 
trauma may be at higher risk and require careful follow-up. Treatment should be individualized, as 
anticoagulation alone may not always suffice. Both open and endovascular reinterventions may 
provide a solution.
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