Prehospital factors predicting mortality in patients with shock: state-wide linkage study.

BACKGROUND: Patients with shock treated by emergency medical services (EMS) have high morbidity and mortality. Knowledge of prehospital factors predicting outcomes in patients with shock remains limited. We aimed to describe the prehospital predictors of mortality in patients with non-traumatic shock transported to hospital by EMS. METHOD: This is a retrospective cohort study of consecutive ambulance attendances for non-traumatic shock in Victoria, Australia (January 2015-June 2019) linked with government-held administrative data (emergency, admissions and mortality records). Predictors of 30-day mortality were assessed using Cox proportional regressions. The primary outcome was 30-day all-cause mortality. RESULTS: Overall, 21 334 patients with non-traumatic shock (median age 69 years, 54.8% female) were successfully linked with state administrative records. Among this cohort, 9 149 (43%) patients died within 30-days. Compared with survivors, non-survivors had a longer median on-scene time: 60 (35-98) versus 30 (19-50), p <0.001. Non-survivors were more likely to be older (median age in years: 74 (61-84) vs 65 (47-78), p<0.001), had prehospital cardiac arrest requiring cardiopulmonary resuscitation (adjusted HR (aHR)=6.26, 95% CI 5.87, 6.69) and had prehospital intubation (aHR=1.07, CI 1.00, 1.14). Reduced 30-day mortality was associated with administration of epinephrine (aHR=0.66, CI 0.62, 0.71) and systolic blood pressures above 80 mm Hg in the prehospital setting. CONCLUSION: The 30-day mortality from non-traumatic shock is high at 43%. Independent predictors of mortality included age, prehospital cardiac arrest and endotracheal intubation. Interventions that target reversible causes of short-term mortality in patients with non-traumatic shock are a high priority.

Sex-Based Outcomes of Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention: A Pairwise and Network Meta-Analysis.

BACKGROUND: Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1-3 months [short-term], 6 months [mid-term], and >12 months [extended] vs. 12 months). METHODS: We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis. RESULTS: Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02-1.28]) and bleeding (1.13 [1.00-1.28]), but not NACCE (1.12 [0.96-1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent (1.11 [1.03-1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01-2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83-1.10; and 0.96 [0.80-1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91-1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17-1.09]). CONCLUSIONS: Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI. CLINICAL TRIALS REGISTRATION: PROSPERO ID: CRD42021278663.

Low-level elevations in high-sensitivity cardiac troponin predict obstructive coronary artery disease and revascularisation in rural patients with non-ST-elevation myocardial infarction referred for coronary angiography.

Rural patients with non-ST-elevation myocardial infarction (NSTEMI) are transferred to metropolitan hospitals for invasive coronary angiography (ICA). Yet, many do not have obstructive coronary artery disease (CAD). In this analysis of rural Western Australian patients transferred for ICA for NSTEMI, low-level elevations in high-sensitivity cardiac troponin (≤5× upper reference limit) were associated with less obstructive CAD and revascularisation. Along with other factors, this may help identify rural patients not requiring transfer for ICA.

Clinical Effectiveness and Utilisation of Cardiac Rehabilitation After Hospital Discharge: Data Linkage Analysis of 84,064 Eligible Discharged Patients (2016-2021).

BACKGROUND: Despite the highest levels of evidence on cardiac rehabilitation (CR) effectiveness, its translation into practice is compromised by low participation. AIM: This study aimed to investigate CR utilisation and effectiveness in South Australia. METHODS: This retrospective cohort study used data linkage of clinical and administrative databases from 2016 to 2021 to assess the association between CR utilisation (no CR received, commenced without completing, or completed) and the composite primary outcome (mortality/cardiovascular re-admissions within 12 months after discharge). Cox survival models were adjusted for sociodemographic and clinical data and applied to a population balanced by inverse probability weighting. Associations with non-completion were assessed by logistic regression. RESULTS: Among 84,064 eligible participants, 74,189 did not receive CR, with 26,833 of the 84,064 (31.9%) participants referred. Of these, 9,875 (36.8%) commenced CR, and 7,681 of the 9,875 (77.8%) completed CR. Median waiting time from discharge to commencement was 40 days (interquartile range, 23-79 days). Female sex (odds ratio [OR] 1.12; 95% CI 1.01-1.24; p=0.024), depression (OR 1.17; 95% CI 1.05-1.30; p=0.002), and waiting time >28 days (OR 1.15; 95% CI 1.05-1.26; p=0.005) were associated with higher odds of non-completion, whereas enrolment in a telehealth program (OR 0.35; 95% CI 0.31-0.40; p<0.001) was associated with lower odds of non-completion. Completing CR (hazard ratio [HR] 0.62; 95% CI 0.58-0.66; p<0.001) was associated with a lower risk of 12-month mortality/cardiovascular re-admissions. Commencing without completing was also associated with decreased risk (HR 0.81; 95% CI 0.73-0.90; p<0.001), but the effect was lower than for those completing CR (p<0.001). CONCLUSIONS: Cardiac rehabilitation (CR) attendance is associated with lower all-cause mortality/cardiovascular re-admissions, with CR completion leading to additional benefits. Quality improvement initiatives should include promoting referral, women's participation, access to telehealth, and reduction of waiting times to increase completion.

Cardiovascular Disease and the Mediterranean Diet: Insights into Sex-Specific Responses.

Cardiovascular disease (CVD) is a leading cause of mortality and disease burden in women globally. A healthy diet is important for the prevention of CVD. Research has consistently favoured the Mediterranean diet as a cardio-protective diet. Several studies have evaluated associations between the Mediterranean diet and cardiovascular outcomes, including traditional risk factors like hypertension, type 2 diabetes mellitus, and obesity. In addition, consistent evidence suggests that the components of the Mediterranean diet have a synergistic effect on cardiovascular risk due to its anti-inflammatory profile and microbiome effects. While the benefits of the Mediterranean diet are well-established, health advice and dietary guidelines have been built on largely male-dominant studies. Few studies have investigated the beneficial associations of the Mediterranean diet in sex-specific populations, including those with non-traditional risk factors that are specific to women, for instance polycystic ovarian syndrome and high-risk pregnancies, or more prevalent in women, such as chronic inflammatory diseases. Therefore, this review aims to provide a comprehensive overview of the current evidence regarding the Mediterranean diet in women in relation to cardiovascular health outcomes.

Sex- and Age-Specific Differences in Risk Profiles and Early Outcomes in Adults With Acute Coronary Syndromes.

BACKGROUND: Adults <55 years of age comprise a quarter of all acute coronary syndromes (ACS) hospitalisations. There is a paucity of data characterising this group, particularly sex differences. This study aimed to compare the clinical and risk profile of patients with ACS aged <55 years with older counterparts, and measure short-term outcomes by age and sex. METHOD: The study population comprised patients with ACS enrolled in the AUS-Global Registry of Acute Coronary Events (GRACE), Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE) and SNAPSHOT ACS registries. We compared clinical features and combinations of major modifiable risk factors (hypertension, smoking, dyslipidaemia, and diabetes) by sex and age group (20-54, 55-74, 75-94 years). All-cause mortality and major adverse events were identified in-hospital and at 6-months. RESULTS: There were 16,658 patients included (22.3% aged 20-54 years). Among them, 20-54 year olds had the highest proportion of ST-elevation myocardial infarction compared with sex-matched older age groups. Half of 20-54 year olds were current smokers, compared with a quarter of 55-74 year olds, and had the highest prevalence of no major modifiable risk factors (14.2% women, 12.7% men) and of single risk factors (27.6% women, 29.0% men), driven by smoking. Conversely, this age group had the highest proportion of all four modifiable risk factors (6.6% women, 4.7% men). Mortality at 6 months in 20-54 year olds was similar between men (2.3%) and women (1.7%), although lower than in older age groups. CONCLUSIONS: Younger adults with ACS are more likely to have either no risk factor, a single risk factor, or all four modifiable risk factors, than older patients. Targeted risk factor prevention and management is warranted in this age group.

Could Computed Tomography Coronary Angiography Replace Invasive Coronary Angiography as a First-Line Diagnostic Investigation in Suspected Acute Coronary Syndromes? A Decision-Analytic Model.

BACKGROUND: The implementation of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice has resulted in the identification of a novel cohort of patients with modestly increased troponin concentrations. Subsequent increases in rates of coronary angiography have been observed, without significant increases in rates of coronary revascularisation. Computed tomography coronary angiography (CTCA) is a non-invasive investigation that offers the opportunity to decouple investigation from the impetus to revascularise, and may provide an alternative, more risk-appropriate initial investigative strategy for the cohort with low to moderate hs-cTn increases. This analysis seeks to define the threshold of pre-test probability of coronary revascularisation in patients with suspected acute coronary syndrome at which a strategy of initial CTCA is safe and a more cost-effective approach than standard invasive coronary angiography (ICA). METHODS: A cost-benefit evaluation was conducted using a decision-analytic model. The primary outcome measure was the incremental cost-effectiveness ratio (ICER) of CTCA in comparison with ICA as an initial diagnostic investigation for patients with hs-cTnT levels between 5 and 100 ng/L. Secondary outcome measures of costs, patient outcomes, and quality-adjusted life years were analysed. RESULTS: Median base case ICER over 1,000 trials was $17,163 AUD but demonstrated large variability. Sensitivity analysis demonstrated that CTCA was cost-effective until the probability of requiring revascularisation was ∼60%, beyond which point CTCA was associated with higher costs and poorer outcomes than ICA. CONCLUSIONS: Computed tomography coronary angiography may be a cost-effective first-line investigation for patients with moderate hs-cTnT rises until/up to a 60% pre-test probability for receiving coronary revascularisation. To objectively assess the optimal circumstances of cost-effectiveness, prospective evaluation incorporating the estimated probability of revascularisation will be required.

Management and outcomes with 5-year mortality of patients with mildly elevated high-sensitivity troponin T levels not meeting criteria for myocardial infarction.

OBJECTIVES: To examine management and outcomes of patients presenting to EDs with symptoms suggestive of acute coronary syndrome, who have mild non-dynamically elevated high-sensitivity troponin T (HsTnT) levels, not meeting the fourth universal definition of myocardial infarction (MI) criteria (observation group). METHODS: Consecutive patients presenting to the ED with symptoms suggestive of acute coronary syndrome at Liverpool Hospital, Sydney, Australia, those having ≥2 HsTnT levels after initial assessment were adjudicated according to the fourth universal definition of MI, as MI ruled-in, MI ruled-out, or myocardial injury in whom MI is neither ruled-in nor ruled-out (>1 level ≥15 ng/L, called observation group); follow-up was 5 years. RESULTS: Of 2738 patients, 547 were in the observation group, of whom 62% were admitted to hospital, 52% to cardiac services, whereas 97% of MI ruled-in patients and 21% of MI ruled-out patients were admitted; P < 0.001. Non-invasive testing occurred in 42% of observation group patients (36% had echo-cardiography), and 16% had coronary angiography. Of observation group patients, MI rates were 1.5% during hospitalisation and 4% during the following year, similar to that in those with MI ruled-in, among those with MI ruled-out, the MI rate was 0.2%. The 1-year death rate was 13% among observation group patients and 11% MI ruled-in patients (P = 0.624), whereas at 5 years among observation group patients, type 1 MI and type 2 MI were 48%, 26% and 58%, respectively (P = 0.001). CONCLUSION: Very few unselected consecutive patients attending ED, with minor stable HsTnT elevation, had MI, although most had chronic myocardial injury. Late mortality rates among observation group patients were higher than those with confirmed type 1 MI but lower than those with type 2 MI.

Pre-stroke anticoagulation for atrial fibrillation in primary English speakers and non-primary English speakers: a multicentre retrospective cohort study.

BACKGROUND: Anticoagulation can prevent most strokes in individuals with atrial fibrillation (AF); however, many people presenting with stroke and known AF are not anticoagulated. Language barriers and poor health literacy have previously been associated with decreased patient medication adherence. The association between language barriers and initiation of anticoagulation therapy for AF is uncertain. AIMS: The aims of this study were to determine whether demographic factors, including non-English primary language, were (1) associated with not being initiated on anticoagulation for known AF prior to admission with stroke, and (2) associated with non-adherence to anticoagulation in the setting of known AF prior to admission with stroke. METHODS: A multicentre retrospective cohort study was conducted for consecutive individuals admitted to the three South Australian tertiary hospitals with stroke units over a 5-year period. RESULTS: There were 6829 individuals admitted with stroke. These cases included 5835 ischaemic stroke patients, 1333 of whom had pre-existing AF. Only 40.0% presenting with ischaemic stroke in the setting of known pre-existing AF were anticoagulated. When controlling for demographics, socioeconomic status and past medical history (including the components of the CHADS2VASC score and anticoagulation contraindications), having a primary language other than English was associated with a lower likelihood of having been commenced on anticoagulant for known pre-stroke AF (odds ratio: 0.52, 95% confidence interval: 0.36-0.77, P = 0.001), but was not associated with a differing likelihood of anticoagulation adherence. CONCLUSIONS: A significant proportion of patients with stroke have pre-existing unanticoagulated AF; these rates are substantially higher if the primary language is other than English. Targeted research and interventions to minimise evidence-treatment gaps in this cohort may significantly reduce stroke burden.

Asia-Pacific Investigators and Asian Enrollment in Cardiometabolic Trials: Insights From Publications Between 2011 and 2020.

Background: A lack of geographic and racial diversity in clinical trial populations may arise from a disproportionate focus on the United States and Europe for trial leadership and conduct. Inadequate diversity may compromise the external validity to the Asia-Pacific (APAC) region, where 60% of global cardiometabolic disease exists. Objectives: This study aimed to assess the proportion and trends of Asian race participants and APAC authorship in cardiometabolic trials. Methods: We performed a systematic review of all cardiovascular, diabetes and obesity-related randomized controlled trials (phase ≥2, n = ≥100) published in these major medical journals: the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association between January 1, 2011, and December 31, 2020. Trial leadership was defined by first authorship, and any listed author was considered a trial collaborator. Temporal trends were evaluated using the Jonckheere-Terpstra proportion test and correlations using Pearson's correlation coefficient. Participant-to-prevalence ratios (PPR) were determined using Global Health Data Exchange registry data. Results: A total of 8.3% (218,613 of 2,619,710) participants identified as being of Asian race and 7.7% of total enrollment occurred in APAC. APAC lead authorship occurred in 52 of 656 (7.9%) trials and collaboration in 10.1% (1312 of 13,000 of authors), which correlated with Asian enrollment (r = 0.63 and r = 0.76, respectively). A marginal increase in the proportion of Asian race (Δ1.40% ± 6.95%/year, P = 0.003) and APAC regional (Δ1.46% ± 8.67%/year, P = 0.003) enrollment was observed; however, severe regional underrepresentation persisted (PPR <0.30). Conclusions: Despite a favorable trend over the past decade, Asian participants and authors from APAC remain significantly underrepresented in seminal cardiometabolic trials; barriers to trial conduct and leadership in this region must be addressed.

Sodium-Glucose Cotransporter 2 Inhibitors in South Australia: The Magic Before the Fame.

BACKGROUND: Recent clinical trials have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), which were previously only indicated in treatment of type 2 diabetes mellitus (T2DM), can markedly reduce heart failure hospitalisation (HFH), with less striking potential reductions in acute coronary syndromes and cardiac arrhythmias. To evaluate the impact of SGLT2i on cardiovascular outcomes in real-world practice, we performed a retrospective cohort analysis on South Australian (SA) data. METHODS: A total of 842 individuals with T2DM receiving SGLT2i were identified from SA public hospitals between 2011 and 2019. Episodes of care were temporally matched with those of 3,128 individuals with T2DM not receiving SGLT2i (control). Baseline characteristics were adjusted using inverse probability treatment weighting. The incidence of cardiovascular events at 12 and 24 months was evaluated using coded (International Classification of Diseases, Tenth Revision, Australian Modification [ICD-10-AM]) data. RESULTS: The primary outcome of HFH was lower with SGLT2i use at 12 months (adjusted hazard ratio [HRadj] 0.44; 95% confidence interval [CI] 0.29-0.68; p<0.001) and 24 months. There were also lower hospitalisations due to acute myocardial infarction (HRadj 0.42; 95% CI 0.21-0.85; p=0.015) and atrial or ventricular arrhythmias (HRadj 0.29; 95% CI 0.14-0.59; p=0.001), with no difference observed in hospitalisation due to ischaemic cerebrovascular events. There was no difference in all-cause mortality at 12 months but interestingly a higher rate at 24 months (HRadj 2.08; 95% CI 1.59-2.72; p<0.001). Despite this, similar reductions in cardiovascular outcomes were observed at 24 months. CONCLUSION: Use of SGLT2i in patients with T2DM in SA was associated with reductions in cardiovascular events even before their recent Pharmaceutical Benefits Scheme (PBS) listing for heart failure. Furthermore, this analysis supports that SGLT2i play a role not only in HFH reduction but also in reducing coronary and tachyarrhythmic events. This real-world evidence supports the use of SGLT2i as broadly protective cardiovascular drugs.

Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

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.

Impacts of high sensitivity troponin T reporting on care and outcomes in clinical practice: Interactions between low troponin concentrations and participant sex within two randomized clinical trials.

BACKGROUND: The impacts of high sensitivity cardiac troponin (hs-cTn) reporting on downstream interventions amongst suspected acute coronary syndrome (ACS) in the emergency department (ED), especially amongst those with newly identified hs-cTn elevations and in consideration of well-established sex-related disparities, has not been critically evaluated to date. This investigation explores the impact of hs-cTnT reporting on care and outcomes, particularly by participant sex. METHODS: Two similarly ED-based randomized controlled trials conducted between July 2011 to March 2013 (n = 1988) and August 2015 to April 2019 (n = 3378) were comparatively evaluated. Clinical outcomes were adjudicated to the Fourth Universal Definition of MI. Changes in practice were assessed at 30 days, and death or MI were explored to 12 months. RESULTS: The HS-Troponin study demonstrated no difference in death or MI with unmasking amongst those with hs-cTnT <30 ng/L, whereas the RAPID TnT study demonstrated a significantly higher rate. In RAPID TnT, there was significant increase in death or MI associated with unmasking for females with hs-cTnT <30 ng/L (masked: 11[1.5%], unmasked: 25[3.4%],HR: 2.27,95%C.I.:1.87-2.77,P < 0.001). Less cardiac stress testing with unmasking amongst those <30 ng/L was observed in males in both studies, which was significant in RAPID TnT (masked: 92[12.0%], unmasked: 55[7.0%], P = 0.008). In RAPID TnT, significantly higher rates of angiography in males were observed with unmasking, with no such changes amongst females <30 ng/L (masked: 28[3.7%], unmasked: 51[6.5%],P = 0.01). CONCLUSION: Compared with males, there were no evident impacts on downstream practices for females with unmasking in RAPID TnT, likely representing missed opportunities to reduce late death or MI.

GDF-15 at admission predicts cardiovascular death, heart failure, and bleeding outcomes in patients with CAD.

AIMS: We aimed to investigate the independent associations between growth differentiation factor 15 (GDF-15) level at admission and cardiovascular (CV) death, thrombotic events, heart failure (HF), and bleeding outcomes in patients with coronary artery disease (CAD). METHODS AND RESULTS: We measured the plasma concentrations of GDF-15 centrally in patients from the BIomarker-based Prognostic Assessment for patients with Stable angina and acute coronary Syndrome (BIPass) registry, which consecutively enrolled patients with CAD from November 2017 to September 2019 at five tertiary hospitals in China. The outcomes included CV death, thrombotic events [myocardial infarction (MI) and ischaemic stroke], HF events [acute HF during hospitalization and hospitalization for HF post-discharge (A/H HF) and cardiogenic shock], and bleeding outcomes [non-coronary artery bypass grafting-related major bleeding and clinically significant bleeding (CSB)] during the 12 month follow-up period after hospitalization. Among 6322 patients with CAD {65.4% male, median age 63.7 [inter-quartile range (IQR)] 56.0-70.1 years}, the median concentration of plasma GDF-15 at admission was 1091 (IQR 790.5-1635.0) ng/L. Higher concentrations of GDF-15 were associated with an increased risk of CV death [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.35-2.88, P < 0.001], A/H HF (HR 2.69, 95% CI 1.92-3.77, P < 0.001), cardiogenic shock (HR 1.46, 95% CI 1.04-2.05, P = 0.029), and CSB (HR 1.48, 95% CI 1.22-1.79, P < 0.001), but not for MI or stroke, after adjusting for clinical risk factors and prognostic biomarkers. Adding GDF-15 to the model with risk factors and biomarkers improved the net reclassification for CV death, A/H HF, cardiogenic shock, and CSB. CONCLUSIONS: In patients with CAD, admission levels of GDF-15 were associated with an increased 1 year risk of CV death, HF, and bleeding outcomes, but not with thrombotic events. GDF-15 may be a prognostic biomarker for CV death, HF, and bleeding outcomes and could be used to refine the risk assessment of these specific clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04044066.

Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syndrome (UKGRIS): parallel group cluster randomised controlled trial.

OBJECTIVE: To determine the effectiveness of risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) for patients presenting to hospital with suspected non-ST elevation acute coronary syndrome. DESIGN: Parallel group cluster randomised controlled trial. SETTING: Patients presenting with suspected non-ST elevation acute coronary syndrome to 42 hospitals in England between 9 March 2017 and 30 December 2019. PARTICIPANTS: Patients aged ≥18 years with a minimum follow-up of 12 months. INTERVENTION: Hospitals were randomised (1:1) to patient management by standard care or according to the GRS and associated guidelines. MAIN OUTCOME MEASURES: Primary outcome measures were use of guideline recommended management and time to the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospital admission, and readmission for cardiovascular event. Secondary measures included the duration of hospital stay, EQ-5D-5L (five domain, five level version of the EuroQoL index), and the composite endpoint components. RESULTS: 3050 participants (1440 GRS, 1610 standard care) were recruited in 38 UK clusters (20 GRS, 18 standard care). The mean age was 65.7 years (standard deviation 12), 69% were male, and the mean baseline GRACE scores were 119.5 (standard deviation 31.4) and 125.7 (34.4) for GRS and standard care, respectively. The uptake of guideline recommended processes was 77.3% for GRS and 75.3% for standard care (odds ratio 1.16, 95% confidence interval 0.70 to 1.92, P=0.56). The time to the first composite cardiac event was not significantly improved by the GRS (hazard ratio 0.89, 95% confidence interval 0.68 to 1.16, P=0.37). Baseline adjusted EQ-5D-5L utility at 12 months (difference -0.01, 95% confidence interval -0.06 to 0.04) and the duration of hospital admission within 12 months (mean 11.2 days, standard deviation 18 days v 11.8 days, 19 days) were similar for GRS and standard care. CONCLUSIONS: In adults presenting to hospital with suspected non-ST elevation acute coronary syndrome, the GRS did not improve adherence to guideline recommended management or reduce cardiovascular events at 12 months. TRIAL REGISTRATION: ISRCTN 29731761.

Twelve-Month Outcomes of Patients With Myocardial Injury not Due to Type-1 Myocardial Infarction.

BACKGROUND: Diagnosis of acute myocardial infarction (AMI) requires a combination of elevated cardiac troponins, and clinical or echocardiographic evidence of coronary ischaemia. Identification of patients with a high likelihood of coronary plaque rupture (Type 1 myocardial infarction [MI]) is crucial as it is these patients for whom coronary intervention has been well-established to provide benefit and reduce subsequent coronary ischemic events. However, high-sensitivity cardiac troponin (hs-cTn) assays have increasingly identified patients with hs-cTn elevations not due to Type 1 MI where recommendations for ongoing care are currently limited. Understanding the profile and clinical outcomes for these patients may inform the development of an emerging evidence-base. METHODS: Using two previously published studies (hs-cTnT study n=1,937, RAPID-TnT study n=3,270) and the Fourth Universal Definition of MI, index presentations of patients to South Australian emergency departments with suspected AMI, defined by high sensitivity cardiac troponin T (hs-cTnT) greater than the upper reference limit (14 ng/L) and without obvious corresponding ischaemia on electrocardiogram (ECG), were classified as either Type 1 MI (T1MI), Type 2 MI (T2MI), acute myocardial injury (AI), or chronic myocardial injury (CI). Patients with non-elevated hs-cTnT (defined as <14 ng/L) were excluded. Outcomes assessed included death, MI, unstable angina, and non-coronary cardiovascular events within 12 months. RESULTS: In total, 1,192 patients comprising 164 (13.8%) T1MI, 173 (14.5%) T2MI/AI, and 855 (71.7%) CI were included. The rate of death or recurrent acute coronary syndrome was greatest in patients with T1MI, but also occurred with moderate frequency in Type 2 MI/AI and CI (T1MI: 32/164 [19.5%]; T2MI/AI: 24/173 [13.1%]; CI:116/885 [13.6%]; p=0.008). Of all the deaths observed, 74% occurred among those with an initial index diagnostic classification of CI. After adjusting for age, gender and baseline comorbidities, the relative hazard ratios for non-coronary cardiovascular readmissions were similar across all groups: Type 2 MI/AI: 1.30 (95% confidence interval 0.99-1.72, p=0.062); CI: 1.10 (95% confidence interval 0.61-2.00, p=0.75). CONCLUSIONS: Non-T1MI accounted for the majority of patients presenting with elevated hs-cTnT without ischaemia on ECG. Patients with T1MI had the highest rates of death or recurrent AMI; however patients with T2MI/AI and CI experienced a substantial rate of non-coronary cardiovascular re-hospitalisations.