Medicine (Austin & Northern Health) - Theses

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Type: PhD thesis × Subject: atrial fibrillation × Subject: cirrhosis ×

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    Cardiovascular Disease in Patients with End-Stage Liver Disease undergoing Transplantation
    Koshy, Anoop Ninan ( 2021)
    It has been known for centuries that the heart and the liver are closely related. Galen suggested the body was controlled by the tripartite system of the liver, heart and brain, with the liver being the source of all veins and the principal instrument of sanguification. The complex interconnectedness of these organ systems is no more apparent than in patients with liver dysfunction. Liver cirrhosis leads to autonomic and neurohormonal dysregulation which can culminate in circulatory and cardiovascular dysfunction. These observations have been brought to the fore with advances in experimental techniques including biomarkers and structural imaging that have highlighted the manifestations of cirrhotic cardiomyopathy. However, the precise clinical consequences of these cardiac maladaptations have remained elusive. Liver transplantation (LT) is a valuable yet scarce resource with the ability to transform the lives of patients with advanced liver disease. Despite improvements in anaesthetic management and surgical techniques, patients undergoing LT are at a substantial risk of perioperative cardiovascular complications. This is pertinent as transplant candidates in the contemporary era are often older and have a higher proportion of vascular comorbidities. In addition, non-alcoholic fatty liver disease is becoming a major aetiology of liver disease and this condition shares similar risk factors to many cardiovascular disease states. As such, optimizing risk stratification of patients prior to LT is a priority to ensure optimal patient and graft outcomes. Moreover, whether transplantation itself confers risk of accelerated atherosclerosis is unclear. This dissertation work explores three key areas. First, it aims to provide an extensive review of the perioperative and long-term cardiovascular mortality of patients undergoing LT in Australia and New Zealand. Second, we investigate the pathophysiological connections that constitute the heart-liver axis in patients with end-stage liver disease undergoing LT. This covers both the structural and electrophysiological alterations that characterize cirrhotic cardiomyopathy with a translational focus. Third, we aimed to evaluate predictors of cardiovascular events in patients undergoing LT, including a prospective study evaluating whether LT leads to accelerated changes in coronary atherosclerosis. Collectively, this thesis explores key epidemiologic data relating to cardiovascular mortality in the LT population, and highlights key cardiac structural, electrophysiological and coronary disease manifestations in patients with end-stage liver disease undergoing transplantation.