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BACKGROUND AND AIMS: Coronary artery disease (CAD) is a complex disease with a strong genetic basis. While previous studies have combined common single-nucleotide polymorphisms (SNPs) into a polygenic risk score (PRS) to predict CAD risk, this association is poorly characterised. We performed a meta-analysis to estimate the effect of PRS on the risk of CAD.METHODS: Online databases were searched for studies reporting PRS and CAD. PRS computation was based on log-odds (PRSLN), pruning or clumping and thresholding (PRSP/C + T), Lassosum regression (PRSLassosum), LDpred (PRSLDpred), or metaGRS (PRSmetaGRS). The reported odds ratio (OR), hazard ratio (HR), C-indexes and their corresponding 95% confidence interval (95% CI) were pooled in a random-effects meta-analysis.RESULTS: Forty-nine studies were included (979,286 individuals). There was a significant association between 1-standard deviation [SD] increment in PRS and adjusted risks of both incident and prevalent CAD (OR [95% CI]: 1.67 [1.57-1.77] for PRSmetaGRS, 1.46 [1.26-1.68] for PRSLDpred). The risk of incident CAD was highest for PRSP/C + T (HR [95% CI]: 1.49 [1.26-1.78]), PRSmetaGRS (1.37 [1.27-1.47]), and PRSLDpred (1.36 [1.31-1.42]). Analysis of model performance demonstrated that PRS predicted incident CAD with C-index of up to 0.71. Importantly, addition of PRS to clinical risk scores resulted in modest but statistically significant improvements in CAD risk prediction, with 1.5% observed for PRSP/C + T (p < 0.001) and 1.6% for PRSLDpred (p < 0.001).CONCLUSIONS: Polygenic risk score is strongly associated with increased risks of CAD. Future prospective studies should explore the usefulness of polygenic risk scores for identifying individuals at a high risk of developing CAD.

Acute decompensated heart failure (ADHF) carries a high event rate following discharge. The complex interplay between age, frailty and decongestion may lend itself to a functional test.In the doorbell test the patient simulates answering the doorbell. They are timed rising from a recumbent position, bending over twice and walking 10 metres, this time is added to the change in respiratory rate. We aimed to determine if the doorbell test was associated with post ADHF events (death or readmission). The test was performed at hospital discharge, with follow up at 30-days and 1-year.In 74 patients at 30-days there was a 14% event rate. At 1-year there were 40 (54%) events (9 deaths and 31 readmissions, 28 were cardiovascular of which 14 were [heart failure] HF). Amongst those who had an event at 30-days only doorbell test scores were different (58 [36,72] vs 32 [26,53] p 0.05). One-year (1-year) events were associated with doorbell test scores (47 [29,62] vs 30 [26,42] p 0.05), body weight (78 kg [68,94] vs 95 [76,105] (p 0.05), creatinine (134 mmol/L [114, 173] vs 99 [82, 133] p 0.01) and age (76 years [61,86] vs 67 [53, 73] p 0.01). Heart failure readmissions were associated with doorbell test scores (56 [46,68] vs 30 [26,47] p 0.001). Death was associated with body weight (74 kg [69,81] vs 88 [72,101] p 0.05) and age (83 years [78,86] vs 69 [55,77] p 0.01). After age stratification, the hazard ratio for heart failure readmission associated with a high doorbell test score was 11.08 (95%C.I. 2.01-61.17 p = 0.006), while the hazard ratio for 1-year cardiovascular readmission was 4.62 (95%C.I. 1.71-12.51 p = 0.003). There was no association with 1-year mortality.The doorbell test represents a novel test of multiple domains of the ADHF pre-discharge state and demonstrates an association with 30-day and 1-year rehospitalisation.

Guidelines recommend referral to cardiac rehabilitation (CR) for cardiac event prevention and risk factor management, but poor attendance persists. Following the development of standardised data and uniform capture, CR services have contributed to three audits in South Australia, Australia. We aimed to determine if CR attendance impacts on cardiovascular readmission, morbidity and mortality.In a retrospective cohort study, CR databases were linked to hospital administrative datasets to compare the characteristics and outcomes of CR patients between 2013 and 2015. Inverse probability weighting methods were used to measure associations between CR attendance versus non-attendance and cardiovascular readmission and the composite of death, new/re-myocardial infarction, atrial fibrillation, heart failure and stroke within 12-months.Of 49,909 eligible separations, 15,089/49,909 (30.2%) were referred to CR with an attendance rate of 4,286/15,089 (28.4%). Referred/declined patients were older (median: 67.3 vs 65.3 years, p 0.001), more likely to be female (32.3% vs 26.5%, p 0.001) with more heart failure (17.1% vs 10.9%, p 0.001) and arrhythmia (6.1% vs 2.1%, p 0.001) admissions and higher socio-economic disadvantage (median Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD): 950.1 vs 960.4, p 0.001). Referred/attended patients had lower cardiovascular readmission, (referred/attended vs not referred: 15.6% vs 22.7% and referred/attended vs referred/declined: 15.6% vs 29.6%, p 0.001). After clinical and social factors adjustment there was no difference in composite outcomes, but attendance was associated with reduced cardiovascular readmission (HR:0.68, 95% IQR: 0.58-0.81, p = 0.001).Audit can measure service effectiveness, identifying areas for improvement. This study highlights patient eligibility, system and program considerations for future CR services.

Objectives: This study sought to determine the long-term prognostic value of myocardial deformation imaging by echocardiography in risk stratification of sudden cardiac death (SCD) and malignant ventricular arrhythmias (VAs) in a large consecutive cohort of patients with left ventricular (LV) systolic impairment, irrespective of its etiology. Background: Left ventricular ejection fraction (LVEF) is limited for prediction of SCD. Echocardiographic strain-derived mechanical dispersion (MD) and global longitudinal strain (GLS) has been linked to VA and SCD. However, due to low event rates, the role of these parameters has not been fully elucidated. Methods: Consecutive clinically stable patients who underwent echocardiographic study performed in an outpatient setting from 2008 to 2014 with a Simpson left ventricular ejection fraction (LVEF) ≤45% were included in the study. Strain analysis was performed in which the LV was separated into 16 segments for regional analysis. Mechanical dispersion (MD) was calculated as the SD of the time to peak of each of the 16 regions. Outcome data were obtained from medical records. Results: A total of 939 patients were included in the study, with median LVEF of 37% (interquartile range 30% to 42%). At follow-up (91.4 ± 23.4 months), 96 VA events had occurred. Multivariate analysis demonstrated that only MD ≥75 ms (hazard ratio: 9.45; 95% confidence interval: 4.75 to 18.81; p < 0.0001) was predictive of VA events. Low MD predicted a low event rate, irrespective of LVEF. Conclusions: Using LVEF alone is inferior for prediction of VA and SCD, particularly in patients with moderately reduced LVEF. MD is easily obtained from standard echocardiographic images and can be used to improve risk prognosis, particularly in patients who are currently excluded from cardiac defibrillator insertion based on LVEF. usc Refereed/Peer-reviewed

Compared with other manifestations of cardiovascular disease, peripheral arterial disease (PAD) is under-diagnosed. This study aims to investigate the prevalence, risk profile and cardiovascular outcomes of undiagnosed PAD in Australian general practices.A sub-study of the Australian Reduction of Atherothrombosis for Continued Health (REACH) Registry, a prospective cohort study of patients at high risk of atherothrombosis recruited from Australian general practices. Eligible patients for this study had no previous clinical diagnosis of PAD and had an ankle-brachial index (ABI) ≤1.4 at recruitment.Peripheral arterial disease was undiagnosed in 34% Australian REACH participants, 28% patients had low ABI (ABI0.9) and 11% had intermittent claudication (IC) based on responses to the Edinburgh Claudication Questionnaire (ECQ). We found no significant differences in risk factor control between patient with or without PAD. Intermittent claudication patients had higher risks of non-fatal cardiovascular events and PAD interventions at one year, whereas all-cause mortality rate was higher among patients with ABI0.9, especially in those who also reported IC. Finally, an ABI0.9, together with poorly controlled risk factors were independent predictors of incident IC at one year.This study suggests a high rate of undiagnosed PAD among high risk patients in Australian primary health care. These patients are at high risk of events and therefore would potentially benefit from better secondary prevention measures.

Risk models integrating new biomarkers to predict cardiovascular events in acute coronary syndromes (ACS) are lacking. Therefore, we evaluated the prognostic value of biomarkers in addition to clinical predictors and developed a biomarker-based risk model for major adverse cardiovascular events (MACE) within 12 months after hospital admission with ACS.Patients (Over 12 months, 196 patients experienced MACE (5.1%/year). Among twelve candidate biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline showed the most prognostic capability independent of clinical predictors. The developed BIPass risk model included age, hypertension, previous myocardial infarction, stroke, Killip class, heart rate, and NT-proBNP. It displayed improved discrimination (C-statistic 0.79, 95% CI 0.73-0.85), calibration (GOF = 9.82,The BIPass risk model, integrating clinical variables and NT-proBNP, is useful for predicting 12-month MACE in ACS. It effectively identifies a gradient risk of cardiovascular events to aid personalized care.National Key RD Program of China (2017YFC0908700, 2020YFC0846600), National ST Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), Taishan Young Scholar Program of Shandong Province (tsqn20161065, tsqn201812129), Youth Top-Talent Project of National Ten Thousand Talents Plan and Qilu Young Scholar Program.

Background: Patients with acute coronary syndromes (ACS), the acute and severe manifestation of coronary artery disease, are highly heterogeneous in their risk for recurrent cardiovascular events. Several biomarkers carry prognostic information for cardiovascular events. However, instruments integrating clinical characteristics and biomarkers to accurately predict the occurrence of cardiovascular events, thus facilitating individualization of ACS care are lacking. Methods: Using data from 4,407 ACS patients enrolled in a prospective and multicenter Chinese cohort, BIomarker-based Prognostic Assessment for Patients with Stable Angina and Acute Coronary Syndromes (BIPass) registry, we developed a risk model to predict the major adverse cardiovascular events (MACE, defined as the composite of cardiac death, myocardial infarction [MI] and ischemic stroke) within 12 months after hospital admission. Validation was performed in 1,409 patients from an independent cohort. Findings: Over 12 months, MACE occurred in 196 patients (incidence rate 5·07 per 100 person- years, 95% CI [4·42-5·81]/100 person-years). Predictors of MACE included N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) biomarkers, and clinical variables of age, hypertension, previous MI, previous stroke, Killip class, and heart rate. The developed BIPass risk model displayed excellent discriminative capability (C statistic 0·82, 95% CI 0·78-0·86) and calibration, outperformed GRACE and TIMI risk scores. Similar discrimination, calibration and clinical decision curves were confirmed in the validation cohort. Cumulative rates for MACE demonstrated good separation in BIPass predicted low, intermediate and high-risk groups in both the development and validation cohorts. The BIPass risk model consistently provided enhanced predictions of MACE over a broad-spectrum of ACS and across clinically important subgroups (i.e. age, diagnosis, coronary revascularization, medications). Interpretation: BIPass risk model integrating clinical variables and biomarkers measured at admission is useful to predict risk of 12-month cardiovascular events in ACS, which offers the potential to identify higher-risk patients as candidates for early aggressive treatments. Trial Registration: NCT04044066 Funding Statement: National Key R＆D Program of China (2017YFC0908700, 2017YFC0908703), National S&T Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), Taishan Young Scholar Program of Shandong Province (tsqn20161065, tsqn201812129). Declaration of Interests: None. Ethics Approval Statement: The BIPass study was approved by the research ethics committee of Qilu Hospital, Shandong University which was accepted by all the collaborating hospitals.

Background Elevated troponin level findings among patients presenting with suspected acute coronary syndrome (ACS) or another intercurrent illness undeniably identifies patients at increased risk of mortality. Whilst enhancing our capacity to discriminate risk, the use of high-sensitivity troponin assays frequently identifies patients with myocardial injury (i.e. troponin rise without acute signs of myocardial ischemia) or type 2 myocardial infarction (T2MI; oxygen supply-demand imbalance). This leads to the clinically challenging task of distinguishing type 1 myocardial infarction (T1MI; coronary plaque rupture) from myocardial injury and T2MI in the context of concurrent acute illness. Diagnostic discernment in this context is crucial because MI classification has implications for further investigation and care. Early invasive management is of well-established benefit among patients with T1MI. However, the appropriateness of this investigation in the heterogeneous context of T2MI, where there is high competing mortality risk, remains unknown. Although coronary angiography in T2MI is advocated by some, there is insufficient evidence in existing literature to support this opinion as highlighted by current national guidelines. Objective The objective is to evaluate the clinical and economic impact of early invasive management with coronary angiography in T2MI in terms of all-cause mortality and cost effectiveness. Design This prospective, pragmatic, multicenter, randomized trial among patients with suspected supply demand ischemia leading to troponin elevation (n=1,800; T2MI [1,500], chronic myocardial injury [300]) compares the impact of invasive angiography (or computed tomography angiography as per local preference) within 5 days of randomization versus conservative management (with or without functional testing at clinician discretion) on all-cause mortality by 2 years. Randomized treatment allocation will be stratified by baseline estimated risk of mortality using the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III risk score. Cost-effectiveness will be evaluated by follow-up on clinical events, quality of life, and resource utilization over 24 months. Summary Ascertaining the most appropriate first-line investigative strategy for these commonly encountered high-risk T2MI patients in a randomized comparative study will be pivotal in informing evidence-based guidelines that lead to better patient and health care outcomes.

Background Socioeconomic status (SES) is a social determinant of both health and receipt of health care services, but its impact is under-studied in acute coronary syndrome (ACS). The aim of this study was to examine the influence of SES on in-hospital care, and clinical events for patients presenting with an ACS to public hospitals in Australia. Methods Data from 9064 ACS patient records were collected from 41 public hospitals nationwide from 2009 as part of the Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE) registry. For this analysis, we divided the cohort into four socioeconomic groups (based on postcode of usual residence) and compared the in-hospital care provided and clinical outcomes before and after adjustment for both patient clinical characteristics and hospital clustering. Results Patients were divided into four SES groups (from the most to the least disadvantaged: 2042 (23%) vs. 2104 (23%) vs. 1994 (22%) vs. 2968 (32%)). Following adjustments for patient characteristics, there were no differences in the odds of receiving coronary angiogram, revascularisation, prescription of recommended medication, or referral to cardiac rehabilitation across the SES groups (p = 0.06, 0.69, 0.89 and 0.79, respectively). After adjustment for clinical characteristics, no associations were observed for in-hospital and cumulative death (p = 0.62 and p = 0.71, respectively). However, the most disadvantaged group were 37% more likely to have a major adverse cardiovascular event (MACE) than the least disadvantaged group (OR (95% CI): 1.37 (1.1, 1.71), p = 0.02) driven by incidence of in-hospital heart failure. Conclusions Although there may be gaps in the delivery of care, this delivery of care does not differ by patient's SES. It is an encouraging affirmation that all patients in Australian public hospitals receive equal in-hospital care, and the likelihood of death is comparable between the SES groups.

Background Cardiac troponin (T and I) are considered the standard markers for detection of myocardial damage and the diagnosis of acute coronary syndrome (ACS) among patients who present to an emergency department with chest pain. However, these markers can be released in other situations and may be associated with short- and long-term clinical outcomes. In this study, we examine late mortality rates among patients presenting with a suspected ACS due to an unstable coronary plaque and those patients having a non-ACS. Methods 4388 patients were hospitalised with suspected ACS, between 14 and 27 May 2012 in the Australia and New Zealand SNAPSHOT ACS study. Those patients were categorised in five diagnostic groups: 1) ST elevation MI (n=419); 2) non-ST elevation MI (n=1012); 3) unstable angina (n=925); 4) non-ACS diagnoses (n=837); and 5) chest pain considered unlikely ischaemic (not otherwise specified, n=1195). Result The respective mortality rates at 18 months in these groups were 16.2%, 16.3%, 6.8%, 12.8%, and 4.8%; Pearson χ2=110 p Conclusions Among patients in the 2012 SNAPSHOT ACS study, non-ACS diagnoses characterised by high rates of elevated troponin levels had high mortality rates similar to those diagnosed with ACS. Therapies known to be effective in ACS patients, including early invasive management, should be examined in these non-ACS patients with troponin elevations within adequately powered randomised trials.

BACKGROUND Protocols incorporating high-sensitivity troponin to guide decision making in the disposition of patients with suspected acute coronary syndromes (ACS) in the emergency department have received a lot of attention. Traditionally, patients with chest pain have required long periods of observation in emergency department before being deemed safe for discharge. In an era of limited health service resources, a protocol that could discharge patients safely within an hour of presentation is extremely attractive. Unfortunately, despite incorporation into some guidelines, these protocols have not been subjected to randomized comparisons evaluating safety, effectiveness, and cost-effectiveness. OBJECTIVE This study is designed to provide the evidence required to allow key decision makers to implement these protocols: specifically, to provide evidence that a decision rule based on 0- and 1-hour high-sensitivity troponin T (hs-TnT) is safe, provides noninferior outcomes in all patients with suspected ACS, and that implementation of a rapid troponin protocol leads to efficient care. DESIGN This prospective pragmatic trial (n=5,400, 5 hospitals) randomly allocates patients with suspected ACS to either a 0/1-hour hs-TnT protocol as advocated in clinical guidelines, versus usual care of standard troponin reporting evaluated at 3 and 6hours. The primary effectiveness composite end points of this study are all-cause death and new/recurrent ACS within 30days. To evaluate cost-effectiveness, follow-up will determine clinical events, quality of life, and resource utilization within 12 months. SUMMARY Demonstrating that a 0/1-hour hs-TnT protocol improves the effectiveness and efficiency of care within a robust comparative study will fill an evidence gap that currently limits the translation of more precise hs-TnT testing into better patient and health service outcomes.

Background Patients with low and intermediate risk chest pain features comprise the greatest proportion presenting to emergency services for evaluation of suspected acute coronary syndromes (ACS). The efficient and timely identification of patients with these features remains a major challenge within clinical practice. Troponin assays are increasingly being used for the determination of risk among patients presenting with chest pain potentially facilitating more appropriate care. To date, no economic evaluation comparing high-sensitivity troponin T (hs-TnT) reporting to standard troponin T (c-TnT) reporting in the routine management of suspected ACS and based on longer-term clinical outcomes has been conducted. Methods and results An economic evaluation was conducted with 1937 participants randomized to either hs-TnT ( n =973) or c-TnT ( n =964) with 12month follow-up. The primary outcome measure was the number of cumulative combined outcomes of all-cause mortality and new or recurrent ACS avoided. Mean per participant Australian Medicare costs were higher in the hs-TnT arm compared to the c-TnT arm (by $1285/patient). Mean total adverse clinical outcomes avoided were higher in the hs-TnT arm (by 0.0120/patient) resulting in an incremental cost-effectiveness ratio (ICER) of $108,552/adverse clinical outcome avoided. An ICER of $49,030/adverse clinical outcome avoided was obtained when the analysis was restricted to patients below the threshold of normal Troponin testing (actual c-TnT levels Conclusions hs-TnT reporting leads to fewer adverse clinical events but at a high ICER. For the routine implementation of hs-TnT to be more cost-effective, substantial changes in clinical practice will be required. Clinical trial registration Australian New Zealand Clinical Trials Registry (ACTRN12614000189628). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365726

Background Non-infarct-related artery (non-IRA) disease is prevalent in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the impact of non-IRA disease on infarct size and clinical outcomes in patients with acute STEMI. Methods The Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP-AMI) trial randomized patients to intra-aortic balloon counterpulsation (IABC) vs no IABC prior to percutaneous coronary intervention in patients with acute STEMI. Infarct size (% left ventricular mass) at 3-5 days post percutaneous coronary intervention and 6-month clinical outcomes were compared between patients with and without non-IRA disease (defined as ≥50% stenosis in at least one non-IRA). Results A total of 324 (96.1%) patients had anterior STEMI, of whom 34.9% had non-IRA disease. There was no difference in infarct size (% left ventricular mass) between patients with and without non-IRA disease (median 39% vs 39%; P = .73). At 6 months, there was no difference in rates of recurrent myocardial infarction (0.9% vs 0.9%; P = .78), major Thrombolysis In Myocardial Infarction bleeding (0.9% vs 0.5%; P = .77), or all-cause death (3.5% vs 2.4%; P = .61) in patients with and without non-IRA disease, respectively. Patients with non-IRA disease had a higher rate of new/worsening heart failure with hospitalization (8.8% vs 1.9%; P = .0050). Conclusions More than one-third of patients with anterior STEMI in the CRISP-AMI study had non-IRA disease. These patients had similar infarct sizes and rates of recurrent myocardial infarction, major bleeding, and all-cause death. Patients with non-IRA disease did have a higher rate of new/worsening heart failure with hospitalization. Further study is needed to understand the mechanisms of outcomes of patients with non-IRA disease.

Variations in the delivery of evidence based care to high risk patients with Acute Coronary Syndromes (ACS) exist between hospitals. We hypothesised that the relative proportion of admitted high risk patients contributes to variation in care and outcomes.Receipt of evidence based therapies (EBT) according to patient risk was documented in the Australian Co-operative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE). Hospitals were stratified into quartiles (Q) by fraction of high risk patients according to: GRACE Risk Score (GRS), chronic kidney disease (CKD), age, Killip class, and myocardial infarction (MI). For each category, EBT and mortality were compared between hospital groups.This study included 8390 ACS patients from 39 hospitals. Patients with GRS130, CKD, and80years, were less likely to receive EBT at high proportion hospitals (p0.0001 for all). After adjustment, proportion of patients with CKD negatively predicted coronary angiography (CA) (Q4 vs Q1: OR 0.21, 95%CI 0.10-0.45). Adjusted 6month mortality was greater in CKD and trended greater in80years in hospitals treating the highest proportions of these patients (Q4 vs Q1 OR 3.80, 95%CI 1.85-7.83, and OR 3.10, 95%CI 0.99-9.70 respectively).Elderly ACS patients and those with CKD are less likely to receive EBT at hospitals seeing high proportions of these patients. Failure to provide EBT to these high risk populations may contribute to avoidable mortality in these institutions.

Background Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event. Methods/Design The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets. Conclusion This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.

Lifestyle changes are believed responsible for temporal trends of reduced population total cholesterol (TC), but it is uncertain whether this applies to patients with known coronary heart disease (CHD) often prescribed lipid lowering therapy (LLT). We studied temporal TC trends at presentation with acute coronary syndrome (ACS) to determine the contribution of LLT given for secondary prevention.TC and LLT were obtained in 5592 patients in annual surveys of ACS admissions in Australia between 1999 and 2013, and annual mean trends analysed by linear and segmented regression.TC declined from 5.13±1.1 to 4.53±1.2mmol/L (p0.001) and LLT (96% statin) use at presentation increased from 37.4% to 47.5% (p=0.005). TC decline was greater in those on LLT vs. those not on therapy, with LLT contributing to 57% of the TC decline. The decline in TC and increase in LLT use was non-linear and much steeper in those with, than without CHD history, and LLT contributed substantially more to the TC decline (79%, p0.001 vs. 27%, p=0.06 respectively). The rapid decline in TC and increase in LLT, plateauing after 2005 in those with CHD history differed markedly from trends in recent population studies, while TC trend for those without CHD history was slower, linear and consistent with population trends.Declining TC level at presentation for ACS was strongly associated with increasing LLT use in those with a history of CHD, indicating that increasing uptake of LLT for secondary prevention has impacted TC changes in the new millennium.

Background Although proof-of-concept for mobile health (mHealth) life-style programs targeting physical inactivity and overweight/obesity has been established in randomized trials, the feasibility and effect of a globally distributed, large-scale, mass-participation mHealth implementation has not been investigated. Objectives The purpose of this study was to determine the effect of Stepathlon, an international, low-cost, mass-participation mHealth intervention, on physical activity, sitting, and weight. Methods We prospectively collected cohort data from participants completing Stepathlon, an annual 100-day global event in 2012, 2013, and 2014. Participants were organized in worksite-based teams, issued pedometers, and encouraged to increase daily steps and physical activity as part of the team-based race. The program was conducted via an interactive multiplatform application available on mobile devices and the Internet. Analysis was performed according to a pre-specified plan. Results A total of 69,219 subjects participated (481 employers, 1,481 cities, 64 countries, all populated continents, age 36 ± 9 years, 23.9% female, 8.0% high-income countries, and 92.0% lower-middle income countries). After Stepathlon completion, participants recorded improved step count (+3,519 steps/day; 95% confidence interval [CI]: 3,484 to 3,553 steps/day; p Conclusions Distributed mHealth implementation of a low-cost life-style intervention is associated with short-term, reproducible, large-scale improvements in physical activity, sitting, and weight. (Effect of the Stepathlon Pedometer Program on Physical Activity, Weight and Well-Being; ACTRN12615001310550 )

Background Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is associated with a requirement for dialysis, a longer stay in the intensive care unit, a longer hospital length of stay, and mortality. An oxygenator arterial outlet temperature greater than 37°C has been reported to be associated with AKI; however, the influence of other rewarming temperatures is unclear. Using multicenter registry data, this study aimed to evaluate the role of CPB rewarming temperatures on AKI. Methods Data from 8,407 adult patients undergoing coronary artery bypass grafting (CABG) or valve repair or replacement, or a combination, were collected using the Perfusion Downunder Collaborative Database. Primary variables of interest were rewarming temperatures, defined as cumulative time the oxygenator arterial outlet temperature was greater than 36°C, greater than 36.5°C, or greater than 37°C. Propensity scores were calculated to determine the predicted probability of hyperthermic perfusion (rewarming temperature >37°C). The influence of temperature on AKI was determined using separate multivariate models adjusting for propensity score in the entire cohort (n = 6,904) and in propensity-matched patients (n = 2,044). Results Overall, 11.8% of patients acquired AKI. The duration of rewarming temperature greater than 36°C or 36.5°C was not associated with AKI. The duration of rewarming temperature greater than 37°C (hyperthermic perfusion) was independently associated with RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) risk classification or greater (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.09–1.77; p = 0.012) and injury classification or greater AKI (OR, 1.52; 95% CI, 1.09–1.97; p = 0.016) in the entire cohort, and injury classification or greater AKI (OR, 1.51; 95% CI, 1.15–1.90; p = 0.006) in propensity-matched patients. Conclusions The duration of hyperthermic perfusion—rewarming temperature greater than 37°C—was an independent predictor of AKI. Avoidance of hyperthermic perfusion may be more beneficial in reducing AKI than avoidance of rewarming.

Hospitalization for atrial fibrillation (AF) is a large and growing public health problem. We examined current trends in the incidence, prevalence, and associated mortality of first-ever hospitalization for AF.Linked hospital admission data were used to identify all Western Australia residents aged 35-84 years with prevalent AF and incident (first-ever) hospitalization for AF as a principal or secondary diagnosis during 1995-2010.There were 57,552 incident hospitalizations, mean age 69.8 years, with 41.4% women. Over the calendar periods, age- and sex-standardized incidence of hospitalization for AF as any diagnosis declined annually by 1.1% (95% CI; 0.93, 1.29), while incident AF as a principal diagnosis increased annually by 1.2% (95% CI; 0.84, 1.50). Incident AF hospitalization was higher among men than women, and 15-fold higher in the 75-84 compared with 35-64 year age group. The age- and sex-standardized prevalence of AF increased annually by 2.0% (95% CI; 1.88, 2.03) over the same period. Comorbidity trends were mixed with diabetes and valvular heart disease increasing, and hypertension, coronary artery disease, heart failure, cerebrovascular disease, and chronic kidney disease decreasing. The 1-year all-cause mortality after incident AF hospitalization declined from 17.6% to 14.6% (trend P0.001), with an adjusted hazard ratio of 0.86 (95% CI; 0.81, 0.91).This contemporary study shows that incident AF hospitalization is not increasing except for AF as a principal diagnosis, while population prevalence of hospitalized AF has risen substantially. The high 1-year mortality following incident AF hospitalization has improved only modestly over the recent period.

Low-range troponin elevations without clear coronary manifestations remain a major diagnostic challenge. We sought to determine if troponin velocity could allow for early identification of patients without an obvious cardiac diagnosis and who are at increased risk for cardiac-specific events.All patients presenting to South Australian public hospitals between 1 September 2011 and 30 September 2012, with at least two troponin measurements during the first 6h after ED presentation were included. Diagnoses were classified as 'coronary', 'non-coronary cardiac', and 'non-cardiac' using the International Classification of Diseases 10 codes. The relationship between troponin velocity and cardiac-specific mortality and combined cardiac outcome (death and myocardial infarction) was assessed using Fine and Gray competing risk models in patients with an initial troponin52 ng/L. Sensitivity analyses were performed using different initial and maximum troponin cut-off values. In total, 7300 patients were identified. A troponin velocity of 2.5 ng/L/h or greater in the non-cardiac (n=2793) patient group was significantly associated with an increased risk for 12-month cardiac mortality (sub-hazard ratio [SHR] 2.90, 95% CI 1.33-6.34) and combined cardiac outcome (SHR 2.08, 95% CI 1.01-4.27). This association was consistent for coronary (n=3835) and non-coronary cardiac (n=672) patient groups, and remained after sensitivity analyses.The significant association observed across all patient groups suggests that troponin velocity could be used for early risk stratification of patients with low-range troponin elevations without clear cardiac symptoms. These results may help guide future clinical trials aimed at assessing the utility of cardiac-targeted interventions in this challenging patient population.

Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited.We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events.The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction.

Background As there are limited data evaluating "clinical intuition" in risk prediction among acute coronary syndromes (ACS) patients. We evaluated the relationship between perceived and "scored" risk in ACS patients, and their association with care and outcome. Methods and results Within a prospective multi-center international ACS study from 58 hospitals in Australia, China, India and Russia enrolling patients between May 2009 and February 2011, at least 2 physicians involved in each patient's care estimated the patient's untreated risk, and the change in risk with invasive management. The association between clinical factors and physician perceived risk was assessed with multilevel mixed-effects regression models. Risk underestimation was defined as when physician-predicted risk was lower than GRACE score calculated risk and was used to compare clinical care and 6month mortality. In total, 1542 patients and 4230 patient-specific physicians' estimates were obtained. By 6months 48/1542 (3.1%) of patients had died compared with an estimated rate of 2.5% with full treatment. Advanced age, hypotension, tachycardia and ST changes on ECG were associated with increased perceived risk, while female gender was associated with lower perceived risk. Clinician risk underestimation was associated with less guideline therapy and higher 6-month mortality (not underestimated: 10/967 (1.0%) vs. one physician underestimated: 25/429 (5.8%) vs. all physician's underestimated: 13/146 (8.9%), any underestimation vs. no underestimation adjusted OR: 6.0 [95% CI: 2.3–15.5, p Conclusions Clinical risk prediction using established risk characteristics is not consistently observed in clinical practice. Studies evaluating the implementation and outcomes associated with objective risk prediction are warranted.

Background We report the findings of the SOURCE-ANZ registry of the clinical outcomes of the Edwards SAPIEN™ Transcatheter Heart Valve (THV) in the Australian and New Zealand (ANZ) clinical environment. Methods This single arm registry of select patients treated in eight centres, represent the initial experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by transfemoral (TF) and transapical (TA) access. Results The total enrolment for the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female: 34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and with procedural success (successful implant without conversion to surgery or death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly different between TF and TA implants. These included one year mortality of 13.6% (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12), pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication of 4.6% (TF) and 5.0% (TA) (p=0.91). Conclusion TAVI in the ANZ clinical environment has demonstrated excellent outcomes for both the TA and TF approaches in highly selected patients. These results are consistent with those demonstrated in European, Canadian registries and the pivotal US clinical trials. ACTRN12611001026910.

Background The high diagnostic accuracy of adenosine stress cardiac magnetic resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity and specificity, is well documented. Prognostic data, particularly in non-low risk study populations and for greater than 12months of follow up, is however lacking or variable in its findings. We present prognostic data, in an intermediate cardiovascular risk cohort undergoing adenosine stress perfusion CMR, over approximately 2years of follow up. Methods The study population comprised 362 patients referred for a clinically indicated stress CMR and included patients with proven coronary artery disease (CAD; n=157) or unknown CAD status, yet an intermediate cardiovascular risk profile (n=205). Perfusion imaging was performed at stress (adenosine 140μg/kg/min) and rest on a 1.5T system. Patient records and state-wide hospital databases were reviewed. Major adverse cardiac events — death, myocardial infarction, revascularisation or ischaemic hospitalisation — were evaluated over a median follow up of 22months. Results Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also negative for late gadolinium enhancement, and in this group MACE was encountered in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%. Conclusions In patients with confirmed coronary artery disease or at intermediate risk for cardiovascular events, a negative stress perfusion CMR is associated with an excellent prognosis over nearly 2years of follow up.

Introduction Microvascular obstruction (MVO) following ST-segment elevation myocardial infarction (STEMI) is associated with larger infarct size and an increased mortality. Although angiographic predictors of MVO in primary percutaneous coronary intervention (primary-PCI) setting have been identified, an earlier and objective "in-lab" predictor may be beneficial, in order to potentially influence therapies administered during primary-PCI. We hypothesised that intracoronary-electrocardiogram (IC-ECG) is a simple, objective and accurate predictor of MVO evaluated by cardiac magnetic resonance (CMR) and is comparable to myocardial blush grade (MBG) and TIMI myocardial perfusion grade (TMPG). Method Intracoronary ECG was performed during primary-PCI. Intracoronary ST-segment measurement was performed before and immediately after opening of infarct-related-artery. Intracoronary ST-segment resolution (IC-STR) was defined as ≥1mm improvement compared to baseline. Contrast enhanced CMR was performed at 4 and 90days post primary-PCI. Primary endpoint was MVO on late gadolinium hyperenhancement assessed by CMR at day 4. Results Sixty-four consecutive patients (age 59±11years; 55 males) were recruited. Intracoronary ST-segment resolution correlated with MVO (p=0.005). Furthermore, IC-STR correlated with infarct-mass, non-viable-mass, peak creatinine kinase and end-systolic-volume at day 4. Intracoronary ST-segment resolution also correlated with favourable left ventricular end-diastolic-volume at day 90 (p=0.022). On multivariate analysis, IC-STR was an independent predictor of MVO. Conclusion Intracoronary ST-segment resolution is a strong in-lab predictor of MVO assessed 4days after STEMI on CMR. Furthermore, IC-STR correlates with infarct size and left ventricular remodelling at 3months. Further studies are required to understand potential clinical utility of this tool.

The evidence-base informing the management of acute coronary syndromes (ACS) is substantial and now encapsulated in numerous local and international clinical practice guidelines. These guidelines have sought to assimilate this evidence into carefully crafted and robustly debated practice recommendations representing the foundation of modern ACS care. [1–5] Yet, registries of Australian and New Zealand clinical practice continue to demonstrate evidence of incomplete clinical care and sub-optimal clinical outcomes among many patients presenting with ACS. [6–10] Disappointingly, sequential registries spanning nearly a decade of clinical experience continue to show significant challenges in the provision of reperfusion for ST segment elevation MI, variation in rates of angiography in non-ST elevation ACS, incomplete utilisation of secondary prevention therapies and low rates of referral to cardiac rehabilitation. This inertia in the evolution of clinical practice suggests that elements beyond physician ‘‘knowledge of the evidence’’ are at play in compromising the optimal adherence to guideline recommended care. Such factors may include