TAVR using the next-generation THV is clinically safe and effective for treating older patients with severe AS at increased operative risk. (CoreValve Evolut R FORWARD Study [FORWARD]; NCT02592369).

Introduction: In short-term studies, testosterone replacement therapy has been shown to protect male subjects from exercise-induced ischaemia and modify cardiovascular risk factors such as insulin resistance, fat mass and lipid profiles. Methods: This randomised parallel group controlled trial was designed to assess the treatment effect of testosterone therapy (Nebido) compared with placebo in terms of exercise-induced ischaemia, lipid profiles, carotid intima-media thickness (CIMT) and body composition during 12 months treatment in men with low testosterone levels and angina. Results: A total of 15 men were recruited but 13 (nZ13) reached adequate duration of follow-up; seven were treated with testosterone and six with placebo. Testosterone increased time to ischaemia (129G48 s versus 12G18, PZ0.02) and haemoglobin (0.4G0.6 g/dl versus K0.03G0.5, PZ0.04), and reduced body mass index (K0.3 kg/m 2 versus 1.3G1, PZ0.04) and triglycerides (K0.36

Many patients have ilio-femoral vessel anatomy unsuitable for conventional transfemoral (TF) trans-catheter aortic valve implantation (TAVI). Safe and practical alternatives to the TF approach are therefore needed. This study compared outcomes of alternative non-femoral routes, trans-apical (TA), direct aortic (DA) and subclavian (SC), with standard femoral access. In this retrospective study, data from 3,962 patients in the UK TAVI registry were analysed. All patients who received TAVI via a femoral, subclavian, transapical or direct aortic approach were eligible for inclusion. The primary outcome measure was survival up to two years. Median Logistic EuroSCORE was similar for SC, DA, and TA, but significantly lower in the TF cohort (22.1% vs 20.3% vs 21.2% vs 17.0% respectively, p<0.0001). Estimated oneyear survival was similar for TF (84.6±0.7%) and SC (80.5±3%, p=0.27), but significantly worse for TA (74.7±1.6%, p<0.001) and DA (75.2±3.3%, p<0.001). A Cox proportional hazard model was used to analyse survival up to 2-years. Survival in the SC group was not significantly different to the TF group (HR 1.22, 95% CI 0.88-1.70, p=0.24). In contrast, survival in the TA (HR 1.74, 95% CI 1. 43-2.11;p<0.001) and DA (HR 1.55, 95% CI 1.13-2.14; p<0.01) cohorts was significantly reduced compared to TF. In conclusion, trans-apical and direct aortic TAVI were associated with similar survival, both significantly worse than with the trans-femoral route. In contrast, subclavian access was not significantly different to trans-femoral, and may represent the safest non-femoral access route for TAVI.

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IMPORTANCE Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes. OBJECTIVE To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.

ObjectiveTo evaluate the impact of increased age on outcome from a strategy of early invasive management and revascularisation in patients with acute coronary syndromes (ACS).DesignRetrospective analysis of a national Acute Coronary Syndrome registry (ACACIA).SettingMultiple Australian (n=39) centres; 25% rural, 52% with onsite cardiac surgery.PatientsUnselected consecutive patients admitted with confirmed ACS, total n=2559, median 99 per centre.InterventionsManagement was at the discretion of the treating physician. Analysis of outcome based on age >75 years was compared using Cox proportional hazard with a propensity model to adjust for baseline covariates.Main outcome measuresPrimary outcome was all-cause mortality. Secondary outcomes were bleeding and a composite of any vascular event or unplanned readmission.ResultsElderly patients were more likely to present with high-risk features yet were less likely to receive evidence-based medical therapies or receive diagnostic coronary angiography (75% vs 49%, p<0.0001) and early revascularisation (50% vs 30%, p<0.0001). Multivariate analysis found early revascularisation in the elderly cohort to be associated with lower 12-month mortality hazard (0.4 (0.2–0.7)) and composite outcome (0.6 (0.5–0.8)). Propensity model suggested a greater absolute benefit in elderly patients compared to others.ConclusionsFollowing presentation with ACS, elderly patients are less likely to receive evidence-based medical therapies, to be considered for an early invasive strategy and be revascularised. Increasing age is a significant barrier to physicians when considering early revascularisation. An early invasive strategy with revascularisation when performed was associated with substantial benefit and the absolute accrued benefit appears to be higher in elderly patients.

Testosterone is reported to have an acute vasodilating action in vitro, an effect that may impart a favourable haemodynamic response in patients with chronic heart failure. However, the effect of chronic testosterone exposure on general vascular reactivity is poorly described. In the present study, fresh subcutaneous resistance arteries were obtained from patients with heart failure (n=10), healthy controls (n=9) and men with androgen-deficiency (n=17). All arteries were studied using a wire myograph to examine the effect of cumulative additions of testosterone (1 nmol/l-100 micromol/l) compared with vehicle control following maximal pre-constriction with KCl (1-100 micromol/l). The vascular reactivity of arteries from androgen-deficient patients was examined further by recording tension concentration curves to cumulative additions of noradrenaline (1 nmol/l-100 micromol/l) and U46619 (1-300 nmol/l), followed by relaxation concentration curves to additions of ACh (acetylcholine; 10 nmol/l-30 micromol/l) and SNP (sodium nitroprusside; 10 nmol-30 micromol/l) respectively. In all cases, statistical analysis was performed by ANOVA. Patients with proven androgen-deficiency were treated according to clinical recommendations for a minimum of 3 months and further arteries (n=19) were taken for experimentation using the same protocol. In all groups, testosterone was confirmed to be an acute concentration-dependent vasodilator at concentrations > or =1 micromol/l (P=0.0001). The dilating effect of testosterone was augmented in patients with androgen-deficiency prior to treatment, and this effect was abrogated following appropriate testosterone replacement. Testosterone therapy significantly reduced the normal vascular dilating response to ACh and SNP (P<0.01) and significantly increased the contractile response to noradrenaline (P<0.01), but not U46619. Testosterone is an acute dose-dependent vasodilator of resistance arteries. Physiological testosterone replacement attenuates general vascular reactivity in androgen-deficient subjects. The numerous perceived benefits of testosterone replacement may be offset by a decline in vascular reactivity and, therefore, further studies and careful monitoring of patients is recommended.

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