Survival of Double Inlet Left Ventricle Patients Without Fontan Circulation

Double Inlet Left Ventricle Clinical Trial

— DILV-S  

Official title:

Survival of Double Inlet Left Ventricle Patients Without Fontan Circulation: Intracardiac Anatomy and Hemodynamics, Functional Status and Quality of Life

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03667144
• Other study ID #: NL59516.042.17
• Status: Not yet recruiting
• Start date: December 3, 2018
• Est. completion date: June 1, 2019

Study information

• Verified date: September 2018
• Source: University of Groningen
• Contact: Sophie L Meyer, BSc
• Phone: 004917681033255
• Email: s.l.meyer[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Patients with univentricular hearts are currently palliated with the Fontan procedures. This results in an unphysiologic circulation with poor long-term survival. On the other hand there is a small, selected subgroup of patients with univentricular hearts of the double inlet left ventricle (DILV) type that survives up to old age without ever having undergone any Fontan procedures. Considering the relatively bleak data on long-term survival of DILV patients palliated with the Fontan procedure, it seems highly relevant to investigate and determine factors that allow a selection of unoperated patients to live to a comparatively high age without apparent major complaints. This might have an impact on how (and if, at all) certain univentricular patients are selected for operation in the future. For some, a different surgical procedure, or even therapeutic nihilism might be a more viable alternative.

The investigators hypothesise that favourable intracardiac streaming plays a role in making these patients viable: certain intracardiac anatomical characteristics allow for favourable flow patterns.

The primary objective of this study is to describe the intracardiac anatomy and hemodynamics of DILV patients without Fontan circulation using 4D MRI. Furthermore, the functional status and quality of life of these patients will be assessed.

Description:

Rationale: Patients with univentricular hearts are currently palliated with a sequence of operations known as the Fontan procedure. This results in an un-physiologic circulation with poor long-term survival. On the other hand there is a small, selected subgroup of patients with univentricular hearts of the double inlet left ventricle (DILV) type that survives up to old age without ever having undergone any Fontan procedure. Considering the relatively bleak data on long-term survival of DILV patients palliated with the Fontan procedure, it is highly relevant to investigate and determine factors that allow for a selection of unoperated patients to live to a comparatively high age without apparent major complaints. This might have an impact on how (and if, at all) certain univentricular patients will be selected for operation in the future. For some, a different surgical procedure, or even therapeutic nihilism might be a more viable alternative. The investigators hypothesize that favourable intracardiac streaming plays a role in making the unpalliated patients viable: certain intracardiac anatomical characteristics allow for favourable flow patterns, resulting in higher systemic oxygen saturations than expected by mixing pulmonary and systemic venous returns.

Objective: The primary objective of this study is to describe the intracardiac anatomy and hemodynamics of DILV patients without Fontan circulation using 4D MRI. Furthermore, the functional status and quality of life of these patients will be assessed and compared to a matched cohort of Fontan patients.

Study design: This will be an observational, cross-sectional study. The investigators aim to include all DILV patients without Fontan circulation known at the congenital heart disease referral centers in the Netherlands and Flanders. The Dutch patients will undergo one 4D MRI, a physical examination, cardiopulmonary exercise testing and have a blood sample taken at the University Medical Center Utrecht. The patients from the Flemish referral centers will undergo the same protocol at the University Medical Center Leuven. Furthermore, patients over the age of 18 will be asked to fill out a quality of life questionnaire.

Study population: Included will be patients over the age of 12 with the diagnosis double inlet left ventricle, which have not undergone the Fontan trajectory. For the 4D MRI, patients with an MRI non-compatible pacemaker in situ will be excluded.

Main study parameters/endpoints: This is primarily an explorative study aiming to describe the anatomy of unpalliated DILV hearts of patients without Fontan palliation. With 4D MRI, the hearts will be grouped according to the angular relationship of the two lines connecting the atrioventricular and the ventriculo-arterial valves. This angle can be divided into three categories: 1) parallel (i.e. 0°), 2) perpendicular (i.e. 90°) or 3) an in-between variant. Accordingly, flow patterns, ranging from linear to turbulent will be measured and correlated to the anatomical variants.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden and risks associated with participation in this study are minimal. Patients need to visit the site of investigation only once, and the tests done at the visit (i.e. 4D MR imaging, exercise and pulmonary function testing and blood sample) are part of standard medical care and as such pose negligible risk on the patients. The quality of life survey is not part of standard medical care and might be confrontational on a psychological level. It is, however, a widely used and scientifically approved survey, which aims to keep this burden very low. Due to the extremely low prevalence of the condition to be studied, it is of great importance to include every single patient, including children under the age of

18. Excluding children from this study would further decrease the sample size to a significantly smaller number, making it difficult to draw conclusions.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: June 1, 2019
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis double inlet left ventricle, established by echocardiograph or MRI

• Not undergone Fontan trajectory in the past

• Be of the age of 12 or older

• Written informed consent

Exclusion Criteria:

• previous (partial) cavopulmonary connection

The following subjects will be excluded from the MRI part of the study, but will still be asked to participate in all the other parts:

• MRI non-compatible pacemaker in situ

Related Conditions & MeSH terms

• Double Inlet Left Ventricle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Groningen

References & Publications (8)

Cook AC, Anderson RH. The anatomy of hearts with double inlet ventricle. Cardiol Young. 2006 Feb;16 Suppl 1:22-6. Review. — View Citation

Franklin RC, Spiegelhalter DJ, Anderson RH, Macartney FJ, Rossi Filho RI, Douglas JM, Rigby ML, Deanfield JE. Double-inlet ventricle presenting in infancy. I. Survival without definitive repair. J Thorac Cardiovasc Surg. 1991 May;101(5):767-76. — View Citation

Frescura C, Thiene G. The new concept of univentricular heart. Front Pediatr. 2014 Jul 7;2:62. doi: 10.3389/fped.2014.00062. eCollection 2014. Review. — View Citation

Gersony WM. Fontan operation after 3 decades: what we have learned. Circulation. 2008 Jan 1;117(1):13-5. doi: 10.1161/CIRCULATIONAHA.107.748566. Review. — View Citation

Macartney FJ, Partridge JB, Scott O, Deverall PB. Common or single ventricle. An angiocardiographic and hemodynamic study of 42 patients. Circulation. 1976 Mar;53(3):543-54. — View Citation

Poterucha JT, Anavekar NS, Egbe AC, Julsrud PR, Connolly HM, Ammash NM, Warnes CA. Survival and outcomes of patients with unoperated single ventricle. Heart. 2016 Feb;102(3):216-22. doi: 10.1136/heartjnl-2015-308440. Epub 2015 Dec 23. — View Citation

Wolff D, van de Wiel HBM, de Muinck Keizer ME, van Melle JP, Pieper PG, Berger RMF, Ebels T, Weijmar Schultz WCM. Quality of life and sexual well-being in patients with a Fontan circulation: An explorative pilot study with a mixed method design. Congenit Heart Dis. 2018 Mar;13(2):319-326. doi: 10.1111/chd.12576. Epub 2018 Mar 12. — View Citation

Wolff D, van Melle JP, Bartelds B, Ridderbos FS, Eshuis G, van Stratum EBHJ, Recinos SJ, Willemse BWM, Hillege H, Willems TP, Ebels T, Berger RMF. Fontan Circulation over Time. Am J Cardiol. 2017 Aug 1;120(3):461-466. doi: 10.1016/j.amjcard.2017.05.005. Epub 2017 May 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Demographics	sex, age, weight, height	1 day
Other	Highest Level of Education	Highest level of education as well as their current Profession and their current work Status will be asked of all participants on the Basis of a questionnaire	1 day
Other	Current Medication use	Participants will be asked to provide the names and the dosage of all medications they are currently using .	1 day
Primary	Angle between atrioventricular and ventriculoarterial valves	This is primarily an explorative study aiming to describe the anatomy of unpalliated DILV hearts. With 4D MRI, the hearts will be grouped according to the angular relationship of the atrioventricular to the ventriculo-arterial valves. This angle can be divided into three categories: 1) parallel (i.e. 0°), 2) perpendicular (i.e. 90°) or 3) an in-between variant. Accordingly, flow patterns, ranging from linear to turbulent will be measured and correlated to the anatomical variants.	1 day
Secondary	New York Heart Association Functional Classification	NYHA functional class I to IV	1 day
Secondary	Peak VO2	peak oxygen uptake (VO2index) during exercise as well as peak VO2 as percentage of predicted (VO2 pred)	1 day
Secondary	Peripheral oxygen saturation	Oxygen saturation at rest, measured with oximetry	1 day
Secondary	Scores for Quality of life Adults	Quality of life survey overall scores, and scores in the subcategories measured with the Short Form (SF)36 (For patients 18 and older). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality physical functioning bodily pain general health perceptions physical role functioning emotional role functioning social role functioning mental health	1 day
Secondary	Scores for Quality of life	Quality of life survey overall scores, and scores in the subcategories measured with PedsQL (for patients younger than 18). The 23-item PedsQL Generic Core Scales were designed to measure the core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. The 4 Multidimensional Scales are: Physical Functioning (8 items) Emotional Functioning (5 items), Social Functioning (5 items), School Functioning (5 items) The summary scores are: Total Scale Score (23 items), Physical Health Summary Score (8 items), Psychosocial Health Summary Score (15 items)	1 day
Secondary	Hematocrit	from venous blood	1 day
Secondary	Haemoglobin	from venous blood	1 day
Secondary	Creatinin	from venous blood	1 day
Secondary	eGFR	from venous blood	1 day
Secondary	high sensitive Troponin T	from venous blood	1 day
Secondary	NT-proBNP	from venous blood	1 day
Secondary	LDH	from venous blood	1 day
Secondary	ASAT	from venous blood	1 day
Secondary	ALAT	from venous blood	1 day
Secondary	Alkaline phosphatase	from venous blood	1 day
Secondary	Gamma-GT	from venous blood	1 day
Secondary	Galectin 3	from venous blood	1 day
Secondary	Bilirubin	from venous blood	1 day