Comprehensive Long-term Follow up of Adults With Arterial Switch Operation - European Collaboration for Prospective Outcome Research in Congenital Heart Disease
Conditions: Transposition of Great Vessels
Sponsor: University of Zurich

Comprehensive long-term follow up of adults with prior arterial switch 
operation – an international prospective cohort study (EPOCH-ASO) 
 
Principal investigator / Sponsor (EPOCH-ASO) 
Matthias Greutmann, MD 
University Heart Center,  
Department of cardiology,  
University of Zurich,  
Raemistrasse 100 
8091 Zurich, Switzerland 
Tel. 044 255 3883 
Matthias.Greutmann@usz.ch 
 
 
Principal investigator / Sponsor of the SACHER-Registry 
Daniel Tobler, MD 
Division of Cardiology,  
University Hospital of Basel 
Switzerland Petersgraben 4 
4031 Basel, Switzerland  
Tel. 061 279 98 22 
daniel.tobler@usb.ch 
 
 
Principal investigator: 
 
 
 
Zurich, 24.08.2019 
 
 
 
Place, Date 
 
Signature 
 
Sponsor: 
 
Basel, 24.08.2019 
 
 
 
 
Place, Date 
 
Signature 
 
 
 

 
 
 
 
 
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1. Background 
A register for adult patients with congenital heart defects has been established in Switzerland 
since 2013 (SACHER; www.sacher-registry.com).1 This register has already been reviewed by 
EKNZ in 2013 (National Register of Adults with Congenital Heart Defects, EK 180/13). All 
university hospitals (Basel, Bern, Geneva, Lausanne and Zurich) as well as the cantonal 
hospitals of Lucerne and St. Gallen, as well as the University Hospital Vienna in Austria 
participate in this register. About 4% of included patients have the diagnosis of an arterial switch 
operation, mostly due to transposition of the great arteries. These patients are the subject of this 
study. 
Transposition of the great arteries is the most frequent cyanotic heart disease in newborns. 
Without open heart surgery survival is unlikely. In the last century, various surgical approaches 
have been applied, the most recent of which is the arterial switch operation (ASO), first 
performed by Dr. Adib Jatene in 1975. In this operation, the aorta and the pulmonary artery are 
detached from their native root and reattached to the opposite root; thus, the pulmonary root 
becomes the neo-aorta, and the aortic root becomes the neo-pulmonary artery. The coronary 
arteries are transplanted from the aorta/neo-pulmonary artery to the pulmonary artery/neo-aorta 
(Figure 1). 
Figure 1: D-TGA with an arterial switch operation 
 
Due to current low surgical mortality, excellent child survival and the expectation that 
complications will be rare, the ASO is the preferred surgical approach today. Although this 
surgery is felt to be an improvement over the earlier atrial switch, late complications such as 
pulmonary artery stenosis, neo-aortic valve insufficiency, aortic root dilatation, and coronary 
obstruction have been reported in children. Patients with prior ASO are now entering adult 

 
 
 
 
 
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congenital cardiac clinics; however, cardiac outcomes in the adult population have not yet been 
well defined. In current literature, studies about late complications in adulthood have still short 
follow-up, numbers of included patients are still low; and predictors of cardiac complications are 
fairly unknown.  
 
The rationale of this international multicenter cohort study is to follow prospectively a large 
number of patients with a prior ASO with standard follow-up of care and a comprehensive 
evaluation of the cardiac anatomy and the functional status; and subsequently to study the 
impact of cardiac anatomy, residual lesions and functional status on lifelong outcome in this 
rapidly growing population of young adults with the aim to enhance their lifelong care and 
outcomes. The study hypotheses are the following: Survival estimates of adults with a prior 
ASO will be lower compared to the healthy population. ASO patients will be at risk for early 
coronary events, for progressive aortic regurgitation; and for decreased exercise capacity due to 
pulmonary branch stenosis and consequent right ventricular dysfunction. 
 
Currently about 120 patients with an ASO are under active care in Switzerland and already 
included in the national registry. In order to increase the number of patients with ASO for a 
scientifically meaningful outcome analysis, we plan to include patients from several large 
European tertiary care centers (Austria: Vienna; Spain: Barcelona, Sevilla, Valencia; France: 
Paris; The Netherlands: Amsterdam) 
 
 
2. Objectives 
 
The primary objective of this study is to analyze long-term survival and cardiac morbidity of 
adults with a prior ASO. The impact of residual lesions such as aortic regurgitation, aortic root 
dilatation, pulmonary branch stenosis and coronary pathologies on long-term cardiac outcomes 
are the second objectives. 
 
 
3. Origin of the data/material 
 
A register for adult patients with congenital heart defects has been established in Switzerland 
since 2013 (SACHER; www.sacher-registry.com). This register has already been reviewed by 
EKNZ in 2013 (National Register of Adults with Congenital Heart Defects, EK 180/13). All 
university hospitals (Basel, Bern, Geneva, Lausanne and Zurich) as well as the cantonal 
hospitals of Lucerne and St. Gallen, as well as the University Hospital Vienna in Austria 
participate in this register. All patients with the diagnosis 'arterial switch', who are already 
included in the register or will be included in the register at the age of 18 can be used for this 

 
 
 
 
 
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project. All clinical and imaging data obtained during routine follow-up can be used for this 
project. 
 
 
4. Inclusion criteria 
 
Signed written informed consent for “National Register of Adults with Congenital Heart Defects”, 
EK 180/13 Adults (≥18 years) with a prior arterial switch operation for D-transposition of the 
great arteries or double outlet right ventricle  
 
 
5. Exclusion criteria 
 
No informed consent; arterial switch operation for other cardiac lesions 
 
 
6. Recruitment, screening and informed consent procedure 
 
All ASO patients who participate in the national registry were informed of the registry's objective 
in a personal interview and have submitted a written declaration of consent (EK 180/13).  
 
 
7. Methods 
 
Project population 
All patients included in the National Register of Adults with Congenital Heart Defect with the 
diagnosis of ASO. 
 
 
Hypothesis 
Survival estimates of adults with a prior ASO will be lower compared to the healthy population. 
ASO patients will be at risk for early coronary events, for progressive aortic regurgitation and for 
decreased exercise capacity due to pulmonary branch stenosis and consequent right ventricular 
dysfunction. 
 
Objectives 
The primary objective of this study is to analyze long-term survival and cardiac morbidity of 
adults with a prior ASO. The impact of residual lesions such as aortic regurgitation, aortic root 
dilatation, pulmonary branch stenosis and coronary pathologies on long-term cardiac outcomes 
are the second objectives. 
 
Primary endpoints:  
Mortality and morbidity in adults with prior ASO after 5, 10, 15, and 20 years follow-up. 
Predictors of death and cardiac endpoints.  The following endpoints will be collected: 
- 
Death any cause 
- 
Cardiovascular death 
- 
Unexpected cardiovascular death 
- 
Heart failure  
- 
Myocardial infarction 
- 
Ventricular tachycardia / ventricular fibrillation 
- 
Atrial fibrillation 
- 
Atrial flutter 
- 
Complete AV block 
- 
Endocarditis 

 
 
 
 
 
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- 
Aortic dissection 
- 
Stroke 
- 
Pulmonary hypertension 
 
Secondary endpoints:  
Comprehensive description of coronary anatomy in ASO patients 
Impact of the coronary anatomy on functional status and cardiac complication 
Progression of aortic valve regurgitation and aortic root dilatation in ASO patients 
Impact of aortic regurgitation on functional status and cardiac complication 
Comprehensive description of the pulmonary branches in adults with ASO 
Impact of pulmonary branch stenos on functional status and cardiac complications 
Cognitive function in adults with ASO 
The clinical significance of ECG changes during exercise in ASO patients 
 
General project design  
This study is an international, multicenter, prospective cohort study.  
All ASO patients under active care in one of the participant centers will be included after having 
given written consent. 
ASO patients will be followed according international standard of care. Within this study project 
no data will be acquired which are not clinically indicated and outside of these international 
recommendations. 
 
 
8. Reporting requirements 
Any change in project management must be notified in advance to the responsible ethics 
committee. 
The completion or termination of the research project will be reported to the Ethics Committee 
within 90 days. 
 
 
9. Data Protection: Encryption and Storage 
The data of each patient included in the national registry appear under a pseudonym specific to 
that patient. Only the treatment center knows the identity of the patients. The pseudonym is 
created by the registry software (SecuTrial) when the patient is created. The coding is further 
used for the analysis. 
 
 
10. Procedure for unencrypted data 
 
The attending physician or a research fellow will collect the data, which are not yet entered in 
the national register for the respective patient, in the center on site and encode them with the 
specific pseudonym of the patient. Only the coded data will be used for further analysis. The 
original data shall remain in the center. 
 
 
11. Storage instructions 
Data Management System  
The CRFs in this trial are implemented electronically using a dedicated electronic data capturing 
(EDC) system (secuTrial®). The EDC system is activated for the trial only after successfully 

 
 
 
 
 
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passing a formal test procedure. All data entered in the CRFs are stored on a Linux server in a 
dedicated Oracle database. 
Responsibility for hosting the EDC system and the database lies with University Hospital Zurich. 
 
Project data will be handled with uttermost discretion and is only accessible to authorized 
personnel who require the data to fulfil their duties within the scope of the research project. On 
the CRFs and other project specific documents, participants are only identified by a unique 
participant number.  
Case Report Forms  
An electronic data capture (EDC) system will be built for the study using the SecuTrial platform. 
The EDC system will include electronic case report forms (eCRFs) designed to capture study 
information, which are completed by trained site staff. All data collected will not be identifiable 
reference to the subjects. The subject’s anonymity will be maintained and the confidentiality of 
records and documents that could identify subjects will be protected, respecting the privacy of 
and confidentiality rules in accordance with applicable regulatory requirements. 
Subjects will be identified only by their assigned study number and initial on all CRFs and other 
records and documents submitted to the investigators, the monitor, and other authorised 
parties. The investigator will keep a Patient Identification List with complete identification 
information (name, address, contact number) on each subject. 
The investigator will maintain all study documents in strict confidence. 
CRF entries will be performed by authorized persons and it will be assured that any authorized 
person can be identified. 
Data security, access and back-up  
The server hosting the EDC system and the database is kept in a locked server-room. Only the 
system administrators have direct access to the server. A role concept with personal passwords 
(site investigator, statistician, monitor, administrator etc.) regulates permission for each user to 
use the system and database as he/she requires. 
All data entered into the CRFs are transferred to the database using Secure Sockets Layer 
(SSL) encryption. Each data point has attributes attached to it identifying the user who entered it 
with the exact time and date. Retrospective alterations of data in the database are recorded in 
an audit table. Time, table, data field and altered value, and the person are recorded (audit 
trail). A multi-level back-up system is implemented.  
Analysis and archiving 
At final analyses, data files will be extracted from the database into statistical packages to be 
analyzed. The status of the database at this time is recorded in special archive tables. 
Electronic and central data validation  
Data is checked by the EDC system for completeness and plausibility. Furthermore, selected 
data points are cross-checked for plausibility with previously entered data for that participant. In 
addition (if applicable), central data reviews will be performed on a regular basis to ensure 
completeness of the data collected and accuracy of the primary outcome data. 
 
12. Duration of storage 
The study database with all archive tables will be securely stored by the University Hospital 
Zurich. The sponsor also keeps the Trial Master File and interim/final reports for at least 10 
years. 
 
 

 
 
 
 
 
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13. Ethical and regulatory requirements 
This project complies with the regulatory requirements of the HFG and the HFV. The 
prerequisite for carrying out the research project is the approval of the Cantonal Ethics 
Commission. 
 
 
14. Financing /Publishing / Declaration of interests 
The study will be funded by internal grants. The results will be published in peer reviewed 
journal. No conflicts of interests.  
 
 
15. Literatur  
1. Swiss Adult Congenital HEart disease Registry (SACHER) - Rationale, design and first 
results. Daniel Tobler, Markus Schwerzmann, Judith Bouchardy, Reto Engel, Dominik 
Stambach, Harald Gabriel, Hans-Peter Kuen, Christoph auf der Maur, Angela Oxenius, Theresa 
Seeliger, Bruno Santos Lopes, Francesca Bonassin, Matthias Greutmann, on behalf of 
SACHER investigators. Swiss Med Wkly. 2017;147:w14519. Doi:10.4414/smw.207.14519