Melbourne Medical School Collected Works - Research Publications
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ItemA new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler.(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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ItemBaseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).(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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ItemUse and Limitations of E/e' to Assess Left Ventricular Filling Pressure by Echocardiography.(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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ItemA comparative analysis of risk stratification tools for emergency department patients with chest pain(BMC, 2014)BACKGROUND: Appropriate disposition of emergency department (ED) patients with chest pain is dependent on clinical evaluation of risk. A number of chest pain risk stratification tools have been proposed. The aim of this study was to compare the predictive performance for major adverse cardiac events (MACE) using risk assessment tools from the National Heart Foundation of Australia (HFA), the Goldman risk score and the Thrombolysis in Myocardial Infarction risk score (TIMI RS). METHODS: This prospective observational study evaluated ED patients aged ≥30 years with non-traumatic chest pain for which no definitive non-ischemic cause was found. Data collected included demographic and clinical information, investigation findings and occurrence of MACE by 30 days. The outcome of interest was the comparative predictive performance of the risk tools for MACE at 30 days, as analyzed by receiver operator curves (ROC). RESULTS: Two hundred eighty-one patients were studied; the rate of MACE was 14.1%. Area under the curve (AUC) of the HFA, TIMI RS and Goldman tools for the endpoint of MACE was 0.54, 0.71 and 0.67, respectively, with the difference between the tools in predictive ability for MACE being highly significant [chi2 (3) = 67.21, N = 276, p < 0.0001]. CONCLUSION: The TIMI RS and Goldman tools performed better than the HFA in this undifferentiated ED chest pain population, but selection of cutoffs balancing sensitivity and specificity was problematic. There is an urgent need for validated risk stratification tools specific for the ED chest pain population.
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ItemPatient Preferences and Willingness-To-Pay for a Home or Clinic Based Program of Chronic Heart Failure Management: Findings from the Which? Trial(PUBLIC LIBRARY SCIENCE, 2013-03-07)BACKGROUND: Beyond examining their overall cost-effectiveness and mechanisms of effect, it is important to understand patient preferences for the delivery of different modes of chronic heart failure management programs (CHF-MPs). We elicited patient preferences around the characteristics and willingness-to-pay (WTP) for a clinic or home-based CHF-MP. METHODOLOGY/PRINCIPAL FINDINGS: A Discrete Choice Experiment was completed by a sub-set of patients (n = 91) enrolled in the WHICH? trial comparing home versus clinic-based CHF-MP. Participants provided 5 choices between hypothetical clinic and home-based programs varying by frequency of nurse consultations, nurse continuity, patient costs, and availability of telephone or education support. Participants (aged 71±13 yrs, 72.5% male, 25.3% NYHA class III/IV) displayed two distinct preference classes. A latent class model of the choice data indicated 56% of participants preferred clinic delivery, access to group CHF education classes, and lower cost programs (p<0.05). The remainder preferred home-based CHF-MPs, monthly rather than weekly visits, and access to a phone advice service (p<0.05). Continuity of nurse contact was consistently important. No significant association was observed between program preference and participant allocation in the parent trial. WTP was estimated from the model and a dichotomous bidding technique. For those preferring clinic, estimated WTP was ≈AU$9-20 per visit; however for those preferring home-based programs, WTP varied widely (AU$15-105). CONCLUSIONS/SIGNIFICANCE: Patient preferences for CHF-MPs were dichotomised between a home-based model which is more likely to suit older patients, those who live alone, and those with a lower household income; and a clinic-based model which is more likely to suit those who are more socially active and wealthier. To optimise the delivery of CHF-MPs, health care services should consider their patients' preferences when designing CHF-MPs.
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ItemHow Similar Are the Mice to Men? Between-Species Comparison of Left Ventricular Mechanics Using Strain Imaging(PUBLIC LIBRARY SCIENCE, 2012-06-29)BACKGROUND: While mammalian heart size maintains constant proportion to whole body size, scaling of left ventricular (LV) function parameters shows a more complex scaling pattern. We used 2-D speckle tracking strain imaging to determine whether LV myocardial strains and strain rates scale to heart size. METHODS: We studied 18 mice, 15 rats, 6 rabbits, 12 dogs and 20 human volunteers by 2-D echocardiography. Relationship between longitudinal or circumferential strains/strain rates (S(Long)/SR(Long), S(Circ)/SR(Circ)), and LV end-diastolic volume (EDV) or mass were assessed by the allometric (power-law) equation Y = kM(β). RESULTS: Mean LV mass in individual species varied from 0.038 to 134 g, LV EDV varied from 0.015 to 102 ml, while RR interval varied from 81 to 1090 ms. While S(Long) increased with increasing LV EDV or mass (β values 0.047±0.006 and 0.051±0.005, p<0.0001 vs. 0 for both) S(Circ) was unchanged (p = NS for both LV EDV or mass). Systolic and diastolic SR(Long) and SR(Circ) showed inverse correlations to LV EDV or mass (p<0.0001 vs. 0 for all comparisons). The ratio between S(Long) and S(Circ) increased with increasing values of LV EDV or mass (β values 0.039±0.010 and 0.040±0.011, p>0.0003 for both). CONCLUSIONS: While S(Circ) is unchanged, S(Long) increases with increasing heart size, indicating that large mammals rely more on long axis contribution to systolic function. SR(Long) and SR(Circ), both diastolic and systolic, show an expected decrease with increasing heart size.
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ItemRole of imaging in the detection of reversible cardiomyopathy.(Korean Society of Echocardiography, 2013-06)Heart failure is a major clinical problem in developed countries with about half of heart failure patients exhibiting decreased left ventricular systolic function. The correct identification and prompt treatment of some specific etiologies can reverse heart failure, and recognition of myocardial recovery may avoid long-term therapy. However, the echocardiographic patterns of patients with a variety of etiologies of heart failure are similar, so the selective use of other imaging techniques is necessary for identification of specific etiologies. The role of repeat imaging in monitoring the therapeutic response is controversial, as is the cessation of medical therapy in patients demonstrating recovery.
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ItemMyocardial scar burden predicts survival benefit with implantable cardioverter defibrillator implantation in patients with severe ischaemic cardiomyopathy: influence of gender(BMJ PUBLISHING GROUP, 2014-02-01)OBJECTIVE: We sought to assess the impact of myocardial scar burden (MSB) on the association between implantable cardioverter defibrillator (ICD) implantation and mortality in patients with ischaemic cardiomyopathy (ICM) and left ventricular EF ≤ 40%. In addition, we sought to determine the impact of gender on survival benefit with ICD implantation. DESIGN: Retrospective observational study. SETTING: Single US tertiary care centre. PATIENTS: Consecutive patients with significant ICM who underwent delayed hyperenhancement-MRI between 2002 and 2006. INTERVENTIONS: ICD implantation. MAIN OUTCOME MEASURES: All-cause mortality and cardiac transplantation. RESULTS: Follow-up of 450 consecutive patients, over a mean of 5.8 years, identified 186 deaths. Cox proportional hazard modelling was used to evaluate associations among MSB, gender and ICD with respect to all-cause death as the primary endpoint. ICDs were implanted in 163 (36%) patients. On multivariable analysis, Scar% (χ² 28.21, p<0.001), Gender (χ² 12.39, p=0.015) and ICD (χ² 9.57, p=0.022) were independent predictors of mortality after adjusting for multiple parameters. An interaction between MSB×ICD (χ² 9.47, p=0.009) demonstrated significant differential survival with ICD based on MSB severity. Additionally, Scar%×ICD×Gender (χ² 6.18, p=0.048) suggested that men with larger MSB had significant survival benefit with ICD, but men with smaller MSB derived limited benefit with ICD implantation. However, the inverse relationship was found in women. CONCLUSIONS: MSB is a powerful independent predictor of mortality in patients with and without ICD implantation. In addition, MSB may predict gender-based significant differences in survival benefit from ICDs in patients with severe ICM.
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ItemReceptor for advanced glycation end products Glycine 82 Serine polymorphism and risk of cardiovascular events in rheumatoid arthritis(BIOMED CENTRAL LTD, 2007)Patients with rheumatoid arthritis (RA) are at risk of excess mortality, predominantly owing to cardiovascular (CV) events. The receptor for advanced glycation end products (RAGE) has been implicated in the perpetuation of the chronic inflammatory response in vascular disease. A Gly82-->Ser polymorphism in the RAGE gene, which is associated with enhanced RAGE signaling, is present more frequently in patients with RA than the general population. To investigate whether RAGE Gly82-->Ser polymorphism is associated with CV events in RA, we examined CV events, CV risk factors, features of RA and RAGE Gly82-->Ser polymorphism in 232 patients with RA attending a tertiary referral hospital. CV events, the duration and severity of RA, and risk factors for CV disease were determined using patient questionnaires, chart review, laboratory analysis and radiographs. DNA was typed for HLA-DRB1 genes and RAGE Gly82-->Ser polymorphism. The RAGE Ser82 allele, which is in linkage disequilibrium with the RA susceptibility allele HLA-DRB1*0401, was carried by 20% of patients. More than 20% of the cohort had suffered a vascular event; a shorter duration of RA, but not the RAGE genotype, was significantly associated with CV events. However, a history of statin use was protective. Thus, the RAGE Ser82 allele, associated with enhanced RAGE signaling, does not predispose to CV events in RA. However, treatment of hyperlipidemia with statins reduces the probability of a CV event.
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ItemCardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study(BMC, 2011-10-03)BACKGROUND: Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known. METHODS: Sixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session, 3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months. RESULTS: Left ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated. CONCLUSIONS: Despite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.