A Longterm Follow-up and Comparison of Morbidity and Heart Health Between Patients With Pulmonary Atresia With Intact Ventricular Septum and Uni- or Biventricular Circulation
Conditions: Pulmonary Atresia With Intact Ventricular Septum
Sponsor: Vastra Gotaland Region

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A comparison of morbidity between paƟents with pulmonary atresia with intact 
ventricular septum and uni- or biventricular circulaƟon 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Research QuesƟon 
Do mortality, quality of life, comorbidity, cardiac funcƟon, and work capacity diﬀer between paƟents 
with pulmonary atresia with intact ventricular septum (PA-IVS) who has univentricular and 
biventricular circulaƟon? 
Overview of the Area 
PA-IVS is a rare congenital heart defect occurring in 4-5 live births per year in Sweden [1]. This 
malformaƟon entails a duct-dependent circulaƟon, which, if leŌ untreated, leads to death. The closed 
pulmonary valve (atresia) can present in various ways, ranging from fused valve leaﬂets to a valve plane 
primarily composed of myocardial Ɵssue. This variaƟon aﬀects the development of the right ventricle 
to diﬀerent degrees during the fetal stage. In the most severe form, there is only an inﬂow porƟon that 
cannot funcƟon as a ventricle, and these paƟents undergo a surgical procedure to establish 
univentricular circulaƟon. This operaƟon involves using cardiopulmonary bypass, and the thymus is 
removed. In milder cases, paƟents can undergo diﬀerent intervenƟons to achieve one-and-a-half- or 
biventricular circulaƟon. Coronary ﬁstulas may also be present between the right ventricle and the 
coronary arteries. In the most severe cases, the coronary circulaƟon is dependent on the right 
ventricle, and ligaƟng the ﬁstulas could risk myocardial ischemia. 
We aim to invesƟgate the well-being of paƟents born with PA-IVS in adulthood, focusing on 
comorbidity, quality of life, and physical capacity. We are interested in comparing paƟents within the 
group with uni- or biventricular circulaƟon. 
Method 
The inclusion criterion is individuals born PA-IVS who are 15 years or older at the start of the study. 
The study populaƟon consists of all individuals with PA-IVS who have been registered in Swedcon (a 
naƟonal register for paƟents with congenital heart defects) or in the NaƟonal PaƟent Register and 
Cause of Death Register since 1980 and meet other inclusion criteria, including age. 
The selecƟon of research subjects has been based on the purpose of the study, which is to conduct a 
long-term follow-up of a rare heart defect where treatment diﬀers between paƟents depending on the 
morphology of the heart defect. We will divide the paƟents into two groups based on whether they 
have uni- or biventricular circulaƟon. The basis for this division is that uni- and biventricular circulaƟon 
provide very diﬀerent condiƟons for meeƟng the increased cardiac output demands. 
We aim to carry out a long-term register-based follow-up study regarding comorbidity in paƟents with 
PA-IVS. AddiƟonally, we want to evaluate work capacity, cardiac health, and quality of life in the same 
paƟent group. 
PaƟents with PA-IVS are idenƟﬁed through Swedcon (a naƟonal register for paƟents with congenital 
heart defects) and the NaƟonal PaƟent Register, where informaƟon on comorbidity (menƟoned below) 
is also requested. To ensure that the diagnosis is correct and that the included research subjects meet 
the inclusion criteria, validaƟon will be conducted through a review of the research subjects’ medical 
records. In the medical record review, we will also note the current NYHA class, cardiac funcƟon 
measured by echocardiography, and results from cardiac funcƟon assessments. The included 
individuals will be grouped based on whether they have uni- or biventricular circulaƟon. The frequency 
of comorbidity (myocardial infarcƟon, heart failure, arrhythmia, stroke, malignancy, autoimmune 
diseases, infecƟons, atopy, certain liver diseases, and protein-losing enteropathy) will be compared 
between these two groups.  

19th of June 2023 
We also intend to send a Quality-of-Life quesƟonnaire (PROMIS Scale v1.2-Global Health) to the 
included research subjects. We will also inquire with all research subjects about their parƟcipaƟon in 
a series of examinaƟons (ergo-spirometry to assess work capacity, echocardiogram, and blood 
sampling to assess cardiac funcƟon and cardiac health) at the cardiology clinic at Queen Silvia’s 
Children's Hospital. 
Diagnoses related to the immune system will be sought as the thymus is involved in immune system 
development, and its early excision can aﬀect the well-being of paƟents later in life [2]. 
We will analyze the material using chi-square test and t-test. 
Clinical Relevance 
Congenital heart defects are one of the most common birth defects, occurring in approximately 1 in 
100 children. PA-IVS is a rare heart defect, but increased knowledge about it can also contribute to 
improved management of children with other heart defects. 
Increased knowledge about the connecƟon between univentricular circulaƟon and other illnesses may 
lead to changes in treatment strategies and thereby improve the prognosis regarding morbidity and 
mortality for this paƟent group. There is a knowledge gap, that we aim to address, regarding 
univentricular circulaƟon with a working leŌ ventricle due to the majority of the research being made 
focuses on the paƟent group with hypoplasƟc leŌ heart syndrome.   
 
References  
1. 
Manhem, S., et al., Survival With Respect to Morphology in Pulmonary Atresia and Intact 
Ventricular Septum in Sweden. World J Pediatr Congenit Heart Surg, 2021. 12(1): p. 27-34. 
2. 
Gudmundsdottir, J., et al., Long-term clinical effects of early thymectomy: Associations with 
autoimmune diseases, cancer, infections, and atopic diseases. J Allergy Clin Immunol, 2018. 
141(6): p. 2294-2297.e8.