Melbourne Medical School Collected Works - Research Publications

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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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    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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    Echocardiographic screening for non-ischaemic stage B heart failure in the community
    Yang, H ; Negishi, K ; Wang, Y ; Nolan, M ; Saito, M ; Marwick, TH (WILEY, 2016-11-01)
    AIMS: Incident heart failure (HF) continues to pose a common and serious problem. We sought to examine the value of echocardiographic predictors of new HF in a community-based elderly population at risk for HF, independent of and incremental to clinical evaluation. METHODS AND RESULTS: Asymptomatic patients ≥65 years old, with ≥1 HF risk factor (hypertension, type 2 diabetes, or obesity) were recruited from the community; patients with valve disease, reduced ejection fraction (EF), and atrial fibrillation (AF) were excluded. Patients underwent standard clinical evaluation including calculation of the Charlson co-morbidity score and a comprehensive echocardiography including global longitudinal strain (GLS). Functional capacity was assessed by 6 min walk test. New HF and cardiovascular death were assessed after a mean follow-up of 14 ± 4 months by three independent cardiologists using Framingham criteria. Of 410 subjects (median age 70 years; 48% men), the prevalence of stage B HF was 13% [by LV hypertrophy (LVH)], 12% (by abnormal E/e'), 33% (by impaired GLS), and 31% [by left atrial enlargement (LAE)]. New HF symptoms developed in 49, and 2 died of cardiovascular causes, giving an event rate of 104/1000 person-years. These patients were older (P = 0.012), had a higher Charlson co-morbidity score (P < 0.001), larger LV mass and left atrium, higher E/e', and lower GLS (P < 0.05). LAE, LVH, abnormal GLS, and E/e' were independent predictors of new HF. In sequential models, LV mass and GLS added incremental information to clinical parameters. GLS significantly reclassified individuals (P = 0.002), but no reclassification improvement was identified using LV mass index, E/e', and left atrial volume index. CONCLUSION: Echocardiographic assessment (especially GLS and LV mass) provides incremental value in predicting incident HF.
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    Alterations in regional myocardial deformation assessed by strain imaging in cardiac amyloidosis
    Lo, Q ; Haluska, B ; Chia, E-M ; Lin, M-W ; Richards, D ; Marwick, T ; Thomas, L (WILEY, 2016-12-01)
    BACKGROUND: Cardiac amyloidosis results in increased left ventricular (LV) wall thickness and diastolic dysfunction (DD). Strain measurements using velocity vector imaging (VVI) may further characterize myocardial dysfunction. METHODS: A total of 43 AL amyloidosis patients were compared to age-matched normals and hypertensive patients (HT). Subgroup analysis within the amyloid group was performed based on LV wall thickness (≤14 mm, >14 mm) and diastolic dysfunction (DD) (Group 1: normal and impaired relaxation, Group 2: pseudonormal, Group 3: restrictive). LV strain (longitudinal, circumferential, and radial strain (S) and strain rate [Sr]) were measured using velocity vector imaging (VVI). RESULTS: Increased LV wall thickness and DD were observed in the amyloid group. Global longitudinal (-13.9±4.1% vs -16.7±3.8%; P=.002) and radial (27.4±13.4% vs 38.8±15.7%; P<.001) strain were lower in the amyloid group vs normal controls, while circumferential strain was similar. Segmental analysis demonstrated reduced mid- and basal segmental strain with relative sparing of apical segments in the amyloid group. Reduced longitudinal and radial strain, with preserved circumferential strain, were observed in patients with wall thickness >14 mm; however, circumferential strain was also altered when severe DD (restrictive filling) was present. CONCLUSION: Reduction in longitudinal and radial S and Sr was evident using VVI strain analysis in amyloidosis, with segmental heterogeneity in longitudinal S. There was relative preservation of circumferential strain, which was reduced only in patients with severe DD.
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    Comparison of 3D echocardiographic-derived indices using fully automatic left ventricular endocardial tracing (heart model) and semiautomatic tracing (3DQ-ADV)
    D'Elia, N ; Appadurai, V ; Mallouhi, M ; Ng, J ; Marwick, T ; Wahi, S (WILEY, 2019-10-17)
    AIMS: The availability of a true 3D dataset provides an opportunity for automation of left ventricular (LV) and left atrial (LA) measurements. Although manual and automated measurements of 3D volumes are known to correlate, the variance is an important parameter for the individual patient. The reasons for discrepancies remain unexplained. We hence aim to explain the disagreement between automated and manual LV and LA volumes. METHODS AND RESULTS: A total of 355 patients underwent standard clinical echo, with offline analysis in both fully- (Heart Model, Philips) and semiautomated (3DQ-Adv, Philips) assessment of routine indices of LV and LA function and shape. Each image was classified according to quality using a 4-point scale as well as the American Society for Echocardiography guidelines for appropriate use of contrast. Bland-Altman plots were used to assess agreement, and t tests were used to assess differences in agreement. Predictors of volume discrepancy were sought with linear regression. Measures of LV and LA volumes were greater with automatic than semiautomatic assessment. The difference in left ventricular end-diastolic volume was dependent on the number of regional wall-motion abnormalities (RWMA) (β = 0.59, P < .04) and image quality (β = 19.71, P = .02). RWMA predicted the difference in left ventricular end-systolic volume (β = 0.83, P < .01) and left atrial end-systolic volume (β = -1.01 P < .01). CONCLUSION: LV and LA volumes were higher with automatic than semiautomatic assessment. Image quality and RWMA may contribute to this discrepancy. These limitations need to be addressed before fully automatic assessment of 3D echocardiograms can be used in the clinic.
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    Association between socioeconomic status and incident atrial fibrillation
    Ramkumar, S ; Ochi, A ; Yang, H ; Nerlekar, N ; D'Elia, N ; Potter, EL ; Murray, IC ; Nattraj, N ; Wang, Y ; Marwick, TH (WILEY, 2019-10-01)
    BACKGROUND: Low socioeconomic status is associated with cardiovascular diseases, and an association with atrial fibrillation (AF) could guide screening. AIM: To investigate if indices of advantage/disadvantage (IAD), index of education/occupation (IEO) and index of economic resources were associated with incident AF, independent of risk factors and cardiac function. METHODS: We studied community-based participants aged ≥65 years with AF risk factors (n = 379, age 70 ± 4 years, 45% men). The CHARGE-AF score (a well validated AF risk score) was used to assess 5-year risk of developing AF. Participants also had baseline echocardiograms. IAD, IEO and index of economic resources were obtained from the 2011 Socio-Economic Indexes for Areas score, in which higher decile ranks indicate more advantaged areas. Patients were followed up for incident AF (median 21 (range 5-31) months), with AF diagnosed by clinical review, including 12-lead electrocardiogram (ECG), as well as single-lead portable ECG monitoring used to record 60 s ECG tracings five times/day for 1 week. Cox proportional hazards models were used to assess the association between socioeconomic status and incident AF. RESULTS: Subjects with AF (n = 50, 13%) were more likely to be male (64 vs 42%, P = 0.003) and had higher CHARGE-AF score (median 7.1% (5.2-12.8%) vs 5.3% (3.3-8.6%), P < 0.001). Areas with lower socioeconomic status (IAD and IEO) had a higher risk of incident AF independent of LV function and CHARGE-AF score (hazard ratio for IAD 1.16, 95% confidence interval 1.05-1.29, P = 0.005 and hazard ratio for IEO 1.18, 95% confidence interval 1.07-1.30, P = 0.001). CONCLUSION: Regional socioeconomic status is associated with risk of incident AF, independent of LV function and clinical risk. This association might permit better regional targeting of prevention.
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    Evaluating the benefits of a rapid access chest pain clinic in Australia
    Black, JA ; Cheng, K ; Flood, J-A ; Hamilton, G ; Parker, S ; Enayati, A ; Khan, FS ; Marwick, T (WILEY, 2019-04-01)
    OBJECTIVES: To compare the outcomes and safety of a rapid access chest pain clinic (RACPC) in Australia with those of a general cardiology clinic. DESIGN: Prospective comparison of the outcomes for patients attending an RACPC and those of historical controls. SETTING: Royal Hobart Hospital cardiology outpatient department. PARTICIPANTS: 1914 patients referred for outpatient evaluation of new onset chest pain (1479 patients seen in the RACPC, 435 patients previously seen in the general cardiology clinic). MAIN OUTCOME MEASURES: Service outcomes (review times, number of clinic reviews); adverse events (unplanned emergency department re-attendances at 30 days and 12 months; major adverse cardiovascular events at 12 months, including unplanned revascularisation, acute coronary syndrome, stroke, cardiac death). RESULTS: Median time to review was shorter for RACPC than for usual care patients (12 days [IQR, 8-15 days] v 45 days [IQR, 27-89 days]). All patients seen in the RACPC received a diagnosis at the first clinic visit, but only 139 patients in the usual care group (32.0%). There were fewer unplanned emergency department re-attendances for patients in the RACPC group at 30 days (1.6% v 4.4%) and 12 months (5.7% v 12.9%) than in the control group. Major adverse cardiovascular events were less frequent among patients evaluated in the RACPC (0.2% v 1.4%). CONCLUSIONS: Patients were evaluated more efficiently in the RACPC than in a traditional cardiology clinic, and their subsequent rates of emergency department re-attendances and adverse cardiovascular events were lower.
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    Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction
    Telles, F ; Nanayakkara, S ; Evans, S ; Patel, HC ; Mariani, JA ; Vizi, D ; William, J ; Marwick, TH ; Kaye, DM (WILEY, 2019-04-01)
    BACKGROUND: Elevated left atrial (LA) pressure, particularly during exercise, is associated with symptomatic status and survival in patients with heart failure with preserved ejection fraction (HFpEF). We aimed to characterize the contribution of abnormal LA mechanical properties to exercise haemodynamics in HFpEF. METHODS AND RESULTS: Simultaneous echocardiography and right heart catheterization were performed in 71 subjects with left ventricular ejection fraction ≥ 50% referred for assessment of exertional dyspnoea. According to haemodynamic evaluation, 49 patients were diagnosed with HFpEF [pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg at rest and/or ≥ 25 mmHg at maximal exertion] and 22 as non-cardiac dyspnoea. Apical two- and four-chamber views were used for blinded two-dimensional LA speckle tracking analysis. HFpEF was characterized by impaired LA reservoir (24.3 ± 9.6 vs. 36.7 ± 8.4%, P < 0.001) and pump strain (-11.5 ± 3.2 vs. -17.0 ± 3.4%, P < 0.001); and increased stiffness (0.8 ± 0.7 vs. 0.2 ± 0.1 mmHg/%, P < 0.001). Reservoir and pump strain correlated with exercise PCWP (r = -0.64 and r = 0.72, P < 0.001), and remained independent predictors after adjusting for left ventricular mass index, LA volume index, mean E/e' and systolic blood pressure (B = -0.66 and B = 1.41, respectively, P < 0.001). LA stiffness was strongly related to B-type natriuretic peptide levels (r = 0.73, P < 0.001; B = 173.0, P < 0.001). Reservoir strain at cut-off of ≤ 33% predicted invasively verified HFpEF diagnosis with 88% sensitivity and 77% specificity, providing a net reclassification improvement of 12% in comparison to the 2016 European Society of Cardiology criteria for non-invasive diagnosis of HFpEF. CONCLUSIONS: Impaired LA reservoir and pump function and increased stiffness are associated with abnormal exercise haemodynamics in HFpEF. These markers provide significant HFpEF diagnostic utility in elderly ambulatory patients with dyspnoea.
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    Cardiovascular and other competing causes of death among patients with cancer from 2006 to 2015: An Australian population-based study
    Ye, Y ; Otahal, P ; Marwick, TH ; Wills, KE ; Neil, AL ; Venn, AJ (WILEY, 2019-02-01)
    BACKGROUND: With improved cancer survivorship, cardiovascular disease (CVD) and other noncancer events compete with cancer as the underlying cause of death, but the risks of mortality in competing-risk settings have not been well characterized. METHODS: The authors identified 21,637 individuals who had a first cancer registered between 2006 and 2013, with follow-up to 2015, in the Australian population-based Tasmanian Cancer Registry. The cumulative incidence of deaths from specific competing events was assessed in competing-risk analyses. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) for deaths from noncancer causes were calculated for comparison with the general population. RESULTS: Overall, 8844 deaths were observed, with 1946 (22%) from competing events. The cumulative incidence of deaths from CVD increased significantly with age at first cancer diagnosis and exceeded other competing events at age ≥65 years. The risk of death from CVD was more common than expected in the first year of follow-up (SMR, 1.44 [95% confidence interval, 1.26-1.64]; AER, 36.8 per 10,000 person-years). The SMR and AER for CVD deaths varied by first cancer site, indicating increased risks after a first diagnosis of lung cancer, hematologic malignancy, and urinary tract cancer. For other noncancer events, the SMRs increased significantly for deaths from infectious disease and respiratory disease and were highest in the first year of follow-up. CONCLUSIONS: CVD was the leading cause of competing mortality among Tasmanian patients with cancer who were diagnosed from 2006 to 2013. The higher than expected occurrence of death from CVD and other noncancer events during the first year after a cancer diagnosis highlights the importance of early preventive interventions.
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    Pathophysiological effects of different risk factors for heart failure
    Yang, H ; Wang, Y ; Negishi, K ; Nolan, M ; Marwick, TH (BMJ PUBLISHING GROUP, 2016-05-01)
    BACKGROUND: Hypertension and type 2 diabetes mellitus (T2DM) are important causes of non-ischaemic heart failure (HF). Understanding the pathophysiology of early HF may guide screening. We hypothesised that the underlying physiology differed according to aetiology. METHODS: In this cross-sectional study of 521 asymptomatic community-based subjects ≥65 years with ≥1 HF risk factors, 187 participants (36%) had T2DM and hypertension (T2DM+/HTN+), 109 (21%) had T2DM with no hypertension (T2DM+/HTN-) and 72 (14%) had neither T2DM nor hypertension (T2DM-/HTN-). In 153 patients (29%), clinic blood pressure was ≥140/90 mm Hg, defined as active hypertension (T2DM-/HTN+). All underwent a comprehensive echocardiogram, including conventional parameters for systolic and diastolic function as well as global longitudinal strain (GLS), diastolic strain (DS) and DS rate (DSR). A 6 min walk (6MW) test was used to assess functional capacity. RESULTS: GLS in T2DM-/HTN+ group (-18.9±2.7%) was similar to that in T2DM-/HTN- group (-19.4±2.4%) and greater than T2DM+/HTN- (-18.0±2.8%, p=0.005). DS in T2DM-/HTN- (0.47±0.15%) exceeded that in T2DM-/HTN+ (0.43±0.14%) and T2DM+/HTN- (0.43±0.13%). 6MW distance was preserved in T2DM-/HTN+ (482±85 m) and reduced in T2DM+/HTN- (469±93, p<0.001). Those with T2DM and active hypertension had worst GLS, DS, DSR and shortest 6MW distance (p<0.002). In multivariable analysis, GLS was associated with T2DM but neither active hypertension nor a history of hypertension. Diastolic markers and left ventricular (LV) mass were associated with hypertension and T2DM. Thus, patients with HF risk factors show different functional disturbances according to aetiology. CONCLUSIONS: Patients with hypertension had relatively less impaired GLS and preserved 6MW distance but more impaired diastolic function.