Clinical trial NCT02414321: The Role of the Pulmonary Vasculature in the Fontan Circulation
Official title: The Role of the Pulmonary Vasculature in the Fontan Circulation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Heart Disease
Fontan Operation
Pulmonary Vascular Resistance
Pulmonary Vascular Remodeling
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2015-04-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adult patients (≥18 years), who attend the University Medical Center Groningen for follow-up after a Fontan completion.

Additionally 5 adult patients (≥18 years) without a Fontan circulation and without a univentricular heart-like diagnosis but with a clinical indication for right heart catheterization and normal values at right heart catheterization measurements will be included to serve as controls for the pulmonary artery OCT analysis.

Brief summary: This study aims to explore the structural and functional characteristics of the pulmonary vasculature in adult Fontan patients.

Objectives:

* Determine the effect of pulmonary vasodilatation on indexed cardiac output during simulated exercise.
* Characterization of structural properties of small pulmonary arteries.

Detailed description: Rationale:

The Fontan circulation is a palliation for patients with a functionally univentricular heart. The Fontan circulation is characterized by impaired exercise capacity and gradual attrition over time. To date treatment options are extremely limited. It has been proposed that pulmonary vascular resistance (PVR) is the controlling and limiting factor of cardiac output in the Fontan circulation. Remodeling of the pulmonary vasculature and increasing PVR are possible key factors in the long term failure of the Fontan circulation. Optical Coherence Tomography (OCT) is an intravascular imaging modality used for structural characterization of blood vessels. Nitric oxide is a pulmonary vasodilator used in pulmonary vascular response tests, aimed at lowering PVR which may improve cardiac output in the Fontan circulation. These two diagnostic procedures are tools to study the structural and functional characteristics of the pulmonary vasculature in the Fontan circulation. The results of this study could identify the pulmonary circulation as a future treatment target in Fontan patients and may provide clues for new therapeutic treatment strategies to improve the long term outcome of these patients.

Study procedure:

The study protocol will be performed during a clinically indicated cardiac catheterization. In the context of this study additional measurements will be performed which will include a pulmonary vascular response test, trans-thoracic echocardiography and pulmonary artery OCT measurements.

Eligibility criteria: Inclusion criteria:

Fontan group

* written informed consent
* Clinical indication for cardiac catheterization

Control group

* written informed consent
* Clinical indication for right heart catheterization
* Absence of pulmonary vascular disease
* Normal pulmonary vascular hemodynamic profile

Exclusion criteria:

Fontan group

* Standard exclusion criteria for cardiac catheterization
* Obstruction in Fontan conduit
* Inability to measure a reliable cardiac index and PVR (rhythm instability, hemodynamic or anatomic reasons)

Control Group

- No specific exclusion criteria apart from the standard exclusion criteria for right heart catheterization.

Primary outcomes:
measure: vasodilatation
timeFrame: change in indexed cardiac output between baseline and after 10 minutes of pulmonary vasodilatation at heart catheterization
measure: number of intimal lesions in small pulmonary arteries
timeFrame: baseline at heart catheterization
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Rolf M Berger, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971 May;26(3):240-8. doi: 10.1136/thx.26.3.240.
citation: Wolff D, van Melle JP, Ebels T, Hillege H, van Slooten YJ, Berger RM. Trends in mortality (1975-2011) after one- and two-stage Fontan surgery, including bidirectional Glenn through Fontan completion. Eur J Cardiothorac Surg. 2014 Apr;45(4):602-9. doi: 10.1093/ejcts/ezt461. Epub 2013 Sep 25.
citation: de Leval MR, Deanfield JE. Four decades of Fontan palliation. Nat Rev Cardiol. 2010 Sep;7(9):520-7. doi: 10.1038/nrcardio.2010.99. Epub 2010 Jun 29.
citation: Gewillig M, Brown SC, Eyskens B, Heying R, Ganame J, Budts W, La Gerche A, Gorenflo M. The Fontan circulation: who controls cardiac output? Interact Cardiovasc Thorac Surg. 2010 Mar;10(3):428-33. doi: 10.1510/icvts.2009.218594. Epub 2009 Dec 7.
citation: Goldberg DJ, Avitabile CM, McBride MG, Paridon SM. Exercise capacity in the Fontan circulation. Cardiol Young. 2013 Dec;23(6):824-30. doi: 10.1017/S1047951113001649.
citation: Khambadkone S, Li J, de Leval MR, Cullen S, Deanfield JE, Redington AN. Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation. Circulation. 2003 Jul 1;107(25):3204-8. doi: 10.1161/01.CIR.0000074210.49434.40. Epub 2003 Jun 23.
citation: Ridderbos FJ, Wolff D, Timmer A, van Melle JP, Ebels T, Dickinson MG, Timens W, Berger RM. Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant. 2015 Mar;34(3):404-13. doi: 10.1016/j.healun.2015.01.005. Epub 2015 Jan 16.