Fontan Circulation and Reproductive Health in a National Swedish Cohort

Fontan Circulation Clinical Trial

Official title: Fontan Circulation and Reproductive Health in a National Swedish Cohort

Status Recruiting

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Fontan Circulation

• NCT number: NCT06258382
• Study type: Observational
• Source: Linkoeping University
• Contact: Caroline Lilliecreutz, PhD, Docent
• Phone: +46708731124
• Email: caroline.lilliecreutz@regionostergotland.se
• Status: Recruiting
• Start date: October 1, 2023
• Completion date: October 1, 2026