Direct Oral Anticoagulation Versus Warfarin in Left Ventricular Thrombus: Pooled Analysis of Randomized Controlled Trials.

Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization. Conventional treatment with vitamin K antagonists (VKAs; e.g., warfarin) puts patients at risk of bleeding, and the use of direct oral anticoagulants (DOACs) appears promising, although data are scant. We searched the published English language literature for randomized controlled trials (RCTs) comparing DOACs with VKAs in LV thrombus. End points were failure to resolve, thromboembolic events (stroke, embolism), bleeding, or any adverse event (composite of thromboembolism or bleeding), or all-cause death. Data were pooled and analyzed in hierarchical Bayesian models. In three eligible RCTs, 141 patients were studied during an average of 4.6 months (53.8 patient-years; n = 71 assigned to DOAC, n = 70 assigned to VKA). A similar number of patients in each treatment arm demonstrated failure to resolve (DOAC: 14/71 vs. VKA: 15/70) and death events (3/71 vs. 4/70). However, patients on DOACs suffered fewer strokes/thromboembolic events (1/71 vs. 7/70; log odds ratio [OR], -2.02 [95% credible interval (CI95 ), -4.53 to -0.31]) and fewer bleeding events (2/71 vs. 9/70; log OR, -1.62 [CI95 , -3.43 to -0.26]), leading to fewer patients on DOACs with any adverse event versus VKAs (3/71 vs. 16/70; log OR, -1.93 [CI95 , -3.33 to -0.75]). In conclusion, pooled analysis of RCT data favors DOACs over VKAs in patients with LV thrombus in terms of both efficacy and safety.

Aortic valve replacement rates in Australia from 2004 to 2019.

BACKGROUND: Several surgical and percutaneous treatments are available for patients with aortic valve disease. AIM: To establish whether trends in aortic valve replacements (AVR) in Australia reflect recent evidence. METHODS: Using the Australian Institute of Health and Welfare data, this study calculated all AVR and balloon aortic valvuloplasty (BAV) procedures conducted in all Australian hospitals from 2004 to 2019. Linear regression analysis was performed to determine whether age-adjusted rates had changed over the study period. RESULTS: There were 80 883 AVR performed. Of these, 66% were men and 64% were aged >70 years. Absolute rates of AVR increased from 3631 to 7277 with a significant 22% age-adjusted rise seen (1.9% increase per year (+0.26 per 100 000 per year; 95% confidence interval 0.19-0.34); P < 0.001). This trend was more pronounced in men than women and in those aged >80 years (+0.23 per 100 000 per year; P < 0.001). Proportion of mechanical AVR implanted fell from 38.4% to 8.6% (P < 0.001). A total of 2683 transcatheter aortic valve implantation (TAVI) procedures was performed in 2019, representing a 52% annual increase from 2014. BAV increased from 66 procedures in 2004 to 862 in 2019. CONCLUSION: Rates of AVR have increased significantly over the past 16 years, particularly in the elderly. Despite international guideline recommendations, fewer mechanical AVR are being used in younger cohorts. The uptake in TAVI rates might reflect evidence that suggests it is a safe alternative, at least in the medium term. BAV has also seen a resurgence during this time period.

Mind The Gap, Aboriginal and Torres Strait Islander Cardiovascular Health: A Narrative Review.

Australia's First Nations Peoples, Aboriginal and Torres Strait Islanders, have reduced life expectancy compared to the wider community. Cardiovascular diseases, mainly driven by ischaemic heart disease, are the leading contributors to this disparity. Despite over a third of First Nations Peoples living in New South Wales, the bulk of the peer-reviewed literature is from Central Australia and Far North Queensland. Regardless of the site of publication, First Nations Peoples are significantly younger at disease onset and have higher rates of comorbidities, in turn driving adverse health events. On top of this, very few First Nations Peoples specific cardiovascular interventions or programs have been shown to improve outcomes. The traditional biomedical model of care is less efficacious and non-traditional models of communication such as clinical yarning may benefit both clinicians and patients. The key purpose of this review is to highlight the deficiencies of our knowledge of cardiovascular burden of disease for First Nations Peoples; and to serve as a catalyst for more dedicated research. We need to have relationships with communities and concentrate on community improvement and partnerships. By involving First Nations Peoples researchers in collaboration with local communities in all levels of health care design and intervention will improve outcomes.

Patient characteristics, short-term and long-term outcomes after incident heart failure admissions in a regional Australian setting.

AIMS: This study aims to (1) define the characteristics of patients with a first admission for heart failure (HF), stratified by type (reduced (HFrEF) vs preserved (HFpEF) ejection fraction) in a regional Australian setting; (2) compare the outcomes in terms of mortality and rehospitalisation and (3) assess adherence to the treatment guidelines. METHODS: We identified all index hospitalisations with HF to John Hunter Hospital and Tamworth Rural Referral Hospital in the Hunter New England Local Health District over a 12 months. We used the recent Australian HF guidelines to classify HFrEF and HFpEF and assess adherence to guideline-directed therapy. The primary outcome of the study was to compare short-term (1 year) and long-term all-cause mortality and the composite of all-cause hospitalisation or all-cause mortality of patients with HFrEF and HFpEF. RESULTS: There were 664 patients who had an index HF admission to John Hunter and Tamworth hospitals in 2014. The median age was 80 years, 47% were female and 22 (3%) were Aboriginal. In terms of HF type, 29% had HFrEF, 37% had HFpEF, while the remainder (34%) did not have an echocardiogram within 1 year of admission and could not be classified. The median follow-up was 3.3 years. HFrEF patients were predominantly male (64%) and in 48% the aetiology was ischaemic heart disease. The 1-year all-cause mortality was 23% in HFpEF subgroup and 29% in HFrEF subgroup (p=0.15). Five-year mortality was 61% in HFpEF and HFrEF patients. Of the HFrEF patients, only 61% were on renin-angiotensin-aldosterone blockers, 74% were on ß-blockers and 39% were on aldosterone antagonist. CONCLUSION: HF patients are elderly and about evenly split between HFrEF and HFpEF. In this regional cohort, both HF types are associated with similar 1-year and 5-year mortality following incident HF hospitalisation. Echocardiography and guideline-directed therapies were underused.

Absorbable Suture Embolization in Distal Coronary Perforation.

Coronary artery perforation is a rare but serious complication during percutaneous coronary intervention. Distal or small vessel perforation is usually treated by coil, fat, or microsphere embolization. We describe 5 cases of distal coronary perforation that were managed successfully by a novel technique that uses absorbable sutures. (Level of Difficulty: Advanced.).

Natural history and prognostic implications of left ventricular end-diastolic pressure in reperfused ST-segment elevation myocardial infarction: an analysis of the thrombolysis in myocardial infarction (TIMI) II randomized controlled trial.

BACKGROUND: The aim of the current study is to assess the natural history and prognostic value of elevated left ventricular end-diastolic pressure (LVEDP) in patients with ST-segment elevation myocardial infarction (STEMI) after reperfusion with thrombolysis; we utilize data from the Thrombolysis in Myocardial Infarction (TIMI) II study. METHODS: A total of 3339 patients were randomized to either an invasive (n = 1681) or a conservative (n = 1658) strategy in the TIMI II study following thrombolysis. To make the current cohort as relevant as possible to modern pharmaco-invasively managed cohorts, patients in the invasive arm with TIMI flow grade ≥ 2 (N = 1201) at initial catheterization are included in the analysis. Of these, 259 patients had a second catheterization prior to hospital discharge, and these were used to define the natural history of LVEDP in reperfused STEMI. RESULTS: The median LVEDP for the whole cohort was 18 mmHg (IQR: 12-23). Patients were divided into quartiles by LVEDP measured during the first cardiac catheterization. During a median follow up of 3 (IQR: 2.1-3.2) years, quartile 4 (highest LVEDP) had the highest incidence of mortality and heart failure admissions. In the cohort with paired catheterization data, the LVEDP dropped slightly from 18 mmHg (1QR: 12-22) to 15 mmHg (IQR: 10-20) (p = 0.01) from the first to the pre-hospital discharge catheterization. CONCLUSIONS: LVEDP remains largely stable during hospitalisation post-STEMI. Elevated LVEDP is a predictor of death and heart failure hospitalization in STEMI patients undergoing successful thrombolysis.

Heart failure outcomes in Aboriginal and Torres Strait Islander peoples in the Hunter New England region of New South Wales.

Background Aboriginal and Torres Strait Islander suffer poor health outcomes, driven predominately by cardiovascular disease. Previous work has focused on remote communities although majority of Aboriginal and Torres Strait Islander patients live in urban New South Wales. We describe the heart failure characteristics and outcomes of the Aboriginal and Torres Strait Islander patients in Hunter New England Health, New South Wales, Australia. Methods A large retrospective, multi-centre cohort study from 2007 till 2016 in a geographically diverse Local Health District. The primary outcomes were all-cause mortality and all-cause readmission. The Aboriginal and Torres Strait Islander cohort was described by demographics, locality, and outcomes relative to the non-Indigenous patients from the same time period. Findings During the study period there were 20,480 index admissions, of which 3.1% identified as Aboriginal and/or Torres Strait Islander. Aboriginal and Torres Strait Islander people admitted were younger by an average of 15 years (81 vs 66 years, p < 0.001), were more likely to live in a non-metropolitan locality (80 vs 61%, p < 0.001). Once adjustments were made for age, there was no significant difference in all-cause mortality. Indigenous status was a strong predictor of readmission on multivariate analysis, hazard ratio of 1.31 (p < 0.001). Interpretation Aboriginal and Torres Strait Islander patients, compared to non-Indigenous patients, who are admitted with heart failure are younger, more commonly live in rural localities and suffer from a higher burden of comorbidities. Once adjustments are made for age and co-morbidities, indigenous status does not portend a worse outcome.

Calcium/Calmodulin-Dependent Protein Kinase II Delta Inhibition and Ventricular Remodeling After Myocardial Infarction: A Randomized Clinical Trial.

Importance: After anterior ST-segment elevation myocardial infarction (STEMI), left ventricular (LV) remodeling results in heart failure and death. Calcium/calmodulin-dependent protein kinase II delta (CaMKIId) is a key molecular mediator of adverse LV remodeling. Objective: To determine whether NP202, an orally active inhibitor of CaMKIId, prevents LV remodeling in patients after anterior STEMI with early residual LV dysfunction. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled multicenter clinical trial of NP202 vs placebo in patients after primary percutaneous coronary intervention (PCI) for anterior STEMI was performed from November 19, 2015, to August 1, 2018. The study was performed at 32 sites across the US, Australia, and New Zealand. Patients presenting with anterior STEMI who underwent PCI within 12 hours of symptom onset and left ventricular ejection fraction (LVEF) less than 45% on screening echocardiogram 48 hours after primary PCI were included in the study. Baseline cardiovascular magnetic resonance (CMR) imaging was performed within 5 days of the STEMI and before administration of the study drug. Follow-up CMR was performed after 3 months. Data were analyzed from November 19, 2015, to August 1, 2018. Interventions: Patients were randomly assigned to NP202, 1000 mg, daily for 3 months vs corresponding placebo. Main Outcomes and Measures: The primary end point was change in LV end-systolic volume index (LVESVi) on CMR. Secondary end points were change in LV end-diastolic volume index, change in LVEF, change in infarct size, and change in diastolic function. Safety and tolerability were also assessed. Results: A total of 147 patients (mean [SD] age, 58 [11] years; 129 men [88%]; 130 White patients [88%]) who experienced anterior STEMI treated with primary PCI were randomized to receive NP202 (73 [49.7%]) or placebo (74 [50.3%]). Baseline LVEF was similar between groups. At baseline, patients randomized to NP202 had greater LVESVi (48.2 mL/m2) than that in the placebo group (41.3 mL/m2; P = .03). However, the groups were otherwise well matched. For the primary end point of change in LVESVi from baseline to 3 months, there was no significant difference between the placebo (median [interquartile range] change, -0.60 [-9.28 to 5.99] mL/m2) and NP202 groups (-3.53 [-9.24 to 4.81] mL/m2) (P = .78). There was also no difference in the secondary efficacy end points assessed by CMR. NP202 was well tolerated and demonstrated an acceptable safety profile. Major adverse cardiac and cerebrovascular event rates were similar between groups. Two deaths occurred in each group during the follow-up period. Conclusions and Relevance: Three months of treatment with NP202 after primary PCI for anterior STEMI with residual LV dysfunction did not improve LV remodeling. The drug was safe and well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT02557217.

Impact of Delay in Surgery on Outcome in Patients Undergoing Cardiac Revascularisation Surgery.

BACKGROUND: Diagnosis of critical coronary artery disease, including after acute coronary syndrome presentation (ACS), represents an important indication for early coronary artery bypass graft (CABG) surgery. The study aims to investigate the influence of time from diagnosis to CABG on outcomes and document barriers to early revascularisation. METHODS: All patients 18 years and older with an acute presentation due to ACS or critical coronary artery disease who were considered to require urgent inpatient cardiac surgery between January 2016-February 2019 were included in the study. The primary endpoints were 30-day all-cause mortality or readmission, 1-year all-cause mortality, all-cause readmission. The secondary endpoint was the rate of complications while waiting for surgery. The time duration between diagnostic coronary angiography and surgery was considered as the time interval. RESULTS: Of 266 eligible patients, 251 underwent surgical revascularisation with 15 (6%) not undergoing surgery due to preoperative complications (n=12) or due to perceived prohibitively high surgical risk (n=3). The majority (85%) were male (mean age 67 years), 37% of patients had diabetes and 71% had hypertension. Non-ST elevation myocardial infarction was documented in 51% of the patients. The median time between diagnosis and inpatient CABG was 7 days (IQR 5-11). Thirty-five per cent (35%) of patients experienced complications while awaiting surgery. Of the 266 patients, 140 patients (53% - cohort 1) underwent surgery within 7 days. The cohort 1 rate of complications was lower than in cohort 2 (surgery after 7 days) (24 vs 47%, p<0.001). Moreover, 1-year mortality was less in cohort 1 (2 vs 8%, p=0.029). CONCLUSION: In patients requiring urgent inpatient CABG, delay for more than 7 days is associated with a higher rate of in-hospital complications and worse 30 day and 12-month outcomes.

Pulmonary Hypertension Due to Left Heart Disease: Diagnosis, Pathophysiology, and Therapy.

Pulmonary hypertension (PH) due to left heart disease (LHD) is the most common type of PH and is defined as mean pulmonary artery systolic pressure of >20 mm Hg and pulmonary capillary wedge pressure >15 mm Hg during right heart catheterization. LHD may lead to elevated left atrial pressure alone, which in the absence of intrinsic pulmonary vascular disease will result in PH without changes in pulmonary vascular resistance. Persistent elevation in left atrial pressure may, however, also be associated with subsequent pulmonary vascular remodeling, vasoconstriction, and an increase in pulmonary vascular resistance. Hence, there are 2 subgroups of PH due to LHD, isolated postcapillary PH and combined post- and precapillary PH, with these groups have differing clinical implications. Differentiation of pulmonary arterial hypertension and PH due to LHD is critical to guide management planning; however, this may be challenging. Older patients, patients with metabolic syndrome, and patients with imaging and clinical features consistent with left ventricular dysfunction are suggestive of LHD etiology rather than pulmonary arterial hypertension. Hemodynamic measures such as diastolic pressure gradient, transpulmonary gradient, and pulmonary vascular resistance may assist to differentiate pre- from postcapillary PH and offer prognostic insights. However, these are influenced by fluid status and heart failure treatment. Pulmonary arterial hypertension therapies have been trialed in the treatment with concerning results reflecting disease heterogeneity, variation in inclusion criteria, and mixed end point criteria. The aim of this review is to provide an updated definition, discuss possible pathophysiology, clinical aspects, and the available treatment options for PH due to LHD.

Heparin Administration, but Not Myocardial Ischemia or Necrosis, Leads to Midkine Elevation.

Midkine (MK) is a heparin-binding growth factor, whose role as a biomarker of coronary artery disease, myocardial ischaemia and necrosis has not been well measured. This study quantified serial MK levels in patients undergoing coronary angiography (CA) and identified factors associated with MK. In this single-centre, parallel cohort study, forty patients undergoing CA had arterial samples collected prior, 10 and 20 min after heparin administration. Four groups were examined: 1-stable coronary artery disease (CAD) without percutaneous coronary intervention (PCI); 2-stable CAD for elective PCI; 3-non-ST elevation myocardial infarction (NSTEMI) with or without PCI; 4-ST elevation myocardial infarction (STEMI) with primary PCI. Groups 1, 2 and 4 were heparin naïve, allowing assessment of the effects of myocardial necrosis between baseline levels; group 3 had received low-molecular-weight heparin. MK levels were analysed by ELISA. Median MK at baseline did not differ between groups, demonstrating that myocardial ischaemia or necrosis does not affect MK levels. Heparin administration had an immediate effect on median MK at 10 min, showing an average 500-fold increase that is dose-dependent (R2 = 0.35, p = 0.001). Median MK levels remained elevated at 20 min following heparin administration. Multivariate analysis showed that the estimated glomerular filtration rate (eGFR) was the only predictor of elevated baseline MK (p = 0.02). Baseline MK did not correlate with high-sensitivity troponin-I (HsTnI) taken just before CA (p = 0.97), or peak HsTnI during admission (p = 0.74). MK is not a reliable marker of myocardial ischaemia or necrosis. MK increased significantly in all patients following heparin administration in a dose-dependent manner.

Targeting elevated left ventricular end-diastolic pressure following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction - a phase one safety and feasibility study.

INTRODUCTION: Elevated left ventricular end diastolic pressure (LVEDP) is an independent predictor of mortality and heart failure in patients with ST-segment elevation myocardial infarction (STEMI). Whether lowering elevated LVEDP improves outcomes remains unknown. METHODS: This non-randomized, single blinded study with prospective enrolment and sequential group allocation recruited patients undergoing primary percutaneous coronary intervention for STEMI with LVEDP ⩾ 20 mmHg measured immediately after primary percutaneous coronary intervention. The intervention arm (n=10) received furosemide 40 mg intravenous bolus plus escalating doses of glyceryl trinitrate (100 µg per min to a maximum of 1000 µg) during simultaneous measurement of LVEDP. The control group (n=10) received corresponding normal saline boluses with simultaneous measurement of LVEDP (10 readings over 10 min). Efficacy endpoints were final LVEDP achieved, and the dose of glyceryl trinitrate needed to reduce LVEDP by ⩾ 20%. Safety endpoint was symptomatic hypotension (systolic blood pressure < 90 mmHg). RESULTS: From 1 April 2017 to 23 August 2017 we enrolled 20 patients (age: 64±9 years, males: 60%, n=12, anterior STEMI: 65%, n=13). The mean LVEDP for the whole cohort (n=20) was 29±4 mmHg (intervention group: 28±3 mmHg vs. control group: 31±5 mmHg; p=0.1). The LVEDP dropped from 28±3 to 16±2 mmHg in the glyceryl trinitrate + furosemide group (p <0.01) but remained unchanged in the control group. The median dose of glyceryl trinitrate required to produce ⩾ 20% reduction in LVEDP in the intervention group was 200 µg (range: 100-800). One patient experienced asymptomatic decline in systolic blood pressure to below 90 mmHg. There was no correlation between LVEDP and left ventricular ejection fraction. CONCLUSION: The administration of glyceryl trinitrate plus furosemide in patients with elevated LVEDP following primary percutaneous coronary intervention for STEMI safely reduces LVEDP.

Cognitive dysfunction is associated with abnormal responses in cerebral blood flow in patients with single ventricular physiology: Novel insights from transcranial Doppler ultrasound.

OBJECTIVES: Improvements in the management of complex congenital heart disease, including those with single ventricle physiology, have resulted in increased survival. As this population ages, the recognition of cognitive impairment is increasingly important. At present, little is known about the potential mechanisms of cognitive dysfunction. In this cross-sectional study, we aimed to characterize the nature of abnormalities in cerebral blood flow and the relationship to cognitive deficits in adults with single ventricular physiology. PATIENTS: Ten adults with single ventricular physiology (age 18-40 years) and 12 age- and gender-matched controls underwent transcranial Doppler ultrasound and accompanying cognitive assessment. OUTCOME MEASURES: Patients underwent neuropsychological testing that assessed differing cognitive domains, with subjective cognitive decline determined from a 24-question survey. Transcranial Doppler ultrasound was used to assess baseline cerebral blood flow as well as change in cerebral blood flow velocities from baseline and during cognitive testing. Age, ethnicity, individual, and parental education levels were considered in the multivariate analyses. RESULTS: On assessment of cognitive function, the patient group performed more poorly across each of the measured domains. The control group had a significantly greater increase in cerebral blood flow in response to cognitive stimuli compared to the patient cohort; these differences in response to cognitive stimuli were seen to a similar extent across each of the measured cognitive domains. CONCLUSION: Adults with Fontan physiology are underperforming in assessments of executive function with associated abnormalities in cerebral perfusion potentially contributing to cognitive deficits.

Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction.

INTRODUCTION: The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart. METHODS: Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-ß1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells. RESULTS: ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role. CONCLUSIONS: ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis.

Trends in the Incidence of First Acute Myocardial Infarction in Metropolitan and Regional Areas of the Hunter Region.

INTRODUCTION: There is conflicting information regarding the contemporary incidence of first acute myocardial infarction (AMI) in Australia. We sought to document the regional variations in first AMI incidence in a large health district. METHODS: We identified all patients presenting with first AMI in the Hunter region of New South Wales from 2004 to 2013. We calculated age and gender adjusted incidence of AMI and evaluated differences between patients from regional and metropolitan areas. We assessed 30-day and 12-month outcomes, including mortality, through linkage with the NSW Registry of Births Deaths and Marriages. RESULTS: The incidence of first AMI in regional areas was persistently higher throughout the study compared to metropolitan areas (IRR 1.244; 95% CI 1.14-1.35; p≤0.001). There were no significant differences between regional and metropolitan areas in 30-day and 12-month outcomes following presentation with first AMI. CONCLUSIONS: The study demonstrates persistently higher rates in regional compared to metropolitan areas, supporting the need for implementation of targeted intervention and prevention strategies.

Mortality and Readmission Following Hospitalisation for Heart Failure in Australia: A Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) is a common, costly condition with an increasing burden on Australian health care system resources. Knowledge of the burden of HF on patients and on the health system is important for resource allocation. This study is the first systematic review to estimate the mortality and readmission rates after hospitalisation for HF in the Australian population. METHODS: We searched for studies of HF hospitalisation in Australia published between January 1990 and May 2016, using a systematic search of PubMed, Medline, Scopus, Web of Science, EMBASE and Cochrane Library databases. Studies reporting 30-day and/or 1-year outcomes for mortality or readmission following hospitalisation were eligible and included in this study. RESULTS: Out of 2889 articles matching the initial search criteria, a total of 13 studies representing 67,255 patients were included in the final analysis. The pooled mean age of heart failure patients was 76.3 years and 51% were male (n=34,271). The pooled estimated 30-day and 1-year all-cause mortality were 8% and 25% respectively. The pooled estimated 30-day and 1-year all-cause readmission rates were 20% and 56% respectively. There is a high prevalence of comorbidities in heart failure patients. There were limited data on readmission and mortality in rural patients and Indigenous people. CONCLUSIONS: Heart failure hospitalisations in Australia are followed by substantial readmission and mortality rates.

Outcomes following heart failure hospitalization in a regional Australian setting between 2005 and 2014.

AIMS: The aim of the current study is to examine 10 year trends in mortality and readmission following heart failure (HF) hospitalization in metropolitan and regional Australian settings. METHODS AND RESULTS: We identified all index HF hospitalizations in the Hunter New England region from 2005 to 2014, using a 10 year 'look back' period. The primary endpoint was a composite of all-cause mortality or all-cause readmission at 1 year. Secondary endpoints included all-cause mortality, all-cause readmission, and HF readmission at 30 days and 1 year. We used logistic regression to explore the predictors of the composite outcome of either all-cause death or readmission at 1 year. There were 12 114 patients admitted with a first episode of HF between 2005 and 2014, followed up until death or the end of 2015. The mean age was 78 ± 12 years and 49% (n = 5906) were male. A total of 4831 (40%) resided in regional areas and the remainder in metropolitan areas. One hundred sixty-eight patients (1.4%) were Aboriginal. Approximately 69% of patients had either died or been readmitted for any cause within 12 months of their index event. The 30 day and 1 year all-cause mortality rates were 13% and 32%, respectively, with no change in the trend over the study period. Age, socio-economic disadvantage, ischaemic heart disease, renal failure, and chronic lower respiratory disease were predictors of the primary endpoint. CONCLUSIONS: Heart failure hospitalizations are followed by high rates of death or readmission. There was no change in this composite endpoint over the 10 year study period.

Clozapine and incidence of myocarditis and sudden death - Long term Australian experience.

BACKGROUND: Clozapine is the cornerstone of therapy for refractory schizophrenia; however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy. METHODS: All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol. RESULTS: A total of 503 patients with treatment-resistant schizophrenia were maintained on clozapine during the study period of which 93 patients (18%) discontinued therapy with 29 (6%) deaths. The incidence of sudden death and myocarditis were 2% (n=10) and 3% (n=14) respectively. Amongst patients with sudden death, 7 out of 10 (70%) were documented to have used illicit drugs prior to death, with a tendency to weight gain also noted. The mean time to myocarditis post clozapine commencement was 15±7days. The reduction in left ventricular ejection fraction in those with myocarditis was 11±2%. CONCLUSION: Myocarditis and sudden cardiac death are uncommon but clinically important complications in a cohort of patients followed while maintained on clozapine undergoing regular cardiac assessment. Further studies are required to document the role of preventive measures for left ventricular dysfunction and sudden cardiac death in this population.