Melbourne Medical School Collected Works - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 36
-
ItemNo Preview AvailableUnderstanding Exercise Capacity: From Elite Athlete to HFpEF(ELSEVIER SCIENCE INC, 2023-11)Exercise capacity is a spectrum that reflects an individual's functional capacity and the dynamic nature of cardiac remodelling along with respiratory and skeletal muscle systems. The relationship of increasing physical activity, increased cardiac mass and volumes, and improved cardiorespiratory fitness (CRF) is well established in the endurance athlete. However, less emphasis has been placed on the other end of the spectrum, which includes individuals with a more sedentary lifestyle and small hearts who are at increased risk of functional disability and poor clinical outcomes. Reduced CRF is an independent predictor of all-cause mortality and cardiovascular events determined by multiple inter-related exogenous and endogenous factors. In this review, we explore the relationship of physical activity, cardiac remodelling, and CRF across the exercise spectrum, emphasising the critical role of cardiac size in determining exercise capacity. In contrast to the large compliant left ventricle of the endurance athlete, an individual with a lifetime of physical inactivity is likely to have a small, stiff heart with reduced cardiac reserve. We propose that this might contribute to the development of heart failure with preserved ejection fraction in certain individuals, and is key to understanding the link between low CRF and increased risk of heart failure.
-
ItemRapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy(FRONTIERS MEDIA SA, 2022-12-15)INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group. METHODS: Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO2peak)-a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO2peak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vO2diff) estimation via the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals. RESULTS: Significant group-by-time interactions were observed for absolute VO2peak (p = 0.006), bodyweight-indexed VO2peak (p = 0.015), LM (p = 0.001) and cardiac reserve (p = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all p ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vO2diff, though a-vO2diff declined 12% in allo-HCT (p = 0.028). CONCLUSION: In summary, allo-HCT severely impairs VO2peak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.
-
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.
-
ItemNo Preview AvailableThe effect of posture on maximal oxygen uptake in active healthy individuals(SPRINGER, 2021-05)PURPOSE: Semi-supine and supine cardiopulmonary exercise testing (CPET) with concurrent cardiac imaging has emerged as a valuable tool for evaluating patients with cardiovascular disease. Yet, it is unclear how posture effects CPET measures. We aimed to discern the effect of posture on maximal oxygen uptake (VO2max) and its determinants using three clinically relevant cycle ergometers. METHODS: In random order, 10 healthy, active males (Age 27 ± 7 years; BMI 23 ± 2 kg m2) underwent a ramp CPET and subsequent constant workload verification test performed at 105% peak ramp power to quantify VO2max on upright, semi-supine and supine cycle ergometers. Doppler echocardiography was conducted at peak exercise to measure stroke volume (SV) which was multiplied by heart rate (HR) to calculate cardiac output (CO). RESULTS: Compared to upright (46.8 ± 11.2 ml/kg/min), VO2max was progressively reduced in semi-supine (43.8 ± 10.6 ml/kg/min) and supine (38.2 ± 9.3 ml/kg/min; upright vs. semi-supine vs. supine; all p ≤ 0.005). Similarly, peak power was highest in upright (325 ± 80 W), followed by semi-supine (298 ± 72 W) and supine (200 ± 51 W; upright vs. semi-supine vs. supine; all p < 0.01). Peak HR decreased progressively from upright to semi-supine to supine (186 ± 11 vs. 176 ± 13 vs. 169 ± 12 bpm; all p < 0.05). Peak SV and CO were lower in supine relative to semi-supine and upright (82 ± 22 vs. 92 ± 26 vs. 91 ± 24 ml and 14 ± 3 vs. 16 ± 4 vs. 17 ± 4 l/min; all p < 0.01), but not different between semi-supine and upright. CONCLUSION: VO2max is progressively reduced in reclined postures. Thus, posture should be considered when comparing VO2max results between different testing modalities.
-
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.
-
ItemUse of a smartphone electrocardiogram to diagnose arrhythmias during exercise in athletes: a case series(OXFORD UNIV PRESS, 2022-04-13)BACKGROUND: While athletes are generally very fit, intense exercise can increase the risk of atrial fibrillation. Moreover, other arrhythmias such as atrial flutter or supraventricular tachycardia can cause distressing, exercise-related symptoms. Given symptoms are infrequent and may occur during intense exertion, traditional monitoring devices are often impractical to use during exercise. Smartphone electrocardiograms (ECGs) such as the Alivecor Kardia device may be the portable and reliable tool required to help identify arrhythmias in this challenging population. This case series highlights the use of such devices in aiding the diagnosis of arrhythmias in the setting of exercise-related symptoms in athletes. CASE SUMMARY: The six cases in this series included one elite non-endurance athlete, two elite cricketers, one amateur middle-distance runner, and two semi-elite ultra-endurance runners, with an age range of 16-48 years. An accurate diagnosis of an arrhythmia was obtained in five cases (atrial fibrillation/flutter and supraventricular tachycardias) using the smartphone ECG, which helped guide definitive treatment. No arrhythmia was identified in the final case despite using the device during multiple symptomatic events. DISCUSSION: The smartphone ECG was able to accurately detect arrhythmias and provide a diagnosis in cases where traditional monitoring had not. The utility of detecting no arrhythmia during symptoms in one case was also highlighted, providing the athlete with the confidence to continue exercising. This reassurance and confidence across all cases is perhaps the most valuable aspect of this device, where clinicians and athletes can be more certain of reaching a diagnosis and undertaking appropriate management.
-
ItemFit, Female or Fifty-Is Cardiac Rehabilitation "Fit" for Purpose for All? A Systematic Review and Meta-Analysis With Meta-Regression(FRONTIERS MEDIA SA, 2022-03-29)AIMS: Cardiac rehabilitation (CR) is an evidence-based intervention promoting risk factor modification following coronary artery disease events but the relative benefits for patient subgroups is not clear. This review synthesizes the available evidence on the effectiveness of modern CR programs and determines outcomes for age, sex and prior level of fitness. METHODS: MEDLINE, CINAHL, and EMBASE were examined for RCT and cohort studies involving exercise prescription or phase II or III CR following Myocardial Infarction (MI), Percutaneous Coronary Intervention (PCI) and cardiac surgery from January 2010 to February 2021. Outcomes assessed included peakVO2max, 6-min walk test and Metabolic Equivalent of Task. Meta-regression was used to determine CR impact for change in fitness and age and sex influences. RESULTS: The mean age of study participants was 59.5 years and 82.7% were male. Females, younger people and those of average or above cardiorespiratory fitness were substantially under-represented in data and attendance, with 13% of study groups with a mean age <55 years. At entry, 73% were below average for fitness vs. age-matched normative values. Fitness improved across all groups following CR with no evidence of sex or age independently affecting outcomes. CONCLUSIONS: Modest improvements in fitness in all groups were shown, but the benefits of CR can be far greater. A modern, innovative approach to CR will likely lead to more substantial benefits. This may require a "Precision Medicine" model which tailors exercise prescription to different populations to ensure all CR participant's needs are met. This will ensure that CR is more flexible and accessible for all.
-
ItemRationale and design of the PROspective ATHletic Heart (Pro@Heart) study: long-term assessment of the determinants of cardiac remodelling and its clinical consequences in endurance athletes(BMJ PUBLISHING GROUP, 2022-03)BACKGROUND: Exercise-induced cardiac remodelling (EICR) results from the structural, functional and electrical adaptations to exercise. Despite similar sports participation, EICR varies and some athletes develop phenotypic features that overlap with cardiomyopathies. Training load and genotype may explain some of the variation; however, exercise 'dose' has lacked rigorous quantification. Few have investigated the association between EICR and genotype. OBJECTIVES: (1) To identify the impact of training load and genotype on the variance of EICR in elite endurance athletes and (2) determine how EICR and its determinants are associated with physical performance, health benefits and cardiac pathology. METHODS: The Pro@Heart study is a multicentre prospective cohort trial. Three hundred elite endurance athletes aged 14-23 years will have comprehensive cardiovascular phenotyping using echocardiography, cardiac MRI, 12-lead ECG, exercise-ECG and 24-hour-Holter monitoring. Genotype will be determined using a custom cardiomyopathy gene panel and high-density single-nucleotide polymorphism arrays. Follow-up will include online tracking of training load. Cardiac phenotyping will be repeated at 2, 5, 10 and 20 years. RESULTS: The primary endpoint of the Pro@Heart study is the association of EICR with both training load and genotype. The latter will include rare variants in cardiomyopathy-associated genes and polygenic risk scores for cardiovascular traits. Secondary endpoints are the incidence of atrial and ventricular arrhythmias, physical performance and health benefits and their association with training load and genotype. CONCLUSION: The Pro@Heart study is the first long-term cohort study to assess the impact of training load and genotype on EICR. TRIAL REGISTRATION NUMBER: NCT05164328; ACTRN12618000716268.
-
ItemWhat Limits Cardiac Performance during Exercise in Normal Subjects and in Healthy Fontan Patients?(HINDAWI LTD, 2010)Exercise is an important determinant of health but is significantly reduced in the patient with a univentricular circulation. Normal exercise physiology mandates an increase in pulmonary artery pressures which places an increased work demand on the right ventricle (RV). In a biventricular circulation with pathological increases in pulmonary vascular resistance and/or reductions in RV function, exercise-induced augmentation of cardiac output is limited. Left ventricular preload reserve is dependent upon flow through the pulmonary circulation and this requires adequate RV performance. In the Fontan patient, the reasons for exercise intolerance are complex. In those patients with myocardial dysfunction or other pathologies of the circulatory components, it is likely that these abnormalities serve as a limitation to cardiac performance during exercise. However, in the healthy Fontan patient, it may be the absence of a sub-pulmonary pump which limits normal increases in pulmonary pressures, trans-pulmonary flow requirements and cardiac output. If so, performance will be exquisitely dependent on pulmonary vascular resistance. This provides a potential explanation as to why pulmonary vasodilators may improve exercise tolerance. As has recently been demonstrated, these agents may offer an important new treatment strategy which directly addresses the physiological limitations in the Fontan patient.
-
ItemAtrial volume and function during exercise in health and disease(BMC, 2017-12-18)BACKGROUND: Although atrial function has prognostic significance in many cardiovascular conditions, changes during exercise have not previously been assessed. The aim of this study was to evaluate left atrial (LA) and right atrial (RA) volume and function during incremental exercise, both in normal individuals, healthy athletes, and in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Fifteen healthy non-athletes, 15 athletes and 15 CTEPH patients underwent multi-slice real-time cardiovascular magnetic resonance imaging at rest and during supine bicycle exercise with simultaneous invasive hemodynamic measurements. RESULTS: At rest, athletes had larger indexed maximal RA and LA volumes (iRAVmax, iLAVmax) than CTEPH patients and non-athletes, the latter two groups having similar values. CTEPH patients had lower RA and LA emptying functions (EmF) at rest. During exercise, RA volumes (maximum and minimum) increased in CTEPH patients, whilst decreasing in athletes and non-athletes (P < 0.001). The exercise-induced change in iLAVmax was similar between groups, but iLAVmin did not decrease in CTEPH patients. Thus exercise-induced increases in RAEmF and LAEmF, as seen in normal physiology, were significantly impaired in CTEPH patients. At peak exercise, RA volumes (maximum and minimum) and EmF correlated strongly with RA pressure (R = 0.70; P = 0.005; R = 0.83; P < 0.001; R = -0.87; P < 0.001). On multivariate analysis, peak exercise RAEmF and iLAVmin were independent predictors of VO2peak in CTEPH patients and together explained 72% of the variance in VO2peak (ß =0.581 and ß = -0.515, respectively). CONCLUSIONS: In normal physiology, RAEmF and LAEmF increase with exercise, whereas CTEPH patients have impaired LAEmF and RAEmF, which becomes more apparent during exercise. Therefore, the changes in atrial volumes and function during exercise enable a far better distinction between physiological and pathological atrial remodeling than resting measures of volumes which are prone to confounding factors (e.g. endurance training). Peak exercise RAEmF is a good marker of poor functional state in CTEPH patients.