Triglyceride-rich lipoprotein, remnant cholesterol, and apolipoproteins CII, CIII, and E in patients with schizophrenia.

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and ß-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, ß-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.

Healthcare exposures and associated risk of endocarditis after open-heart cardiac valve surgery.

BACKGROUND: Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE). METHODS: In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis. RESULTS: In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3-8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1-5.4), coronary angiogram (HR = 4.0, 95% CI 2.3-7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3-4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8-8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5-4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1-1.5, p = 0.002). CONCLUSIONS: The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.

Cardiovascular outcomes for people hospitalised with COVID-19 in Australia, and the effect of vaccination: an observational cohort study.

OBJECTIVES: To assess the frequency of clinical cardiovascular outcomes for people hospitalised with coronavirus disease 2019 (COVID-19), and the impact of vaccination. STUDY DESIGN: Observational cohort study. SETTING, PARTICIPANTS: All index admissions of adults with laboratory-confirmed COVID-19 to 21 hospitals participating in the Australian Cardiovascular COVID-19 Registry (AUS-COVID), 4 September 2020 - 11 July 2022. MAIN OUTCOME MEASURES: Frequency of elevated troponin levels, new arrhythmia, new or deteriorating heart failure or cardiomyopathy, new pericarditis or myocarditis, new permanent pacemaker or implantable cardioverter-defibrillator, and pulmonary embolism. SECONDARY OUTCOMES: impact of COVID-19 vaccination on likelihood of in-hospital death, intubation, troponin elevation, and clinical cardiovascular events. RESULTS: The mean age of the 1714 people admitted to hospital with COVID-19 was 60.1 years (standard deviation, 20.6 years); 926 were men (54.0%), 181 patients died during their index admissions (10.6%), 299 required intensive care (17.4%). Thirty-eight patients (2.6%) developed new atrial fibrillation or flutter, 27 (2.6%) had pulmonary embolisms, new heart failure or cardiomyopathy was identified in 13 (0.9%), and pre-existing cardiomyopathy or heart failure was exacerbated in 21 of 110 patients (19%). Troponin was elevated in 369 of the 986 patients for whom it was assessed (37.4%); in-hospital mortality was higher for people with elevated troponin levels (86, 23% v 23, 3.7%; P < 0.001). The COVID-19 vaccination status of 580 patients was known (no doses, 232; at least one dose, 348). The likelihood of in-hospital death (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.18-0.79) and intubation (aOR, 0.30; 95% CI, 0.15-0.61) were lower for people who had received at least one vaccine dose, but not the likelihood of troponin elevation (aOR, 1.44; 95% CI, 0.80-2.58) or clinical cardiovascular events (aOR, 1.56; 95% CI, 0.59-4.16). CONCLUSIONS: Although troponin levels were elevated in a considerable proportion of people hospitalised with COVID-19, clinical cardiovascular events were infrequent, and their likelihood was not influenced by vaccination. COVID-19 vaccination, however, was associated with reduced likelihood of in-hospital death and intubation. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12620000486921 (prospective).

Trends in Isolated Mitral Valve Repair or Replacement Surgery in Australia: A Statewide Cohort Linkage Study.

BACKGROUND: Global trends in mitral valve surgery (MVSx) suggest increasing repair compared with replacement, especially in the United States and European countries. The relative use, and outcomes of, MV repair and replacement in Australia are unknown. METHODS: New South Wales residents who underwent isolated MVSx between 2001 and 2017 were identified from the Admitted-Patient-Data-Collection database. Mortality outcomes were tracked to 31 Dec 2018 and adjusted based on age, sex, urgency of operation, and comorbidity status. RESULTS: The study cohort comprised 5,693 patients: 2020 (35%) underwent repair (MVr), 1,656 (29%) underwent mechanical replacement (mech.MVR), and 2017 (35%) underwent bioprosthetic replacement (bio.MVR). Respective median ages [interquartile range] were 67 yo [59-75 yo], 64 yo [55-71 yo], and 75 yo [68-80 yo] (p<0.001 across groups). Between 2001 and 2017, total MVSx increased steadily with population growth. Whereas the relative use of MVr remained static (34% to 38%), that for bio.MVR (22% to 50%) and mech.MVR (45% to 13%) changed significantly. MVr had the best outcome with 1.2% in-hospital, 2.5% 1-year, and 21.6% total cumulative mortality during a median follow-up of 6.5 years. Compared to MVr, the adjusted hazard ratio (aHR) for mech.MVR and bio.MVR for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) and 1.73 (95% CI=1.53-1.95), respectively. Heart failure and sepsis were the main cardiovascular and noncardiovascular causes of death in all groups. CONCLUSION: In this statewide Australian cohort examined over 17 years, MVr is potentially underutilised despite having superior outcomes to MVR. Access to quality dataset which provides the indication for MVSx and quantitative clinical factors is critical to further improve MVr coverage and outcome MVSx.

Identification of a Distinct Platelet Phenotype in the Elderly: ADP Hypersensitivity Coexists With Platelet PAR (Protease-Activated Receptor)-1 and PAR-4-Mediated Thrombin Resistance.

BACKGROUND: Thrombin (via PAR [protease-activated receptor]-1 and PAR-4) and ADP (via P2Y12 receptors) are potent endogenous platelet activators implicated in the development of cardiovascular disease. We aimed to assess whether platelet pathways alter with aging. METHODS: We characterized platelet activity in community-dwelling volunteers (n=174) in the following age groups: (1) 20 to 30 (young); (2) 40 to 55 (middle-aged); (3) ≥70 years (elderly). Platelet activity was assessed by aggregometry; flow cytometry (surface markers [P-selectin: alpha granule release, CD63: dense granule release, PAC-1: measure of conformationally active GPIIb/IIIa at the fibrinogen binding site]) measured under basal conditions and after agonist stimulation [ADP, thrombin, PAR-1 agonist or PAR-4 agonist]); receptor cleavage and quantification; fluorometry; calcium flux; ELISA. RESULTS: The elderly had higher basal platelet activation than the young, evidenced by increased expression of P-selectin, CD63, and PAC-1, which correlated with increasing inflammation (IL [interleukin]-1ß/IL-6). The elderly demonstrated higher P2Y12 receptor density, with greater ADP-induced platelet aggregation (P<0.05). However, elderly subjects were resistant to thrombin, achieving less activation in response to thrombin (higher EC50) and to selective stimulation of both PAR-1 and PAR-4, with higher basal PAR-1/PAR-4 cleavage and less inducible PAR-1/PAR-4 cleavage (all P<0.05). Thrombin resistance was attributable to a combination of reduced thrombin orienting receptor GPIbα (glycoprotein Ibα), reduced secondary ADP contribution to thrombin-mediated activation, and blunted calcium flux. D-Dimer, a marker of in situ thrombin generation, correlated with platelet activation in the circulation, ex vivo thrombin resistance, and circulating inflammatory mediators (TNF [tumor necrosis factor]-α/IL-6). CONCLUSIONS: Aging is associated with a distinctive platelet phenotype of increased basal activation, ADP hyperreactivity, and thrombin resistance. In situ thrombin generation associated with systemic inflammation may be novel target to prevent cardiovascular disease in the elderly.

Lifestyle changes and quality of life a year after attending Rapid Access Cardiology Clinics: an observational study.

We examined behavioural risk factors and quality of life (QoL) in women and men, younger and older adults 12 months after a Rapid Access Cardiology Clinic (RACC) visit. Routine clinical care data were collected in person from three Sydney hospitals between 2017 and 2018 and followed up by questionnaire at 365 days. 1491 completed the baseline survey, at 1 year, 1092 provided follow-up data on lifestyle changes, and 811 completed the EQ-5D-5L (QoL) survey. 666 (44.7%) were women, and 416 (27.9%) were older than 60 years of age. Almost 50% of participants reported improving physical activity and diet a year after their RACC visit. These changes were less likely in women and older participants.

Synchronous Carotid Endarterectomy and Anaortic Off-Pump Coronary Artery Bypass Surgery.

BACKGROUND: There is ongoing debate regarding the optimal strategy and timing for the surgical management of patients with severe concomitant carotid and coronary artery disease. Anaortic off-pump coronary artery bypass (anOPCAB), which avoids aortic manipulation and cardiopulmonary bypass, has been shown to reduce the risk of perioperative stroke. We present the outcomes of a series of synchronous carotid endarterectomy (CEA) and anOPCAB. METHODS: A retrospective review was performed. The primary endpoint was stroke at 30 days post-operation. Secondary endpoints included transient ischaemic attack, myocardial infarction and mortality 30 days post-operation. RESULTS: From 2009 to 2016, 1,041 patients underwent anOPCAB with a 30-day stroke rate of 0.4%. The majority of patients had preoperative carotid-subclavian duplex ultrasound screening and 39 were identified with significant concomitant carotid disease who underwent synchronous CEA-anOPCAB. The mean age was 71±7.5 years. Nine patients (23.1%) had previous neurological events. Thirty (30) patients (76.9%) underwent an urgent operation. For CEA, a conventional longitudinal carotid endarterectomy with patch angioplasty was performed in all patients. For anOPCAB, total arterial revascularisation rate was performed in 84.6% and the mean number of distal anastomoses was 2.9±0.7. In the 30-day postoperative period, there was one stroke (2.63%), two deaths (5.26%), two transient ischaemic attacks (TIAs) (5.26%) and no myocardial infarction. Two patients experienced acute kidney injury (5.26%), one of which required haemodialysis (2.63%). Mean length of stay was 11.37±7.9 days. CONCLUSION: Synchronous CEA and anOPCAB is a safe and effective option for patients' severe concomitant disease. Preoperative carotid-subclavian ultrasound screening allows identification of these patients.

Outcomes Following Triple Cardiac Valve Surgery Over 17-years: A Multicentre Population-Linkage Study.

INTRODUCTION: Studies have reported increasing triple valve surgery (TVS, defined as concomitant aortic, mitral and tricuspid valves surgery) incidence and improved postoperative survival. The epidemiology and outcome of TVS is not known in Australia. METHODS: From the Admission-Patient-Data-Collection registry, all New South Wales residents who underwent cardiac valve surgery between 1 July 2001 and 31 December 2018 were identified, with cause-specific mortality tracked from the death registry. RESULTS: Triple valve surgery comprised 1.2% (347/28,667 cases) of all valvular surgeries. Volumes rose from eight cases-per-annum in 2002 to a peak of 37 in 2012, and between 23 and 30 cases-per-annum since. Mean (±SD) age of study cohort (n=340 persons) was 68.2±15.2 years (50% male); 20.3% had concomitant coronary-artery-bypass-surgery (males vs females: 29.4% vs 11.2%, p<0.001). Main surgery on aortic and mitral valves was replacement (95.9% and 70.6% respectively). Tricuspid valve annuloplasty was performed in 90.6% of patients. Cumulative in-hospital, 180-day, and total mortality (mean follow-up=4.9±4.0 yrs) was 7.4%, 11.8% and 42.6%, respectively. Heart failure (24.0% in-hospital, 22.5% post-discharge) and sepsis (24.0% in-hospital, 20.0% post-discharge) were the main cause-specific deaths. There was no in-hospital stroke-related death. Age (median >72 yrs; hazard ratio [HR]=1.95, 95%CI=1.37-2.79), malignancy (HR=6.35, 95%CI=2.21-18.26), heart failure (HR=1.79, 95%CI=1.25-2.57) and chronic kidney disease (CKD) (HR=2.21, 95%CI=1.39-3.51) (all p<0.005) were independent predictors during intermediate-term follow-up. CONCLUSIONS: Triple valve surgery remains rare in Australia and is associated with high mortality. Multi-centred collaboration and access to comprehensive clinical data are required to identify the drivers of poor outcome.

When Cancer and Cardiovascular Disease Intersect: The Challenge and the Opportunity of Cardio-Oncology.

Cancer and cardiovascular disease (CVD) commonly coexist, with increasing evidence that long-term cancer survivors are more likely to die from CVD than the general population. Effective management of CVD and its risk factors requires identification of patients at increased risk who may benefit from early intervention and their appropriate monitoring across the disease trajectory. Improving outcomes requires new models of multidisciplinary cancer care supported by care pathways. Such pathways require a clear delineation of the roles and responsibilities of all team members and provision of appropriate enablers for their delivery. These include accessible point-of-care tools/risk calculators, patient resources, and the provision of tailored training opportunities for health care providers.

Artificial Intelligence in Cardiology: An Australian Perspective.

Significant advances have been made in artificial intelligence technology in recent years. Many health care applications have been investigated to assist clinicians and the technology is close to being integrated into routine clinical practice. The high prevalence of cardiac disease in Australia places overwhelming demands on the existing health care system, challenging its capacity to provide quality patient care. Artificial intelligence has emerged as a promising solution. This discussion paper provides an Australian perspective on the current state of artificial intelligence in cardiology, including the benefits and challenges of implementation. This paper highlights some current artificial intelligence applications in cardiology, while also detailing challenges such as data privacy, ethical considerations, and integration within existing health infrastructures. Overall, this paper aims to provide insights into the potential benefits of artificial intelligence in cardiology, while also acknowledging the barriers that need to be addressed to ensure safe and effective implementation into an Australian health system.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

Colchicine as a Modulator of Platelet Function: A Systematic Review.

The microtubule inhibitor and anti-inflammatory agent colchicine is used to treat a range of conditions involving inflammasome activation in monocytes and neutrophils, and is now known to prevent coronary and cerebrovascular events. In vitro studies dating back more than 50 years showed a direct effect of colchicine on platelets, but as little contemporary attention has been paid to this area, we have critically reviewed the effects of colchicine on diverse aspects of platelet biology in vitro and in vivo. In this systematic review we searched Embase, Medline, and PubMed for articles testing platelets after incubation with colchicine and/or reporting a clinical effect of colchicine treatment on platelet function, including only papers available in English and excluding reviews and conference abstracts. We identified 98 relevant articles and grouped their findings based on the type of study and platelet function test. In vitro, colchicine inhibits traditional platelet functions, including aggregation, clotting, degranulation, and platelet-derived extracellular vesicle formation, although many of these effects were reported at apparently supraphysiological concentrations. Physiological concentrations of colchicine inhibit collagen- and calcium ionophore-induced platelet aggregation and internal signaling. There have been limited studies of in vivo effects on platelets. The colchicine-platelet interaction has the potential to contribute to colchicine-mediated reduction in cardiovascular events, but there is a pressing need for high quality clinical research in this area.

Achieving lipid targets within 12 months of an acute coronary syndrome: an observational analysis.

OBJECTIVES: To assess lipid levels in people six or 12 months after hospitalisation with acute coronary syndrome (ACS); to identify factors associated with not achieving lipid level targets. DESIGN, SETTING: Retrospective cohort study; analysis of data from CONCORDANCE, an Australian ACS registry, 2009-2018. PARTICIPANTS: Adult patients who had experienced confirmed ACS of cardiovascular origin, for whom serum lipid levels had been assessed on admission and six or 12 months after discharge. MAIN OUTCOME MEASURES: Not achieving lipid targets by most recent follow-up (in order of priority: low-density lipoprotein cholesterol [LDL-C] ≤ 1.8 mmol/L or total cholesterol ≤ 4 mmol/L); factors associated with not achieving target lipid levels. RESULTS: Lipid levels measured at 6- or 12-month follow-up were available for 2671 of 10 578 people discharged from hospital alive; 1194 (45%) had not achieved lipid targets at their most recent follow-up, including 876 (73%) who had been prescribed intensive lipid-lowering therapy at discharge. People under 65 years of age, those using lipid-lowering therapy or with higher cholesterol levels on admission, patients prescribed fewer than four evidence-based therapies or not prescribed intensive lipid-lowering therapy on discharge, and women were more likely to not reach lipid level targets. CONCLUSION: Almost half the patients did not achieve target lipid levels within 12 months of an admission to hospital with ACS. These people are at elevated risk of recurrent cardiovascular disease, and therapy could be optimised (eg, dose escalation, drug combinations, novel therapies) to improve outcomes.

Comparison of P2Y12 Inhibitors in Acute Coronary Syndromes in the Australian Population.

BACKGROUND: Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces recurrent ischaemic events compared to aspirin alone. Further reductions in events have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit with increases in bleeding. There are few studies documenting the patterns of use of P2Y12 inhibitors or their association with outcomes in the Australian population. AIMS: To describe the patterns of use of each P2Y12 inhibitor and to determine the associations between initial P2Y12 inhibitor use and outcomes. METHODS: Data were extracted from Cooperative National Registry of ACS, Guideline Adherence and Clinical Events (CONCORDANCE)-a prospective database of patients presenting to 43 sites across Australia with ACS. Patients were stratified based on first antiplatelet agent received. Baseline clinical characteristics were compared between these patient groups and hospital investigations, management as well as in-hospital and 12 months outcomes (death, a composite of cardiac-related death, myocardial infarction, and stroke, and major bleeding) were compared between the three treatment cohorts after adjustment for differences in baseline characteristics. RESULTS: Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347) cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor 82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel 1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%, prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel 7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent after multivariable adjustment. There was no difference in outcomes between cohorts at 12 months. CONCLUSIONS: In Australia, ticagrelor and prasugrel are used in younger patients who are more likely to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy. Patients receiving clopidogrel were more likely to experience in hospital ischaemic or bleeding events but this was explained by their higher baseline risk. Selection of therapy was not associated with any difference in outcomes at 12-month follow-up, but our findings suggest there is room for improvement towards guideline-driven usage of P2Y12 inhibitors.

Rapid Access Chest Pain Clinics: An Australian Cost-Benefit Study.

OBJECTIVE: Chest pain is a large health care burden in Australia and around the world. Its management requires specialist assessment and diagnostic tests, which can be costly and often lead to unnecessary hospital admissions. There is a growing unmet clinical need to improve the efficiency and management of chest pain. This study aims to show the cost-benefit of rapid access chest pain clinics (RACC) as an alternative to hospital admission. DESIGN: Retrospective cost-benefit analysis for 12 months. SETTING: RACCs in three Sydney tertiary referral hospitals. MAIN OUTCOME MEASURES: Cost per patient. RESULTS: Hospitals A, B and C implemented RACCs but each operating with slightly different staffing, referral patterns, and diagnostic services. All RACCs had similar costs per patient of AUD$455.25, AUD$427.12 and AUD$474.45, hospitals A, B and C respectively, and similar cost benefits per patient of AUD$1,168.75, AUD$1,196.88 and AUD$1,149.55, respectively. At least 28%, 26% and 29% of these RACC patients for hospitals A, B, and C, respectively, would have otherwise had to have been admitted to hospital for the model to be cost-beneficial. CONCLUSION: This study shows that a RACC model of care is cost-beneficial in the state of NSW as an alternative strategy to inpatient care for managing chest pain. Scaling up to a national level could represent an even larger benefit for the Australian health system.

In Hospital Outcomes for High-Risk Percutaneous Coronary Intervention (PCI) in Patients Referred From a Rural Centre to Metropolitan Sites.

BACKGROUND: Cardiac Society of Australia and New Zealand (CSANZ) guidelines recommend elective high-risk percutaneous coronary intervention (PCI) is not performed in sites greater than 1 hour from cardiac surgery. METHODS: In hospital outcomes for all patients from Orange Health Service (OHS) from January 2017 to January 2020 who were transferred electively to tertiary centres in Sydney for high risk PCI were examined. RESULTS: One hundred and fourteen (114) patients were identified, with 1,259 PCIs performed at OHS over the same period without transfer. The mean age of these 114 patients was 71 years, with 74.6% male. Receiving hospitals were Royal Prince Alfred Hospital, Sydney, NSW (66.7%), Concord Repatriation General Hospital, Concord, NSW (19.3%) and Strathfield Private Hospital, Strathfield, NSW (14%). The definition of high risk and indication for transfer included at least one of: moderate or greater calcification of the target lesion or proximal segment (34%), single or multiple target lesions that in aggregate jeopardised over 50% of remaining viable myocardium (27%), degenerated saphenous vein grafts (14.8%), chronic total occlusions (7.0%) and severe left ventricular (LV) impairment (3.9%). American Heart Society/American College of Cardiology (AHA/ACC) lesion types were A (1%), B1 (4.2%), B2 (40.2%), and C (54.6%). PCI was performed via the femoral route in 96.2%. The mean procedure duration was 72 minutes, mean combined fluoroscopy time was 19 minutes and mean radiation dose as defined by Reference Air Kerma was 1,630 mGy. Complications occurred in 13 patients and were: acute vessel dissection requiring stenting (4), perforation (2), acute vessel closure (4), puncture site related (1), and life-threatening arrhythmia (2). There were no cases of emergent coronary artery bypass graft (CABG) or death. CONCLUSION: This contemporary cohort of high-risk patients transferred electively from a regional PCI centre to a tertiary cardiac unit underwent lengthy PCI procedures, with high radiation doses, and a modest rate of peri-procedural complications, but had otherwise excellent procedural and clinical outcomes.

Increased ABCA1 (ATP-Binding Cassette Transporter A1)-Specific Cholesterol Efflux Capacity in Schizophrenia.

OBJECTIVE: Patients with schizophrenia have increased long-term mortality attributable to cardiovascular disease and commonly demonstrate features of mixed dyslipidemia with low HDL-C (high-density lipoprotein cholesterol). The removal of cholesterol from cells by HDL via specific ATP-binding cholesterol transporters is a major functional property of HDL, and its measurement as cholesterol efflux capacity (CEC) can predict cardiovascular risk. Whether HDL function is impaired in patients with schizophrenia is unknown. Approach and Results: We measured basal and ABCA1 (ATP-binding cassette transporter A1)- and ABCG1 (ATP-binding cassette transporter G1)-dependent CEC, comparing patients with schizophrenia with age- and sex-matched healthy controls, and related our findings to nuclear magnetic resonance analysis of lipoprotein subclasses. Total plasma cholesterol and LDL-C (low-density lipoprotein cholesterol) were comparable between healthy controls (n=51) and patients (n=120), but patients with schizophrenia had increased total plasma triglyceride, low HDL-C and apo (apolipoprotein) A-I concentrations. Nuclear magnetic resonance analysis indicated a marked (15-fold) increase in large triglyceride-rich lipoprotein particle concentration, increased small dense LDL particles, and fewer large HDL particles. Despite lower HDL-C concentration, basal CEC was 13.7±1.6% higher, ABCA1-specific efflux was 35.9±1.6% higher, and ABCG1 efflux not different, in patients versus controls. In patients with schizophrenia, ABCA1-specific efflux correlated with the abundance of small 7.8 nm HDL particles but not with serum plasminogen or triglyceride levels. CONCLUSIONS: Patients with schizophrenia have increased concentrations of atherogenic apoB-containing lipoproteins, decreased concentrations of large HDL particles, but enhanced ABCA1-mediated CEC. In this population, preventative strategies should focus on reducing atherogenic lipoproteins rather than increasing CEC.

Free Thiol ß2-GPI (ß-2-Glycoprotein-I) Provides a Link Between Inflammation and Oxidative Stress in Atherosclerotic Coronary Artery Disease.

OBJECTIVE: Atherosclerotic coronary artery disease is well recognised as an inflammatory disorder that is also influenced by oxidative stress. ß2-GPI (ß-2-glycoprotein-I) is a circulating plasma protein that undergoes post-translational modification and exists in free thiol as well as oxidized forms. The aim of this study was to assess the association between these 2 post-translational redox forms of ß2-GPI and atherosclerotic coronary artery disease. Approach and Results: Stable patients presenting for elective coronary angiography or CT coronary angiography were prospectively recruited. A separate group of patients after reperfused ST-segment-elevation myocardial infarction formed an acute coronary syndrome subgroup. All patients had collection of fasting serum and plasma for quantification of total and free thiol ß2-GPI. Coronary artery disease extent was quantified by the Syntax and Gensini scores. A total of 552 patients with stable disease and 44 with acute coronary syndrome were recruited. While total ß2-GPI was not associated with stable coronary artery disease, a higher free thiol ß2-GPI was associated with its presence and extent. This finding remained significant after correcting for confounding variables, and free thiol ß2-GPI was a better predictor of stable coronary artery disease than hs-CRP (high-sensitivity C-reactive protein). Paradoxically, there were lower levels of free thiol ß2-GPI after ST-segment-elevation myocardial infarction. CONCLUSIONS: Free thiol ß2-GPI is a predictor of coronary artery disease presence and extent in stable patients. Free thiol ß2-GPI was a better predictor than high-sensitivity C-reactive protein.

Outcomes of 1,098 Patients Following Transcatheter Aortic Valve Implantation: A Statewide Population-Linkage Cohort Study.

BACKGROUND: The increasing implementation of transcatheter aortic valve implantation (TAVI) in Australia warrants real-world data on the prevalence and outcomes of these patients. The aim of this study is to describe trends in case-volumes of TAVI in New South Wales (NSW), Australia and associated mortality outcomes. METHODS: From the Centre of Health Record Linkage registry, all NSW residents who underwent TAVI between 5 June 2013 and 30 June 2018 were identified. Cause-specific mortality was tracked from the statewide death registry. Temporal trends in case-volumes between 2013 and 2018 were assessed by linear regression. Binary logistic regression was used to compare differences in in-hospital and 30-day mortality, while Cox proportional hazards regression was used to compare mortality beyond 30 days. RESULTS: Case-volumes increased from 30 in 2013 to 345 by 2017. The cohort comprised 1,098 persons (mean[±SD] age: 83.3±7.7 yrs). Cumulative in-hospital, 180-day and at end-of-study (mean: 1.8±1.2 yrs) all-cause mortality were 1.3% (n=14), 4.9% (n=54) and 20.3% (n=224) respectively. Heart failure (14.3%, n=2), myocardial infarction (14.3%, n=2), and sepsis (14.3%, n=2) were the primary causes of in-hospital death. Post-discharge, sepsis (25.2%, n=53) was the main cause-specific death, while combined cardiovascular deaths accounted for 46% (n=97), mostly from heart failure (n=35). Heart failure, chronic kidney disease, and requirement for ventilation post-TAVI were independent predictors of in-hospital death and at 180 days. TAVI procedure in low-volume public centres was a predictor of mortality at 180 days. CONCLUSION: The number of TAVI procedures increased 10-fold between 2013 and 2017 state-wide, with mortality rates comparable to international cohorts at short and medium-term follow-up. Pre-existing comorbidities and site-specific caseloads may be important determinants of outcome, emphasising the importance of appropriate patient selection and treating centre.

Long-Term Outcomes Following Rapid Access Chest Pain Clinic Assessment: First Australian Data.

Australian guidelines recommend prompt evaluation of patients presenting to emergency departments with chest pain, found to be low risk for acute coronary syndromes, and cardiologist-led Rapid Access Chest Pain Clinics (RACPC) have been proposed as a model to provide such care. Initial Australian experience of RACPCs suggests excellent short-term outcomes, and that they are cost-beneficial, though little data exists examining longer-term outcomes. The present study therefore examines such longer-term outcomes to beyond 5 years following presentation to an RACPC in an Australian tertiary metropolitan centre.