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BACKGROUND: The impact of age on outcomes in cardiogenic shock (CS) is poorly described in the pre-hospital setting. We assessed the impact of age on outcomes of patients treated by emergency medical services (EMS). METHODS: This population-based cohort study included consecutive adult patients with CS transported to hospital by EMS. Successfully linked patients were stratified into tertiles by age (18-63, 64-77, and > 77 years). Predictors of 30-day mortality were assessed through regression analyses. The primary outcome was 30-day all-cause mortality. RESULTS: A total of 3523 patients with CS were successfully linked to state health records. The average age was 68 ± 16 years and 1398 (40%) were female. Older patients were more likely to have comorbidities including pre-existing coronary artery disease, hypertension, dyslipidemia, diabetes mellitus, and cerebrovascular disease. The incidence of CS was significantly greater with increasing age (incidence rate per 100,000 person years 6.47 [95% CI: 6.1-6.8] in age 18-63 years, 34.34 [32.4-36.4] in age 64-77 years, 74.87 [70.6-79.3] in age > 77 years, P < 0.001). There was a step-wise increase in the rate of 30-day mortality with increasing age tertile. After adjustment, compared to the lowest age tertile, patients aged > 77 years had increased risk of 30-day mortality (adjusted hazard ratio = 2.26 [95% CI: 1.96-2.60]). Older patients were less likely to receive inpatient coronary angiography. CONCLUSION: Older patients with EMS-treated CS have significantly higher rates of short-term mortality. The reduced rates of invasive interventions in older patients underscore the need for further development of systems of care to improve outcomes for this patient group.

Recent guidelines suggest that coronary angiography (CAG) should be considered for out-of-hospital cardiac arrest (OHCA) survivors, including those without ST elevation (STE) and without shockable rhythms. However, there is no prospective data to support CAG for survivors with nonshockable rhythms and no STE post resuscitation.This was a re-analysis of the PEARL study (randomized OHCA survivors without STE to early CAG versus not). Patients were subdivided by initial rhythm as nonshockable (Nsh) vs shockable (Sh). The primary outcome was coronary angiographic evidence of acute culprit lesion, with secondary outcomes being survival to hospital discharge and neurological recovery.The PEARL study included 99 patients with OHCA from a presumed cardiac etiology, 24 with nonshockable and 75 with shockable rhythms. There was no difference in the frequency of CAG between the two groups [71% (Nsh) and 75% (Sh); p = 0.79], presence of CAD [81% (Nsh) and 68% (sh); p = 0.37, or culprit lesions identified in each group [50% (Nsh) and 45% (Sh); p = 0.78. Nonshockable patients had worse discharge survival [33% (Nsh) vs 57% (Sh); p = 0.04] and those survived, had worse neurological recovery [30% (Nsh) vs 54% (Sh); p = 0.02] compared to shockable patients.OHCA survivors presenting with nonshockable rhythms and no STE post resuscitation had similar prevalence of culprit coronary lesions to those with shockable rhythms. CAG may be considered in patients with OHCA without STE regardless of initial presenting rhythm. There was no benefit of emergent CAG both in shockable and non-shockable rhythms.

Background Ambulance off-load delays in transferring patient care to emergency departments (EDs) are increasingly common, but it is unclear whether clinical outcomes are impacted. Methods Population-based cohort study of ambulance attendances for non-traumatic chest pain transported to ED in Victoria, Australia (1/1/2015–30/6/2019) excluding patients transported to hospital with “lights and sirens” or triaged as ED category 1. Multivariable models were used to assess the relationship between ambulance off-load times and 30-day mortality and ambulance re-attendance for chest pain. Results The study included 213,544 ambulance attendances for chest pain (mean age 62 [SD 18] years; 51% female). Median ambulance off-load times increased across the study period from 21 minutes (interquartile range [IQR] 15–30) in 2015 to 24 minutes (IQR 17–37) in 2019. Patients were divided into tertiles according to off-load times with 69,247 patients included in tertile 1 (0–17 minutes), 73,109 patients in tertile 2 (18–28 minutes), and 71,188 patients in tertile 3 (>28 minutes). In multivariable models, ambulance off-load delays were associated with higher unadjusted and adjusted rates of 30-day mortality (1.57% tertile 3 vs. 1.29% tertile 1, adjusted risk difference 0.28% [95% CI 0.16% - 0.42%], p Conclusions Delays in ambulance off-load times appear to be associated with increased mortality and ambulance re-attendance risk among chest pain cohorts. This study has important policy implications given the increasing frequency of off-load delays in many healthcare settings. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Alfred health

Background Cardiovascular disease is the most common cause of indirect maternal mortality worldwide, and cardiac arrest occurs in up to 1 in 12,000 pregnancies. Objective To define rates, clinical and pathologic factors of out-of-hospital cardiac arrest (OHCA) in pregnant and post-partum females. Methods A prospective state-wide cardiac arrest registry combining ambulance, hospital and forensic data captured all OHCAs from 2019–2021. Clinical and pathological details for pregnant patients were identified. Results 1,482 OHCAs occurred, including 376 females of child-bearing age of whom eight were pregnant or post-partum. OHCA incidence was lower in pregnant females compared to non-pregnant females of child-bearing age (5.2 OHCAs per 100,000 pregnant females vs 23.1 per 100,000 females of child-bearing age, p Conclusion Maternal OHCA affects approximately 1 in 20,000 pregnancies with high maternal mortality rates. OHCA occurs at one-quarter the rate in non-pregnant females of child-bearing age. Approximately two-thirds of maternal OHCAs had an underlying cardiac cause, but low rates of cardiac diagnosis pre-arrest. OHCAs differ markedly from IHCAs in pregnant females, requiring ongoing evaluation as to specific causes and preventability. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): NHMRC, NHF

Background Previous studies examining temporal variation in cardiovascular care have largely been limited to assessing weekend and after-hours effects whereby those presenting on the weekend or after-hours have a poorer outcome. However, emerging evidence suggests more complex patterns in patterns and outcomes may exist. Purpose We aimed to determine patterns of temporal variation in chest pain presentations and subsequent health-care quality and outcomes. Methods This was an observational, prospective-cohort study of adult patients aged 18 and over who were attended by emergency medical services for non-traumatic chest pain between 1 January 2015 and 30 June 2019 in Victoria, Australia. Major exclusion criteria included pre-hospital diagnosis of ST elevation myocardial infarction or an out of hospital cardiac arrest. The exposure variable was time of day and day of week stratified into 168 hourly time periods. The primary outcome measure was 30-day mortality. Results The study cohort comprised 196,365 ambulance attendances for acute non-traumatic chest pain; mean age 62.4 years (SD 18.3) and 99,497 (50.7%) females. Three temporal patterns were observed for chest pain presentations (Figure 1): (1) a diurnal pattern with a sharp increase in presentations from 8 am, peaking around midday, before decreasing into late evening with a nadir between 3–4 am, (2) a weekend effect where Saturday and Sunday had a relatively lower rate of presentations compared to during the week, and (3) a Monday – Sunday gradient where more presentations were likely earlier in the week, than later. Six patterns were identified across pre-hospital and hospital key performance indicators (KPI) (diurnal, in/after-hours, weekend effect, Monday – Sunday gradient, a peak period and morning vs afternoon/evening effect. Risk of 30-day mortality was associated with weekend presentation (OR 1.15, 95% CI 1.06–1.24, p=0.001) and morning presentation between midnight and midday (OR 1.17, 95% CI 1.09–1.25, p Conclusion Chest pain presentations, care quality and outcomes demonstrate complex temporal variation beyond the already established weekend and after-hours effect. Such relationships should be considered during resource allocation and quality improvement programs in order to improve treatment quality across all days and times of the week. Funding Acknowledgement Type of funding sources: None.

Background Obesity is common in young sudden cardiac death (SCD) victims but it is unclear whether it is more common than in the general population. This study aimed to contextualize young SCD obesity rates, identifying clinical and pathologic features in WHO class II and III obesity. Methods A prospective state-wide out-of-hospital cardiac arrest registry included all SCDs in Victoria, Australia from 2019–2021. Body mass indices (BMIs) of patients 18–50 years were compared to age-referenced general population. Characteristics of SCD patients with WHO Class II obesity (BMI ≥30kg/m2) and non-obesity (BMI 50kg/m2 were assessed. Results 504 patients were included. Obesity was strongly over-represented in young SCD compared to the age-matched general population (55.0% vs 28.7%, p50 kg/m2 represented 8.5% of young SCD. LVH (n=26, 60.5%) was their predominant cause of death and only 10 (9.3%) patients died from coronary disease. Conclusion Over half of young Australian SCD patients are obese, with all obesity classes over-represented compared to the general population. Obese patients had more cardiac risk factors. Almost two thirds of patients with BMI>50 kg/m2 died with LVH, with fewer than 10% dying from coronary disease. Funding Acknowledgement Type of funding sources: None.

Background Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young sudden cardiac death (SCD) patients are uncertain. Purpose To identify rates of illicit drug use in young SCD patients in Australia. Methods A prospective multi-centre registry identified out of hospital cardiac arrest (OHCA) patients aged 1–50 years between April 2019 and April 2020. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included stimulants such as amphetamine-type substances and cocaine, or non-stimulants such as heroin, cannabis and novel psychoactive substances (cathinones and synthetic cannabinoids). Results 770 OHCAs occurred, with 555 patients undergoing forensic assessment. 287 patients had confirmed cardiac cause of OHCA, with 274 undergoing toxicological assessment and 79 (28.8%) having positive toxicology for illicit drugs (n=60) or reported regular drug use (n=19). An additional 121 patients experienced non-cardiac SCD due to illicit drug toxicity, resulting in a total of 200 patients (36.0% of OHCAs) with illicit drug use. Patients with SCD and illicit drug use were more commonly male (86.1% vs 72.3%, p=0.015), regular smokers (36.7% vs 21.5%, p=0.009), had cardiomegaly (76.5% vs 57.5%, p=0.007), and higher rates of coronary disease and cardiomyopathy (coronary disease 44.3% vs 33.3%, cardiomyopathy 30.4% vs 18.5%, p=0.003). Methamphetamines (n=42, 53.1%) were the most common illicit drug identified and polysubstance abuse occurred frequently (n=15, 19.0%). Conclusion Approximately one-third of young SCD patients use illicit drugs, with high rates of polysubstance abuse. Illicit drug use in SCD patients is associated with coronary disease and cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background/Introduction Following percutaneous coronary intervention (PCI), outpatient cardiac rehabilitation (CR) is essential for secondary prevention.(1) However, uptake of CR is suboptimal(2), despite strong evidence demonstrating benefits. The aim of this study was to identify contemporary trends and predictors of CR referral of PCI patients in Victoria. Methods A prospective, observational study using anonymised data from the Victorian Cardiac Outcomes Registry was undertaken. A total of 41,739 patients were discharged following PCI over the study period (2017-2020) and included for analyses. Results CR referral was 85%, with an increasing trend over time observed (p Conclusion Referral to CR in Australia for PCI patients has improved over time compared to previously published reports. Pleasingly, we did not observe a gender difference in rate of CR referral. However, older, more acute or co-morbid patients require consideration for CR referral as these patients may have the most to gain. We also included novel key hospital characteristics in our analysis, such as high-volume STEMI hospitals, which increase the odds of CR referral. Referral does not imply attendance, nor completion of CR and we need better linked data in Australia to examine these outcomes.

Background Climate change has led to increased interest in studying adverse health effects relating to ambient temperatures. It is unclear whether incident chest pain is associated with non-optimal temperatures and how chest pain presentation rates might be affected by climate change. Methods The study included ambulance data of chest pain presentations in Melbourne, Australia from 1/1/2015 to 30/6/2019 with linkage to hospital and emergency discharge diagnosis data. A time series quasi-Poisson regression with a distributed lag nonlinear model was fitted to assess the temperature-chest pain presentation associations, after adjusting for season, day of the week and long-term trend. Future excess chest pain presentations associated with cold and heat were projected under six general circulation models under medium and high emission scenarios. Results In 206,789 chest pain presentations, mean (SD) age was 61.2 (18.9) years and 50.3% were female. Significant heat- and cold-related increased risk of chest pain presentations were observed for mean air temperatures above and below 20.8°C, respectively (Figure 1). Excess chest pain presentations related to heat were observed in all subgroups, but appeared to be attenuated for older patients (≥70 years) and patients of higher socioeconomic status (SES). We projected no significant change in net temperature-related chest pain presentations with climate change under medium- and high-emission scenarios, with increases in heat-related chest pain presentations offset by decreases in chest pain presentations related to cold temperatures. Conclusions Heat- and cold-exposure appear to increase risk of chest pain presentations, especially among younger patients and patients of lower SES. In Melbourne, Australia, chest pain presentations overall were not projected to increase with climate change, but increases in heat-related chest pain presentations highlight the importance of risk mitigation strategies to minimise adverse health impacts on hotter days. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Alfred Health.

Background In patients with prior CABG requiring subsequent PCI there is uncertainty whether bypass grafts or native coronary arteries should be targeted. Methods We analysed data from 2,764 patients with prior CABG in the Melbourne Interventional Group registry (2005–2018), divided into two groups: those undergoing PCI to a native vessel (n=1,928) and those with PCI to a graft vessel (n=836). Results Patients with a graft vessel PCI were older, had more high-risk clinical characteristics (prior MI, heart failure, ejection fraction Conclusions Early clinical outcomes and risk-adjusted long-term mortality are similar for patients with prior CABG undergoing PCI to a native vessel or a bypass graft. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): The Alfred Hospital

Background Coronary artery anomalies (CAAs) have been previously implicated as a major cause of young sudden cardiac death (SCD), particularly in exercise-related SCD with a reported prevalence of up to 33%. Methods A state-wide prospective out-of-hospital cardiac arrest registry identified all patients aged 1–50 years who experienced an SCD and underwent autopsy from April 2019 to April 2021. Rates of normal anatomy, normal variants and CAAs were identified and circumstances and cause of death for patients with CAAs examined. Results Of 1,477 patients who experienced cardiac arrest during the study period, 490 underwent autopsy and were confirmed to have experienced SCD. Of these 490 patients, five (1.0%) had a CAA identified with three having anomalies of coronary origin and two having anomalies of coronary course. In no cases was the CAA deemed responsible for the SCD. In two cases, severe coronary disease and intra-coronary thrombus with histological evidence of acute myocardial infarction were identified, in the third critical coronary disease was found, the fourth had an unrelated thoracic aortic dissection and the fifth had cardiomegaly in the setting of illicit drug use. Of 27 patients who experienced their SCD during exercise, only one had a CAA identified (the patient with thoracic aortic dissection). Conclusion In this prospective cohort of consecutive young patients with SCD who underwent autopsy, CAAs occurred in 1.0% of patients and did not cause any deaths. The role of CAAs in causing young SCD appears to be less significant than previously hypothesised. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): NHMRC, NHF

Background High systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events. Objectives The purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI). Methods The study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low 70 mm Hg, low ≤70 mm Hg). Results Mean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04). Conclusions Pulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies.

© 2020 Lippincott Williams and Wilkins. All rights reserved. Background: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves result in proinflammatory effects that are resolved with TAVI. Methods: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined with a single-chain antibody, MAN-1, which is specific for the activated β2-integrin Mac-1. Monocyte function was further characterized by the adhesion of myocytes to stimulated endothelial cells, phagocytic activity, uptake of oxidized low-density lipoprotein, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca2+imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Last, we stained for monocytes in explanted stenotic aortic human valves. Results: The resolution of high shear stress through TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized low-density lipoprotein uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics and pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress-dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that the expression of this receptor is shear stress dependent and downregulated in patients receiving TAVI. Last, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. Conclusions: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions, and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. We demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.

Percutaneous coronary intervention (PCI) continues to evolve with shifting patient demographics, treatments, and outcomes. We sought to document the specific changes observed over a 9-year period in a contemporary Australian PCI cohort. The Melbourne Interventional Group is an established multicenter PCI registry in Melbourne, Australia. Data were collected prospectively with 30-day and 12-month follow-ups. Demographic, procedural, and outcome data for all consecutive patients were analyzed with a year-to-year comparison from 2005 to 2013. National Death Index linkage was performed for long-term mortality analysis; 19,858 procedures were captured over 9 years. Patient complexity and acuity increased with a higher proportion of traditional risk factors and more elderly patients who underwent PCI. Angiographic lesion complexity increased with more multivessel coronary artery disease and more American College of Cardiology/American Heart Association type B2/C lesions proceeding to PCI. The 30-day rate of death, myocardial infarction, or target vessel revascularization has not changed nor has 12-month mortality, myocardial infarction, or major adverse cardiovascular event rates. The strongest independent predictor of long-term mortality was cardiogenic shock at presentation (hazard ratio [HR] 2.95, p

Guidelines strongly recommend patients with ST-elevation myocardial infarction (STEMI) receive timely mechanical reperfusion, defined as door-to-balloon time (DTBT) ≤90 minutes. The impact of timely reperfusion on clinical outcomes in patients aged 75-84 and ≥85 years is uncertain. We analysed 2,972 consecutive STEMI patients who underwent primary percutaneous coronary intervention from the Melbourne Interventional Group Registry (2005-2014). Patients aged

The mortality rate post admission to hospital after successful resuscitation from out-of-hospital cardiac arrest is high, with significant variation between regions and individual institutions. While prehospital factors such as age, bystander cardiopulmonary resuscitation and total cardiac arrest time are known to influence outcome, several aspects of post-resuscitative care including therapeutic hypothermia, coronary intervention and goal-directed therapy may also influence patient survival. Regional systems of care have improved provider experience and patient outcomes for those with ST elevation myocardial infarction and life-threatening traumatic injury. In particular, hospital factors such as hospital size and interventional cardiac care capabilities have been found to influence patient mortality. This paper reviews the evidence supporting the possible development and implementation of Australian cardiac arrest centres.