The PAtients pResenTing With COngenital HeaRt DIseAse Register (ARTORIA-R) (ARTORIA-R)

The PAtients pResenTing With COngenital HeaRt DIseAse Register (ARTORIA-R): A Global Register to Investigate Factors Associated With Morbidity and Mortality in Adult Patients With Congenital Heart Disease (ACHD) on the Waiting List for Heart or Heart/Lung Transplantation

Advances in surgical and medical care have led to improved outcomes in patients with congenital heart disease (CHD). As a consequence, the majority of patients nowadays survives to adulthood (adults with CHD, that is, adult CHD [ACHD]) with good quality of life. Despite the surgical success, the morbidity and mortality of ACHD is higher than in the general population and is linked to the development of heart failure (HF) in adulthood.

HF occurs in approximately 25% of patients with ACHD, even in those patients in whom the congenital mal-formation has been corrected successfully in childhood. The time course and presentation are heterogeneous owing to variable congenital malformation and limitation of treatment options. ACHD with an anatomic right ventricle as the systemic ventricle (e.g., atrial switch operation in patients with transposition of the great arteries [TGAs]) and those with a functional single ventricle (e.g., Fontan circulation) appear to be at higher risk of developing HF. Young age at initial corrective surgery-often in the first 2 years of life-and lack of specific medical therapies can contribute to a high and early demand for heart transplantation in patients with ACHD.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Ventricular Dysfunction; Congenital Heart Disease; Arrythmia; Transplant; Complication, Failure

Detailed Description

The ARTORIA-R is an international, observational research project collecting retrospective data from 17 countries in the period 1989 to 2020 and will thereafter include data prospectively (Figure 1). These data include patient profiles at time of evaluation for listing, listing, waiting list dynamics, post-transplant data and basic donor data. Future data will be updated annually in July each year and each institution willing to contribute anonymised data to the register is invited to participate. Furthermore, the institutions and organ allocation agencies have to obtain a positive vote of the ethic committee responsible for the data transmission of anonymized patient data.

The inclusion criteria are: a. The patient has to be listed as an adult transplant candidate in the country the data is obtained with an age ≥18 years b. The patient has to have a congenital heart defect or an inherited cardiomyopathy (specific; hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or non-compaction cardiomyopathy) which is often included into the category ACHD c. Data is obtained from the first evaluation for listing or listing for heart-only or heart-combined organ transplantation d. Transfer of anonymised data e. The institution/organization agrees to the memorandum how data is managed, and scientific cooperation is planned between all institutions. The registry has the aim to achieve meticulous information regarding the underlying congenital heart defect and the previous treatment of the patient. With these information the patients can be divided into different cohorts with a systemic left ventricle, a systemic right ventricle or a single ventricle (which can be either an anatomic left or right ventricle). Further data is acquired regarding the medical treatment, the haemodynamic evaluation of the patient, laboratory testing to assess additional organ function of the kidney or liver, treatment in the intermediate care or intensive care unit. As it is of special relevance in ACHD patient treatment of arrhythmia, antiarrhythmic medication and use of ICD or cardiac resynchronization therapy are evaluated. Were available the data regarding imaging at listing with ejection fraction for the systemic ventricle with echocardiography or cardiac magnetic resonance imaging are obtained.

The exclusion criteria is: a. The patient is listed for a second heart transplantation (retransplantation) During the ongoing study additional institutions and organizations will be asked to include their data as well. Although the initial data is retrospective additional data into the register will be entered prospectively.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: Christoph Sinning, MD; Phone Number: 004915222817675; Email: c.sinning@uke.de
• Study Contact Backup: Name: Christina Magnussen, MD; Email: c.magnussen@uke.de

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • University Heart and Vascular Center Hamburg
    • Contact: Christoph Sinning, MD; Phone Number: 004915222817675; Email: c.sinning@uke.de
    • Contact: Christina Magnussen, MD; Email: c.magnussen@uke.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The PAtients pResenTing with COngenital HeaRt DIseAse Register (ARTORIA-R) will collect data from patients with ACHD evaluated or listed for heart or heart-combined organ transplantation from 17 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989 - 2020 and will include patients prospectively. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list.

Description

Inclusion Criteria:

1. The patient has to be listed as an adult transplant candidate in the country the data is obtained with an age ≥18 years
2. The patient has to have a congenital heart defect or an inherited cardiomyopathy (specific; hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or non-compaction cardiomyopathy) which is often included into the category ACHD
3. Data is obtained from the first evaluation for listing or listing for heart-only or heart-combined organ transplantation
4. Transfer of anonymised data
5. The institution/organization agrees to the memorandum how data is managed, and scientific cooperation is planned between all institutions

Exclusion Criteria:

a. The patient is listed for a second heart transplantation (retransplantation)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patient transplanted due to ACHD and heart failure; Patients successfully transplanted due to congenital heart failure.
ACHD listed due to heart failure for heart or heart and combined organ transplantation; Patients on the actual waiting list for heart or heart and combined organ transplantation. They can have either outcome transplantation or the primary outcome death on the waiting list or delisting due to clinical worsening. The secondary outcome is as well delisting due to clinical improvement.
ACHD evaluated for heart transplantation; All patients evaluated for heart or heart and combined organ transplantation at the hospital level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delisting due to clinical worsening or death on the waiting list	If the patients has a clinical worsening of their status due to advanced heart failure he or she is removed from the waiting list. Patients can as well die while on the waiting list as a consquence of heart failure	The primary outcome will be assessed at entering data into the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delisting due to clinical improvement	Patients can improve from the status at listing and can be removed from the waiting list due to clinical improvement of their clinical status	The secondary outcome will be assessed at entering data into the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality following transplantation	When a patient was succesfully transplanted and receives follow-up visits at transplant center, the patient might have died due to various causes which is reflected by this outcome measure	The patient status will be included into the study database at entry

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
• Investigators: Principal Investigator: Christoph Sinning, MF, University Heart & Vascular Center Hamburg

Publications and helpful links

General Publications

• Sinning C, Zengin E, Diller GP, Onorati F, Castel MA, Petit T, Chen YS, Lo Rito M, Chiarello C, Guillemain R, Coniat KN, Magnussen C, Knappe D, Becher PM, Schrage B, Smits JM, Metzner A, Knosalla C, Schoenrath F, Miera O, Cho MY, Bernhardt A, Weimann J, Gossling A, Terzi A, Amodeo A, Alfieri S, Angeli E, Ragni L, Napoleone CP, Gerosa G, Pradegan N, Rodrigus I, Dumfarth J, de Pauw M, Francois K, Van Caenegem O, Ancion A, Van Cleemput J, Milicic D, Moza A, Schenker P, Thul J, Steinmetz M, Warnecke G, Ius F, Freyt S, Avsar M, Sandhaus T, Haneya A, Eifert S, Saeed D, Borger M, Welp H, Ablonczy L, Schmack B, Ruhparwar A, Naito S, Hua X, Fluschnik N, Nies M, Keil L, Senftinger J, Ismaili D, Kany S, Csengeri D, Cardillo M, Oliveti A, Faggian G, Dorent R, Jasseron C, Blanco AP, Marquez JMS, Lopez-Vilella R, Garcia-Alvarez A, Lopez MLP, Rocafort AG, Fernandez OG, Prieto-Arevalo R, Zatarain-Nicolas E, Blanchart K, Boignard A, Battistella P, Guendouz S, Houyel L, Para M, Flecher E, Gay A, Epailly E, Dambrin C, Lam K, Ka-Lai CH, Cho YH, Choi JO, Kim JJ, Coats L, Crossland DS, Mumford L, Hakmi S, Sivathasan C, Fabritz L, Schubert S, Gummert J, Hubler M, Jacksch P, Zuckermann A, Laufer G, Baumgartner H, Giamberti A, Reichenspurner H, Kirchhof P. Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R). ESC Heart Fail. 2021 Dec;8(6):5542-5550. doi: 10.1002/ehf2.13574. Epub 2021 Sep 12.
• Becher PM, Schrage B, Weimann J, Smits J, Magnussen C, Reichenspurner H, Gossling A, Rodrigus I, Dumfarth J, de Pauw M, Francois K, van Caenegem O, Ancion A, Van Cleemput J, Milicic D, Moza A, Schenker P, Rohrich L, Schonrath F, Thul J, Steinmetz M, Schmack B, Ruhparwar A, Warnecke G, Rojas SV, Sandhaus T, Haneya A, Eifert S, Welp H, Ablonczy L, Wagner F, Westermann D, Bernhardt AM, Knappe D, Blankenberg S, Kirchhof P, Zengin E, Sinning C. Clinical characteristics and outcomes of patients with adult congenital heart disease listed for heart and heart-lung transplantation in the Eurotransplant region. J Heart Lung Transplant. 2020 Nov;39(11):1238-1249. doi: 10.1016/j.healun.2020.07.012. Epub 2020 Jul 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 2, 2020
• Primary Completion (ANTICIPATED): July 30, 2030
• Study Completion (ANTICIPATED): July 30, 2030

Study Registration Dates

• First Submitted: April 7, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (ACTUAL): April 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 27, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Ventricular Dysfunction
• Other Study ID Numbers: WF163-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data is shared with investigators participating in the register and provide patient data to the register
• IPD Sharing Time Frame: The data base is shared with the researchers institution on demand. The researcher will receive a password protected copy of the study data base. The data base only includes anonymized data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No