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Aims: Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk., Methods and Results: We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80)., Conclusion: The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Studies estimating risks following cardiac surgery for patients receiving kidney replacement therapy have been limited by the size and generalizability of those cohorts. This study used data linked between registries to estimate short-term postoperative outcomes for large patient cohorts receiving kidney replacement therapy at the time of surgery., Methods: This population-based observational cohort study included adult patients who had undergone cardiac surgery in Australia between 2010 and 2019. Patient data were linked with a kidney replacement therapy registry to accurately identify cohorts and extract relevant data. Multivariable logistic regression estimated risk of operative (30-day) mortality and other postoperative outcomes for long-term dialysis and functioning kidney transplant cohorts compared with each other and the general cardiac surgical population., Results: Of 114,496 surgeries, 1,241 were for patients receiving long-term dialysis and 298 for those with a kidney transplant. The mortality rate was highest for valve-with-coronary artery bypass grafting for dialysis (18.78 per 100 surgeries (95% CI 13.37,25.25) and transplant patients (14.00 [5.82,26.74]). Dialysis patients had higher adjusted odds of mortality (odds ratio [OR] 4.17 [95% CI 3.31,5.25]) and all other measured outcomes than the general population. Kidney transplant recipients had similarly elevated odds of mortality (OR 3.52 [95% CI 2.16,5.72])., Conclusions: Despite the younger age of dialysis and transplant cohorts at surgery, operative mortality rates were higher, and for valve-with-coronary artery bypass grafting were 3.7- to 5-fold those of the general population. Dialysis patients were a high risk for cardiac surgery, and the prognosis for kidney transplant recipients was similarly poor., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Previously published studies have consistently identified significant variation in red blood cell (RBC) transfusions during cardiac surgery. Clinical guidelines can be effective at improving the average quality of care; however, their impact on variation in practice is rarely studied. Herein, we estimated how variation in RBC use across cardiac surgeons changed after the publication of national patient blood management guidelines., Materials and Methods: We performed a pre-post study estimating change in variation in RBC transfusions across 80 cardiac surgeons in 29 hospitals using a national cardiac surgery registry. Variation across surgeons was estimated using fixed-effects regressions controlling for surgery and patient characteristics and an empirical Bayes shrinkage to adjust for sampling error. RBC use was measured by three metrics-the total number of units transfused, the proportion of patients transfused and the number of units transfused, conditional on receiving RBC., Results: The primary analysis utilized 35,761 elective cardiac surgeries performed between March 2009 and February 2015 and identified a 24.5% reduction (p < 0.0001) in mean total units transfused accompanied by a 37.2% reduction (p = 0.040) in the variation across surgeons. The reduction in mean total units was driven by both the proportion of patients transfused and the number of units transfused, conditional on receiving RBC, while the reduction in variation was only driven by the latter., Conclusion: In our study of RBC transfusions across cardiac surgeons, the surgeons who used more RBC in the pre-guideline period experienced larger reductions in RBC use after the guidelines were published., (© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: Australia has experienced extreme fire weather in recent years. Information on the impact of fine particulate matter (PM 2.5 ) from landscape fires (LFs) on cardiorespiratory hospital admissions is limited., Methods: We conducted a population-based time series study to assess associations between modelled daily elevated PM 2.5 at a 1.5×1.5 km resolution using a modified empirical PM 2.5 exposure model during LFs and hospital admissions for all-cause and cause-specific respiratory and cardiovascular diseases for the study period (2015-2017) in Perth, Western Australia. Multivariate Poisson regressions were used to estimate cumulative risk ratios (RR) with lag effects of 0-3 days, adjusted for sociodemographic factors, weather and time., Results: All-cause hospital admissions and overall cardiovascular admissions increased significantly across each elevated PM 2.5 concentration on most lag days, with the strongest associations of 3% and 7%, respectively, at the high level of ≥12.60 µg/m 3 on lag 1 day. For asthma hospitalisation, there was an excess relative risk of up to 16% (RR 1.16, 95% CI 1.00 to 1.35) with same-day exposure for all people, up to 93% on a lag of 1 day in children and up to 52% on a lag of 3 days in low sociodemographic groups. We also observed an increase of up to 12% (RR 1.12, 95% CI 1.02 to 1.24) for arrhythmias on the same exposure day and with over 154% extra risks for angina and 12% for heart failure in disadvantaged groups., Conclusions: Exposure to elevated PM 2.5 concentrations during LFs was associated with increased risks of all-cause hospital admissions, total cardiovascular conditions, asthma and arrhythmias., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Among ST-elevation myocardial infarction (STEMI) patients, those with no standard modifiable risk factors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, and smoking) have higher 30-day mortality than those with SMuRFs. Differences in coronary lesion characteristics remain unclear., Methods: Data from STEMI patients aged ≤60 years from the Asia Pacific Evaluation of Cardiovascular Therapies Network (Australia, Hong Kong, Malaysia, Singapore, and Vietnam) was retrospectively analysed. Exclusion criteria included incomplete SMuRF data, prior myocardial infarction, or prior coronary revascularisation. Lesion type was defined using the American College of Cardiology criteria. Major adverse cardiovascular events (MACE) were defined as peri-procedural myocardial infarction, emergency coronary artery bypass surgery, cerebrovascular event, or mortality. Multiple logistic regressions were used., Results: Of 4404 patients, 767 (17.4%) were SMuRFless. SMuRFless patients were more frequently younger (median age 51 vs. 53 years; p < 0.001), female (22.6% vs. 15.5%; p < 0.001), thrombolysed (20.1% vs. 12.5%; p < 0.001), and in cardiogenic shock (11.2% vs. 8.6%; p = 0.020). SMuRFless patients had significantly higher in-hospital MACE (7.2% vs. 4.3%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 1.24-4.08; p = 0.008) but 1-year mortality was not significantly different (3.6% vs. 5.7%, aOR 0.58; 95% CI 0.06-6.12; p = 0.549). Compared with patients with SMuRFs (4918 lesions), the SMuRFless (940 lesions) had fewer type B2/C lesions (60.8% vs. 65.6%; p = 0.020) and fewer lesions ≥20 mm (51.1% vs. 57.1%; p = 0.002) but more procedural complications (5.1% vs. 2.7%; p < 0.001)., Conclusions: Among young STEMI patients, the SMuRFless have shorter and less complex lesions, but worse procedural and short-term MACE outcomes., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Implantation of bioprosthetic valves is more common as the population ages and there is a shift towards implanting bioprosthetic aortic valves in an increasingly younger surgical population. Bioprosthetic heart valve insertion, however, carries the long-term risk of valve failure through structural valve degeneration. Re-operative surgical aortic valve replacement has historically been the only definitive management option for patients with prosthetic valve dysfunction, however, data on the short- and long-term outcomes following re-operative surgery in Australia and New Zealand is limited., Method: Data on all patients who underwent redo aortic valve surgery, over a 20-year period (up to 2021) was obtained from the Australian and New Zealand Society of Cardiothoracic Surgery Registry., Results: A total of 1,199 patients (770 males; 64.2% and 429 females; 35.8%) were included in the overall analysis. The 30-day mortality was 6.4% with operative urgency status the most important risk factor for peri-operative mortality. The long-term survival rate of 1,145 patients was 90.5% (95% confidence interval [CI] 88.8%-92.3%), 77% (95% CI 73.9%-80.2%) and 57.2% (95% CI 55.2%-62.8%) at 1-, 5- and 10-years post-procedure, respectively, with a median survival of 12.7 years. Pre-existing chronic kidney disease was strongly associated with poorer long-term survival. For patients under 70 years of age the 1-, 5- and 10-year survival rates were 92.9% (95% CI 90.9%-95.1%), 83.6% (95% CI 80.1%-87.3%) and 73.1% (95% CI 67.4%-79.3%), respectively., Conclusions: The results from this registry study indicate that in Australia and New Zealand, a repeat surgical aortic valve replacement can result in a relatively low mortality rate, serving as a reference point for medical procedures in these regions., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

High-quality randomized trial evidence is lacking on whether low-dose aspirin exerts significant effects on blood pressure (BP) in older adults. The authors assessed longitudinal BP changes in participants enrolled in ASPirin in Reducing Events in the Elderly (ASPREE), a randomized, placebo-controlled trial of 100 mg daily aspirin in 19 114 community-dwelling Australian and U.S. adults without cardiovascular disease (CVD), dementia, or independence-limiting physical disability. Participants' BP was recorded at baseline and annual study visits, and managed by their usual care provider. BP trajectories for aspirin versus placebo during 4.7 years of follow-up were examined for systolic and diastolic BP separately, using linear mixed models to account for between and within-individual variability in BP. Analyses by subgroups were also explored with inclusion of interaction terms in the models. The difference in mean change in systolic BP between aspirin and placebo during study follow-up was -0.03 mm Hg (95% confidence interval [CI]: -0.13, 0.07; p = .541) (aspirin minus placebo), while the mean difference for change in diastolic BP was -0.05 mm Hg (95% CI: -0.11, 0.01; p = .094). These small, non-significant differences in BP change between the aspirin and placebo groups were consistent across baseline levels of BP and antihypertensive treatment status (treated/untreated). Likewise, subgroups of age, sex, chronic kidney disease, diabetes, and frailty revealed no interaction effect between the subgroup, aspirin treatment, and time. Interval-censored Cox proportional hazards regression showed no difference in rates of incident treated hypertension between aspirin and placebo-treated participants. The authors conclude that daily low-dose aspirin does not significantly affect BP in older adults when managed by usual care., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Study Objectives: Obstructive sleep apnea (OSA) may increase risk of dementia. A potential pathway for this risk is through cerebral small vessel disease (CSVD). In the context of an existing randomized trial of aspirin for primary prevention, we aimed to investigate OSA's impact on CSVD imaging measures and explore whether aspirin effects these measures over 3 years that differ in the presence or absence of OSA., Methods: A sub-study of the ASPirin in Reducing Events in the Elderly randomized placebo-controlled trial of low-dose aspirin. Community-dwelling participants aged 70 years and above, without cognitive impairment, cardiovascular disease or known OSA completed an unattended limited-channel sleep study that calculated the oxygen desaturation index and apnea-hypopnea index. At baseline and 3 years later, volumes of white matter hyperintensities (WMH) and silent brain infarctions (SBI) were measured on 1.5 Tesla brain magnetic resonance imaging, and retinal vessel calibers were calculated from retinal vascular imaging., Results: Mild and moderate/severe OSA was detected in 48.9% and 29.9%, respectively, of the 311 participants, who had a mean age of 73.7 years (SD 3.4 years), 38.6% female. OSA of any severity did not associate with WMH volumes, SBI, nor with retinal vessel calibers at baseline, nor with change in these measures in the 277 participants with repeated measures acquired after 3 years. OSA of any severity did not interact with aspirin on change in these measures over 3 years., Conclusion: In healthy older adults undiagnosed OSA was not associated with retinal vascular calibers and neuroimaging measures of CSVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Low-renin hypertension affects 1 in 4 people with hypertension, but the optimal management of this condition is not known. We hypothesize that a large proportion of people with low-renin hypertension is mediated by excess mineralocorticoid receptor (MR) activation and that targeted treatment with an MR antagonist (MRA) will be beneficial. This randomized, single-blinded, titration-to-effect aims to investigate whether targeted treatment in low-renin hypertension with MRA is better compared to standard antihypertensives in terms of blood pressure control and end-organ protection. Adults with hypertension, who are treatment naïve or are receiving up to two antihypertensive agents and have a low direct renin concentration <10 mU/L will be included. Participants with severe hypertension, a secondary cause of hypertension, pregnant, breastfeeding, with moderate-severe cardiovascular and chronic kidney disease, or on medications that confound interpretation of the plasma direct renin or aldosterone concentrations will be excluded. Eligible participants will be randomized 1:1 to either MRA therapy (spironolactone) or standard anti-hypertensive therapy (perindopril+/- amlodipine) for 48 weeks. Anti-hypertensives will be up-titrated every 12 weeks until target blood pressure is achieved. The primary objective will be to determine the total defined daily dose of antihypertensives required to achieve the target blood pressure and change in mean clinic systolic blood pressure at week 48. Current hypertension guidelines do not have specific recommendations for the choice of anti-hypertensive medications for people with low-renin hypertension. The results of this trial could guide future hypertension guidelines., (© 2024. The Author(s).)

Background: Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults., Methods: A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use., Results: Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, 'any' AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and β-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk., Conclusions: Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and β-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults., Competing Interests: DISCLOSURES Dr. Shah reports being the site principal investigator or sub-investigator for Alzheimer’s disease clinical trials for which his institution (Rush University Medical Center) is compensated [Amylyx Pharmaceuticals, Inc., Athira Pharma, Inc., Edgewater NEXT, Eli Lilly & Co., Inc., Genentech, Inc.]. The remaining authors declare that they have no conflict of interests.

Importance: It is unclear whether counseling to promote walking reduces the risk of major adverse cardiovascular events (MACE) in people with peripheral artery disease (PAD)., Objective: To test whether a counseling intervention designed to increase walking reduced the risk of MACE in patients with PAD., Design, Setting, and Participants: The BIP trial was a randomized clinical trial, with recruitment performed between January 2015 and July 2018 and follow-up concluded in August 2023. Participants with walking impairment due to PAD from vascular departments in the Australian cities of Brisbane, Sydney, and Townsville were randomly allocated 1:1 to the intervention or control group. Data were originally analyzed in March 2024., Intervention: Four brief counseling sessions aimed to help patients with the challenges of increasing physical activity., Main Outcomes and Measures: The primary outcome was the between-group difference in risk of MACE, which included myocardial infarction (MI), stroke, and cardiovascular death. The relationship between Intermittent Claudication Questionnaire (ICQ) scores, PAD Quality of Life (PADQOL) scores, and MACE was examined with Cox proportional hazard regression analyses., Results: A total of 200 participants were included, with 102 allocated to the counseling intervention (51.0%) and 98 to the control group (49.0%).Participants were followed up for a mean (SD) duration of 3.5 (2.6) years. Median (IQR) participant age was 70 (63-76) years, and 56 of 200 participants (28.0%) were female. A total of 31 individuals had a MACE (composed of 19 MIs, 4 strokes, and 8 cardiovascular deaths). Participants allocated to the intervention were significantly less likely to have a MACE than participants in the control group (10 of 102 participants [9.8%] vs 21 of 98 [21.4%]; hazard ratio [HR], 0.43; 95% CI, 0.20-0.91; P = .03). Greater disease-specific quality of life (QOL) scores at 4 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P < .001; PADQOL factor 3 [symptoms and limitations in physical functioning]: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .01) and at 12 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P = .003; PADQOL factor 3: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .02) were associated with a lower risk of MACE. In analyses adjusted for ICQ or PADQOL factor 3 scores at either 4 or 12 months, allocation to the counseling intervention was no longer significantly associated with a lower risk of MACE., Conclusions and Relevance: This post hoc exploratory analysis of the BIP randomized clinical trial suggested that the brief counseling intervention designed to increase walking may reduce the risk of MACE, possibly due to improvement in QOL., Trial Registration: anzctr.org.au Identifier: ACTRN12614000592640.

Background: Guidelines and international appropriate use criteria increasingly endorse non-invasive stress testing to evaluate patients with suspected chronic coronary disease (CCD). We sought to review the real-world utilisation of non-invasive stress testing and investigate whether their use prior to PCI associates with outcomes in patients with CCD., Methods: Consecutive patients from a multicentre registry who underwent PCI for CCD between 2006 and 2018 were included. Clinical characteristics and outcomes were stratified according to whether stress testing was performed prior to PCI (stress vs no-stress groups). The primary outcome was 3-year all-cause mortality., Results: Among the 8251 patients included, 4970 (60.2 %) underwent pre-PCI stress testing and this proportion increased over time (p-for-trend<0.001). The stress group had a lower prevalence of prior revascularization, myocardial infarction, or heart failure, and a lower incidence of triple vessel disease, in stent re-stenosis, and ACC/AHA class B2/C lesions (all p < 0.001). When comparing post-procedural outcomes, the stress group had lower rates of arrhythmia (1.5 % vs 2.6 %, p = 0.001), new heart failure (0.2 % vs 0.8 %, p = 0.001), renal impairment, and a shorter length of stay (1.6 vs 2.1 days, p < 0.001). Mortality at 3-years was lower in those undergoing PCI following stress testing (5.8 % vs 8.8 %, p < 0.001). After adjusting for key clinical variables, stress guided revascularization was associated with a significantly lower risk of 3-year mortality (adjusted Hazard Ratio 0.77, 95 % CI 0.64-0.92)., Conclusions: In patients with CCD, PCI guided by non-invasive stress testing is increasingly utilized and associated with improved survival. Further studies are necessary to investigate whether this results from differences in patient characteristics, optimized patient selection, or refined choice of target vessel., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To determine the influence of presenting electrocardiographic (ECG) changes on prognosis in acute coronary syndrome cardiogenic shock (ACS-CS) patients undergoing percutaneous coronary angiography (PCI)., Background: The effect of initial ECG changes such as ST-elevation myocardial infarction (STEMI) versus non-STEMI among patients ACS-CS on prognosis remains unclear., Methods: We analysed data from consecutive patients with ACS-CS enrolled in the Victorian Cardiac Outcomes registry between 2014 and 2020. Inverse probability of treatment weighting analysis (IPTW) was used to assess the effect of ECG changes on 30-day mortality., Results: Of 1564 patients with ACS-CS who underwent PCI, 161 had non-STEMI and 1403 had STEMI on ECG. The mean age was 66 ± 13 years, and 74 % (1152) were males. Patients with non-STEMI compared to STEMI were older (70 ± 12 vs 65 ± 13 years), had higher rates of diabetes (34 % vs 21 %), prior coronary artery bypass graft surgery (14 % vs 3.3 %), peripheral arterial disease (10.6 % vs 4.1 %, p < 0.01), and lower baseline eGFR (53.8 [37.1, 75.4] vs 65.3 [46.3, 87.8] ml/min/1.73m 2 ), all p ≤ 0.01. Non-STEMI patients were more likely to have a culprit left circumflex artery (29 % vs 20 %) and more often underwent multivessel percutaneous coronary intervention (30 % vs 20 %) but had lower rates of out-of-hospital cardiac arrest (21 % vs 39 %), all p ≤ 0.01. Propensity score analysis with IPTW confirmed that non-STEMI ECG was associated with lower odds for 30-day all-cause mortality (OR 0.47 [0.32, 0.69], p < 0.001), and 30-day major adverse cardiovascular and cerebrovascular events (OR 0.48 [0.33, 0.70])., Conclusions: In patients undergoing PCI, Non-STEMI as compared to STEMI on index ECG was associated with approximately half the relative risk of both 30-day mortality and 30-day MACCE and could be a useful variable to integrate in ACS-CS risk scores., Competing Interests: Declaration of competing interest Dr. N D’Elia – None; ndelia@utas.edu.au Ms Sara Vogrin – None; sara.vogrin@unimelb.edu.au Ms Angela Brennan – None; angela.brennan@monash.edu Ms Diem Dinh – None; diem.dinh@monash.edu Dr. Jeffrey Lefkovits – None; lefkovits@me.com Professor Christopher Reid – None; christopher.reid@curtin.edu.au A/Prof Dion Stub - Proctor for Medtronic, Edwards and Abbott. Research supported by the National Heart Foundation and NHMRC fellowships; dion.stub@monash.edu Dr. Jason Bloom – None; jason.elliott.bloom@gmail.com Dr. Kawa Haji – None; kaawa22@hotmail.com Dr. Samer Noaman – None; Samerkn@yahoo.com Professor David Kaye – None; david.kaye@alfred.org.au A/Prof Nicholas Cox – None; Nicholas.Cox@wh.org.au A/Prof William Chan – None; william.chan@unimelb.edu.au, (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: While significant sensation recovery improvements in neurotized breasts following reconstruction have been reported, sensation testing methods and surgical techniques have been widely variable. This narrative review aims to summarize available literature on current neurotization practices and sensory recovery outcomes in patients undergoing innervated breast reconstruction., Methods: A comprehensive literature search of PubMed Medline, Web of Science, and Embase was conducted to identify all studies reporting outcomes of neurotization in breast reconstruction surgeries. Data analyzed included operative times, neurotization techniques, sensory outcomes, and methods as well as patient reported outcomes., Key Content and Findings: Despite the heterogeneity of various studies reviewed, all forms of neurotization achieved earlier and superior sensory recovery throughout the reconstructed breast skin compared to non-innervated breasts. In absence of randomized controlled trials or high-quality comparative studies, further evidence is required to objectively confirm this technique offers better sensory recovery., Conclusions: Neurotization at the time of breast reconstruction may lead to improved sensation and patient reported outcomes delineating improved quality of life compared to non-innervated breasts. Future studies need to standardize the way that breast sensation is measured and determine pre-operative variables leading to expected changes in final sensation recovery to help manage surgical outcome expectations of both the surgeon and the patient., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-504/coif). The series “Breast Reconstruction” was commissioned by the editorial office without any funding or sponsorship. O.J.M. served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Annals of Translational Medicine from July 2022 to June 2024. The authors have no other conflicts of interest to declare., (2024 Annals of Translational Medicine. All rights reserved.)

Background: The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD)., Methods: Post hoc analysis using a target trial emulation framework applied to the immediate post-trial period (2017-2021) of a study of low-dose aspirin initiation in adults aged ≥ 70 years (ASPREE; NCT01038583). Participants from Australia and the USA were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0. The two groups in the target trial were as follows: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term) and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models., Results: We included 6103 CVD-free participants (cessation: 5427, continuation: 676). Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE, and all-cause mortality (HRs, at 3 and 48 months respectively, were 1.23 and 0.73 for CVD, 1.11 and 0.84 for MACE, and 0.23 and 0.79 for all-cause mortality, p > 0.05), but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p < 0.05). Similar findings were seen for all outcomes at 6 and 12 months, except for a lowered risk of all-cause mortality in the cessation group at 12 months., Conclusions: Our findings suggest that deprescribing prophylactic aspirin might be safe in healthy older adults with no known CVD., (© 2024. The Author(s).)

Background: Cardiovascular disease contributes substantially to global mortality and morbidity. Respiratory tract infections, particularly influenza, may trigger an increase in the short-term risk of acute myocardial infarction (AMI) and stroke. Recent studies have also linked this risk to other respiratory viruses, including respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pathogen-specific relative contributions, the strength of their associations, and overall public health significance are poorly understood. Assuming causal links, understanding, quantifying, and comparing the effects of different pathogens as triggering factors for acute cardiovascular events is critical to guide future research and prevention. Our aim is to conduct a systematic review to examine the relative effects of laboratory-confirmed respiratory virus infections as triggers for acute myocardial infarction and stroke., Methods: We will conduct a comprehensive search of Ovid MEDLINE, PubMed, Ovid Embase, Cochrane Library Central Register of Controlled Trials, and Web of Science, from inception to the end of March 2024. Studies capturing respiratory viral infection(s) using laboratory-confirmatory methods, incidence of AMI or stroke (ischaemic or haemorrhagic), and those involving human participants in any country, will be assessed for eligibility. We will include the following analytical epidemiological study types: randomised controlled trials, cohort and case-control studies, self-controlled case series, and case-crossover designs. We will not impose restrictions on the date, language, study population, geographical region, or sample size, to minimise the risk of introducing biases. Search results will be screened for eligibility by two independent reviewers, and discrepancies resolved by consensus and/or arbitration by a third reviewer. We will assess the risk of bias among the included studies by adopting the Cochrane Collaboration tools for randomised and non-randomised studies. The overall quality of studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will examine sources of heterogeneity, and if studies are sufficiently homogeneous, a meta-analysis will be conducted to calculate the pooled effect sizes. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42024494997., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort., Method: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest., Results: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality., Conclusions: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future., Competing Interests: Disclosures AB is supported by a University of Melbourne Research Training Program Scholarship. DS is supported by an Australian National Heart Foundation grant. ZN is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (#1146809). CMR is supported by an NHRMC Principal Research Fellowship (GNT 1136372). EA is supported by an NHRMC Postgraduate Scholarship (#2003449). The remaining authors report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Acute decompensated heart failure (ADHF) is a leading cause of cardiovascular disease hospitalisations associated with significant morbidity and mortality. In hospitals, HF patients are typically managed by cardiology or physician teams, with differences in patient demographics and clinical outcomes. This study utilises contemporary HF registry data to compare patient characteristics and outcomes in those with ADHF admitted into General Medicine and Cardiology units., Methods: The Victorian Cardiac Outcomes Registry was utilised to identify patients hospitalised with ADHF 30-day period in each of four consecutive years. We compared patient characteristics, pharmacological management and outpatient follow-up of patients admitted to General Medicine and Cardiology units. Primary outcome measures included in-hospital mortality, 30-day readmission, and 30-day mortality., Results: Between 2014 and 2017, a total of 1,253 patients with ADHF admissions were registered, with 53% admitted in General Medicine units and 47% in Cardiology units. General Medicine patients were more likely to be older (82 vs 71 years; p<0.001), female (51% vs 34%; p<0.001), and have higher prevalence of comorbidities and preserved left ventricular function (p<0.001). There were no differences in primary outcome measures between General Medicine and Cardiology in terms of: in-hospital mortality (5.0% vs 3.9%; p=0.35), 30-day readmission (23.4% vs 23.6%; p=0.93), and 30-day mortality (10.0% vs 8.0%; p=0.21)., Conclusions: Hospitalised patients with HF continue to have high mortality and rehospitalisation rates. The choice of treatment by General Medicine or Cardiology units, based on the particular medical profile and individual needs of the patients, provides equivalent outcomes., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated., Method: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m 2 ) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke., Results: RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality., Conclusions: RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: The American College of Cardiology / American Heart Association (ACC/AHA) introduced a coronary lesion classification in 1988 to stratify coronary lesions for probability of procedural success and complications after coronary angioplasty. Our aim is to assess the validity of the ACC/AHA lesion classification in predicting outcomes of percutaneous coronary intervention (PCI) in a contemporary cohort of patients., Methods: Consecutive PCI procedures performed between 2005 and 2018, were divided into three periods. At each period, the ACC/AHA lesion classification (A, B1, B2, C) was analysed with respect to procedural characteristics, in-hospital and 30-day outcomes, as well as long-term mortality by linkage to the National Death Index (NDI)., Results: In total, 21,437 lesions were included with 7399 lesions (2005-2009), 6917 lesions (2010-2014) and 7121 lesions (2015-2018). There was a progressive increase in the number of complex lesions treated over time with ACC/AHA type C (15 %, 21 % and 26 %, p < 0.01). The rate of PCI procedural success decreased with increase in the complexity of lesions treated across all three periods (p < 0.01). Further, in-hospital and 30-day major adverse cardiovascular events (MACE), major adverse cardiac and cerebrovascular events (MACCE) increased across all three time periods (all p < 0.05)., Conclusions: Our study validates the ACC/AHA lesion classification as a meaningful tool for prediction of PCI outcomes. Despite advances in PCI techniques and technology, complex lesion PCI defined by this classification continues to be associated with adverse outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dion Stub reports a relationship with National Heart Foundation of Australia that includes: funding grants. Dion Stub reports a relationship with National Health and Medical Research Council that includes: funding grants. Disclosure A/Prof. Dion Stub is supported by the National Heart Foundation of Australia and Australian National Health and Medical Research Council fellowships., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs., Methods: We analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression., Results: From 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97))., Conclusions: The proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality., Competing Interests: Competing interests: The Melbourne Interventional Group acknowledges funding from Abbott Vascular, AstraZeneca, Bristol Myers Squibb, Medtronic, and Pfizer. These companies do not have access to data and do not have the right to review manuscripts or abstracts before publication., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Gender influences cardiovascular disease (CVD) through norms, social relations, roles and behaviours. This study identified gender-specific aspects of socialisation associated with CVD., Methods: A longitudinal study was conducted, involving 9936 (5,231 women and 4705 men) initially healthy, community-dwelling Australians aged 70 years or more from the ASPirin in Reducing Events in the Elderly (ASPREE) study and ASPREE Longitudinal Study of Older Persons, with a median follow-up time of 6.4 years. Variable categorisation, variable selection (using machine learning (ML) models; Elastic Net and extreme gradient boosting) and Cox-regression were employed separately by binary gender to identity socialisation factors (n=25 considered) associated with CVD., Results: Different socialisation factors were identified using the ML models. In the Cox model, for both genders, being married/partnered was associated with a reduced risk of CVD (men: HR 0.76, 95% CI 0.60 to 0.96; women: HR 0.67, 95% CI 0.58 to 0.95). For men, having 3-8 relatives they felt close to and could call on for help (HR 0.76, 95% CI 0.58 to 0.99; reference <3 relatives), having 3-8 relatives they felt at ease talking with about private matters (HR 0.70, 95% CI 0.55 to 0.90; reference <3 relatives) or playing games such as chess or cards (HR 0.82, 95% CI 0.67 to 1.00) was associated with reduced risk of CVD. For women, living with others (HR 0.71, 95% CI 0.55 to 0.91) or having ≥3 friends they felt at ease talking with about private matters (HR 0.74, 95% CI 0.58 to 0.95; reference <3 friends) was associated with a lower risk of CVD., Conclusions: This study demonstrates the need to prioritise gender-specific social factors to improve cardiovascular health in older adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study evaluates primary care practices' engagement with various features of a quality improvement (QI) intervention for patients with coronary heart disease (CHD) in four Australian states., Methods: Twenty-seven practices participated in the QI intervention from November 2019 -November 2020. A combination of surveys, semi-structured interviews and other materials within the QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease (QUEL) study were used in the process evaluation. Data were summarised using descriptive statistical and thematic analyses for 26 practices., Results: Sixty-four practice team members and Primary Health Networks staff provided feedback, and nine of the 63 participants participated in the interviews. Seventy-eight percent (40/54) were either general practitioners or practice managers. Although 69% of the practices self-reported improvement in their management of heart disease, engagement with the intervention varied. Forty-two percent (11/26) of the practices attended five or more learning workshops, 69% (18/26) used Plan-Do-Study-Act cycles, and the median (Interquartile intervals) visits per practice to the online SharePoint site were 170 (146-252) visits. Qualitative data identified learning workshops and monthly feedback reports as the key features of the intervention., Conclusion: Practice engagement in a multi-featured data-driven QI intervention was common, with learning workshops and monthly feedback reports identified as the most useful features. A better understanding of these features will help influence future implementation of similar interventions., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134., Competing Interests: The funding body and industry partners were not involved in the design of the study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Amgen and Sanofi Australia have provided cash support to the main study. MW is a consultant to Amgen, Freeline and Kyowa Kirin. Other authors have nothing to disclose. This does not alter our adherence to PLOS ONE policy on sharing data and materials., (Copyright: © 2024 Hafiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering., (© 2024. The Author(s).)

Background: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension., Methods: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs., Results: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m 2 ; P =0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P ≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, β, 0.17 [0.02-0.31] g/m 2 ) or centrally (24-hour systolic BP, β, 0.16 [0.01-0.32] g/m 2 )., Conclusions: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP., Registration: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729., Competing Interests: Disclosures J.E. Sharman is principal investigator of a National Health and Medical Research Council of Australia partnership grant (S0026615) that includes a medical technology company that manufactures a central blood pressure (BP) device, not referred to in this article. He has no personal financial conflicts relating to BP technology. S. Stewart is supported by a National Health and Medical Research Council of Australia Fellowship (GNT 1135894). The other authors report no conflicts.

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: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals., Methods: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke., Results: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants., Conclusions: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention., (© 2024. The Author(s).)

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: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer., Methods: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups., Results: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19)., Conclusions: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI., Methods: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort)., Results: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively., Conclusions: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials., Competing Interests: Disclosures None.

Background: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals., Methods: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models., Results: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05)., Conclusions: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: It is uncertain if the evidence on improved long-term survival of total arterial coronary artery bypass grafting applies to female patients. This study aims to compare the long-term survival outcomes of using total arterial revascularization (TAR) versus at least 1 saphenous vein graft separately for men and women., Methods: This retrospective analysis of the Australian and New Zealand Society of Cardiac-Thoracic Surgical Database had administrative linkage to the National Death Index. We identified all patients undergoing primary isolated coronary bypass from June 2001 to January 2020 inclusive. Following sex stratification, propensity score matching with 36 variables and Cox proportional hazard regression were used to facilitate adjusted comparisons. A Cox interaction-term analysis was performed to investigate the impact of sex on TAR survival benefit. The primary outcome was all-cause mortality., Results: Of the 69 624 eligible patients receiving at least 2 grafts, 13 019 (18.7%) were female patients. Matching generated 14 951 male and 3530 female pairs. Compared to vein-dependent procedures, TAR was associated with significantly reduced incidence of long-term all-cause mortality for both male (hazard ratio, 0.86; 95% confidence interval, 0.81-0.91; P < 0.001) and female (hazard ratio, 0.82; 95% confidence interval, 0.73-0.91; P < 0.001) cohorts. Interaction-term analysis indicated no significant subgroup effect from sex (P = 0.573) on the survival advantage of TAR. The treatment effect provided by TAR remained significant across most sex-stratified disease subgroups., Conclusions: TAR, when compared to the use of at least 1 saphenous vein graft, provides comparable superior long-term survival outcomes in both females and males., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management., Methods and Analysis: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used., Ethics and Dissemination: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings., Trial Registration Number: NCT05972785., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Parker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To optimize the early prediction of prolonged postoperative mechanical ventilation after cardiac surgery (>24 hours postoperatively)., Design: The authors performed a retrospective analysis., Setting: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) database was utilized., Participants: All patients included in the ANZSCTS database between January 2015 and December 2018 were analyzed., Interventions: No interventions were performed in this observational study., Measurements and Main Results: A previously developed model was modified to allow retrospective risk calculation and model assessment (Modified Hessels score). The database was split into development and validation sets. A new risk model was developed using forward and backward stepwise elimination (ANZ-PreVent score). The authors assessed 48,382 patients, of whom 5004 (10.3%) were ventilated mechanically for >24 hours post-operatively. The Modified Hessels score demonstrated good performance in this database, with a c-index of 0.78 (95% CI 0.77-0.78) and a Brier score of 0.08. The newly developed ANZ-PreVent score demonstrated better performance (validation cohort, n = 12,229), with a c-index of 0.84 (95% CI 0.83-0.85) (p < 0.0001) and a Brier score of 0.07. Both scores performed better than the severity of illness scores commonly used to predict outcomes in intensive care., Conclusions: The authors validated a modified version of an existing prediction score and developed the ANZ-PreVent score, with improved performance for identifying patients at risk of ventilation for >24 hours. The improved score can be used to identify high-risk patients for targeted interventions in future randomized controlled trials., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults., Methods: ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (≥65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia. For the post-hoc analysis, we excluded participants with diabetes at baseline or with incomplete or missing incident diabetes data during follow-up. Participants were randomly assigned 1:1 to oral 100 mg daily enteric-coated aspirin or placebo. Incident diabetes was defined as self-reported diabetes, commencement of glucose-lowering medication, or a FPG concentration of 7·0 mmol/L or more assessed at annual follow-up visits among participants with no diabetes at baseline. We used Cox proportional hazards models and mixed-model repeated measures to assess the effect of aspirin on incident diabetes and FPG concentrations in the intention-to-treat population. We assessed major bleeding in participants who had taken at least one dose of study medication., Findings: Between March 10, 2010, and Dec 24, 2014, a total of 16 209 participants were included (8086 [49·9%] randomly assigned to aspirin and 8123 [50·1%] randomly assigned to placebo). During a median follow-up of 4·7 years (IQR 3·6-5·7), 995 (in 6·1% individuals) incident cases of type 2 diabetes were recorded (459 in the aspirin group and 536 in the placebo group). Compared with placebo, the aspirin group had a 15% reduction in risk of incident diabetes (hazard ratio 0·85 [95% CI 0·75 to 0·97]; p=0·013) and a slower rate of increase in FPG concentration at year 5 (between-group difference estimate -0·048 mmol/L [95% CI -0·079 to -0·018]; p=0·0017). Major bleeding (major gastrointestinal bleeding, intracranial bleeding, and clinically significant bleeding at other sites) occurred in 510 (3·2%) of 16 104 participants (300 [3·7%] in the aspirin group and 210 [2·6%] in the placebo group). Compared with placebo, the aspirin group had a 44% increase in risk of major bleeding (hazard ratio 1·44 [95% CI 1·21 to 1·72]; p<0·0001)., Interpretation: Aspirin treatment reduced the incidence of type 2 diabetes and slowed the increase in FPG concentration but increased major bleeding among community-dwelling older adults. Given the increasing prevalence of type 2 diabetes among older adults, the potential for anti-inflammatory agents such as aspirin to prevent type 2 diabetes or improve glucose levels warrants further study with a comprehensive assessment of all potential safety events of interest., Funding: US National Institute on Aging, US National Cancer Institute, National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency., Competing Interests: Declaration of interests MRN reported receiving a meeting honorarium from Bayer and trial product in ASPREE provided by Bayer and Australian National Health and Medical Research Council grant support for STAREE. CMR reported being funded through an Australian National Health and Medical Research Council Principal Research Fellowship. SZ has received payment to their institution from Eli Lilly Australia, Boehringer-Ingelheim, Merck Sharp & Dohme Australia, AstraZeneca, Novo Nordisk, Sanofi, and Servier for consultancy work outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain., Methods: Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up., Results: Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated., Conclusions: High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP., Trial Registration: ClinicalTrials.gov NCT01038583 and ISRCTN83772183., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multimorbidity is strongly associated with disability or functional decline, poor quality of life and high consumption of health care services. This study aimed (1) To identify patterns of multimorbidity among patients undergoing first recorded percutaneous coronary intervention (PCI); (2) To explore the association between the identified patterns of multimorbidity on length of hospital stay, 30-day and 12- month risk of major adverse cardiac and cerebrovascular events (MACCE) after PCI., Methods: A retrospective cohort study of the Melbourne Interventional Group (MIG) registry. This study included 14,025 participants who underwent their first PCI from 2005 to 2015 in Victoria, Australia. Based on a probabilistic modelling approach, Latent class analysis was adopted to classify clusters of people who shared similar combinations and magnitude of the comorbidity of interest. Logistic regression models were used to estimate odd ratios and 95% confidence interval (CI) for the 30-day and 12-month MACCE., Results: More than two-thirds of patients had multimorbidity, with the most prevalent conditions being hypertension (59%) and dyslipidaemia (60%). Four distinctive multimorbidity clusters were identified each with significant associations for higher risk of 30-day and 12-month MACCE. The cluster B had the highest risk of 30-day MACCE event that was characterised by a high prevalence of reduced estimated glomerular filtration rate (92%), hypertension (73%) and reduced ejection fraction (EF) (57%). The cluster C, characterised by a high prevalence of hypertension (94%), dyslipidaemia (88%), reduced eGFR (87%), diabetes (73%) and reduced EF (65%) had the highest risk of 12-month MACCE and highest length of hospital stay., Conclusion: Hypertension and dyslipidaemia are prevalent in at least four in ten patients undergoing coronary angioplasty. This study showed that clusters of patients with multimorbidity had significantly different risk of 30-day and 12-month MACCE after PCI. This suggests the necessity for treatment approaches that are more personalised and customised to enhance patient outcomes and the quality of care delivered to patients in various comorbidity clusters. These results should be validated in a prospective cohort and to evaluate the potential impacts of these clusters on the prevention of MACCE after PCI., (© 2024. The Author(s).)

Background: Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown., Methods: We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality., Results: Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001)., Conclusion: In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hinton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women., Methods: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a &gt;1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio., Results: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26])., Conclusion: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Current evidence suggests that percutaneous coronary intervention for unprotected left main coronary artery disease (LMPCI) in selected patients is a safe alternative to coronary artery bypass grafting. However, real-world long-term survival data is limited., Methods: We analyzed 24,644 patients from the MIG (Melbourne Interventional Group) registry between 2005 and 2020. We compared baseline clinical and procedural characteristics, in-hospital and 30-day outcomes, and long-term survival between unprotected LMPCI and non-LMPCI among patients without ST-segment elevation myocardial infarction, cardiogenic shock, or cardiac arrest., Results: Unprotected LMPCI patients (n = 185) were significantly older (mean age 72.0 vs. 64.6 years, p < 0.001), had higher prevalence of impaired ejection fraction (EF <50 %; 27.3 % vs. 14.9 %, p < 0.001) and lower estimated glomerular filtration rate < 60 ml/min/1.73m 2 (40.9 % vs. 21.5 %, p < 0.001), and had greater use of intravascular ultrasound (21 % vs. 1 %, p < 0.001) and drug-eluting stents (p < 0.001). LMPCI was associated with longer hospital stay (4 days vs. 2 days, p < 0.001). There was no significant difference in other in-hospital outcomes, 30-day mortality (0.6 % vs. 0.6 %, p = 0.90), and major adverse cardiac events (1.7 % vs. 3 %, p = 0.28). Although the unadjusted Kaplan-Meier survival to 8 years was significantly less with LMPCI compared to non-LMPCI (p < 0.01), LMPCI was not a predictor of long-term survival up to 8 years after Cox regression analysis (HR 0.67, 95 % CI 0.40-1.13, p = 0.13)., Conclusion: In this study, non-emergent unprotected LMPCI was uncommonly performed, and IVUS was underutilized. Despite greater co-morbidities, LMPCI patients had comparable 30-day outcomes to non-LMPCI, and LMPCI was not an independent predictor of long-term mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dion Stub reports a relationship with National Heart Foundation of Australia that includes: funding grants. Dion Stub reports a relationship with National Health and Medical Research Council that includes: funding grants., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ)., Method: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI., Results: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy., Conclusions: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Left ventricular (LV) dysfunction and ischaemic heart disease (IHD) are common among women. However, women tend to present later and are less likely to receive guideline-directed medical therapy (GDMT) compared with men., Methods: We analysed prospectively collected data (2005-2018) from a multicentre registry on GDMT 30 days after percutaneous coronary intervention in 13,015 patients with LV ejection fraction <50%. Guideline-directed medical therapy was defined as beta blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker±mineralocorticoid receptor antagonist. Long-term mortality was determined by linkage with the Australian National Death Index., Results: Women represented 20% (2,634) of the total cohort. Mean age was 65±12 years. Women were on average >5 years, with higher body mass index and higher rates of hypertension, diabetes, renal dysfunction, prior stroke, and rheumatoid arthritis. Guideline-directed medical therapy was similar between sexes (73% vs 72%; p=0.58), although women were less likely to be on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80% vs 82%; p=0.02). Women were less likely to be on statin therapy (p<0.001) or a second antiplatelet agent (p=0.007). Women had higher unadjusted long-term mortality (25% vs 19%; p<0.001); however, there were no differences in long-term mortality between sexes on adjusted analysis (hazard ratio 0.99; 95% confidence interval 0.87-1.14; p=0.94)., Conclusions: Rates of GDMT for LV dysfunction were high and similar between sexes; however, women were less likely to be on appropriate IHD secondary prevention. The increased unadjusted long-term mortality in women was attenuated in adjusted analysis, which highlights the need for optimisation of baseline risk to improve long-term outcomes of women with IHD and comorbid LV dysfunction., Competing Interests: Competing Interest Statement SJD’s work is supported by a National Health and Medical Research Council of Australia (NHMRC) Grant (number 1111170). CMR’s work is supported by a NHMRC Principal Research Fellowship (reference no. 1136372)., (Copyright © 2023 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Insufficient data exists regarding the relationship between body mass index (BMI) and the prognosis of chronic heart failure (CHF) specifically within low- and middle-income Asian countries. The objective of this study was to evaluate the impact of BMI on adverse outcomes of ambulatory patients with CHF in Vietnam., Methods: Between 2018 and 2020, we prospectively enrolled consecutive outpatients with clinically stable CHF in an observational cohort, single-center study. The participants were stratified according to Asian-specific BMI thresholds. The relationships between BMI and adverse outcomes (all-cause death and all-cause hospitalization) were analyzed by Kaplan-Meier survival curves and Cox proportional-hazards model., Results: Among 320 participants (age 63.5 ± 13.3 years, 57.9% male), the median BMI was 21.4 kg/m 2 (IQR 19.5-23.6), and 10.9% were underweight (BMI <18.50 kg/m 2 ). Over a median follow-up time of 32 months, the cumulative incidence of all-cause mortality and hospitalization were 5.6% and 19.1%, respectively. After multivariable adjustment, underweight patients had a significantly higher risk of all-cause mortality than patients with normal BMI (adjusted hazard ratios = 3.03 [95% CI: 1.07-8.55]). Lower BMI remained significantly associated with a worse prognosis when analyzed as a continuous variable (adjusted hazard ratios = 1.27 [95% CI: 1.03-1.55] per 1 kg/m 2 decrease for all-cause mortality). However, BMI was not found to be significantly associated with the risk of all-cause hospitalization ( p  > 0.05)., Conclusion: In ambulatory patients with CHF in Vietnam, lower BMI, especially underweight status (BMI < 18.5 kg/m 2 ), was associated with a higher risk of all-cause mortality. These findings suggest that BMI should be considered for use in risk classification, and underweight patients should be managed by a team consisting of cardiologists, nutritionists, and geriatricians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Ha, Tran, Nguyen, Pham, Tran, Pham, Allison, Reid and Kirkpatrick.)

Background and Objectives: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults., Methods: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE -ε4 genetic data with additional adjustment for APOE -ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied., Results: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time ( p ≤ 0.05)., Discussion: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies., (© 2023 American Academy of Neurology.)

Background: It is unknown if the presence of saphenous vein grafting (SVG) adversely affects late survival following coronary surgery with multiple arterial grafting (MAG) versus single arterial grafting., Methods and Results: A retrospective, observational, multicenter cohort study from 2001 to 2020 was conducted using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Database linked to the National Death Index. Patients undergoing primary isolated coronary artery bypass grafting with ≥2 grafts were included, and exclusions were patients aged <18 years, reoperations, concomitant or previous cardiac surgery, and the absence of arterial grafting. Demographics, comorbidities, medication, and operative configurations were propensity score matched between cohorts. The primary outcome was all-cause late death. Of 59 689 eligible patients, 35 113 were MAG (58.8%), and 24 576 were single arterial grafting (41.2%). Of the MAG cohort, 17 055 (48.6%) patients did not receive supplementary SVG (total arterial revascularization). Matching separately generated 22 764 patient pairs for MAG versus single arterial grafting, and 11 137 patient pairs for MAG with total arterial revascularization versus MAG with ≥1 supplementary vein grafts. At a median follow-up duration of 5.0 years postoperatively, the mortality rate was significantly lower for MAG than single arterial grafting (hazard ratio [HR], 0.79 [95% CI, 0.76-0.83]; P <0.001). The stratified MAG analysis found that MAG with total arterial revascularization had a lower risk of late death (HR, 0.85 [95% CI, 0.80-0.91]; P <0.001) compared with MAG with ≥1 supplementary vein grafts. Sensitivity analyses produced consistent outcomes as the primary analysis. Following adjustment for the presence of SVG in the Cox model, the survival advantage of incremental number of arteries was lost., Conclusions: Multiple arterial grafting has significantly improved long-term survival compared with single arterial grafting. A further incremental survival benefit exists when no SVG is used.

Background: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP., Methods: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index., Results: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P <0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P <0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P <0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P =0.001)., Conclusions: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality., Competing Interests: Disclosures None.

Importance: Catheter ablation for patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction (LVEF) and survival compared with medical therapy. Nonrandomized studies have reported improved success with posterior wall isolation (PWI)., Objective: To determine the impact of pulmonary vein isolation (PVI) with PWI vs PVI alone on outcomes in patients with HFrEF., Design, Setting, and Participants: This was an ad hoc secondary analysis of the CAPLA trial, a multicenter, prospective, randomized control trial that involved 11 centers in 3 countries (Australia, Canada, and UK). CAPLA featured 338 patients with persistent AF randomized to either PVI plusPWI or PVI alone. This substudy included patients in the original CAPLA study who had symptomatic HFrEF (LVEF <50% and New York Heart Association class ≥II)., Interventions: Pulmonary vein isolation with PWI vs PVI alone., Main Outcomes and Measures: The primary end point was freedom from any documented atrial arrhythmia greater than 30 seconds, after a single ablation procedure, without the use of antiarrhythmic drug (AAD) therapy at 12 months., Results: A total of 98 patients with persistent AF and symptomatic HFrEF were identified (mean [SD] age, 62.1 [9.8] years; 79.5% men; and mean [SD] LVEF at baseline, 34.6% [7.9%]). After 12 months, 58.7% of patients with PVI plus PWI were free from recurrent atrial arrhythmia without the use of AAD therapy vs 61.5% with PVI alone (hazard ratio, 1.02; 95% CI, 0.54-1.91; P = .96). There were no significant differences in freedom from atrial arrhythmia with or without AAD therapy after multiple procedures (PVI plus PWI vs PVI alone, 60.9% vs 65.4%; P = .73) or AF burden (median, 0% in both groups; P = .78). Mean LVEF improved substantially in PVI plus PWI (∆ LVEF, 19.3% [13.0%; P < .01) and PVI alone (18.2% [14.1%; P < .01), with no difference between groups (P = .71). Normalization of LV function occurred in 65.2% of patients in the PVI plus PWI group and 50.0% of patients with PVI alone (P = .13)., Conclusions and Relevance: The results of this study indicate that addition of PWI to PVI did not improve freedom from arrhythmia recurrence or recovery of LVEF in patients with persistent AF and symptomatic HFrEF. Catheter ablation was associated with significant improvements in systolic function, irrespective of ablation strategy used. These results caution against the routine inclusion of PWI in patients with HFrEF undergoing first-time catheter ablation for persistent AF., Trial Registration: http://anzctr.org.au Identifier: ACTRN12616001436460.

Background: Whether the relative effects of blood pressure (BP)-lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain., Methods: We conducted an individual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data., Results: We included data from 51 randomized controlled trials involving 358 636 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89-0.95] for women and 0.90 [0.88-0.93] for men; P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14)., Conclusions: The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment., Competing Interests: Disclosures K. Rahimi reports personal fees from the BMJ Heart and PLoS Medicine outside the submitted work. M. Woodward reports personal funding from Amgen, Kyowa Kirin, and Freeline outside the current work. The other authors report no conflicts.

Background: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions., Methods: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement., Conclusions: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care., Trial Registration: ACTRN12622001583730., Competing Interests: Disclosures JES is principal investigator of a National Health and Medical Research Council partnership grant (S0026615) on cardiovascular disease risk assessment; among the partners listed on that grant is a medical technology company that manufactures a central BP monitor. AES received speaker honoraria from device manufacturers, Omron and Aktiia. GSS received consulting and lecture fees from several manufacturers for developing blood pressure measuring technologies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)