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The dual antiplatelet therapy (DAPT) score was developed to identify patients undergoing percutaneous coronary intervention (PCI) who are likely to derive benefit (score ≥ 2) or harm (score < 2) from extended DAPT beyond 1 year after PCI in terms of ischemic and bleeding outcomes. We examined the associations between DAPT score at index PCI and long-term mortality from an all-comers PCI registry in patients receiving DAPT according to the standard of care.

Graphical AbstractGraphical abstract displacing increased waiting times for women for transcather aortic vale implantation.PCI: Percutaneous coronary intervention. TAVI: Transcatheter aortic valve implantation* Matched for mean pressure gradient across aortic valve, left ventricular ejection fraction, NHYA status, insurance class, ethnicity, procedure date (before versus after start of the pandemic), urgent-inpatient procedure, prior balloon valvuloplasty and valve sheath access method (percutaneous versus surgical cut-down), need for general anaesthesia during procedure

Graphical AbstractCMR final infarct size adjusted for area-at-risk; myocardial salvage index; and LV remodelling in doxycycline- and placebo-treated patients (A& B) and in LAD subgroup (C& D). fIS/AAR, final infarct size adjusted for area-at-risk; MSI, myocardial salvage index; ΔLVEDVi, change in left ventricular end-diastolic volume index and the acute infarct size; LAD, left anterior descending coronary artery. afIS/AAR is multiplied by 100 for graphical presentation.

ObjectiveWe aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD).MethodsPatients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12).ResultsThe mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03).ConclusionsPatients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).

A study was conducted to investigate the short-term and long-term outcomes of percutaneous coronary interventions (PCIs) among contemporary Australian population. Results indicated that there was not much difference in mortality rates and stent thrombosis among patients with drug-eluding stents or bare-metal stents.

AimsThere is a paucity of evidence supporting routine beta blocker (BB) use in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). The aim of this study was to evaluate BB use post PCI and its association with mortality. Furthermore, the study aimed to evaluate the association between BB and mortality in the subgroups of patients with left ventricular ejection fraction (LVEF) <35%, LVEF 35%–50% and LVEF >50%.MethodsUsing a large PCI registry, data from patients with ACS between January 2005 and June 2017 who were alive at 30 days were analysed. Those patients taking BB at 30 days were compared with those who were not taking BB. The primary outcome was all-cause mortality. The mean follow-up was 5.3±3.5 years.ResultsOf the 17 562 patients, 83.3% were on BB. Mortality was lower in the BB group (13.1% vs 19.5%, p=0.0001). Multivariable Cox proportional hazards model showed that BB use was associated with lower overall mortality (adjusted HR 0.87, 95% CI 0.78 to 0.97, p=0.014). In the subgroup analysis, BB use was associated with reduced mortality in LVEF <35% (adjusted HR 0.63, 95% CI 0.44 to 0.91, p=0.013), LVEF 35%–50% (adjusted HR 0.80, 95% CI 0.68 to 0.95, p=0.01), but not LVEF >50% (adjusted HR 1.03, 95% CI 0.87 to 1.21, p=0.74).ConclusionBB use remains high and is associated with reduced mortality. This reduction in mortality is primarily seen in those with reduced ejection fraction, but not in those with preserved ejection fraction.

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Background:Glycoprotein IIb/IIIa inhibitors (GPIs) are a treatment option in the management of acute coronary syndromes (ACSs). Evidence supporting the use of GPIs predates trials establishing the benefits of P2Y12 inhibitors, routine early invasive therapy, and thrombectomy devices in patients with ACS. Objective:The aim of this study was to determine trends in GPI use and their associated outcomes in contemporary practice. Methods:We assessed GPI use in patients with ACS undergoing percutaneous coronary intervention (PCI) from the Melbourne Interventional Group registry (2005-2013). The primary endpoint was the 30-day incidence of major adverse cardiovascular events (MACE). The safety endpoint was in-hospital major bleeding. Results:GPIs were used in 40.5% of 12 357 patients with ACS undergoing PCI. GPI use decreased over the study period (Pfor trend <0.0001). Patients were more likely to receive GPIs if they were younger, presented with a ST-elevation myocardial infarction (STEMI), had more complex (B2/C-type) lesions, and when thrombectomy devices were used (all P< 0.0001). MACE were higher in patients receiving GPI (4.9% vs 4.1%, P= 0.03). Propensity score matching revealed no difference in 30-day mortality and 30-day MACE (odds ratio [OR] = 1.00; 95% CI = 0.99-1.004 and OR = 1.01; 95% CI = 0.99-1.02, respectively). GPI use was associated with more bleeding complications (3.6% vs 1.8%, P< 0.0001). Conclusion and Relevance:GPI use in ACS patients undergoing PCI has declined, and use appears to be dictated by ACS type and lesion complexity, as opposed to high-risk comorbidities. GPI use was associated with a doubling in bleeding complications.

The use of drug-eluting stents (DESS) in patients undergoing percutaneous coronary interventions (PCIs) in Victorian public hospitals, where DESS were implanted in patients having high risk of restenosis based on the guidelines of the Department of Human Services is described. The findings observed that more use of DESS in these patients can improve outcomes by reducing the need for repeat revascularization.

The Problem of Evil in the Western Tradition From the Book of Job to Modern Genetics By Joseph F. Kelly Liturgical Press. 256p $17.95 (paper) ISBN 0814651046 Andrew Delbanco has [...]

The prognosis of patients undergoing percutaneous coronary intervention (PCI) for different subtypes of acute coronary syndromes (ACS) remains unclear. We compared short- and long-term mortality in patients undergoing PCI for unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).

WHEN RELIGION BECOMES EVIL By Charles Kimball HarperCollins, 240 pages, $21.95 Some time ago, Hans Kung sagely observed, 'There can be no world peace without religious peace.' Flash points of [...]

Contrast-induced nephropathy (CIN) is a common condition that is associated with short- and, likely, long-term adverse outcomes. Although periprocedural intravenous hydration is the simplest and most widely used technique to prevent CIN, the limited ability of this approach to mitigate the CIN risk in high-risk populations has provided an impetus to develop new preventive strategies. A range of potentially useful device-based approaches offers new preventive techniques. Well-designed and adequately powered randomized studies of these device-based therapies are urgently needed to determine the expanding role they will play in future clinical practice.

Experimental studies suggest that deferoxamine (DFO) limits the generation of reactive oxygen species by chelating redox-active iron and thereby may reduce ischemia-reperfusion injury and myocardial infarct (MI) size. We investigated whether DFO administered before reperfusion by primary percutaneous coronary intervention (PPCI) would ameliorate oxidative stress and MI size.

High-density lipoprotein (HDL) is best known for its anti-atherosclerotic actions; however, emerging evidence suggests that it also has direct beneficial actions on plasma glucose control through multiple mechanisms. This Review discusses emerging evidence for the role of HDL-mediated glucose regulation in the pathophysiology of type 2 diabetes mellitus and the therapeutic potential for HDL elevation to prevent and manage the disease.

We recently demonstrated that reconstituted high-density lipoprotein (rHDL) modulates glucose metabolism in humans via both AMP-activated protein kinase (AMPK) in muscle and by increasing plasma insulin. Given the key roles of both AMPK and insulin in fatty acid metabolism, the current study investigated the effect of rHDL infusion on fatty acid oxidation and lipolysis. Thirteen patients with type 2 diabetes received separate infusions of rHDL and placebo in a randomized, cross-over study. Fatty acid metabolism was assessed using steady-state tracer methodology, and plasma lipids were measured by mass spectrometry (lipidomics). In vitro studies were undertaken in 3T3-L1 adipocytes. rHDL infusion inhibited fasting-induced lipolysis (P = 0.03), fatty acid oxidation (P < 0.01), and circulating glycerol (P = 0.04). In vitro, HDL inhibited adipocyte lipolysis in part via activation of AMPK, providing a possible mechanistic link for the apparent reductions in lipolysis observed in vivo. In contrast, circulating NEFA increased after rHDL infusion (P < 0.01). Lipidomic analyses implicated phospholipase hydrolysis of rHDL-associated phosphatidylcholine as the cause, rather than lipolysis of endogenous fat stores. rHDL infusion inhibits fasting-induced lipolysis and oxidation in patients with type 2 diabetes, potentially through both AMPK activation in adipose tissue and elevation of plasma insulin. The phospholipid component of rHDL also has the potentially undesirable effect of increasing circulating NEFA.

There is some controversy regarding whether vascular responses to endothelin are altered in hypercholesterolemia. Studies performed to date have been compromised by the use of endothelin antagonists at inappropriate concentrations. In the current study, we examine the role of endothelin-1 in hypercholesterolemic patients using lower, more selective doses of specific endothelin antagonists. Twenty-two patients with hypercholesterolemia (total plasma cholesterol > 6.0 mmol/l) and 17 healthy controls were recruited. Forearm vascular responses to endothelin-1 (5 pmol/min), the endothelin A antagonist BQ-123 (10 nmol/min), and the endothelin B antagonist BQ-788 (1 nmol/min) were obtained. Endothelin-1 caused a significant vasoconstriction in both hypercholesterolemic and control subjects, an effect that was not significantly different between the two groups (P = 0.784). BQ-123 caused a significant vasodilatation that was not significantly different between the two groups (P = 0.899). Similarly, responses to BQ-788 (P = 0.774) and mean plasma endothelin-1 levels were not different (control vs. hypercholesterolemia, 1.16 ± 0.18 vs. 1.06 ± 0.15 fmol/ml; P = 0.64). Responses to neither exogenous nor endogenous endothelin are influenced by plasma cholesterol levels in humans. It is thus unlikely that the endothelin system contributes to early vascular disease pathology in patients with hypercholesterolemia.

ABSTRACTTheologians have long recognized that the Augustinian formulation of the doctrine of original sin, based on a historicized reading of Genesis 3, is at odds with biblical scholarship and with what science has established concerning our evolutionary origins. Setting aside Augustine's anti-Gnostic Adamic myth, some attempt to recast the doctrine within an evolutionary worldview by developing an anthropology within the framework of genetics and sociobiology, now evolutionary psychology. This essay argues that a wholly biological explanation of the human tendency to evil is inadequate, even reductionist, and it attempts a constructive reformulation of the doctrine that, while incorporating insights of evolutionary psychology, appeals also to ontological, psychological, and social dimensions of humanity that must also be considered if we are to retrieve the central, still valid point of the doctrine, that deep within human being there inheres a proclivity to evil.

There continues to be considerable interest in the concept that antioxidant therapy may reduce cardiovascular risk. Phenols have antioxidant properties and may be important micronutrients. Epidemiological studies have demonstrated a strong link between phenolic intake and reduced cardiovascular risk, but the mechanism of benefit has not been determined.

Studies have recently demonstrated that long-term oestrogen therapy improves endothelium-dependent and endothelium-independent vasodilatation in the conductance vessels of biological males. We sought to determine if an acute single dose of oestrogen might similarly improve vasodilator function in young males. In a randomized, double-blind, placebo-controlled, crossover study, we compared the effects of 1 mg of sublingual 17β-oestradiol (E2) and placebo on endothelium-dependent and endothelium-independent vasodilatation in the brachial artery using a non-invasive ultrasound technique. We recruited 30 young males based on a power calculation. Neither acute sublingual oestrogen nor placebo affected flow-mediated vasodilatation [5.32±0.78% and 5.28±0.60% respectively (mean±S.E.M.), P = 0.94]. Responses to nitroglycerine were similar after oestrogen or placebo (16.01±0.86% and 15.29±1.19%, P = 0.47). Basal blood flow and flow during reactive hyperaemia did not differ after oestrogen or placebo. Heart rate and blood pressure were similar during both treatment phases of the study. The absolute change in serum oestradiol levels was greater after the oestrogen treatment phase than after placebo (1509±87 versus -13±4 pmol/l, P < 0.0001). Despite achieving supra-physiological oestradiol levels, the acute administration of sublingual E2 does not appear to improve endothelium-dependent or endothelium-independent vasodilatation, at least acutely, in the brachial artery of young males. In keeping with our previous study, these data suggest that a period of oestrogen ‘priming’ (possibly to induce receptor-mediated nitric oxide synthesis) may be required to yield an improvement in vascular function in males.

High-resolution solid-state 27Al and 31P MAS NMR has been used to investigate the nature of aluminium- and phosphorus-containing solids formed during wastewater treatment. Although difficult to characterize by conventional techniques, these amorphous solids can be characterized by MAS NMR, providing information about their short-range ordering. In the present study, most of the solids were precipitated under conditions of high alkalinity, similar to those encountered during wastewater treatment. The ageing time of the aluminum hydroxide prior to the addition of phosphate (t1), the ageing time of the aluminum hydroxyphosphates after the addition of phosphate (t2), and the phosphorus to aluminum molar ratio were controlled while the effects of changing the parameters were examined. It was found that the aluminum MAS NMR chemical shift was related to the amount of phosphate present in the solid, which in turn was related to t1, t2, and the P:Al molar ratio. The results also lend support to the hypothesis that phosphate removal occurs through an adsorption process onto amorphous aluminum hydroxide, rather than through direct precipitation of aluminum phosphate. The increased understanding of aluminum and phosphate chemistry and the species formed during wastewater treatment will be useful in optimizing wastewater treatment processes. Keywords: aluminum, phosphate, NMR, activated sludge, wastewater treatment.

Objectives. This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women.

Background:Recent studies indicate that transcatheter aortic valve replacement (TAVR) is non-inferior to surgical aortic valve replacement (SAVR) in low-risk patients with severe symptomatic aortic stenosis (AS). However, the cost-effectiveness of TAVR in these patients is unknown. We aimed to perform a cost-effectiveness analysis comparing balloon-expandable and self-expanding TAVR to SAVR in patients with severe AS at low surgical risk.Methods:A Markov model with monthly cycles was constructed to estimate the cost-effectiveness of TAVR compared to SAVR over a ten-year horizon. The perspective was that of the Australian healthcare system. Key data inputs for the model were drawn from the PARTNER 3 trial for balloon-expandable TAVR, and from the Evolut Low Risk trial for self-expanding TAVR. Deterministic and probabilistic sensitivity analyses were performed to assess model uncertainty.Results:Although procedural costs were higher for TAVR than SAVR, overall costs for TAVR were lower due to a shorter length of hospital and intensive care stay, lower acute complication costs and reduced need for rehabilitation. Over ten years, balloon-expandable TAVR lowered costs by AUD$3,085 (USD$2,141) and increased quality-adjusted life years (QALYs) by 0.15 compared to SAVR, while self-expanding TAVR lowered costs by AUD$425 (USD$295) and increased QALYs by 0.07. Thus, from a health economic perspective, TAVR was dominant over SAVR. Results were robust to sensitivity analyses, with balloon-expandable TAVR being dominant in 61% of 10,000 Monte Carlo iterations and cost-effective in 85% of iterations (at an incremental cost-effectiveness ratio threshold of AUD$50,000 per QALY saved). Self-expanding TAVR was dominant in 51% of iterations and cost-effective in 67% of iterations.Conclusions:Among low-risk patients with severe symptomatic AS, both balloon-expandable and self-expanding TAVR are likely to be cost-effective relative to SAVR.

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Aims The suitability of percutaneous coronary intervention (PCI), compared with coronary artery bypass grafting (CABG), for patients with complex multivessel coronary artery disease (MVCAD) remains a contentious topic. While the body of evidence regarding the clinical effectiveness of these revascularization strategies is growing, there is limited evidence concerning their long-term cost-effectiveness. We aim to critically appraise the body of literature investigating the cost-effectiveness of CABG compared with PCI using stents, and to assess the quality of the economic evidence available. Methods and results A systematic review was performed across six electronic databases; Medline, Embase, the NHS Economic Evaluation Database, the Database of Abstracts of Reviews of Effects, the health technology assessment database, and the Cochrane Library. All studies comparing economic attractiveness of CABG vs. PCI using bare-metal stents (BMS) or drug-eluting stents (DES) in balanced groups of patients were considered. Sixteen studies were included. These comprised studies of conventional CABG vs. BMS (n = 8), or DES (n = 4); off-pump CABG vs. BMS (n = 2), or DES (n = 1); and minimally invasive direct CABG vs. BMS (n = 2). The majority adopted a healthcare payer perspective (n = 14). The incremental cost-effectiveness ratios (ICERs) reported across studies varied widely according to perspective and time horizon. Favourable lifetime ICERs were reported for CABG in three trials. For patients with left main coronary artery disease, however, DES was reported as the dominant (more effective and cost-saving) strategy in one study. Conclusion Overall, CABG rather than PCI was the favoured cost-effective treatment for complex MVCAD in the long term. While the evidence base for the cost-effectiveness of DES compared with CABG is growing, there is a need for more evaluations adopting a societal perspective, and time horizons of a lifetime or 10 or more years.

Objective: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. Methods: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-<$O_SCPLOW>L<$C_SCPLOW>-arginine (<$O_SCPLOW>L<$C_SCPLOW>-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n=20) and control (n=20) subjects were age- and gender-matched. Results: Total cholesterol (6.9±0.3 vs. 4.6±0.1 mmol/l, P<0.0001), low density lipoprotein (4.9±0.4 vs. 2.7±0.1 mmol/l, P<0.001) and triglyceride (1.3±0.2 vs. 0.8±0.1 mmol/l, P=0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1±1.9 vs. 17.6±2.2 ml/100 ml/min, P=0.03), and reduced the peak response to sodium nitroprusside (6.0±0.4 vs. 8.1±0.6 ml/100 ml/min, P<0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1±1.0 vs. 13.2±1.0 ml/100 ml/min, P=1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by <$O_SCPLOW>L<$C_SCPLOW>-NMMA to a similar degree (by 33% vs. 40%, P=0.17) in both groups. Although <$O_SCPLOW>L<$C_SCPLOW>-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P=0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. Conclusions: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.