Medicine (RMH) - Research Publications

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    The "Super-Fontan" Phenotype: Characterizing Factors Associated With High Physical Performance
    Tran, DL ; Celermajer, DS ; Ayer, J ; Grigg, L ; Clendenning, C ; Hornung, T ; Justo, R ; Davis, GM ; d'Udekem, Y ; Cordina, R (FRONTIERS MEDIA SA, 2021-12-07)
    Background: People with a Fontan circulation usually have moderately impaired exercise performance, although a subset have high physical performance ("Super-Fontan"), which may represent a low-risk phenotype. Methods: People with a "Super-Fontan" phenotype were defined as achieving normal exercise performance [≥80% predicted peak oxygen uptake (VO2) and work rate] during cardiopulmonary exercise testing (CPET) and were identified from the Australian and New Zealand Fontan Registry. A Fontan control group that included people with impaired exercise performance (<80% predicted VO2 or work rate) was also identified based on a 1:3 allocation ratio. A subset of participants were prospectively recruited and completed a series of physical activity, exercise self-efficacy, and health-related quality of life questionnaires. Results: Sixty CPETs ("Super-Fontan", n = 15; control, n = 45) were included. A subset ("Super-Fontan", n = 10; control, n = 13) completed a series of questionnaires. Average age was 29 ± 8 years; 48% were males. Exercise capacity reflected by percent predicted VO2 was 67 ± 17% in the entire cohort. Compared to the "Super-Fontan" phenotype, age at Fontan completion was higher in controls (4.0 ± 2.9 vs. 7.2 ± 5.3 years, p = 0.002). Only one (7%) person in the "Super-Fontan" group had a dominant right ventricle compared to 15 (33%) controls (p = 0.043). None of those in the "Super-Fontan" group were obese, while almost a quarter (22%) of controls were obese based on body mass index (p = 0.046). Lung function abnormalities were less prevalent in the "Super-Fontan" group (20 vs. 70%, p = 0.006). Exercise self-efficacy was greater in the "Super-Fontan" group (34.2 ± 3.6 vs. 27.9 ± 7.2, p = 0.02). Self-reported sports participation and physical activity levels during childhood and early adulthood were higher in the "Super-Fontan" group (p < 0.05). The total average time spent participating in structured sports and physical activity was 4.3 ± 2.6 h/wk in the "Super-Fontan" group compared to 2.0 ± 3.0 h/wk in controls, p = 0.003. There were no differences in self-reported current total physical activity score or health-related quality of life between groups (p ≥ 0.05). Conclusions: The "Super-Fontan" phenotype is associated with a healthy weight, lower age at Fontan completion, better exercise self-efficacy, and higher overall levels of sport and physical activity participation during physical development.
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    Exercise Intolerance, Benefits, and Prescription for People Living With a Fontan Circulation: The Fontan Fitness Intervention Trial (F-FIT)-Rationale and Design
    Tran, DL ; Gibson, H ; Maiorana, AJ ; Verrall, CE ; Baker, DW ; Clode, M ; Lubans, DR ; Zannino, D ; Bullock, A ; Ferrie, S ; Briody, J ; Simm, P ; Wijesekera, V ; D'Almeida, M ; Gosbell, SE ; Davis, GM ; Weintraub, R ; Keech, AC ; Puranik, R ; Ugander, M ; Justo, R ; Zentner, D ; Majumdar, A ; Grigg, L ; Coombes, JS ; d'Udekem, Y ; Morris, NR ; Ayer, J ; Celermajer, DS ; Cordina, R (FRONTIERS MEDIA SA, 2022-01-06)
    Background: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safe-and for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials. Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)-a phase III clinical trial-aims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (≥16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (<16 years) will be randomized to either a physical activity and exercise program of moderate-to-vigorous intensity or usual care in a two-arm trial with a 1:1 allocation. The primary outcome is a change in aerobic exercise capacity (peak oxygen uptake) at 4-months. Secondary outcomes include safety, and changes in cardiopulmonary exercise testing measures, peripheral venous pressure, respiratory muscle and lung function, body composition, liver stiffness, neuropsychological and neurocognitive function, physical activity levels, dietary and nutritional status, vascular function, neurohormonal activation, metabolites, cardiac function, quality of life, musculoskeletal fitness, and health care utilization. Outcome measures will be assessed at baseline, 4-months, and 12-months. This manuscript will describe the pathophysiology of exercise intolerance in the Fontan circulation and the rationale and protocol for the F-FIT.
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    Pre- and Post-operative determinants of transplantation-free survival after Fontan. The Australia and New Zealand experience
    Poh, CL ; Cordina, RL ; Iyengar, AJ ; Zannino, D ; Grigg, LE ; Wheaton, GR ; Bullock, A ; Ayer, J ; Alphonso, N ; Gentles, TL ; Celermajer, DS ; D'Udekem, Y (ELSEVIER IRELAND LTD, 2021-08)
    BACKGROUND: This review identifies the predictors of late mortality and heart transplantation that remain relevant in the contemporary population of patients with a Fontan circulation, focusing on the potential impact of post-Fontan morbidities on the late outlook of these patients. METHODS AND RESULTS: A total of 1561 patients who had survived the Fontan operation in Australia or New Zealand from 1975 to 2018 were included in this review. Over a median duration of 11.4 years, there was a total of 117 deaths (7%) and 32 heart transplantations (2%). Freedom from death and heart transplantation at 10, 20 and 35 years post Fontan surgery were 94% (95% CI 93-95%), 87% (95 %CI 85-90%) and 66% (95 %CI 57-78%) respectively. Being male, having an atriopulmonary Fontan, pre-Fontan atrioventricular valve intervention, or prolonged pleural effusions post Fontan were predictive of late death or heart transplantation. However, time-dependent variables such as the development of atrial arrhythmia, protein/losing enteropathy or late ventricular dysfunction were stronger predictors of the same outcome. Patients who developed a time-dependent risk factor had a freedom from death and heart transplantation rate of 54% (95 %CI 43-66) at 15 years and 44% (95 %CI 33-57) at 25 years post Fontan. However, 95% (95 %CI 91-99) of patients without any of the identified risk factors were free from death or heart transplantation rate at 25 years post Fontan. CONCLUSION: In conclusion, the occurrence of post-operative complications such as PLE, arrhythmia and ventricular dysfunction will likely precede the late demise of these patients.
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    Long-term outcome of adult survivors of tetralogy of Fallot
    Lee, MGY ; Yao, JV ; Binny, S ; Larobina, M ; Skillington, P ; Grigg, LE ; Zentner, D (ELSEVIER, 2021-08)
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    Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position Statement
    Zentner, D ; Celermajer, DS ; Gentles, T ; d'Udekem, Y ; Ayer, J ; Blue, GM ; Bridgman, C ; Burchill, L ; Cheung, M ; Cordina, R ; Culnane, E ; Davis, A ; du Plessis, K ; Eagleson, K ; Finucane, K ; Frank, B ; Greenway, S ; Grigg, L ; Hardikar, W ; Hornung, T ; Hynson, J ; Iyengar, AJ ; James, P ; Justo, R ; Kalman, J ; Kasparian, N ; Le, B ; Marshall, K ; Mathew, J ; McGiffin, D ; McGuire, M ; Monagle, P ; Moore, B ; Neilsen, J ; O'Connor, B ; O'Donnell, C ; Pflaumer, A ; Rice, K ; Sholler, G ; Skinner, JR ; Sood, S ; Ward, J ; Weintraub, R ; Wilson, T ; Wilson, W ; Winlaw, D ; Wood, A (ELSEVIER SCIENCE INC, 2020-01)
    The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.
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    Remote Device Interrogation Kiosks (ReDInK)-Pharmacy Kiosk Remote Testing of Pacemakers and Implantable Cardioverter-Defibrillators for Rural Victorians. A Novel Strategy to Tackle COVID-19
    Wong, J ; Longhitano, A ; Yao, J ; Jayadeva, P ; Arendshorst, K ; Grigg, L ; Wynn, G ; Stevenson, I (ELSEVIER SCIENCE INC, 2021-07)
    BACKGROUND: In the era of COVID-19, travel restrictions and social distancing measures have changed the landscape for device interrogations of pacemakers and defibrillators for rural Victorians. Previously, device checks were performed infrequently in large volume, face-to-face rural clinics by visiting cardiologists and technicians. Access to remote areas and social distancing restrictions have made these clinics unfeasible to operate. The Cardiac Society of Australia and New Zealand (CSANZ) and Heart Rhythm Society (HRS) COVID-19 consensus statements have suggested the utilisation of remote monitoring to minimise the potential spread of COVID-19 infections between clinicians and high-risk patients. A novel solution to this challenge was the implementation of a remote device interrogation (RI) service located in two kiosks at two rural pharmacies. This service was termed Remote Device Interrogation Kiosks (ReDInK). AIM: This cross-sectional observational study aimed to describe the set-up process, safety and efficacy of RI and customer satisfaction of the ReDInK program. METHODS: Two-hundred-and-ninety-two (292) rurally located patients with implantable cardiac devices were identified via the cardiology department database. Of these, 101 (44%) were enrolled into the ReDInK program across two rurally located pharmacies between April and July 2020. RI was performed and download outcomes were reviewed. A customer satisfaction survey assessed attitudes towards the program and explored options of ongoing service application. RESULTS: Of 101 patients enrolled into ReDInK, 96 (95%) resulted in satisfactory device checks. Four (4) individuals failed-to-attend and one individual experienced technical download issues. Of the 96 satisfactory device checks, three required in-person follow-up for reasons including battery replacement, lead repositioning and in-person programming. No adverse events were reported. A satisfaction telephone survey was conducted with 81 (83%) participants enrolled in ReDInK. Seventy-one (71) individuals (88%) of those surveyed expressed satisfaction and 73 (90%) labelled the process as efficiently conducted. Sixty-nine (69) (85%) participants felt reassured that this service was established during the pandemic. However 47 (58%) participants reported they would still feel comfortable to undergo in-person reviews despite social distancing recommendations. CONCLUSIONS: With the COVID-19 pandemic posing restrictions to social distancing and reducing unnecessary in-person interaction, the ReDInK program emerges as an efficacious and safe solution for patients in rural Victoria. The program's widely positive reception and successful conduction in rural Victoria invites further opportunity for a wider application of similar programs, expanding its role to metropolitan areas.
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    Hepatic adenoma masquerading as a hepatocellular carcinoma in a patient with a Fontan procedure on the oral contraceptive pill
    Yao, JV ; Sood, S ; Lokan, J ; Murugasu, A ; Grigg, L ; Zentner, D (WILEY, 2021-04)