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Objectives Epidemiological studies of air pollution on cardiovascular health show associations of cardiac mortality and admissions with exposure to nitrogen dioxide (NO(2)) at low concentrations. These associations could be causal or NO(2) could be acting as a surrogate measure for another air pollutant, most likely ultrafine particles. No studies of cardiac susceptibility to acute exposure to NO(2) have been undertaken. Methods Randomised controlled exposures to NO(2) (400 ppb for 1 h) and air in subjects with coronary heart disease and impaired left ventricular systolic function not taking [beta] adrenoceptor blocking drugs. Results There were no significant changes in heart rate, blood pressure, leucocyte coping capacity or any heart rate variability measure following NO(2) exposure compared with air. Conclusion These findings suggest that NO(2) does not affect heart rate variability at these concentrations (which are high for urban background levels) and in the absence of other pollutants. While a synergistic effect has not been ruled out, these data lend support to the idea that the epidemiological data associating cardiac outcomes with NO(2) are more likely due to an associated pollutant rather than NO(2) itself. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cardiovascular complications are important causes of morbidity and mortality in elective non-cardiac surgery. Although difficult to diagnose, perioperative myocardial infarction (MI) remains prognostically important. High-sensitivity troponin T (hs-TnT) assays allow detection of very minor damage to cardiac muscle. These assays are yet to be fully evaluated in the perioperative setting. Our aim was to determine the incidence and predictors of myocardial necrosis in patients at high cardiovascular risk undergoing elective non-cardiac surgery using hs-TnT. DESIGN: Prospective observational cohort study. PATIENTS: 352 consecutive patients undergoing elective major non-cardiac surgery prescribed antiplatelet therapy for primary or secondary cardiovascular event prevention. MAIN OUTCOME MEASURE: The incidence of elevated preoperative hs-TnT (>=14 ng/litre), hs-TnT-defined perioperative myocardial necrosis (>= 14ng/litre and 50% increase from preoperative level), and perioperative MI were determined in relation to patient and surgical factors. RESULTS: Preoperative hs-TnT was elevated in 31% and postoperative myocardial necrosis occurred in 22% of patients. Predictors of elevated baseline hs-TnT included age (OR 1.10, p<0.001), male gender (OR 2.91, p<0.001), diabetes requiring insulin therapy (OR 4.85, p=0.004) and chronic kidney disease (OR 3.60, p<0.001). Independent predictors of perioperative myocardial necrosis were age (OR 1.07, p<0.001), intraoperative hypotension (OR 3.67, p=0.001) and orthopaedic surgery (OR 2.46, p=0.005). Only 2% of patients suffered clinically apparent MI. Elevated preoperative hs-TnT did not predict perioperative myocardial necrosis or MI. CONCLUSIONS: Perioperative myocardial damage occurs frequently in patients undergoing elective non-cardiac surgery, although the majority of events are clinically undetected. Age and intraoperative hypotension are independent predictors of myocardial necrosis in this setting. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the prognostic value of a noninvasive measure of left ventricular diastolic pressure (LVDP) early after acute myocardial infarction (MI). Background: The early diastolic velocity of the mitral valve annulus (e') reflects the rate of myocardial relaxation. When combined with measurement of the early transmitral flow velocity (E), the resultant ratio (E/e') correlates well with mean LVDP. In particular, an E/e' ratio >15 is an excellent predictor of an elevated mean LVDP. We hypothesized that an E/e' ratio >15 would predict poorer survival after acute MI. Methods: Echocardiograms were obtained in 250 unselected patients 1.6 days after admission for MI. Patients were followed for a median of 13 months. The end point was all-cause mortality. Results: Seventy-three patients (29%) had an E/e' >15. This was associated with excess mortality (log-rank statistic 21.3, p < 0.0001) and was the most powerful independent predictor of survival (risk ratio 4.8, 95% confidence interval 2.1 to 10.8, p = 0.0002). The addition of E/e' >15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001). Conclusions: E/e' is a powerful predictor of survival after acute MI. An E/e' ratio >15 is superior, in this respect, to other clinical or echocardiographic features. Furthermore, it provides prognostic information incremental to these parameters. [ABSTRACT FROM AUTHOR]

Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) levels more accurately predict renal end points than the conventional markers. Cases were defined as those who developed a renal end point (doubling of serum creatinine to at least 200 μmol/l, the need for renal replacement therapy, or death due to renal disease) during the study. Using propensity scoring, two controls were selected for each of 281 cases. Participants who developed renal end points had significantly higher total TGF-β1, lower BMP-7 levels, and a higher total TGF-β1 to BMP-7 ratio at baseline. A graded increase in risk was found in individuals with lower BMP-7 levels (odds ratio 24.07, for the lowest to the highest tertile), or significantly higher TGF-β1 levels (odds ratio for the highest to the lowest tertile, 8.43). The area under the receiver operating characteristic curve (c-statistic) for the conventional predictors was 0.73. Using BMP-7 and total and active TGF-β1, the c-statistic was 0.94 (significantly higher to conventional predictors). Thus, our results suggest these novel kidney markers are better predictors of renal progression than the conventional predictors in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Degenerative aortic stenosis is a growing clinical problem owing to the high incidence in an aging population and its significant morbidity and mortality. Currently, aortic valve replacement remains the only treatment. Despite promising observational data, pharmacological management to slow or halt progression of aortic stenosis has remained elusive. Nevertheless, with a greater understanding of the mechanisms which underpin aortic stenosis, research has begun to explore novel treatment strategies. This review will explore the historical agents used to manage aortic stenosis and the emerging agents that are currently under investigation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis., Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis., Design, Setting, and Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024., Intervention: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management., Main Outcomes and Measures: The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months., Results: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70])., Conclusions and Relevance: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT03094143.

Background: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'., Methods: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life., Results: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up., Conclusions: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes., Competing Interests: Declaration of competing interest GPM is supported by a NIHR Research Professorship (2017-08-ST2-007). DEN is supported by the British Heart Foundation (CH/09/002, RE/24/130012, RG/F/22/110093). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. GJM is supported by the British Heart Foundation (CH/12/1/29419, RG/17/9/32812, and AA/18/3/34220). PSM is supported by an Australian National Health and Medical Research Council Investigator Grant (ID 2008079). GSH is supported by a WA Health Research Excellence Award. GPM, AS and GJM receive support from the NIHR Leicester Biomedical Research Centre., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined., Methods: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study., Conclusions: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04347330)., Competing Interests: Conflict of interest The principal Investigators of CRAFT study have no disclosures of financial and other competing interests. CSA reports receiving funding from the Medical Research Council (MRC) and Medical Research Foundation (MRF) of the UK, and the National Health and Medical Research (NHMRC) of Australia, and Penumbra and Takeda. AP is the nonremunerated Chair of the Board of George Medicines, a commercial spin-out of The George Institute that is aiming to bring a novel fixed-dose antihypertensive combination to market, and reports receiving funding from NHMRC., (Copyright © 2024. Published by Elsevier Inc.)

Background: The MINT trial raised concern for harm from a restrictive versus liberal transfusion strategy in patients with acute myocardial infarction (MI) and anemia. Type 1 and type 2 MI are distinct pathophysiological entities that may respond differently to blood transfusion. This analysis sought to determine if the effects of transfusion varied among patients with a type 1 or a type 2 MI and anemia. We hypothesized that the liberal transfusion strategy would be of greater benefit in type 2 than in type 1 MI., Methods: We compared rates of death or MI at 30 days in patients with type 1 (n=1460) and type 2 (n=1955) MI and anemia who were randomly allocated to a restrictive (threshold of 7 to 8 g/dL) or a liberal (threshold of 10 g/dL) transfusion strategy., Results: The primary outcome of death or MI was observed in 16% of type 1 MI and 15.4% of type 2 MI patients. The rate of death or MI was higher in patients with type 1 MI randomized to a restrictive (18.2%) versus liberal (13.2%) transfusion strategy (RR 1.32, 95% CI 1.04 - 1.67) with no difference observed between the restrictive (15.8% ) and liberal (15.1% ) transfusion strategies in patients with type 2 MI (RR 1.05 95% CI 0.85-1.29). The test for a differential effect of transfusion strategy by MI type was not statistically significant (P- interaction = 0.16)., Conclusions: The concern for harm with a restrictive transfusion strategy in patients with acute MI and anemia raised in the MINT primary outcome manuscript may be more apparent in patients with type 1 than type 2 MI., Clinical Trial Registration: ClinicalTrials.gov number, NCT02981407.

Rural patients with non-ST-elevation myocardial infarction (NSTEMI) are transferred to metropolitan hospitals for invasive coronary angiography (ICA). Yet, many do not have obstructive coronary artery disease (CAD). In this analysis of rural Western Australian patients transferred for ICA for NSTEMI, low-level elevations in high-sensitivity cardiac troponin (≤5× upper reference limit) were associated with less obstructive CAD and revascularisation. Along with other factors, this may help identify rural patients not requiring transfer for ICA., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail., Methods: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes., Results: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill., Conclusion: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain., Methods: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP)., Results: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P =0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P >0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit., Conclusions: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target., Registration: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404., Competing Interests: Disclosures The George Institute for Global Health (TGI) has submitted patent applications in respect of low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. A. Rodgers and C. Chow are listed as inventors. A. Rodgers is employed by TGI and seconded part-time to George Medicines Pty Ltd (GM). George Health Enterprises Pty Ltd (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise arm of TGI. A. Rodgers and C. Chow do not have direct financial interests in these patent applications or investments. The other authors report no conflicts.

Background: Chest pain is a common cause of presentation to the emergency department (ED), and its outcomes are affected by various diagnostic tests and timely management. Our aim was to identify determinants of invasive coronary angiography (ICA) in a chest pain cohort following ED presentation, and to compare outcomes by time to ICA., Methods: We identified all adults aged ≥20 years presenting with chest pain to public teaching hospital EDs in Perth, Western Australia, from 1 January 2016 to 31 March 2017. Data were obtained from linked administrative ED, hospitalisation, pathology, and death records. Multivariable logistic regression was used to identify determinants of ICA within 90 days of ED presentation. Restricted cubic splines fitted in multivariable Cox regression models showed the relationship between time to ICA and outcomes of death and major cardiovascular events., Results: The cohort comprised 16,974 people, with 8,609 (51%) male patients and a mean age of 56 years; 986 (5.8%) patients had ICA within 1 day of presentation, 394 (2.3%) within 2-3 days, 543 (3.2%) within 4-90 days, and 15,051 (88.7%) had no ICA or had ICA after 90 days. Age, sex, residential area, triage code, troponin classification, ED diagnosis, and medical history were all significantly associated with 90-day ICA. The adjusted odds ratio of women receiving ICA was 0.53 (95% confidence interval 0.47-0.61) in comparison with men. Restricted cubic splines showed a biphasic relationship between time to ICA and death., Conclusions: The determinants of ICA reflect clinical practice guidelines, although ICA remains less likely in women than in men. Early ICA is associated with lower risk of death but may not affect myocardial infarction or composite outcomes after adjusting for cofactors., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To determine the cost-effectiveness and cost-utility of a quadpill containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg in comparison with irbesartan 150 mg for people with hypertension who are either untreated or receiving monotherapy., Methods: We conducted a within-trial and modelled economic evaluation of the Quadruple UltrA-low-dose tReaTment for hypErTension trial. The analysis was preplanned, and medications and health service use captured during the trial. The main outcomes were incremental cost-effectiveness ratios (ICERs) for cost per mm Hg systolic blood pressure (BP) reduction at 3 months, and modelled cost per quality-adjusted life year (QALY) over a lifetime., Results: The within-trial analysis showed no clear difference in cost per mm Hg BP lowering between randomised treatments at 3 months ($A10 (95% uncertainty interval (UI) $A -18 to $A37) per mm Hg per person) for quadpill versus monotherapy. The modelled cost-utility over a lifetime projected a mean incremental cost of $A265 (95% UI $A166 to $A357) and a mean 0.02 QALYs gained (95% UI 0.01 to 0.03) per person with quadpill therapy compared with monotherapy. Quadpill therapy was cost-effective in the base case (ICER of $A14 006 per QALY), and the result was sensitive to the quadpill cost in one-way sensitivity analysis., Conclusions: Quadpill in comparison with monotherapy is comparably cost-effective for short-term BP lowering. In the long-term, quadpill therapy is likely to be cost-effective., Trial Registration Number: ANZCTRN12616001144404., Competing Interests: Competing interests: The George Institute for Global Health (TGI) has submitted patent applications with respect to low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. AR and CKC are listed as inventors. AR is employed by TGI and seconded part-time to George Medicines (GM). George Health Enterprises (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise group of TGI. AR and CKC do not have direct financial interests in these patent applications or investments., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with ST-elevation myocardial infarction (STEMI) with no standard modifiable risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, and smoking) have worse short-term mortality than those with SMuRFs. Whether this association extends to younger patients is unclear. A retrospective cohort study was performed of patients aged 18 to 45 years with STEMI at 3 Australian hospitals between 2010 and 2020. Nonatherosclerotic causes of STEMI were excluded. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 1 and 2-year mortality. Cox proportional hazards analysis was used. Of 597 patients, the median age was 42 (interquartile range 38 to 44) years, 85.1% were men and 8.4% were SMuRF-less. Patients who are SMuRF-less were >2 times more likely to have cardiac arrest (28.0% vs 12.6%, p = 0.003); require vasopressors (16.0% vs 6.8%, p = 0.018), mechanical support (10.0% vs 2.3%, p = 0.046), or intensive care admission (20.0% vs 5.7%, p <0.001); and have higher rate of left anterior descending artery infarcts than those with SMuRFs (62.0% vs 47.2%, p = 0.045). No significant differences in thrombolysis or percutaneous intervention were observed. Guideline-directed medical therapy at discharge was high (>90%), and not different in the SMuRF-less. 30-day mortality was almost fivefold higher in the SMuRF-less (hazard ratio 4.70, 95% confidence interval 1.66 to 13.35, p = 0.004), remaining significant at 1 and 2 years. In conclusion, young patients who are SMuRF-less have a higher 30-day mortality after STEMI than their counterparts with SMuRFs. This may be partially mediated by higher rates of cardiac arrest and left anterior descending artery territory events. These findings further highlight the need for improved prevention and management of SMuRF-less STEMI., Competing Interests: Declaration of Competing Interest Dr. Lan has received research funding from Sanofi as part of a Clinical Fellowship in Endocrinology and Diabetes; education support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, and Novartis; and speaker honoraria from Boehringer Ingelheim, Eli Lilly, and Sanofi and has participated in advisory boards for Eli Lilly. Dr. Dwivedi reports paid lectures from AstraZeneca, Pfizer, and Amgen not related to the topic in the manuscript and provides consultancy services and has equity interest in Artrya Ltd. Dr. Figtree reports paid lectures from Amgen, AstraZeneca, and Novartis; and has equity interest in Prokardia. Dr. Ihdayhid is a consultant for Abbott Medical, Boston Scientific, and Artrya Ltd (including equity interest). The remaining authors have no conflicts of interest to declare., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the severity of coronary artery disease (CAD) in people from rural or remote Western Australia referred for invasive coronary angiography (ICA) in Perth and their subsequent management; to estimate the cost savings were computed tomography coronary angiography (CTCA) offered in rural centres as a first line investigation for people with suspected CAD., Design: Retrospective cohort study., Setting, Participants: Adults with stable symptoms in rural and remote WA referred to Perth public tertiary hospitals for ICA evaluation during the 2019 calendar year., Main Outcome Measures: Severity and management of CAD (medical management or revascularisation); health care costs by care model (standard care or a proposed alternative model with local CTCA assessment)., Results: The mean age of the 1017 people from rural and remote WA who underwent ICA in Perth was 62 years (standard deviation, 13 years); 680 were men (66.9%), 245 were Indigenous people (24.1%). Indications for referral were non-ST elevation myocardial infarction (438, 43.1%), chest pain with normal troponin level (394, 38.7%), and other (185, 18.2%). After ICA assessment, 619 people were medically managed (60.9%) and 398 underwent revascularisation (39.1%). None of the 365 patients (35.9%) without obstructed coronaries (< 50% stenosis) underwent revascularisation; nine patients with moderate CAD (50-69% stenosis; 7%) and 389 with severe CAD (≥ 70% stenosis or occluded vessel; 75.5%) underwent revascularisation. Were CTCA used locally to determine the need for referral, 527 referrals could have been averted (53%), the ICA:revascularisation ratio would have improved from 2.6 to 1.6, and 1757 metropolitan hospital bed-days (43% reduction) and $7.3 million in health care costs (36% reduction) would have been saved., Conclusion: Many rural and remote Western Australians transferred for ICA in Perth have non-obstructive CAD and are medically managed. Providing CTCA as a first line investigation in rural centres could avert half of these transfers and be a cost-effective strategy for risk stratification of people with suspected CAD., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Introduction: Many people with type 2 diabetes progress to end-stage diabetic kidney disease (DKD) despite blockade of the renin-angiotensin system, suggesting the need for innovative treatment options for DKD. To capture the findings of recent studies, we performed an updated systematic review and meta-analysis of the efficacy and safety of sodium glucose co-transporter 2 (SGLT2) inhibitors combined with standard care involving angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) on the development and progression of DKD in people with type 2 diabetes compared with standard care alone., Methods: The Cochrane Library, MEDLINE, EMBASE, PubMed and clinical trials registers were systematically searched for randomized controlled trials published before 1 September 2022. Primary outcomes were urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Secondary outcomes were glycated hemoglobin (HbA1c) and systolic blood pressure (SBP). Relative risk was calculated for adverse events., Results: Eight studies enrolling 5512 participants were included. In the meta-analysis (n = 1327), SGLT2 inhibitors were associated with a statistically significant reduction in UACR (weighted mean difference [WMD] -105.61 mg/g, 95 % CI -197.25 to -13.98, I 2  = 99 %, p = 0.02). There was no statistically significant difference in relation to eGFR (n = 1375; WMD -0.23 mL/min/1.73m 2 , 95 % CI -4.34 to 3.89, I 2  = 94 %, p = 0.91)., Conclusions: SGLT2 inhibitors in addition to standard care including ACE inhibitors and/or ARBs significantly reduced albuminuria, HbA1c and SBP when compared to standard care alone, supporting their routine use in people with type 2 diabetes., Competing Interests: Conflict of interest statement MPS has received research support from Boehringer-Ingelheim, Medtronic, Abbott, Novartis, Servier, Pfizer, and consulting/lecture fees from Medtronic and Abbott. The authors declare there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Computed tomography coronary angiography (CTCA) is a non-invasive diagnostic modality that provides a comprehensive anatomical assessment of the coronary arteries and coronary atherosclerosis, including plaque burden, composition and morphology. The past decade has witnessed an increase in the role of CTCA for evaluating patients with both stable and acute chest pain, and recent international guidelines have provided increasing support for a first line CTCA diagnostic strategy in select patients. CTCA offers some advantages over current functional tests in the detection of obstructive and non-obstructive coronary artery disease, as well as for ruling out obstructive coronary artery disease. Recent randomised trials have also shown that CTCA improves prognostication and guides the use of guideline-directed preventive therapies, leading to improved clinical outcomes. CTCA technology advances such as fractional flow reserve, plaque quantification and perivascular fat inflammation potentially allow for more personalised risk assessment and targeted therapies. Further studies evaluating demand, supply, and cost-effectiveness of CTCA for evaluating chest pain are required in Australia. This discussion paper revisits the evidence supporting the use of CTCA, provides an overview of its implications and limitations, and considers its potential role for chest pain evaluation pathways in Australia., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: Community pharmacists have regular interactions with people living with type 2 diabetes to supply medications, and have a potential role in supporting other primary care professionals in the screening, management, monitoring and facilitation of timely referral of microvascular complications. This study aimed to investigate the contemporary and future roles of community pharmacists in diabetes-related microvascular complication management., Methods: This study involved an online Australian nation-wide survey of pharmacists administered via Qualtrics® and distributed through social media platforms, state and national pharmacy organisations, and via major banner groups. Descriptive analyses were undertaken using SPSS., Results: Among 77 valid responses, 72% of pharmacists already provided blood pressure and blood glucose monitoring services for the management of type 2 diabetes. Only 14% reported providing specific microvascular complication services. Over 80% identified a need for a comprehensive microvascular complication monitoring and referral service, and agreed it is feasible and within the scope of practice of a pharmacist. Almost all respondents agreed that they would implement and provide a monitoring and referral service if provided with appropriate training and resources. Potential barriers to service implementation were competing demands and lack of remuneration and awareness among consumers and health professionals., Conclusions: Type 2 diabetes services in Australian community pharmacies do not currently focus on microvascular complication management. There appears to be strong support for implementing a novel screening, monitoring and referral service via community pharmacy to facilitate timely access to care. Successful implementation would require additional pharmacist training, and identification of efficient pathways for service integration and remuneration., Competing Interests: The authors declare that they have no competing interests., (© 2023 Woodhams et al.)

Cardiovascular disease remains the leading cause of death and disability for patients across the world. Our understanding of atherosclerosis as a primary cholesterol issue has diversified, with a significant dysregulated inflammatory component that largely remains untreated and continues to drive persistent cardiovascular risk. Macrophages are central to atherosclerotic inflammation, and they exist along a functional spectrum between pro-inflammatory and anti-inflammatory extremes. Recent clinical trials have demonstrated a reduction in major cardiovascular events with some, but not all, anti-inflammatory therapies. The recent addition of colchicine to societal guidelines for the prevention of recurrent cardiovascular events in high-risk patients with chronic coronary syndromes highlights the real-world utility of this class of therapies. A highly targeted approach to modification of interleukin-1-dependent pathways shows promise with several novel agents in development, although excessive immunosuppression and resulting serious infection have proven a barrier to implementation into clinical practice. Current risk stratification tools to identify high-risk patients for secondary prevention are either inadequately robust or prohibitively expensive and invasive. A non-invasive and relatively inexpensive method to identify patients who will benefit most from novel anti-inflammatory therapies is required, a role likely to be fulfilled by functional imaging methods. This review article outlines our current understanding of the inflammatory biology of atherosclerosis, upcoming therapies and recent landmark clinical trials, imaging modalities (both invasive and non-invasive) and the current landscape surrounding functional imaging including through targeted nuclear and nanobody tracer development and their application., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Several definitions of night-time BP exist for the calculation of nocturnal blood pressure (BP) based on 24-h BP measurements. How much these methods differ regarding the resulting nocturnal blood pressure values, under which circumstances these differences become clinically meaningful, and under which circumstances diary-adjusted measurements should be used preferentially remains uncertain., Methods: Data of 512 24-h BP recordings were analysed regarding differences in nocturnal BP based on three alternative definitions of night-time: 2300-0700 h, 0100-0500 h, and diary-adjusted measures., Results: Mean systolic nocturnal BP between 2300-0700 h was 2.5 mmHg higher than between 0100 and 0500 h and 1.6 mmHg higher than diary adjusted estimates. Up to 38.3% of individuals showed BP differences of more than 5 mmHg when comparing temporal definitions of night-time, resulting in significant proportions of individuals being re-classified as hypertensive. When diary-derived sleeping patterns differed by less than 2 h from the 2300 to 0700 h fixed time definition, mean BP discrepancies remained below 3 mmHg. Absolute time discrepancies between diary and 2300-0700 h fixed time definition of 2-4, 4-8 or at least 8 h led to SBP/DBP differences of 4.1/3.1, 6.8/6.1, and 14.5/9.1mmHg, respectively., Conclusion: Average differences of nocturnal BP between varying definitions in study/cohort data are small and would be of limited relevance in many settings. However, substantial differences can be observed in individual cases, which may affect clinical decision-making in specific patients. In patients whose sleeping patterns differs by more than 2 h from defined fixed night-times, diaries should be used for adjustment., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tobacco smoking is a leading preventable cause of death and increases perioperative risk. Determinants of smoking abstinence after noncardiac surgery and the association between smoking and 1-yr vascular outcomes are not fully elucidated., Methods: We did a prospective cohort study of 40 004 patients, aged ≥45 yr, enrolled between August 2007 and November 2013, and followed for 1 yr after surgery. Patients were categorised as never smokers, ex-smokers (quit >4 weeks preoperatively), and current smokers (smoking ≤4 weeks preoperatively). Primary outcome was abstinence at 1 yr. Secondary outcome was a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 yr., Results: Of 4658 current smokers, 1838 (39.5%) were abstinent 1 yr after surgery. Median (inter-quartile range) time to resumption was 7 (3-23) days post-surgery. Perioperatively, 7.2% of current smokers obtained smoking cessation pharmacotherapy. Older age (adjusted risk ratio [aRR] 1.21; 95% confidence interval [CI]: 1.12-1.32); having recent coronary artery disease (aRR 1.41; 95% CI: 1.29-1.55); cancer (aRR 1.37; 95% CI: 1.18-1.59); and undergoing major vascular (aRR 1.20; 95% CI: 1.02-1.41), urgent/emergent (aRR 1.14; 95% CI: 1.05-1.23), or thoracic (aRR 1.41; 95% CI: 1.26-1.56) surgeries increased abstinence. One-year abstinence was less likely when patients stopped smoking 0-1 day (aRR 0.53; 95% CI: 0.43-0.66) and 2-14 days (aRR 0.76; 95% CI: 0.71-0.82) before surgery compared with >14 days before surgery. Current smokers (adjusted hazard ratio [aHR] 1.14; 95% CI: 1.01-1.29) and ex-smokers (aHR 1.11; 95% CI: 1.03-1.21) had higher risk of the 1-yr vascular outcome compared with never smokers., Conclusions: Long-term tobacco abstinence is more likely after major surgery in those with serious medical comorbidities. Interventions to prevent smoking resumption after surgery remain a priority. Clinical trial registration NCT00512109., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Low-dose colchicine is effective in reducing the risks of recurrent cardiovascular events following an acute myocardial infarction (MI). However, the influence of colchicine on inflammation remains inconclusive. In the current study, we conducted a combined analysis using individual patient data from the COLCOT and LoDoCo-MI trials to assess the effect of low-dose colchicine on high-sensitivity C reactive protein (hs-CRP) in patients with acute MI., Methods: We performed a combined analysis of individual patient data from two clinical trials (COLCOT, LoDoCo-MI). Paired pre-treatment and post-treatment hs-CRP (mg/L) were available in 222 patients for LoDoCo-MI and 207 patients for COLCOT (n pooled  = 429). We evaluated the effect of colchicine vs. placebo on post-treatment hs-CRP coded continuously and ≤ 1.0 mg/L in adjusted mixed-model multi-level regression analyses., Results: Colchicine was not significantly associated with post-treatment hs-CRP when it was considered as a continuous variable (beta: -0.41, P = 0.429). However, the intervention was significantly associated with increased odds of achieving post-treatment hs-CRP values ≤1.0 mg/L compared to placebo (odds ratio: 1.64, 95% confidence interval: 1.07 to 2.51, P = 0.024)., Conclusions: Reduction of inflammation may be a key component in the clinical efficacy of low-dose colchicine with respect to decreased risk of recurrent cardiovascular events following MI. Systematic sampling of hs-CRP before and after treatment with colchicine may be relevant., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: TEXTMEDS (Text Messages to Improve Medication Adherence and Secondary Prevention After Acute Coronary Syndrome) examined the effects of text message-delivered cardiac education and support on medication adherence after an acute coronary syndrome., Methods: TEXTMEDS was a single-blind, multicenter, randomized controlled trial of patients after acute coronary syndrome. The control group received usual care (secondary prevention as determined by the treating clinician); the intervention group also received multiple motivational and supportive weekly text messages on medications and healthy lifestyle with the opportunity for 2-way communication (text or telephone). The primary end point of self-reported medication adherence was the percentage of patients who were adherent, defined as >80% adherence to each of up to 5 indicated cardioprotective medications, at both 6 and 12 months., Results: A total of 1424 patients (mean age, 58 years [SD, 11]; 79% male) were randomized from 18 Australian public teaching hospitals. There was no significant difference in the primary end point of self-reported medication adherence between the intervention and control groups (relative risk, 0.93 [95% CI, 0.84-1.03]; P =0.15). There was no difference between intervention and control groups at 12 months in adherence to individual medications (aspirin, 96% vs 96%; β-blocker, 84% vs 84%; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 77% vs 80%; statin, 95% vs 95%; second antiplatelet, 84% vs 84% [all P >0.05]), systolic blood pressure (130 vs 129 mm Hg; P =0.26), low-density lipoprotein cholesterol (2.0 vs 1.9 mmol/L; P =0.34), smoking ( P =0.59), or exercising regularly (71% vs 68%; P =0.52). There were small differences in lifestyle risk factors in favor of intervention on body mass index <25 kg/m 2 (21% vs 18%; P =0.01), eating ≥5 servings per day of vegetables (9% vs 5%; P =0.03), and eating ≥2 servings per day of fruit (44% vs 39%; P =0.01)., Conclusions: A text message-based program had no effect on medical adherence but small effects on lifestyle risk factors., Registration: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364448; Unique identifier: ANZCTR ACTRN12613000793718.

Background: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations., Methods: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex)., Results: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit., Conclusions: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.)., (Copyright © 2022 Massachusetts Medical Society.)

Background and Objectives: Ambulatory blood pressure monitoring (ABPM) is usually reported in descriptive values such as circadian averages and standard deviations. Making use of the original, individual blood pressure measurements may be advantageous, particularly for research purposes, as this increases the flexibility of the analytical process, enables alternative statistical analyses and provide novel insights. Here we describe the development of a new multistep, hierarchical data extraction algorithm to collect raw data from .pdf reports and text files as part of a large multi-center clinical study., Methods: Original reports were saved in a nested file system, from which they were automatically extracted, read and saved into databases with custom made programs written in Python 3. Data were further processed, cleaned and relevant descriptive statistics such as averages and standard deviations calculated according to a variety of definitions of day- and night-time. Additionally, data control mechanisms for manual review of the data and programmatic auto-detection of extraction errors was implemented as part of the project., Results: The developed algorithm extracted 97% of the data automatically, the missing data consisted mostly of reports that were saved incorrectly or not formatted in the specified way. Manual checks comparing samples of the extracted data to original reports indicated a high level of accuracy of the extracted data, no errors introduced due to flaws in the extraction software were detected in the extracted dataset., Conclusions: The developed multistep, hierarchical data extraction algorithm facilitated collection from different file formats and paired with database cleaning and data processing steps led to an effective and accurate assembly of raw ABPM data for further and adjustable analyses. Manual work was minimized while data quality was ensured with standardized, reproducible procedures., Competing Interests: Declaration of Competing Interest JMN and the other authors declare that they have no conflict of interest. MPS is supported by an NHMRC Research Fellowship and has received consulting fees, and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer-Ingelheim., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Treatment inertia is a recognised barrier to blood pressure control, and simpler, more effective treatment strategies are needed. We hypothesised that a hypertension management strategy starting with a single pill containing ultra-low-dose quadruple combination therapy would be more effective than a strategy of starting with monotherapy., Methods: QUARTET was a multicentre, double-blind, parallel-group, randomised, phase 3 trial among Australian adults (≥18 years) with hypertension, who were untreated or receiving monotherapy. Participants were randomly assigned to either treatment, that started with the quadpill (containing irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups, starting with amlodipine at 5 mg. Participants were randomly assigned using an online central randomisation service. There was a 1:1 allocation, stratified by site. Allocation was masked to all participants and study team members (including investigators and those assessing outcomes) except the manufacturer of the investigational product and one unmasked statistician. The primary outcome was difference in unattended office systolic blood pressure at 12 weeks. Secondary outcomes included blood pressure control (standard office blood pressure <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete., Findings: From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed for eligibility, 152 ineligible or declined, 300 participants randomly assigned to intervention of initial quadpill treatment, and 291 to control of initial standard dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD 12); 356 (60%) were male and 235 (40%) were female; 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity; and baseline mean unattended office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%) of 300 participants had additional blood pressure medications in the intervention group compared with 115 (40%) of 291 participants in the control group. Systolic blood pressure was lower by 6·9 mm Hg (95% CI 4·9-8·9; p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58%; relative risk [RR] 1·30, 95% CI 1·15-1·47; p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4%; p=0·27). Among the 417 patients who continued, uptitration occurred more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2-10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62%; RR 1·32, 95% CI 1·16-1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group., Interpretation: A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy., Funding: National Health and Medical Research Council, Australia., Competing Interests: Declaration of interests The George Institute for Global Health (TGI) has submitted patent applications with respect to low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. AR and CKC are listed as inventors. AR is employed by TGI and seconded part-time to George Medicines (GM). George Health Enterprises (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise group of TGI. AR and CKC do not have direct financial interests in these patent applications or investments. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (β)-blockers. There is observational evidence that cardioselective β-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective β-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective β-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity., Methods and Analyses: This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV 1 ) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months., Ethics and Dissemination: The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital., Trial Registration Numbers: NCT03917914; CTRI/2020/08/027322., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement., Methods: This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days., Results: The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort., Conclusions: Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe., Trial Registration Number: ACTRN12618000797279., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)