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Tetralogy of Fallot (TOF) is the most common cyanotic congenital cardiac defect with a global annual incidence of 40,000 cases. Advances in surgery and perioperative care led to improvements in perioperative mortality and, thus, a growing number of survivors. TOF survivors often suffer from complications related to a failing right ventricle. Follow-up studies evaluating TOF repair strategies suggest an association between the type of surgical repair strategy and late right ventricular health. However, surgical practices remain unchanged and led by institution-level biases. The body of evidence addressing outcomes based on TOF surgical repair strategy is weak and controversies persists on the management of these patients.  This thesis comprises 6 chapters that form the foundation of a multi-centre research program on outcomes after TOF surgical repair. The program uses various methodologies to generate evidence with a vision to change surgical practices.  Chapter 1 is an introduction providing background on TOF and contemporary areas of controversy.  Chapter 2 presents the results of a retrospective analysis evaluating the use of early echocardiogram parameters in predicting late cardiac magnetic resonance imaging evaluation of the right ventricle.  Chapter 3 presents the results of a retrospective cohort exploring the association between TOF repair strategy and development of right bundle branch block.  Chapter 4 presents the results of a multinational survey aiming to explore contemporary biases in TOF surgical repair strategy selection.  Chapter 5 presents the background, rationale, design and baseline cohort characteristics of the Tetralogy of Fallot for Life (TOF LIFE) study. The study is a multi-centre inception cohort study with a follow-up period of 2 years.  Finally, Chapter 6 discusses the conclusion, limitations, and future implications of this research program. / Thesis / Doctor of Science (PhD)

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Background: Autism spectrum disorder (ASD) is a lifelong developmental disability defined by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Over the last few decades, the global prevalence of autism has increased by twentyfold to thirtyfold. In the United States, the prevalence of ASD has increased rapidly with one out of every fifty-nine children (1.7%) diagnosed with the condition. With the increasing prevalence of ASD, the financial cost has been estimated to exceed those of Diabetes and Attention Deficit Hyperactivity Disorder (ADHD) by 2025. Furthermore, ASD has been found to be about 4-5 times more prevalent in males, compared to females, and there has been a noted increase in the prevalence of congenital abnormalities in patients with ASD. Objective: As part of an ongoing multi-year retrospective chart review of the patients seen at the Genetics Clinic for suspected or confirmed cases of ASD, we sought to identify the demographic characteristics of these patients and to see how they compare with documented studies. Methods: The overall study is an ongoing multi-year, retrospective chart review of patients seen at the ETSU Medical Genetics Clinic, with features suggestive of ASD. For this preliminary study, we extracted data from the Electronic health record (Allscripts) for 80 patients (n=80), on the gender, term status at birth (term defined as gestational age at delivery of 37 weeks or more, preterm defined as those delivered at less than 37 weeks), twin status, presence of congenital abnormalities, and the state of residence. We entered all the extracted data into REDCap and carried out a descriptive analysis of the data using the Statistical Package for Social Sciences (SPSS). Results: It was found that of the eighty patients, eighteen (22.5%) were females while sixty-two (77.5%) were males, (male to female ratio of 3.4 to 1). Fifty-nine patients (73.8%) were born at term, eighteen (22.5%) born preterm and three (3.8%) with unknown term status. Seventy-seven patients (96.3%) were twins and three (3.8%) were not. Thirty patients (37.5%) had no congenital abnormalities at birth while fifty patients (62.5%) had at least one congenital abnormality at birth. Sixty-one patients (76.3%) were from Tennessee while nineteen (23.8%) were from Virginia. Conclusions: This preliminary finding revealed an increased proportion of males compared to females, as well as an increased proportion of the population with congenital abnormalities compared to those without such abnormality. These findings agree with documented data from previous studies on ASD. In our future analysis, we would examine the rate of diagnosis of ASD in the clinic, the type of mutation and the genes involved and identify any trend for specific genes, and/or specific mutation.

The purpose of this literature review is to discuss the mechanisms of a cardiac arrest and how it contributes to the high-risk classification of congenital heart disease patients. While assessing the diagnoses process and types of treatments applied to cardiac arrest and congenital heart disease separately, we further explain this information’s significance by combining their incidence rates and analyzing their associations as it relates to surgical operations. A narrative review of studies is conducted in pediatrics and adults to reveal distinctions in lesion characteristics and interventions, as well as limitations that permit inconsistencies in data reports on health outcomes. There is not adequate research and data collection in reference to perioperative cardiac arrest in congenital heart disease patients and the aim of this paper is to highlight the need for further studies and to present current research that has been conducted to fill the gaps of this global health issue.

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