Cardiopulmonary Function in Adults Born With a Ventricular Septal Defect

1. Title Cardiopulmonary capacity past the age of 40 - adults with either a persistent or a surgically repaired ventricular septal defect
2. Background:

Over the last decades, the treatment possibilities in pediatric cardiology and cardiac surgery have improved markedly and accordingly, more than 90% of children born with a congenital heart disease now reach adulthood [1,2]. As a result, the population of adults is today greater than that of children with congenital cardiac defects [3] and consequently, the focus has started to shift more towards the long-term outcome of the growing adult population. Among the most common cardiac defects is the ventricular septal defect (VSD), seen as a hole of varying position, size and significance in the wall separating the two pumping chambers of the heart. The VSD occurs at a rate of 2-3 per 1000 life-births [4,5] and is at large diagnosed during childhood. In the first decade of life, approximately 30% of the VSDs will close spontaneously[6], with a declining number closing naturally with increasing age[7]. VSDs that do not close spontaneously are considered to be of either hemodynamic importance or not. Patients born with a hemodynamically significant and operable VSD will undergo surgical or catheter-based closure, mostly at an early age, whereas the rest are considered too small and insignificant to be of any hemodynamic importance.

Common for both the surgically closed and the small, unrepaired VSDs is that the long-term outcome of these patients is thought to be excellent. Patients who have undergone closure of their defect are considered to be "cured" and few years following successful surgery, they are discharged from further follow-up visits in the health care system. Similarly, patients with small, unrepaired VSDs are followed in their first decades of life with follow-up visits, with the majority being discharged when they reach adulthood. Therefore, very little is known on the possible consequences of a congenital VSD on the physical functioning in later adulthood. Recently, researchers from our institution assessed the physical capacity in both open and closed VSDs, focusing on the early adulthood, and found a number of physical parameters affected in patients when comparing them with their healthy peers. In patients in their early twenties with an operated VSD, a 20% lower exercise capacity and an abnormal contractility was found during physical activity compared with a group of healthy controls [8,9]. Young adults, in their mid-twenties, with small, open VSDs exhibited a similarly reduced exercise capacity as compared with healthy peers [10,11], and in both open and closed patients, health-related quality of life was found to be affected with a lower self-assessed physical functioning compared with healthy controls [9,10].

Young adults with open and closed VSDs also demonstrated a reduced ventilatory response during exercise [10,12]. This led to further detailed examination of their pulmonary function in a newly completed study on similarly aged patients with either open or closed VSDs[13]. Both patient groups displayed a degree of limited pulmonary function, especially in the dynamic measurements and most pronounced in the surgically corrected patients. Other recent studies have also found degrees of limitations in these patients [14-16]. However, common for all studies is that the patients investigated are usually in their mid-twenties with no patient reaching the age of 40 years. Therefore, it is not yet known whether any of these documented limitations will progress, decrease or stay unchanged with increasing age. As the group of patients with congenital VSDs grows older, age-related factors such as acquired hypertension, coronary artery disease, and other cardiovascular problems will start emerging and perhaps accelerate any former trivial symptoms related to their underlying cardiac anomaly. How this will further affect the already found limitations in young adults is unknown. Therefore, we feel there is an unmet need for a prospective, clinical study investigating how these patients are doing past the age of 40 as compared with their peers. 3. Study objectives and purpose:

3.1 Objectives: The overall objective of this study is to investigate a group of adults, age 40 or above, who are living with a small, unrepaired or a surgically corrected ventricular septal defect. Outcomes will be illustrated through an extensive pulmonary function study performed at rest, questionnaires, two different exercise studies and a study on heart rate variability through Holter monitor. Results of the two patient groups will be compared with those of healthy, age-matched controls.