Right Ventricular Diastolic Function in Chronic Adverse RV Loading And Congenital Heart Disease

Not Applicable

• Conditions: Pulmonary Regurgitation; Congenital Heart Disease
• Interventions: Diagnostic Test: Acquisition of pressure-volume-loops

• Registration Number: NCT03471936
• Lead Sponsor: Heart Center Leipzig - University Hospital

Brief Summary

The aim of the study is to assess the characteristics, incidence and predictors of load-independent right ventricle (RV) diastolic dysfunction in patients with congenital heart disease (CHD) and adverse RV loading conditions by acquiring pressure-volume loops and compare these results to a population of patients with exclusion of coronary artery disease and absence of any known disease affecting the RV.

Detailed Description

One of the major problems in the expanding population of patients with congenital heart disease (CHD) is dysfunction of the right ventricular (RV) outflow tract (OT). Initial surgical repair for complex conditions or repeated surgery for free pulmonary regurgitation often includes the creation of an artificial RV to main pulmonary artery connection. Over time, these conduits are prone to develop valvar incompetence or obstruction. There is clear evidence that pulmonary stenosis and pulmonary regurgitation are associated with exercise intolerance, arrhythmias and an increased risk of sudden death. Timely pulmonary valve replacement can halt and may reverse such unfavourable outcomes. However, this means that patients have to undergo multiple open-heart surgeries in order to reduce the haemodynamic burden on the right ventricle. Decision making in these patients with RVOT dysfunction is based on the aim to perform pulmonary valve replacement as late as possible to minimise the total number of open-heart surgeries required in individual patients, but before functional impairment might be irreversible. Importantly, this point of 'no return' in right ventricular pressure and/or volume overload is still unknown and represents one of the most challenging problems in the field of CHD. Ideally, quality of life, survival and freedom from atrial and ventricular arrhythmia should be the endpoints for any study trying to optimise timing of pulmonary valve replacement. However, such studies would require long follow-up in large patient populations and will not help to improve management of right ventricular outflow tract (RVOT) dysfunction in the short-term. In order to design studies with surrogate functional endpoints, a sound understanding of physiological consequences of altering RV loading and its implications for bi-ventricular function or exercise capacity is pivotal.

The investigators established a method of acquiring robust RV pressure-volume-loops at our institution. In the context of a research study, the investigators performed RV conductance catheter measurements in 22 patients with heart failure with preserved ejection fraction and in 11 patients with no evidence of any RV disease. Within the RaDICAL study the investigators aim further to compare these results to pressure-volume loops acquired in patients with congenital heart disease (CHD) and adverse RV loading conditions in order to evaluate characteristics, incidence and predictors of load-independent right ventricle (RV) diastolic dysfunction.

Study Timeline

• Study Start: 2016-07-07
• Study First Submitted: 2018-02-01
• Study First Submitted QC: 2018-03-12
• Study First Posted: 2018-03-21
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-06
• Last Update Posted: 2021-05-10
• Primary Completion: 2021-08
• Study Completion: 2022-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Patient with CHD involving the RV
• Chronic RV volume and/or pressure overload as defined by:
• more than mild pulmonary regurgitation and/or
• more than mild tricuspid regurgitation and/or
• a gradient across the RV outflow tract of ≥ 3 m/s on echocardiography and/or
• estimated RV systolic pressure > 65 mmHg
• Clinical indication for cardiac catheterization
• Age 12 to 80 years
• Informed consent

Exclusion Criteria

• Contraindication for magnetic resonance imaging or cardiopulmonary exercise testing
• Pregnancy
• RV systolic function on magnetic resonance imaging < 45%

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Acquisition of pressure-volume loops	Acquisition of pressure-volume-loops	-

Primary Outcome Measures

Name	Time	Method
Presence of RV diastolic dysfunction in CHD and RVOT dysfunction	Baseline	Determination of load-independent stiffness constant in CHD

Secondary Outcome Measures

Name	Time	Method
Link between RV load-independent stiffness constant and functional capacity	Baseline	Oxygen uptake (VO2 max) in correlation to load-independent stiffness constant
Association between E/É and RV stiffness in CHD	Baseline	Correlation between E/É and load-independent stiffness constant
Association between RV stiffness expressed as E/É and functional outcome after surgical or percutaneous pulmonary valve replacement	6 months	Correlation between E/É before intervention and VO2 max change after pulmonary valve replacement

Trial Locations

Locations (1)

Heart Center of the University Leipzig; 🇩🇪 Leipzig, Germany