Melbourne Medical School Collected Works - Research Publications

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    A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler.
    Haluska, BA ; Jeffriess, L ; Mottram, PM ; Carlier, SG ; Marwick, TH (Springer Science and Business Media LLC, 2007-01-31)
    BACKGROUND: Non-invasive assessment of arterial pressure wave forms using applanation tonometry of the radial or carotid arteries can be technically challenging and has not found wide clinical application. 2D imaging of the common carotid arteries is routinely used and we sought to determine whether arterial waveform measurements could be derived from tissue Doppler imaging (TDI) of the carotid artery. METHODS: We studied 91 subjects (52 men, age 52 +/- 14 years) with and without cardiovascular disease. Tonometry was performed on the carotid artery simultaneously with pulsed wave Doppler of the LVOT and acquired digitally. Longitudinal 2D images of the common carotid artery with and without TDI were also acquired digitally and both TDI and tonometry were calibrated using mean and diastolic cuff pressure and analysed off line. RESULTS: Correlation between central pressure by TDI and tonometry was excellent for maximum pressure (r = 0.97, p < 0.0001). The mean differences between central pressures derived by TDI and tonometry were minimal (systolic 5.36 +/- 5.5 mmHg; diastolic 1.2 +/- 1.2 mmHg). CONCLUSION: Imaging of the common carotid artery motion with tissue Doppler may permit acquisition of a waveform analogous to that from tonometry. This method may simplify estimation of central arterial pressure and calculation of total arterial compliance.
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    Application of a risk-guided strategy to secondary prevention of coronary heart disease: analysis from a state-wide data linkage in Queensland, Australia
    Huynh, QL ; Nghiem, S ; Byrnes, J ; Scuffham, PA ; Marwick, T (BMJ PUBLISHING GROUP, 2022-05-01)
    OBJECTIVE: This study sought whether higher risk patients with coronary heart disease (CHD) benefit more from intensive disease management. DESIGN: Longitudinal cohort study. SETTING: State-wide public hospitals (Queensland, Australia). PARTICIPANTS: This longitudinal study included 20 426 patients hospitalised in 2010 with CHD as the principal diagnosis. Patients were followed-up for 5 years. PRIMARY AND SECONDARY OUTCOMES AND MEASURES: The primary outcome was days alive and out of hospital (DAOH) within 5 years of hospital discharge. Secondary outcomes included all-cause readmission and all-cause mortality. A previously developed and validated risk score (PEGASUS-TIMI54) was used to estimate the risk of secondary events. Data on sociodemography, comorbidity, interventions and medications were also collected. RESULTS: High-risk patients (n=6573, risk score ≥6) had fewer DAOH (∆=-142 days (95% CI: -152 to -131)), and were more likely to readmit or die (all p<0.001) than their low-risk counterparts (n=13 367, risk score <6). Compared with patients who were never prescribed a medication, those who consumed maximal dose of betablockers (∆=39 days (95% CI: 11 to 67)), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (∆=74 days (95% CI: 49 to 99)) or statins (∆=109 days (95% CI: 90 to 128)) had significantly greater DAOH. Patients who received percutaneous coronary intervention (∆=99 days (95% CI: 81 to 116)) or coronary artery bypass grafting (∆=120 days (95% CI: 92 to 148)) also had significantly greater DAOH than those who did not. The effect sizes of these therapies were significantly greater in high-risk patients, compared with low-risk patients (interaction p<0.001). Analysis of secondary outcomes also found significant interaction between both medical and interventional therapies with readmission and death, implicating greater benefits for high-risk patients. CONCLUSIONS: CHD patients can be effectively risk-stratified, and use of this information for a risk-guided strategy to prioritise high-risk patients may maximise benefits from additional resources spent on intensive disease management.
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    Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).
    McMurray, JJV ; Anand, IS ; Diaz, R ; Maggioni, AP ; O'Connor, C ; Pfeffer, MA ; Solomon, SD ; Tendera, M ; van Veldhuisen, DJ ; Albizem, M ; Cheng, S ; Scarlata, D ; Swedberg, K ; Young, JB ; RED-HF Committees Investigators, (Wiley, 2013-03)
    AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.
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    Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy.
    Bonsignore, A ; Marwick, TH ; Adams, SC ; Thampinathan, B ; Somerset, E ; Amir, E ; Walker, M ; Abdel-Qadir, H ; Koch, CA ; Ross, HJ ; Woo, A ; Wintersperger, BJ ; Haykowsky, MJ ; Thavendiranathan, P (Elsevier BV, 2021-12)
    BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in cancer survivors and predicts cardiovascular disease (CVD)-related and all-cause mortality. However, routine measurement of CRF is not always feasible. OBJECTIVES: The purpose of this study was to identify clinical, cardiac biomarker, and imaging measures associated with reduced peak oxygen consumption (VO2peak) (measure of CRF) early post-breast cancer therapy to help inform CVD risk. METHODS: Consecutive women with early-stage HER2+ breast cancer receiving anthracyclines and trastuzumab were recruited prospectively. Within 6 ± 2 weeks of trastuzumab completion, we collected clinical information, systolic/diastolic echocardiographic measures, high-sensitivity troponin I, B-type natriuretic peptide, and VO2peak using a cycle ergometer. Regression models were used to examine the association between VO2peak and clinical, imaging, and cardiac biomarkers individually and in combination. RESULTS: Among 147 patients (age 52.2 ± 9.3 years), the mean VO2peak was 19.1 ± 5.0 mL O2·kg-1·min-1 (84.2% ± 18.7% of predicted); 44% had a VO2peak below threshold for functional independence (<18 mL O2·kg-1·min-1). In multivariable analysis, absolute global longitudinal strain (GLS) (β = 0.58; P = 0.007), age per 10 years (β: -1.61; P = 0.001), and E/e' (measure of diastolic filling pressures) (β = -0.45; P = 0.038) were associated with VO2peak. GLS added incremental value in explaining the variability in VO2peak. The combination of age ≥50 years, E/e' ≥7.8, and GLS <18% identified a high probability (85.7%) of compromised functional independence, whereas age <50 years, E/e' <7.8, and GLS ≥18% identified a low probability (0%). High-sensitivity troponin I and B-type natriuretic peptide were not associated with VO2peak. CONCLUSIONS: Readily available clinical measures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.
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    Cost-Effectiveness of Obstructive Sleep Apnea Screening and Treatment Before Catheter Ablation for Symptomatic Atrial Fibrillation.
    Kawakami, H ; Saito, M ; Kodera, S ; Fujii, A ; Nagai, T ; Uetani, T ; Tanno, S ; Oka, Y ; Ikeda, S ; Komuro, I ; Marwick, TH ; Yamaguchi, O (Japanese Circulation Society, 2020-08-27)
    Background: Although management of obstructive sleep apnea (OSA) has been recommended to improve outcomes of catheter ablation (CA) in patients with symptomatic atrial fibrillation (AF), the most cost-effective way of preprocedural OSA screening is undetermined. This study assessed the cost-effectiveness of OSA management before CA for symptomatic AF. Methods and Results: A Markov model was developed to assess the cost-effectiveness of 3 OSA detection strategies before CA: no screening; Type 3 portable monitor (PM)-guided screening; and polysomnography (PSG)-guided screening. The target population consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with 50% prevalence of OSA. We used a 5-year horizon, with sensitivity analyses for significant variables and scenario analyses for lower and higher OSA prevalence (30% and 70%, respectively). In the base-case, both types of OSA screening were dominant (less costly and more effective) relative to no screening. Although PSG-guided management was more effective than PM-guided management, it was more costly and therefore did not show clear benefit. These findings were replicated in cohorts with lower and higher OSA risks. Conclusions: OSA screening before CA is cost-effective in patients with symptomatic AF, with PM screening being the most cost-effective. Physicians should consider OSA management using this simple tool in the decision making for treatment of symptomatic AF.
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    Use and Limitations of E/e' to Assess Left Ventricular Filling Pressure by Echocardiography.
    Park, J-H ; Marwick, TH (Korean Society of Echocardiography, 2011-12)
    Measurement of left ventricular (LV) filling pressure is useful in decision making and prediction of outcomes in various cardiovascular diseases. Invasive cardiac catheterization has been the gold standard in LV filling pressure measurement, but carries the risk of complications and has a similar predictive value for clinical outcomes compared with non-invasive LV filling pressure estimation by echocardiography. A variety of echocardiographic measurement methods have been suggested to estimate LV filling pressure. The most frequently used method for this purpose is the ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), which has become central in the guidelines for diastolic evaluation. This review will discuss the use the E/e' ratio in prediction of LV filling pressure and its potential pitfalls.
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    Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle of healthy people: role of incretins
    Roberts-Thomson, KM ; Parker, L ; Betik, AC ; Wadley, GD ; Della Gatta, PA ; Marwick, TH ; Keske, MA (WILEY, 2022-02-01)
    Insulin infusion increases skeletal muscle microvascular blood flow (MBF) in healthy people but is impaired during insulin resistance. However, we have shown that eliciting insulin secretion via oral glucose loading in healthy people impairs muscle MBF, whilst others have demonstrated intravenous glucose infusion stimulates MBF. We aimed to show that the route of glucose administration (oral versus intravenous) influences muscle MBF, and explore potential gut-derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120 min oral glucose tolerance test (OGTT; 75 g glucose) and on a subsequent occasion an intravenous glucose tolerance test (IVGTT, bypassing the gut) matched for similar blood glucose excursions. Femoral artery and thigh muscle microvascular (contrast-enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT/IVGTT. Plasma insulin, C-peptide, glucagon, non-esterified fatty acids and a range of gut-derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(GLP-1)) were measured at baseline and throughout the OGTT/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3-fold versus 0.5-fold from baseline, respectively, P = 0.0006). The impairment in MBF during the OGTT occurred despite producing 2.8-fold higher plasma insulin concentrations (P = 0.0001). The change in MBF from baseline (ΔMBF) negatively correlated with ΔGIP concentrations (r = -0.665, P < 0.0001). The natural log ratio of incretins GLP-1:GIP was positively associated with ΔMBF (r = 0.658, P < 0.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia per se does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans. KEY POINTS: Insulin or mixed nutrient meals stimulate skeletal muscle microvascular blood flow (MBF) to aid in the delivery of nutrients; however, this vascular effect is lost during insulin resistance. Food/drinks containing large glucose loads impair MBF in healthy people; however, this impairment is not observed when glucose is infused intravenously (bypassing the gut). We investigated skeletal muscle MBF responses to a 75 g oral glucose tolerance test and intravenous glucose infusion and aimed to identify potential gut hormones responsible for glucose-mediated changes in MBF. Despite similar blood glucose concentrations, orally ingested glucose impaired, whereas intravenously infused glucose augmented, skeletal muscle MBF. The incretin gastric inhibitory polypeptide was negatively associated with MBF, suggestive of an incretin-mediated MBF response to oral glucose ingestion. This work provides new insight into why diets high in glucose may be detrimental to vascular health and provides new avenues for novel treatment strategies targeting microvascular dysfunction.
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    Global Longitudinal Strain Monitoring to Guide Cardioprotective Medications During Anthracycline Treatment
    Marwick, TH (SPRINGER, 2022-03-03)
    PURPOSE OF THE REVIEW: Anthracycline chemotherapy carries a risk of myocardial dysfunction and heart failure even at relatively low doses, and the clinical prediction of cancer treatment-related cardiac dysfunction (CTRCD) is inexact. Careful imaging or biomarker surveillance during chemotherapy can identify CTRCD before the development of heart failure. Currently, this surveillance is performed using ejection fraction (EF). While this is a reliable and reproducible test with three-dimensional techniques, the most widely used imaging technique is two-dimensional echocardiography, for which EF measurements have broad confidence intervals. RECENT FINDINGS: The use of global myocardial strain (GLS) provides a more reliable and reproducible means of assessing global cardiac function and shows meaningful changes before a significant change of EF. Observational studies have shown that although absolute measurements of GLS, both at baseline and during therapy, are predictive of CTRCD risk, the most reliable approach is to assess the change of GLS with therapy - a meaningful relative change of 10-15% being significant. A clinical trial comparing GLS to EF surveillance did not show a significant change of EF in the overall study group, but did show that patients managed with a the GLS-guided approach were less likely to develop a meaningful change of cardiac function to an abnormal level. In at-risk patients, there is good evidence for the protective value of neurohormonal antagonists and statins: the use of GLS enables these benefits to be directed to those most likely to benefit, while minimizing their use in the majority of people, who do not need them. Although GLS requires an element of training and efforts to ensure uniformity, it has proven to be a feasible, robust, and reproducible technique, ready for wide adoption.
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    An m-Health intervention to improve education, self-management, and outcomes in patients admitted for acute decompensated heart failure: barriers to effective implementation
    Zisis, G ; Carrington, MJ ; Oldenburg, B ; Whitmore, K ; Lay, M ; Huynh, Q ; Neil, C ; Ball, J ; Marwick, TH (Oxford University Press (OUP), 2021-12-29)
    Abstract Aims Effective and efficient education and patient engagement are fundamental to improve health outcomes in heart failure (HF). The use of artificial intelligence (AI) to enable more effective delivery of education is becoming more widespread for a range of chronic conditions. We sought to determine whether an avatar-based HF-app could improve outcomes by enhancing HF knowledge and improving patient quality of life and self-care behaviour. Methods and results In a randomized controlled trial of patients admitted for acute decompensated HF (ADHF), patients at high risk (≥33%) for 30-day hospital readmission and/or death were randomized to usual care or training with the HF-app. From August 2019 up until December 2020, 200 patients admitted to the hospital for ADHF were enrolled in the Risk-HF study. Of the 72 at high-risk, 36 (25 men; median age 81.5 years; 9.5 years of education; 15 in NYHA Class III at discharge) were randomized into the intervention arm and were offered education involving an HF-app. Whilst 26 (72%) could not use the HF-app, younger patients [odds ratio (OR) 0.89, 95% confidence interval (CI) 0.82–0.97; P &lt; 0.01] and those with a higher education level (OR 1.58, 95% CI 1.09–2.28; P = 0.03) were more likely to enrol. Of those enrolled, only 2 of 10 patients engaged and completed ≥70% of the program, and 6 of the remaining 8 who did not engage were readmitted. Conclusions Although AI-based education is promising in chronic conditions, our study provides a note of caution about the barriers to enrolment in critically ill, post-acute, and elderly patients.
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    Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case-Control Study.
    Kosmala, W ; Negishi, T ; Thavendiranathan, P ; Penicka, M ; De Blois, J ; Murbræch, K ; Miyazaki, S ; Shirazi, M ; Santoro, C ; Vinereanu, D ; Cho, G-Y ; Hristova, K ; Popescu, BA ; Kurosawa, K ; Izumo, M ; Negishi, K ; Przewlocka-Kosmala, M ; Marwick, TH (MDPI AG, 2022-02-09)
    The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case-control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP-), and matched with patients without CTRCD (CTRCD-BP+ and CTRCD-BP-). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD-BP+ patients. The CTRCD+BP- patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD-BP- peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001-1.042; p < 0.04) was the only feature independently associated with CTRCD-BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.