Fontan circulation: Analysis of its Impact on quality of life and Rate of deterioration (FAIR study)

The Fontan procedure is performed since 1971 in children who are born with a
univentricular heart. This Fontan operation creates a unique, on-physiological
circulation (the Fontan circulation) in which the systemic venous return flows
passively through the lungs without passing the pumping heart. Due to this
abnormal physiology there is an increased risk of short and long term
complications. The short term consequences of the Fontan circulation have
already been extensively investigated. Among others, due to the adjustments of
pre-operative patients selection criteria and developments of the operation
technique the short term survival has increased and is now satisfactory. With
increased short term survival and longer follow-up times attention has shifted
towards long term survival. We are now starting to recognize an attrition or
failure of the Fontan circulation after ten till fifteen years. This failure is
probably related to the abnormal physiology, which results in chronic increased
central venous pressures, progressive rise of the pulmonary vascular
resistance, chronic decreased pre-load and increased after-load of the heart.
When this attrition develops, not many treatment options are left, and the
patients usually die as young adults.
The failure of the Fontan circulation can be subdivided in four mechanisms
which may be responsible. First, the heart function may decrease due to the
chronic abnormal circulation (decreased pre-load and increased after-load) and
intrinsic myocardial abnormalities because of the congenital heart disease.
Secondly, the un-physiological Fontan circulation results in a chronic
increased central venous pressure. This can cause protein losing enteropathy,
liver cirrhosis and other hepatic disorders. Combined with the slowed systemic
venous return this can cause trombo-embolic complications. The third mechanism
concerns the progressive rise of the pulmonary vascular resistance. About this
mechanism there is still a lot unknown. Lastly, the autonomic nervous system
and neuro-humeral axis activation are likely to contribute to the failure of
the Fontan circulation.
The above mentioned mechanisms are insufficiently clarified. Besides,
differences in the time and degree in which the attrition develops are major
between the individual Fontan patients. It is still unknown how the attrition
develops, what is the rate of de development of the attrition and which
patients will development this attrition. The objective of this study is to
investigate the course and rate of the attrition and the impact on the quality
of life of these patients. As an important part of the qualtity of life,
special attention will be given to the sexual and obstetric functioning in
these patients. Despite the great probability of sexual dysfunction due to the
chronic illness, unphysiological circulation, autonomic dysregulation and
reduced exercise tolerance, no research has yet been done to quantify this.
With increased insights in the attrition of the Fontan circulation, we might be
able to increase the therapeutic options when the attrition develops or even
delaying the attrition of the Fontan circulation. So we make significant
improvements in the care for patients who are born with a univentricular heart.

Primary Objective:
- Investigating the rate of the attrition and predictors of the failing Fontan
circulation, defined as decrease in functional capacity.

Secondary Objective(s):
- Investigating predictors of decrease in NYHA class of Fontan patients
- Investigating predictors of mortality of Fontan patients
- Investigating the relationship between clinical parameters (i.e. heart, lung,
liver, kidney function test) and the quality of life of Fontan patients.
-Investigating the correlation between ventricle functioning on
echocardiography and on magnetic resonance imaging with the NTproBNP levels in
venous blood.
- Investigating the correlation between liver cirrhosis/congestion on magnetic
resonance imaging and parameters for liver disease in venous blood (ASAT, ALAT,
γGT).
- Investigating the correlation between ventricle functioning on
echocardiography and endothelin-1 measurements.
- Investigating sexual dysfunction in Fontan patients compared to healthy
subjects.

This study is a longitudinal investigation.
We will evaluate two measurements with an interval of two years (2012-2014).
For both measurements we will investigate the standardized follow-up tests for
heart, lung, liver, kidney function and exercise tolerance. These parameters
will be evaluated with an echocardiogram, blood samples, VO2max, spirometry,
Holter test, magnetic resonance imaging and heart catheterization.

For our study, we will add an once only evaluation, in the first measurement,
of hepatic disorders with magnetic resonance imaging and an evaluation of the
quality of life using a questionnaire. For better assessment of the perception
of the patients on any sexual problems, ten patients will be randomly chosen
for interviewing by a psychologist about their sexual wellbeing. These
interviews are semi-structured and will take around 30-45 minutes.
In 2012 as well as in 2014 measurements in venous blood, ie endothelin-1, will
be calculated. This requires an extra blood sample to be taken from the
patients, which will be done during the venous puncture in context of the
regular patient care. Besides that, at the second measurement the patients will
be asked to fill in a questionnaire which consists of the questions about
general wellbeing only.

Most of the parameters that are investigated are part of the regular follow-up
of the Fontan patients.
The additional procedures for this research include the MRI liver, lab
measurements and questionnaires about the quality of life. The MRI liver will
be conducted simultaneously with the regular MRI for heart and lung. This does
not create an extra burden for the patients.
It is possible newly developed hepatic disorders will be diagnosed. If
medically relevant, the patient will be informed and referred to his/her GP.
The lab measurements will be executed as supplement to the regular venous blood
samples taken in context of the regular patient care. This means one extra
blood sample has to be taken.
The questionnaires and interviews will only be taken in patients who are 16
years or older to avoid an additional load for our minor patients and because
of the evaluation of sexual and obstetric function. For the patients older or
equal to sixteen years it may cause an emotional burden to fill in the forms
and answer the questions of the interview due to the personal questions. This
is why the patients can indicate on the Informed Consentform whether they want
to particate in the part of the study about sexual functioning.