Systemic Right Ventricle Long-term Outcome

Transposition of the Great Arteries Clinical Trial

— SINCERE  

Official title:

Systemic Right Ventricle Long-term Outcome: a Multicentre Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06258083
• Other study ID #: 202100379
• Status: Completed
• Start date: August 26, 2022
• Est. completion date: August 24, 2023

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Patients with the transposition of great arteries (TGA) who undergo atrial switch operation and congenitally corrected TGA (ccTGA) patients have the right ventricle as their systemic ventricle. Function of the systemic right ventricle (SRV) could deteriorate which is associated with impaired prognosis. It is of paramount importance to understand the course and fate of these patients during a long-term follow-up to identify the determinants of adverse outcomes.

Description:

In the year 2000, the prevalence of congenital heart diseases (CHD) patients with transposition of great arteries (TGA) was 0.027% in living children and 0.004% in living adults (1). Considering a complete transition to arterial switch operation in the 1990s, it is expected that the number of patients with systemic right ventricle (SRV) decrease over time (2). However, considering the existing number of patients with the TGA who have not undergone arterial switch surgery, SRV remains a challenging issue in the practice of adult congenital heart disease (ACHD) specialists. TGA is characterized by AV concordance and ventriculo-arterial discordance and is called simple without the presence of associated congenital anomalies. However, complex TGA is when other anomalies are present including VSD (∼45%), LVOTO (∼25%), and CoA (∼5%). TGA's pathogenesis is controversial and there is rare familial occurrence. Male are two times more affected than females. The prognosis of TGA patients without surgery is poor and only exceptional cases survive to adulthood (3). Heart failure and sudden cardiac death (SCD) are the predominant causes of mortality in TGA patients (4). Patients who undergo atrial switch operation and congenitally corrected TGA (ccTGA) patients are at risk of developing SRV failure in the future (3). The RV is a thin-walled triangular structure acting as a low pressure pump in the normal heart. Because of having only 2 layers, the RV cannot cause the torsion caused by the LV. Due to this geometry and anatomy, the right ventricular function is highly dependent on the loading conditions. The increased afterload that the RV faces in the systemic position causes compensatory RV dilation to maintain the stroke volume. Subsequently, there is increased myocardial wall stress and oxygen demand. The development of heart failure in the SRV is multifactorial. Other potential factors contributing to the SRV failure are impaired coronary reserve or ischemia, myocardial fibrosis, chronotropic incompetence, volume overload from tricuspid regurgitation and arrhythmias (4). Another contributing factor is the reduced baffle compliance in patients with atrial switch. This impairs the preload and stroke volume, especially when there is increased demand. The non-contractile atrial baffles cause impaired atrioventricular transport during tachycardia, therefore causing an inadequate RV filling (4). Unfortunately, at the moment, the hypothesis that angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), aldosterone antagonists, and beta-blockers can improve the outcome of such patients alone or in combination is not supported by data and evidence. There is no solid recommendation in the 2020 guidelines for the management of ACHD (3). Previous studies evaluating the fate and outcome of patients with an SRV are either mostly single-centered with a small number of patients or have a short follow-up period (5,6). In a study done by Richard Dobson and colleagues on a national cohort in Scotland, the investigators concluded that patients with an SRV who survive to adulthood have low mortality and good functional status up to the age of 40 (7). It is of paramount importance to understand the course and fate of these patients during a long-term follow-up to identify the determinants of adverse outcomes. This will enable the investigators to investigate mechanistic pathways of such outcomes. By understanding the risk factors and pathophysiological basis, the investigators can also investigate new diagnostic methods and therapeutic options to improve the quality of life and reduce the mortality of patients with an SRV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 542
• Est. completion date: August 24, 2023
• Est. primary completion date: August 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 12 years old and older
• Surgically corrected transposition of the great arteries (TGA) patients with a systemic right ventricle (SRV) (Mustard, Senning)
• Congenitally corrected TGA patients with a systemic right ventricle

Exclusion Criteria:

• None.

Related Conditions & MeSH terms

• Systemic Right Ventricle
• Transposition of Great Vessels
• Transposition of the Great Arteries

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Leuven	Leuven
Netherlands	Amsterdam University Medical Centre	Amsterdam
Netherlands	Medisch Spectrum Twente Enschede	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Centre	Leiden
Netherlands	Maastricht University Medical Centre	Maastricht
Netherlands	Radboud University Medical Centre	Nijmegen
Netherlands	Erasmus University Medical Centre	Rotterdam
Netherlands	University Medical Centre Utrecht	Utrecht

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	Hartekind, Hartstichting

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (7)

Andrade L, Carazo M, Wu F, Kim Y, Wilson W. Mechanisms for heart failure in systemic right ventricle. Heart Fail Rev. 2020 Jul;25(4):599-607. doi: 10.1007/s10741-019-09902-1. — View Citation

Baumgartner H, De Backer J, Babu-Narayan SV, Budts W, Chessa M, Diller GP, Lung B, Kluin J, Lang IM, Meijboom F, Moons P, Mulder BJM, Oechslin E, Roos-Hesselink JW, Schwerzmann M, Sondergaard L, Zeppenfeld K; ESC Scientific Document Group. 2020 ESC Guidelines for the management of adult congenital heart disease. Eur Heart J. 2021 Feb 11;42(6):563-645. doi: 10.1093/eurheartj/ehaa554. No abstract available. — View Citation

Bull C, Yates R, Sarkar D, Deanfield J, de Leval M. Scientific, ethical, and logistical considerations in introducing a new operation: a retrospective cohort study from paediatric cardiac surgery. BMJ. 2000 Apr 29;320(7243):1168-73. doi: 10.1136/bmj.320.7243.1168. — View Citation

Dennis M, Kotchetkova I, Cordina R, Celermajer DS. Long-Term Follow-up of Adults Following the Atrial Switch Operation for Transposition of the Great Arteries - A Contemporary Cohort. Heart Lung Circ. 2018 Aug;27(8):1011-1017. doi: 10.1016/j.hlc.2017.10.008. Epub 2017 Oct 31. — View Citation

Dobson R, Danton M, Nicola W, Hamish W. The natural and unnatural history of the systemic right ventricle in adult survivors. J Thorac Cardiovasc Surg. 2013 Jun;145(6):1493-501; discussion 1501-3. doi: 10.1016/j.jtcvs.2013.02.030. Epub 2013 Mar 13. Erratum In: J Thorac Cardiovasc Surg. 2015 Mar;149(3):950. — View Citation

Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation. 2007 Jan 16;115(2):163-72. doi: 10.1161/CIRCULATIONAHA.106.627224. Epub 2007 Jan 8. — View Citation

Smood B, Kirklin JK, Pavnica J, Tresler M, Johnson WH Jr, Cleveland DC, Mauchley DC, Dabal RJ. Congenitally Corrected Transposition Presenting in the First Year of Life: Survival and Fate of the Systemic Right Ventricle. World J Pediatr Congenit Heart Surg. 2019 Jan;10(1):42-49. doi: 10.1177/2150135118813125. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality	Death	Through study completion, an average of 18 years
Primary	Incident heart failure	Initiation or increase in dosage (if previously prescribed for another cause, i.e. hypertension) of loop diuretic, ACE-inhibitor/ARB therapy, or evidence-based beta blocker therapy because of new heart failure signs and symptoms (shortness of breath, fatigue, reduced exercise tolerance) AND AT LEAST 1 OF THE FOLLOWING: • BNP =400 pg/mL OR the following NT-proBNP levels according to age: < 50 years, =450 ng/L; 50-75 years, =900 ng/L; >75 years, =1800 ng/L OR systolic dysfunction (Systemic ventricle EF <50%) OR • BNP 100-400 pg/mL (or NT-proBNP levels below the thresholds according to age given above) AND structural or functional heart disease	Through study completion, an average of 18 years
Primary	Number of patients with heart failure hospitalization	Rehospitalization, emergency ward visit, 24h observation stay AND Treatment with or increase in dosage if previously prescribed for another cause (i.e.hypertension) of loop diuretics or treatment with IV vasoactive agents.	Through study completion, an average of 18 years
Primary	Number of patients with arrhythmias	Events that cause emergency ward visit or hospitalization.	Through study completion, an average of 18 years
Primary	Number of patients with thromboembolic events	Cerebrovascular events including any of (Hemorrhagic or ischemic): 1, TIA (symptoms less than 24 hours) 2, CVA (symptoms more than 24 hours) and also pulmonary embolism.	Through study completion, an average of 18 years
Primary	Infective endocarditis	Definitie Infective Endocarditis	Through study completion, an average of 18 years
Primary	Number of patients with tricuspid valve surgery	Tricuspid valve surgery	Through study completion, an average of 18 years
Primary	Number of patients with ventricular Assist Device implantation	Implantation of ventricular assist device	Through study completion, an average of 18 years
Primary	Number of patients with heart transplantation	Heart transplantation	Through study completion, an average of 18 years
Primary	Number of patients with aortic aneurysm or dissection	Aortic root more than 40 mm or aneurysm in other parts of aorta. Aortic dissection.	Through study completion, an average of 18 years
Primary	Number of patients with pulmonary artery hypertension	Mean PAP of more than 25mmHg or systolic PAP of more than 40 mmHg.	Through study completion, an average of 18 years
Primary	Number of patients with baffle interventions	Surgical or angiographic reintervention of baffles in patients with surgically corrected transposition of the great arteries (due to stenosis or leakage).	Through study completion, an average of 18 years
Primary	Number of patients with coronary artery interventions	Due to ischemia. Angiographic or surgical intervention.	Through study completion, an average of 18 years
Primary	Number of patients with device implantation	Including pacmakers, ICDs and CRTs.	Through study completion, an average of 18 years
Secondary	Number of patients with decreased exercise capacity	Evaluated by cardiopulmonary exercise test results.	At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Secondary	Number of patients with right ventricular systolic dysfunction	Measured by echocardiography qualitatively	At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Secondary	Number of patients with left ventricular systolic dysfunction	Measured by echocardiography qualitatively	At two time points. 1: Baseline 2. Through study completion, an average of 18 years