Systemic Right Ventricle Long-term Outcome (SINCERE)

February 5, 2024 updated by: University Medical Center Groningen

Systemic Right Ventricle Long-term Outcome: a Multicentre Study

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

542

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • Universitair Ziekenhuis Leuven
  • Netherlands
      • Amsterdam, Netherlands
        • Amsterdam University Medical Centre
      • Enschede, Netherlands
        • Medisch Spectrum Twente Enschede
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Leiden, Netherlands
        • Leiden University Medical Centre
      • Maastricht, Netherlands
        • Maastricht University Medical Centre
      • Nijmegen, Netherlands
        • Radboud university medical centre
      • Rotterdam, Netherlands
        • Erasmus University Medical Centre
      • Utrecht, Netherlands
        • University Medical Centre Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with systemic right ventricles who are followed up in different academic centers in the Netherlands and Belgium.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Systemic right ventricle patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality
Time Frame: Through study completion, an average of 18 years
Death
Through study completion, an average of 18 years
Incident heart failure
Time Frame: Through study completion, an average of 18 years
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
Number of patients with heart failure hospitalization
Time Frame: Through study completion, an average of 18 years
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
Number of patients with arrhythmias
Time Frame: Through study completion, an average of 18 years
Events that cause emergency ward visit or hospitalization.
Through study completion, an average of 18 years
Number of patients with thromboembolic events
Time Frame: Through study completion, an average of 18 years
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
Infective endocarditis
Time Frame: Through study completion, an average of 18 years
Definitie Infective Endocarditis
Through study completion, an average of 18 years
Number of patients with tricuspid valve surgery
Time Frame: Through study completion, an average of 18 years
Tricuspid valve surgery
Through study completion, an average of 18 years
Number of patients with ventricular Assist Device implantation
Time Frame: Through study completion, an average of 18 years
Implantation of ventricular assist device
Through study completion, an average of 18 years
Number of patients with heart transplantation
Time Frame: Through study completion, an average of 18 years
Heart transplantation
Through study completion, an average of 18 years
Number of patients with aortic aneurysm or dissection
Time Frame: Through study completion, an average of 18 years
Aortic root more than 40 mm or aneurysm in other parts of aorta. Aortic dissection.
Through study completion, an average of 18 years
Number of patients with pulmonary artery hypertension
Time Frame: Through study completion, an average of 18 years
Mean PAP of more than 25mmHg or systolic PAP of more than 40 mmHg.
Through study completion, an average of 18 years
Number of patients with baffle interventions
Time Frame: Through study completion, an average of 18 years
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
Number of patients with coronary artery interventions
Time Frame: Through study completion, an average of 18 years
Due to ischemia. Angiographic or surgical intervention.
Through study completion, an average of 18 years
Number of patients with device implantation
Time Frame: Through study completion, an average of 18 years
Including pacmakers, ICDs and CRTs.
Through study completion, an average of 18 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with decreased exercise capacity
Time Frame: At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Evaluated by cardiopulmonary exercise test results.
At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Number of patients with right ventricular systolic dysfunction
Time Frame: At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Measured by echocardiography qualitatively
At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Number of patients with left ventricular systolic dysfunction
Time Frame: At two time points. 1: Baseline 2. Through study completion, an average of 18 years
Measured by echocardiography qualitatively
At two time points. 1: Baseline 2. Through study completion, an average of 18 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

Hartekind
Hartstichting

Investigators

  • Principal Investigator: Joost P van Melle, MD, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 26, 2022

Primary Completion (Actual)

August 24, 2023

Study Completion (Actual)

August 24, 2023

Study Registration Dates

First Submitted

November 14, 2023

First Submitted That Met QC Criteria

February 5, 2024

First Posted (Estimated)

February 14, 2024

Study Record Updates

Last Update Posted (Estimated)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202100379

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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