Melbourne Medical School Collected Works - Research Publications
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ItemNo Preview AvailableDisease specific determinants of cardiopulmonary fitness in systemic sclerosis(W B SAUNDERS CO-ELSEVIER INC, 2023-02)OBJECTIVES: We aimed to quantify the burden of exercise intolerance in systemic sclerosis (SSc) and explore the disease features that contribute to impaired exercise capacity (measured as peak oxygen uptake, peak VO2) to provide novel mechanistic insights into the causes of physical disability in SSc. METHODS: Thirty-three SSc patients with no history of cardiac disease and no active myositis underwent cardiac and skeletal muscle MRI, transthoracic echocardiography, pulmonary function tests and cardiopulmonary exercise testing (CPET). CPET results were compared to an age-, sex-, and weight-matched controls with no overt cardiopulmonary disease. Native T1 and T2-mapping sequences were used to quantify diffuse fibroinflammatory myocardial disease and qualitative assessment of skeletal muscle oedema was performed. The associations between parameters of cardiorespiratory function and skeletal muscle abnormalities and peak VO2 were evaluated with linear regression analysis. RESULTS: Exercise capacity was markedly impaired in SSc and significantly reduced when compared to control subjects (percent predicted peak VO2: 70% vs 98%, p < 0⋅01). Diffuse myocardial fibroinflammatory disease (p < 0⋅01) and skeletal muscle oedema (p = 0⋅01) were significantly associated with reduced exercise capacity. There was no association between impaired exercise capacity and left ventricular ejection fraction. CONCLUSION: SSc is associated with marked functional impairment that is not explained by commonly used parameters of cardiac function such as left ventricular ejection fraction. Rather, only more sensitive measures of organ involvement are associated with impaired exercise tolerance. Our results show diffuse interstitial changes of the myocardium and skeletal muscle affect oxygen uptake and are important contributors to functional limitation in SSc.
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ItemUsing magnetic resonance imaging to map the hidden burden of muscle involvement in systemic sclerosis(BMC, 2022-04-11)BACKGROUND: Skeletal muscle can be directly affected by systemic sclerosis (SSc); however, a significant burden of SSc-associated myopathy is undetected because clinical parameters such as weakness and creatine kinase (CK) are unreliable biomarkers of muscle involvement. This study presents qualitative and quantitative magnetic resonance imaging (MRI) findings that quantify the prevalence of myopathy and evaluate any association between skeletal and cardiac muscle involvement in SSc. METHODS: Thirty-two patients with SSc who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria underwent skeletal muscle MRI in addition to cardiac MRI. Skeletal muscles were independently assessed by two musculoskeletal radiologists for evidence of oedema, fatty infiltration and atrophy. Skeletal muscle T2 mapping times and percentage fat fraction were calculated. Linear regression analysis was used to evaluate the clinical and myocardial associations with skeletal muscle oedema and fatty infiltration. Cardiac MRI was performed using post gadolinium contrast imaging and parametric mapping techniques to assess focal and diffuse myocardial fibrosis. RESULTS: Thirteen participants (40.6%) had MRI evidence of skeletal muscle oedema. Five (15.6%) participants had fatty infiltration. There was no association between skeletal muscle oedema and muscle strength, creatine kinase, inflammatory markers or fibroinflammatory myocardial disease. Patients with skeletal muscle oedema had higher T2-mapping times; there was a significant association between subjective assessments of muscle oedema and T2-mapping time (coef 2.46, p = 0.02) and percentage fat fraction (coef 3.41, p = 0.02). Diffuse myocardial fibrosis was a near-universal finding, and one third of patients had focal myocardial fibrosis. There was no association between skeletal myopathy detected by MRI and burden of myocardial disease. CONCLUSIONS: MRI is a sensitive measure of muscle oedema and systematic assessment of SSc patients using MRI shows that myopathy is highly prevalent, even in patients without symptoms or other signs of muscle involvement. Similarly, cardiac fibrosis is highly prevalent but occurs independently of skeletal muscle changes. These results indicate that novel quantitative MRI techniques may be useful for assessing sub-clinical skeletal muscle disease in SSc.
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ItemLeft atrial, pulmonary vein, and left atrial appendage anatomy in Indigenous individuals: Implications for atrial fibrillation(ELSEVIER IRELAND LTD, 2021-06)BACKGROUND: Indigenous Australians experience a greater burden of AF. Whether this is in-part due to differences in arrhythmogenic structures that appear to contribute to AF differences amongst other ethnicities is not known. METHODS: We studied forty individuals matched for ethnicity and other AF risk factors. Computed tomography imaging was used to characterise left atrial (LA), pulmonary vein (PV), and left atrial appendage (LAA) anatomy. RESULTS: There were no significant differences in LA diameters or volumes between Indigenous and non-Indigenous Australians. Similarly, we could not detect any consistent differences in PV number, morphology, diameters, or ostial characteristics according to ethnicity. LAA analyses suggested that Indigenous Australians may have a greater proportion of non chickenwing LAA type, and a tendency for eccentric, oval-shaped LAA ostia; however, there were no other differences seen with regards to LAA volume or depth. Indexed values for LA, PV and LAA anatomy corrected for body size were broadly similar. CONCLUSIONS: In a cohort of individuals matched for AF risk factors, we could find no strong evidence of ethnic differences in LA, PV, and LAA characteristics that may explain a predisposition of Indigenous Australians for atrial arrhythmogenesis. These findings, in conjunction with our previous data showing highly prevalent cardiometabolic risk factors in Indigenous Australians with AF, suggest that it is these conditions that are more likely responsible for the AF substrate in these individuals. Continued efforts should therefore be directed towards risk factor management in an attempt to prevent and minimise the effects of AF in Indigenous Australians.
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ItemExercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness(BMC, 2020-09-07)BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.
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ItemImpact of sex, socio-economic status, and remoteness on therapy and survival in heart failure(WILEY PERIODICALS, INC, 2019-10)AIMS: This study aims to determine if traditional markers of disadvantage [female sex, low socio-economic status (SES), and remoteness] are associated with lower prescription of evidence-based therapy and higher mortality among patients with moderate-severe heart failure with reduced ejection fraction. METHODS AND RESULTS: We recruited 452 consecutive class II-III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence-based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow-up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74-1.92, 0.48). There was no difference in prescription of beta-blockers [χ2 (1) = 0.91, 0.66], angiotensin-converting enzyme inhibitors [χ2 (1) = 0.001, 0.97], nor aldosterone antagonists [χ2 (1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter-defibrillator implantation in men compared with women [χ2 (1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit. CONCLUSIONS: In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents.