A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility.

Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical Gαq/11-RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron's epigenetic state.

ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER.

Cellular versatility depends on accurate trafficking of diverse proteins to their organellar destinations. For the secretory pathway (followed by approximately 30% of all proteins), the physical nature of the vessel conducting the first portage (endoplasmic reticulum [ER] to Golgi apparatus) is unclear. We provide a dynamic 3D view of early secretory compartments in mammalian cells with isotropic resolution and precise protein localization using whole-cell, focused ion beam scanning electron microscopy with cryo-structured illumination microscopy and live-cell synchronized cargo release approaches. Rather than vesicles alone, the ER spawns an elaborate, interwoven tubular network of contiguous lipid bilayers (ER exit site) for protein export. This receptacle is capable of extending microns along microtubules while still connected to the ER by a thin neck. COPII localizes to this neck region and dynamically regulates cargo entry from the ER, while COPI acts more distally, escorting the detached, accelerating tubular entity on its way to joining the Golgi apparatus through microtubule-directed movement.

An open-access volume electron microscopy atlas of whole cells and tissues.

Understanding cellular architecture is essential for understanding biology. Electron microscopy (EM) uniquely visualizes cellular structures with nanometre resolution. However, traditional methods, such as thin-section EM or EM tomography, have limitations in that they visualize only a single slice or a relatively small volume of the cell, respectively. Focused ion beam-scanning electron microscopy (FIB-SEM) has demonstrated the ability to image small volumes of cellular samples with 4-nm isotropic voxels1. Owing to advances in the precision and stability of FIB milling, together with enhanced signal detection and faster SEM scanning, we have increased the volume that can be imaged with 4-nm voxels by two orders of magnitude. Here we present a volume EM atlas at such resolution comprising ten three-dimensional datasets for whole cells and tissues, including cancer cells, immune cells, mouse pancreatic islets and Drosophila neural tissues. These open access data (via OpenOrganelle2) represent the foundation of a field of high-resolution whole-cell volume EM and subsequent analyses, and we invite researchers to explore this atlas and pose questions.

Outcomes of thrombus aspiration during primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Previous large multi-centre randomised controlled trials have not provided clear benefit with routine intracoronary thrombus aspiration (TA) as an adjunct to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). AIM: To determine whether there is a difference in outcomes with the use of manual TA prior to PCI, compared with PCI alone in a cohort of patients with STEMI. METHODS: We analysed data from 6270 consecutive patients undergoing primary PCI for STEMI prospectively enrolled in the Melbourne Interventional Group registry between 2007 and 2018. Multivariable analysis was performed to determine predictors of 30-day major adverse cardiovascular and cerebrovascular events (MACCE) and long-term mortality. RESULTS: We compared 1621 (26%) patients undergoing primary PCI with TA to 4649 (74%) patients undergoing PCI alone. Male gender (81% vs 78%; P < 0.01), younger age (61 vs 63 years; P = 0.03), GP-IIb/IIIa use (76% vs 58%, P < 0.01), and current smoking (40% vs 36%; P < 0.01) were more common in the TA group. TA was more likely to be used in patients with complex lesions (83% vs 66%; P < 0.01) with TIMI 0 flow (77% vs 56%; P < 0.01). No significant difference in post-procedural TIMI flow, stroke, 30-day mortality, or long-term mortality were identified. Multivariable analysis demonstrated a reduction in 30-day MACCE (hazard ratio (HR) 0.75; confidence interval (CI) 0.63-0.89; P < 0.01) in the TA group, but was not associated with long-term mortality (HR 0.98; CI 0.85-1.1; P = 0.73). CONCLUSION: The use of TA in patients undergoing primary PCI for STEMI was not associated with improved short or long-term mortality when compared with PCI alone.

Impact of prehospital opioid dose on angiographic and clinical outcomes in acute coronary syndromes.

BACKGROUND: An adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS. METHODS: Patients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not. RESULTS: 10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001). CONCLUSIONS: Opioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.

Sex Differences in Pharmacotherapy and Long-Term Outcomes in Patients With Ischaemic Heart Disease and Comorbid Left Ventricular Dysfunction.

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.

Long-term mortality in asymptomatic patients with stable ischemic heart disease undergoing percutaneous coronary intervention.

OBJECTIVES: Patients with stable ischemic heart disease (SIHD) may present with a variety of symptoms including typical angina, angina equivalents such as dyspnea or no symptoms. We sought to determine whether symptom status affects periprocedural safety and long-term mortality in patients undergoing PCI. METHODS: Prospectively enrolled consecutive patients undergoing PCI for SIHD at six hospitals in Australia between 2005 to 2018 as part of the Melbourne Interventional Group registry. Symptom status was recorded at the time of PCI and patients undergoing staged PCI were excluded. RESULTS: Overall, 11,730 patients with SIHD were followed up for a median period of 5 years (maximum 14.0 years, interquartile range 2.2-9.0 years) with 1,317 (11.2%) being asymptomatic. Asymptomatic patients were older, and more likely to be male, have triple-vessel disease, with multiple comorbidities including renal failure, diabetes and heart failure (all P < .01). These patients had significantly higher rates of periprocedural complications and major adverse cardiovascular events at 30-days. Long-term mortality was significantly higher in asymptomatic patients (27.2% vs 18.0%, P < .001). On cox regression for long-term mortality, after adjustment for more important clinical variables, asymptomatic status was an independent predictor (Hazard ratio (HR) 1.39 95% CI 1.16-1.66, P < .001). CONCLUSIONS: In a real-world cohort of patients undergoing revascularization for SIHD, absence of symptoms was associated with higher rates of periprocedural complications and, after adjustment for more important clinical variables, was an independent predictor of long-term mortality. As the primary goal of revascularization in SIHD remains angina relief, the appropriateness of PCI in the absence of symptoms warrants justification.

Diabetes mellitus is independently associated with early stent thrombosis in patients undergoing drug eluting stent implantation: Analysis from the Victorian cardiac outcomes registry.

BACKGROUND: Diabetes mellitus (DM) is a predictor of restenosis and late stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting-stents (DES). Real-world data on rates of early ST is lacking. We compared clinical outcomes of patients with and without DM from the Victorian cardiac outcomes registry. METHODS: Consecutive patients undergoing PCI with DES were analyzed with primary outcome being ST at 30-days. Secondary outcomes including major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Of 43,209 patients included, 9730 (22.5%) had DM. At 30 days, DM was independently associated with higher rates of early ST (0.7% vs. 0.5%) OR 1.41 (95% confidence interval; 1.05-1.87, p = 0.02), MACE (4.1% vs. 3.5%, p = 0.004) and mortality (1.9% vs. 1.5%, p = 0.01). Increased risk was not simply due to treatment. Patients with DM requiring insulin were equally affected in regard to MACE (4.7% vs. 3.9%, p = 0.069) and mortality (1.9%, vs. 1.8%, p = 0.746). On National Death Index linkage, patients with DM had increased all-cause mortality over five-year follow-up (OR 1.69 CI 1.55-1.83, p = < 0.001). CONCLUSION: In this large real-world-registry, DM was an independent predictor of early ST, MACE and mortality at 30 days. These data suggest additional therapeutic strategies are required to reduce the risk of early complications in patients with DM undergoing PCI with DES.

Adverse 30-Day Clinical Outcomes and Long-Term Mortality Among Patients With Preprocedural Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: Approximately 5-10% of patients presenting for percutaneous coronary intervention (PCI) have concurrent atrial fibrillation (AF). To what extent AF portends adverse long-term outcomes in these patients remains to be defined. METHODS: We analysed data from the multicentre Melbourne Interventional Group Registry from 2014-2018. Patients were identified as being in AF or sinus rhythm (SR) at the commencement of PCI. The primary endpoint was long-term mortality, obtained via linkage with the National Death Index. RESULTS: 13,286 procedures were included, with 800 (6.0%) patients in AF and 12,486 (94.0%) in SR. Compared to SR, patients with AF were older (72.9±10.9 vs 64.1±12.0 p<0.001) and more likely to have comorbidities including diabetes mellitus (31.3% vs 25.0% p<0.001), hypertension (74.4% vs 65.1% p<0.001) and moderate to severe left ventricular systolic dysfunction (36.6% vs 19.5% p<0.001). Atrial fibrillation was associated with an increased risk of in-hospital mortality (11.0% vs 2.5% p<0.001) and MACE (composite of all-cause mortality, myocardial infarction, or target vessel revascularisation) (11.9% vs 4.2% p<0.001). In-hospital major bleeding was more common in the AF group (3.1% vs 1.0% p<0.001). On Cox proportional hazards modelling, AF was an independent predictor of long-term mortality (adjusted HR 1.38 95% CI 1.11-1.72 p<0.004) at a mean follow-up of 2.3±1.5 years. CONCLUSIONS: Preprocedural AF is common among patients presenting for PCI. Preprocedural AF is associated with high-rates of comorbid illnesses and portends higher risk of short- and long-term outcomes including mortality underscoring the need for careful evaluation of its risks prior to PCI.

Trends and Real-World Safety of Patients Undergoing Percutaneous Coronary Intervention for Symptomatic Stable Ischaemic Heart Disease in Australia.

BACKGROUND: Percutaneous coronary intervention (PCI) in stable ischaemic heart disease (SIHD) has not been shown to improve prognosis but can alleviate symptoms and improve quality of life. Appropriately selected patients with symptoms refractory to medical therapy therefore stand to benefit, provided safety is proven. METHODS: Consecutive patients undergoing PCI for SIHD between 2005-2018 in a prospective registry were included. Yearly comparisons evaluated trends, and a sub-analysis was performed comparing proximal left anterior descending artery (prox-LAD) to other-than-proximal LAD (non-pLAD) PCI. Outcomes included peri-procedural characteristics, in-hospital and 30-day event rates including MACE, and 5-year National Death Index (NDI) linked mortality. RESULTS: There were 9,421 procedures included. Over time, patients were increasingly co-morbid and had higher rates of AHA/ACC class B2/C lesions, ostial stenoses, bifurcation lesions, and chronic total occlusions (all p-for-trend ≤0.001). Over 14 years, major bleeding reduced (1.05% in 2005/06 vs 0.29% in 2017/18, p-for-trend <0.001), while other in-hospital and 30-day event rates were stably low. There were only seven (0.07%) in hospital deaths and 5-year mortality was 10.3%. No differences were found in outcomes between patients who underwent prox-LAD compared to non-pLAD PCI. Major independent predictors of NDI linked all-cause mortality included an eGFR <30 mL/min/1.73 m2 (HR 4.06, 95% CI 3.26-5.06), chronic obstructive pulmonary disease (COPD) (HR 2.25, 95% CI 1.89-2.67) and LVEF <30% (HR 2.13, 95% CI 1.57-2.89). CONCLUSIONS: Although patient and procedural complexity increased over time, a high degree of procedural success and safety was maintained, including in those undergoing prox-LAD PCI. These real-world data can enhance shared decision making discussions regarding whether PCI should be pursued in patients with symptomatic SIHD refractory to medical therapy.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

Effect of Age on Clinical Outcomes in Elderly Patients (>80 Years) Undergoing Percutaneous Coronary Intervention: Insights From a Multi-Centre Australian PCI Registry.

OBJECTIVES: To evaluate the effect of age in an all-comers population undergoing percutaneous coronary intervention (PCI). BACKGROUND: Age is an important consideration in determining appropriateness for invasive cardiac assessment and perceived clinical outcomes. METHODS: We analysed data from 29,012 consecutive patients undergoing PCI in the Melbourne Interventional Group (MIG) registry between 2005 and 2017. 25,730 patients <80 year old (78% male, mean age 62±10 years; non-elderly cohort) were compared to 3,282 patients ≥80 year old (61% male, mean age 84±3 years; elderly cohort). RESULTS: The elderly cohort had greater prevalence of hypertension, diabetes and previous myocardial infarction (all p<0.001). Elderly patients were more likely to present with acute coronary syndromes, left ventricular ejection fraction <45% and chronic kidney disease (p<0.0001). In-hospital, 30-day and long-term all-cause mortality (over a median of 3.6 and 5.1 years for elderly and non-elderly cohorts, respectively) were higher in the elderly cohort (5.2% vs. 1.9%; 6.4% vs. 2.2%; and 43% vs. 14% respectively, all p<0.0001). In multivariate Cox regression analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (HR 3.8, 95% CI: 3.4-4.3), cardiogenic shock (HR 3.0, 95% CI: 2.6-3.4), ejection fraction <30% (HR 2.5, 95% CI: 2.1-2.9); and age ≥80 years (HR 2.8, 95% CI: 2.6-3.1) were independent predictors of long-term all-cause mortality (all p<0.0001). CONCLUSION: The elderly cohort is a high-risk group of patients with increasing age being associated with poorer long-term mortality. Age, thus, should be an important consideration when individualising treatment in elderly patients.

Clinical outcomes following ST-elevation myocardial infarction secondary to stent thrombosis treated by percutaneous coronary intervention.

OBJECTIVES: To assess the clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) secondary to stent thrombosis (ST) compared to those presenting with STEMI secondary to a de novo culprit lesion and treated by percutaneous coronary intervention (PCI). BACKGROUND: ST is an infrequent but serious complication of PCI with substantial associated morbidity and mortality, however with limited data. METHODS: We studied consecutive patients who underwent PCI for STEMI from 2005 to 2013 enrolled prospectively in the Melbourne Interventional Group registry. Patients were divided into two groups: the ST group comprised patients where the STEMI was due to ST and the de novo group formed the remainder of the STEMI cohort and all patients were treated by PCI. The primary endpoint was 30-day all-cause mortality. RESULTS: Compared to the de novo group (n = 3,835), the ST group (n = 128; 3.2% of STEMI) had higher rates of diabetes, hypertension and dyslipidemia, established cardiovascular diseases, myocardial infarction, and peripheral vascular disease, all p < .01. Within the ST group, very-late ST was the most common form of ST, followed by late and early ST (64, 19, and 17%, respectively). There was no significant difference in the primary outcome between the ST group and the de novo group (4.7 vs. 7.1%, p = .29). On multivariate analysis, ST was not an independent predictor of 30-day mortality (odds ratio: 0.62, 95% confidence interval: 0.07-1.09, p = .068). CONCLUSION: The short-term prognosis of patients with STEMI secondary to ST who were treated by PCI was comparable to that of patients with STEMI due to de novo lesions.

Outcomes of cardiogenic shock complicating acute coronary syndromes.

OBJECTIVES: We aimed to assess the outcomes of cardiogenic shock (CS) complicating acute coronary syndromes (ACS). BACKGROUND: CS remains the leading cause of mortality in patients presenting with ACS despite advances in care. METHODS: We studied 13,184 patients undergoing percutaneous coronary intervention (PCI) for all subtypes of ACS enrolled prospectively in a large multicentre Australian registry (Melbourne Interventional Group registry) from 2005 to 2013. All-cause mortality was obtained via linkage to the National Death Index. Patients were divided into those with and those without CS. RESULTS: Compared to the non-CS group (n = 12,548, 95.2%), the CS group (n = 636, 4.8%) had a higher proportion of out-of-hospital cardiac arrest (OHCA) (31.1 vs. 2.2%) and ST-elevation myocardial infarction (STEMI) presentation (89 vs. 34%), both p < .01. Patients in the CS group had higher rates of in-hospital (40.4 vs. 1.2%) and 30-day (41 vs. 1.7%) mortality compared to the non-CS group. Long-term mortality over a median follow-up of 4.2 years was higher in the CS group (50.6 vs. 13.8%), p < .001. Trends of in-hospital and 30-day mortality rates of CS complicating ACS were relatively stable from 2005 to 2013. Predictors of long-term NDI-linked mortality within the CS group include severe left ventricular systolic dysfunction (HR 3.0), glomerular filtration rate (GFR) <30 (HR 2.56), GFR 30-59 (HR 1.94), OHCA (HR 1.46), diabetes (HR 1.44), and age (HR 1.02), all p < .05. CONCLUSIONS: Rates of CS-related mortality complicating ACS have remained very high and steady over nearly a decade despite progress in STEMI systems of care, PCI techniques, and medical therapy.

Trends of Use and Outcomes Associated With Glycoprotein-IIb/IIIa Inhibitors in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

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 (P for 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 Impact of Out-of-Hours Presentation on Clinical Outcomes in ST-Elevation Myocardial Infarction.

BACKGROUND: Systems of care have been established to ensure patients with ST-elevation myocardial infarction (STEMI) get timely access to primary percutaneous coronary intervention (PPCI). In this study, we evaluated whether patients undergoing PPCI both in-hours and out-of-hours experience similar care and clinical outcomes. METHODS: Of 9,865 patients who underwent PCI for STEMI from 2005 to 2016 and were enrolled in the multi-centre Melbourne Interventional Group registry, patients who had initially presented to a non-PCI capable hospital, received thrombolysis or presented >12hourspost-symptom onset were excluded. Our final study cohort of 4,590 patients were dichotomised by whether PPCI was performed in-hours or out-of-hours, and compared. The primary outcome was 30-day mortality. RESULTS: The in-hours group included 1,865 patients (40.6%) while 2,725 patients (59.4%) had out-of-hours PPCI. Patients presenting out-of-hours had longer median door-to-balloon time (DTBT; 83 [IQR 61-109] vs. 60 [IQR 41-88] mins, p<0.01) and were more likely to receive a drug-eluting stent (p=0.001). Procedural characteristics were otherwise similar although rates of radial access were low overall (18.4%). No differences in in-hospital, 30-day or 12-month mortality were observed between the groups (p=NS). On Cox proportional hazards modelling, out-of-hours presentation was not an independent predictor of 30-day mortality (HR 0.94, 95% CI 0.71-1.22). A landmark analysis of data from 2012 did not change the primary outcome. CONCLUSION: Despite a slightly longer DTBT, patients undergoing PPCI out-of-hours experienced similar care and clinical outcomes to the in-hours group. Given the majority of patients with STEMI present out-of-hours, these data have implications for STEMI systems of care.

Trends and predictors of recurrent acute coronary syndrome hospitalizations and unplanned revascularization after index acute myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: Repeat hospitalizations for recurrent acute coronary syndrome (ACS) or unplanned revascularization after acute myocardial infarction (MI) are common, costly and potentially preventable. We aim to describe 10-year trends and identify independent risk factors of these repeat hospitalizations. METHODS: We analyzed data from 9615 patients from the Melbourne Interventional Group registry (2005-2014) who underwent percutaneous coronary intervention (PCI) for their index MI and survived to discharge. Patients with ≥1 hospitalization for recurrent ACS events and/or unplanned revascularization in the year after discharge were included in the recurrent coronary hospitalization group. We assessed yearly trends of recurrent coronary events and identified independent predictors using multivariate analysis. RESULTS: Recurrent coronary hospitalization occurred in 1175 (12.2%) patients. There was a significant decrease in the rate of recurrent ACS hospitalization (15.3%-7.6%, P for trend <.001) and unplanned revascularization (4.2%-2.1%, P for trend = .01), but not in all-cause re-hospitalizations (P for trend = .28). On multivariate analysis, female gender, diabetes mellitus, previous coronary bypass surgery, previous PCI, reduced ejection fraction, heart failure, multi-vessel coronary disease and obstructive sleep apnea were independent predictors of recurrent coronary hospitalizations (all P < .05). CONCLUSIONS: Recurrent hospitalization for ACS or unplanned revascularization has decreased significantly over the past decade. Risk factors for such events are numerous and largely non-modifiable, however they identify a cohort of patients in whom non-culprit vessel PCI in multi-vessel disease, optimization of left ventricular dysfunction and diabetes management may improve outcomes.

Outcomes in patients with peripheral vascular disease following percutaneous coronary intervention.

OBJECTIVES: To evaluate the clinical characteristics and outcomes of patients with peripheral vascular disease (PVD) undergoing percutaneous coronary intervention (PCI) in a contemporary setting, and to determine whether use of drug-eluting stents (DESs) improves outcomes. BACKGROUND: PVD was an independent risk factor for adverse outcomes following PCI in the bare-metal stent (BMS) era. It is not known whether outcomes in these patients have improved with advances in interventional techniques and stent technology, as they have for the general population. METHODS: Eighteen thousand three hundred and eighty patients undergoing PCI from an Australian registry between 2005 and 2013 were studied. Clinical and procedural data, 30-day and 12-month outcomes were compared in those with and without a reported history of PVD. Outcomes were also compared between patients with PVD who received DES and those who received BMS. Long-term mortality was compared using Australian National Death Index (NDI) linkage. RESULTS: Patients with PVD (n = 1,251, 6.8%) were older and had more prevalent diabetes, hypertension, cerebrovascular disease, heart failure, renal impairment, ostial lesions, left main, and multi-vessel disease (p < 0.001). Patients with PVD had significantly higher rates of major adverse cardiovascular events (MACEs) compared with those without PVD, in-hospital (5.7% vs. 4.1%, p < 0.008), at 30-days (8.6% vs. 5.8%, p < 0.001) and at 12-months (24.6% vs. 13.2%, p < 0.001). At 4.9 ± 2.6 years follow-up, there was significantly greater mortality in the PVD group. PVD patients who received DES experienced significantly less MACE than PVD patients treated with BMS at 30-days (4.8 vs. 10.1%, p < 0.001) and 12-months (19.4 vs. 26.4%, p < 0.005). CONCLUSIONS: PVD is an independent predictor of adverse outcomes in patients undergoing PCI. PVD patient who received DES had improved outcomes compared with those receiving BMS.

Guidance for elective single-embryo transfer should be applied to frozen embryo transfer cycles.

PURPOSE: To provide clinicians with data showing the benefits of transferring a single blastocyst in frozen embryo transfer (FET) cycles so that they may counsel their patients accordingly. METHODS: This is a closed cohort study of 678 FET cycles occurring between January 2011 and December 2017 in a private IVF laboratory and associated physicians' practice. Patients included in the analysis were less than 38 years of age at oocyte collection, had at least two vitrified blastocysts, and were undergoing their first autologous FET cycle. The patients were categorized into four groups after they had chosen either elective single-embryo transfer (eSET) or double-embryo transfer (eDET). Outcomes for eSET and eDET were compared within groups of patients having freeze-all IVF cycles (PGT-A patient vs. non-PGT-A patient) and fresh IVF transfer groups (negative outcome vs. pregnant/delivered in fresh cycle). Main outcome measures of the study were live birth, multiple pregnancy, and implantation rates. RESULTS: There were no statistically significant differences observed in live birth rates for eSET (54-62%) vs. eDET (54-66%) (P = 0.696-1.000) in the four patient groups evaluated. Multiple pregnancy rates were significantly decreased in all eSET groups (0-3%), compared with eDET groups (24-65%) (P = 0.0001-0.037). CONCLUSIONS: This data shows that transfer of a single vitrified-warmed blastocyst maintains live birth rates, while decreasing multiple pregnancies, and may become more acceptable to physicians and patients.