Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06258382 |
| Other study ID # |
2023-02526-01 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2023 |
| Est. completion date |
October 1, 2026 |
Study information
| Verified date |
February 2024 |
| Source |
Linkoeping University |
| Contact |
Caroline Lilliecreutz, PhD, Docent |
| Phone |
+46708731124 |
| Email |
caroline.lilliecreutz[@]regionostergotland.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
In the Swedish registry for congenital heart defects, SWEDCON, over 230 patients with
single-ventricle circulation are registered in the adult section.
Congenital heart defects affect career choices, family planning, and leisure activities.
Questions regarding heredity and pregnancy are common.
The impact of Fontan circulation on reproductive health and fertility needs to be
illuminated, and additional studies are required from both medical and psychosocial
perspectives.Cognitive impairment is common among patients with congenital heart defects but
is likely an overlooked cause of long-term illness.
Objective To study a large national population (n=200) of adults with Fontan circulation and
their potential partners regarding.
- the prevalence and explanatory factors for sexual dysfunction and infertility in women
and men with Fontan circulation (Study A).
- the outcomes of pregnancy, choice of delivery mode, and complications in patients with
Fontan circulation (Study B).
- the experiences and perceptions of becoming parents among women (n=20) and men (n=20),
as well as elucidate reasoning and family planning among women and men (n=20) who have
not become parents (Study C).
- Investigate the prevalence and explanatory factors for (Sub-study D):
- Fatigue
- In-depth cognitive screening to describe specific cognitive functions such as auditory
memory, visuospatial memory, attention, cognitive speed, and executive functions.
The aim of this research is to gain more knowledge in an area that has been relatively
underexplored, thus improving care for women and men with congenital heart defects.
Description:
Background Every year, approximately 2000 children are born with congenital heart defects in
Sweden. In a small percentage of these cases, the heart defects are so severe that they
cannot be corrected to resemble or function like a healthy heart. Instead, these highly
complex heart defects are operated on to establish "single-ventricle circulation," also known
as Fontan circulation or TCPC circulation (total cavopulmonary connection). This means there
is only one chamber in circulation, pumping blood into the body's main artery. To facilitate
venous blood flow to the lungs for oxygenation and back to the heart chamber, high venous
pressure and low resistance in the lung circulation are required.
This type of blood circulation can lead to severe complications later in life, including
heart failure, low oxygen saturation, blood clot formation, liver cirrhosis, bleeding,
protein-losing enteropathy, arrhythmias, and reduced physical capacity. In the Swedish
registry for congenital heart defects, SWEDCON, over 230 patients with single-ventricle
circulation are registered in the adult section.
Congenital heart defects affect career choices, family planning, and leisure activities.
Questions regarding heredity and pregnancy are common. The severity of different heart
defects varies and has varying degrees of impact on patients' daily lives. Pregnancy and
childbirth exert significant stress on a woman and her body. Due to the increased metabolic
needs of the fetus and the mother, hemodynamics change during a normal pregnancy, with
approximately a 40-50% increase in cardiac output and plasma volume. Pregnancy is often well
tolerated by women with congenital heart defects, but there might be an increased risk of
complications associated with pregnancy and childbirth. Women with complex congenital heart
defects have a higher risk of experiencing cardiovascular events during pregnancy compared to
women with simpler congenital heart defects. There is also a greater risk of infertility for
these women. The modified WHO classifications system (mWHO class I-IV) can be used to assess
risk associated with pregnancy and childbirth for women with heart disease, where higher
class is associated with increased morbidity and mortality. In Fontan circulation, the risk
of complications during pregnancy is considered high if the woman is classified as mWHO III
or IV. If a woman experiences complications due to Fontan circulation before pregnancy, she
is classified as mWHO IV and will be discouraged from pregnancy due to a very high risk for
both maternal and fetal complications. During pregnancy, there is an increased risk of
arrhythmias, heart failure symptoms, and thrombosis. Miscarriage risk is high for women with
Fontan circulation, and preterm delivery is common, often resulting in low birth weight for
gestational age. There is also an increased risk of peripartum bleeding. It is recommended
that patients with Fontan circulation have frequent check-ups during pregnancy and in the
first weeks after delivery.
Some women with complex congenital heart defects choose not to undergo pregnancy due to their
heart condition. Others choose to become pregnant despite being informed about the high risks
and advice against pregnancy, which places high demands on the care and follow-up of these
patients. How men with Fontan circulation perceive their parental abilities and the
possibility of having children is poorly studied, as well as how a partner of a person with
complex congenital heart defects thinks and reasons about parenthood.
The impact of Fontan circulation on reproductive health and fertility needs to be
illuminated, and additional studies are required from both medical and psychosocial
perspectives.
Cognitive impairment is common among patients with congenital heart defects but is likely an
overlooked cause of long-term illness. We have previously shown that 60% of patients with
Fontan circulation experience severe to very severe general fatigue. Cognitive function and
fatigue significantly affect all aspects of quality of life, including employment
opportunities, educational level, and the ability to maintain meaningful social
relationships, such as marriage. How this affects reproductive health is not fully
understood. Further studies are needed regarding cognitive impairment, its causes, and
consequences in adults with Fontan circulation.
Objective To study a large national population (n=200) of adults with Fontan circulation and
their potential partners regarding.
- the prevalence and explanatory factors for sexual dysfunction and infertility in women
and men with Fontan circulation (Study A).
- the outcomes of pregnancy, choice of delivery mode, and complications in patients with
Fontan circulation (Study B).
- the experiences and perceptions of becoming parents among women (n=20) and men (n=20),
as well as elucidate reasoning and family planning among women and men (n=20) who have
not become parents (Study C).
- Investigate the prevalence and explanatory factors for (Sub-study D):
- Fatigue
- In-depth cognitive screening to describe specific cognitive functions such as auditory
memory, visuospatial memory, attention, cognitive speed, and executive functions.
Work Plan The study is a national study involving six national centers: Gothenburg,
Linköping, Lund, Stockholm, Umeå and Uppsala. Each participating center includes all patients
with Fontan circulation. This involves approximately 200 patients and their potential
partners.
In Sweden, there are an estimated 40,000 adults with congenital heart defects. We have a
unique national register for congenital heart defects, The Swedish Registry of Congenital
Heart Disease (SWEDCON), which started in the 1990s with Grown Up Congenital Heart disease
(GUCH) and expanded in 2009 to include pediatric cardiology, heart interventions, and now
fetal cardiology in congenital heart defects.
Design: Observational study.
Inclusion Criteria:
- Fontan circulation, age ≥18 years at inclusion, follow-up at specialist clinics, ability
to fill in questionnaires in the Swedish language (no other alternative available) or
- Partner of a person with Fontan circulation, age ≥18 years at inclusion, and ability to
fill in questionnaires in the Swedish language (no other alternative available).
The following information are collected in the study. Fontan patient
- Demographics: age; gender, height, weight, marital status, number of children, education
level, occupation, and employment rate.
- Medical information: Diagnosis; previous interventions; arrhythmia; heart failure; PLE
(protein-losing enteropathy); lung restriction; FALD (Fontan-associated liver disease);
comorbidities (diabetes, Venous thrombosis, Stroke/TIA, Cognitive impairment, Scoliosis,
Perioperative severe injury). NYHA functional class; pulmonary hypertension.
- Blood test reflecting, heart, kidney, liver functions
- Physical performance ability: Work capacity; Oxygen uptake; Desaturation during work;
Physical activity according to SWEDCON, NYHA class
- Hand strength, toe lifts, and shoulder flexion to measure muscular endurance.
Additionally, maximal muscle strength in m. quadriceps femoris extension is measured
using a load cell. All tests are validated and used in both research and clinical
practice in adults with congenital heart defects.
- Questionnaire Health Behavior Scale- Congenital Heart Disease (HBS-CHD): lifestyle,
smoking, snuffing, drugs.
Partner:
- Demographics: Age, education level, occupation, and employment rate.
- Medical information: Significant medical conditions
Research Question Study A: Sexual dysfunction and infertility:
- Reproductive health questionnaire for Woman/reproductive health questionnaire for Man,
and a questionnaire for the potential partner, designed for this study.
- International Index of Erectile Function (IIEF5) to assess erectile (dys)function and
the Female Sexual Function Index (FSFI) for the analysis of sexual (dys)function.
- Quality life and health assessment. EQ-5D is an instrument to describe and measure
health and health-related quality of life. It consists of five questions and a VAS scale
for self-rated health. Historical data on EQ-5Dis available in SWEDCON and evaluated as
clinical routine during our visits.
Research Question Study B: Obstetric and Cardiological variables before, during, and after
pregnancy
- Cardiological check-ups and measures during each pregnancy; Preconception assessment;
mWHO class, Medication; Clinic visits (when, number);
- Pregnancy conference; Heart monitoring during delivery; Invasive monitoring during
delivery venous/arterial
- Cardiological complications during pregnancy, at delivery, first 6 months
- During pregnancy; arrhythmias, heart failure, thrombosis
- During delivery; arrhythmias, heart failure
- Up to 6 months postpartum; arrhythmias, heart failure, thrombosis Obstetric variables
during pregnancy;
- Pregnancy complications: Number of pregnancies , Gestational diabetes, Pregnancy-induced
hypertension, Preeclampsia, Anemia, Hyperemesis gravidarum, Thromboembolic event,
hepatosis, Chorioamnionitis-other infection/sepsis, Vaginal bleeding, Placental
complications, Preterm Premature rupture of membranes (PPROM)
- Relevant medication during pregnancy, Type of anticoagulation during and after
parturition
- Delivery data: Gestational week at partus, Premature delivery exact gestational week and
day - spontaneous and iatrogenic cause, Induction with indication, Delivery method;
uncomplicated vaginal delivery, instrumental vaginal delivery (indication e.g.,
impending fetal asphyxia, weak contractions, positional correction) Cesarean section
(elective/emergency/urgent) (indication for cesarean section noted) Bleeding (ml) at
partus, Anesthesia at partus spinal, epidural anesthesia (EDA), general anesthesia (GA),
other pain relief, Birth trauma - perineal tear degree I-IV, Placental retention,
Maternal death.
- Neonatal data: Admission to neonatal ward, Neonatal complication (e.g., jaundice,
infection, hypoglycemia) Child malformations- Type-, Neonatal death, Birth weight, small
for gestational age (SGA), large for gestational age (LGA), average for gestational age
(AGA) Apgar, pH in umbilical vein and artery.
Research Question Study C: Describe experiences and perceptions of parenthood in women:
- Thoughts, fears, and hopes
- Information and knowledge before and during pregnancy
- Follow-ups during pregnancy and their extent
- Need for special contact at the clinic for congenital heart defects during pregnancy
- Physical and mental well-being during and after childbirth
- Describe experiences and perceptions of parenthood in men
- Information about reproductive health
- Thoughts, fears, and hopes
- Describe reasoning among those who have not become parents
- Information about reproductive health
- Reasoning about reproductive health
- Long-term follow-up; additional pregnancy, intervention, hospitalization for heart
failure/arrhythmia/FALD/endocarditis/infection/stroke, transplantation, cardiovascular
death, non-cardiovascular death after 2.5, 10, and 15 years .
Control group: As control subjects, 200 age- and gender-matched individuals are recruited via
the population registry. They must not have congenital heart disease. They will complete the
same questionnaires as the study participants and will be asked questions about health
status.
Sub-study D: Cognitive function:
- For fatigue assessment, Multidimensional Fatigue Inventory (MFI-20) is used, a validated
instrument. The protocol measures five dimensions: general fatigue, physical fatigue,
mental fatigue, reduced motivation, and reduced activity. The questionnaire consists of
20 statements for which the participant is required to rate on a five-point scale how
well the statement applies to them. We have used the protocol in the current patient
group.
- In-depth cognitive screening using validated instruments: Montreal Cognitive Assessment
(MoCA) : to obtain an overall clinical picture of the group's cognition. MoCA stands for
The Montreal Cognitive Assessment and is a rapid assessment tool used in cognitive
assessment. It evaluates attention and concentration, executive functions, memory,
language ability, visuospatial abilities, abstract thinking, numerical ability, and time
and space orientation. We aim to conduct an in-depth analysis complementing the planned
MoCA with more specific tests to evaluate different cognitive domains such as auditory
memory, visuospatial memory, attention, cognitive speed, and executive functions).
- We will conduct these cognitive tests: SDMT - Symbol Digit Modalities Test. Measures
cognitive speed/processing speed and attention .
- TMT A and B - Trail Making Test. Measures cognitive speed/processing speed and executive
functions.
- BVMT-R - Brief Visuospatial Memory Test. Measures visuospatial learning and memory .
- CWIT - Color Word Interference Test. Measures executive functions, cognitive flexibility
.
- FAS - Verbal Fluency Test. Measures semantic memory and executive functions, cognitive
flexibility (14).
- DEX - Dysexecutive Questionnaire. Self-assessment test in complex thinking and reasoning
.
- HADs- Hospital Anxiety and Depression Scale, self-assessment test evaluating anxiety and
depression. BDI II- Beck Depression Inventory, an assessment tool measuring the level of
depression.
Significance The aim of this research is to gain more knowledge in an area that has been
relatively underexplored, thus improving care for women and men with congenital heart
defects. It is relatively common for women with congenital heart defects to avoid pregnancy
due to their heart condition. In cases of aortic valve and/or pulmonary valve disease,
Tetralogy of Fallot, and transposition of the great arteries, up to a third of women reported
they did not want to have children because of their heart condition .
Therefore, there is significant patient benefit in conducting research among women and men
with congenital heart defects. By gaining more knowledge in a new and relatively unexplored
area, care can be improved, enabling these women to give birth if they wish without having to
avoid it due to their chronic disabilities. Women with less complex heart disease and better
functional status can also benefit from new knowledge and improved care, especially since
there is a link between maternal congenital heart defects and lower birth weight in infants.
