Predicting multifaceted risks using machine learning in atrial fibrillation: insights from GLORIA-AF study.

Aims: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke and death. While anticoagulants are effective at reducing these risks, they increase the risk of bleeding. Current clinical risk scores only perform modestly in predicting adverse outcomes, especially for the outcome of death. We aimed to test the multi-label gradient boosting decision tree (ML-GBDT) model in predicting risks for adverse outcomes in a prospective global AF registry. Methods and results: We studied patients from phase II/III of the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation registry between 2011 and 2020. The outcomes were all-cause death, ischaemic stroke, and major bleeding within 1 year following the AF. We trained the ML-GBDT model and compared its discrimination with the clinical scores in predicting patient outcomes. A total of 25 656 patients were included [mean age 70.3 years (SD 10.3); 44.8% female]. Within 1 year after AF, ischaemic stroke occurred in 215 (0.8%), major bleeding in 405 (1.6%), and death in 897 (3.5%) patients. Our model achieved an optimized area under the curve in predicting death (0.785, 95% CI: 0.757-0.813) compared with the Charlson Comorbidity Index (0.747, P = 0.007), ischaemic stroke (0.691, 0.626-0.756) compared with CHA2DS2-VASc (0.613, P = 0.028), and major bleeding (0.698, 0.651-0.745) as opposed to HAS-BLED (0.607, P = 0.002), with improvement in net reclassification index (10.0, 12.5, and 23.6%, respectively). Conclusion: The ML-GBDT model outperformed clinical risk scores in predicting the risks in patients with AF. This approach could be used as a single multifaceted holistic tool to optimize patient risk assessment and mitigate adverse outcomes when managing AF.

Clinical outcomes and health care costs of transferring rural Western Australians for invasive coronary angiography, and a cost-effective alternative care model: a retrospective cross-sectional study.

OBJECTIVES: To examine the severity of coronary artery disease (CAD) in people from rural or remote Western Australia referred for invasive coronary angiography (ICA) in Perth and their subsequent management; to estimate the cost savings were computed tomography coronary angiography (CTCA) offered in rural centres as a first line investigation for people with suspected CAD. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Adults with stable symptoms in rural and remote WA referred to Perth public tertiary hospitals for ICA evaluation during the 2019 calendar year. MAIN OUTCOME MEASURES: Severity and management of CAD (medical management or revascularisation); health care costs by care model (standard care or a proposed alternative model with local CTCA assessment). RESULTS: The mean age of the 1017 people from rural and remote WA who underwent ICA in Perth was 62 years (standard deviation, 13 years); 680 were men (66.9%), 245 were Indigenous people (24.1%). Indications for referral were non-ST elevation myocardial infarction (438, 43.1%), chest pain with normal troponin level (394, 38.7%), and other (185, 18.2%). After ICA assessment, 619 people were medically managed (60.9%) and 398 underwent revascularisation (39.1%). None of the 365 patients (35.9%) without obstructed coronaries (< 50% stenosis) underwent revascularisation; nine patients with moderate CAD (50-69% stenosis; 7%) and 389 with severe CAD (≥ 70% stenosis or occluded vessel; 75.5%) underwent revascularisation. Were CTCA used locally to determine the need for referral, 527 referrals could have been averted (53%), the ICA:revascularisation ratio would have improved from 2.6 to 1.6, and 1757 metropolitan hospital bed-days (43% reduction) and $7.3 million in health care costs (36% reduction) would have been saved. CONCLUSION: Many rural and remote Western Australians transferred for ICA in Perth have non-obstructive CAD and are medically managed. Providing CTCA as a first line investigation in rural centres could avert half of these transfers and be a cost-effective strategy for risk stratification of people with suspected CAD.

Performance of multilabel machine learning models and risk stratification schemas for predicting stroke and bleeding risk in patients with non-valvular atrial fibrillation.

BACKGROUND: Appropriate anticoagulant therapy for patients with atrial fibrillation (AF) requires assessment of stroke and bleeding risks. However, risk stratification schemas such as CHA2DS2-VASc and HAS-BLED have modest predictive capacity for patients with AF. Multilabel machine learning (ML) techniques may improve predictive performance and support decision-making for anticoagulant therapy. We compared the performance of multilabel ML models with the currently used risk scores for predicting outcomes in AF patients. METHODS: This was a retrospective cohort study of 9670 patients, mean age 76.9 years, 46% women, who were hospitalized with non-valvular AF, and had 1-year follow-up. The outcomes were ischemic stroke (167), major bleeding (430) admissions, all-cause death (1912) and event-free survival (7387). Discrimination and calibration of ML models were compared with clinical risk scores by area under the curve (AUC). Risk stratification was assessed using net reclassification index (NRI). RESULTS: Multilabel gradient boosting classifier chain provided the best AUCs for stroke (0.685 95% CI 0.676, 0.694), major bleeding (0.709 95% CI 0.703, 0.716) and death (0.765 95% CI 0.763, 0.768) compared to multi-layer neural networks and classifier chain using support vector machine. It provided modest performance improvement for stroke compared to AUC of CHA2DS2-VASc (0.652, NRI = 3.2%, p-value = 0.1), but significantly improved major bleeding prediction compared to AUC of HAS-BLED (0.522, NRI = 22.8%, p-value < 0.05). It also achieved greater discriminant power for death compared with AUC of CHA2DS2-VASc (0.606, p-value < 0.05). ML models identified additional risk features such as hemoglobin level, renal function. CONCLUSIONS: Multilabel ML models can outperform clinical risk stratification scores for predicting the risk of major bleeding and death in non-valvular AF patients.

Alcohol Consumption and Cardiovascular Outcomes in Patients With Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study.

Low-level alcohol consumption is associated with reduced cardiovascular disease (CVD) in the general population. It is unclear whether this association is seen in patients with nonalcoholic fatty liver disease (NAFLD) who have an increased risk of CVD. We examined the association between alcohol consumption and CVD-related outcomes in subjects with NAFLD from a general population cohort. Subjects participating in the 1994-1995 Busselton Health survey underwent clinical and biochemical assessment. NAFLD was identified using the Fatty Liver Index of >60, and alcohol consumption quantified using a validated questionnaire. CVD hospitalizations and death during the ensuing 20 years were ascertained using the Western Australian data linkage system. A total of 659 of 4,843 patients were diagnosed with NAFLD. The average standard drinks per week was 8.0 for men and 4.0 for women. Men consuming 8-21 drinks per week had a 38% (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.43-0.90) lower risk of CVD hospitalization as compared with men consuming 1-7 drinks per week. With both men and women combined, consumption of 8-21 drinks per week was associated with a 32% (HR 0.68, 95% CI 0.49-0.93) reduction in CVD hospitalization in minimally adjusted and 29% (HR 0.71, 95% CI 0.51-0.99) in fully adjusted models. No protective association was observed with binge drinking. There was no association between alcohol consumption and CVD death. Conclusion: Low to moderate alcohol consumption is associated with fewer CVD hospitalizations but not CVD death in subjects with NAFLD.

Impact of Pre-Hospital Activation of STEMI on False Positive Activation Rate and Door to Balloon Time.

BACKGROUND: Pre-hospital identification of ST-segment elevation myocardial infarction (STEMI) by paramedical staff reduces reperfusion time. However, the impact of this approach on the rate of unnecessary activation of coronary catheterisation lab (CCL) remains unclear. METHODS: The study reviewed consecutive STEMI patients over 3 years (July 2015 to June 2018) from all primary percutaneous coronary intervention (PPCI) centres and inter-hospital transfers (IHT) from non-PPCI capable centres in Western Australia. Out-of-hospital cardiac arrests (OOHCA) and STEMI calls for in-patients receiving treatment for other medical reasons were excluded. RESULTS: During the 3 years study period, 1,736 STEMI cases were recorded. Pre-hospital (PH) activation occurred in 799 (46%) cases. Median door to balloon time (D2BT) was 68 minutes (IQR 63 mins). D2BT for PH activation (40 min [IQR 25 min]) was significantly lower than both the PPCI centre emergency department (ED) activation (86 min [IQR 55 min]) and IHT activation groups (108 min [IQR 55 min]), p-value <0.00001. In PH activation group 98% patients received primary PCI in less than 90 minutes compared to 54% and 26% patients in the ED and the IHT activation groups, respectively. False positive STEMI activation rate was lower in the PH activation group (2.75%) compared to ED activation (5.4%) and IHT group (6%), p-value 0.0115. The false positive rate did not vary significantly between working hours and out-of-hour calls (5% vs 4%, p-value=0.304). Pericarditis, coronary artery disease other than STEMI, atypical chest pain, and stress induced cardiomyopathy were the common diagnoses in false positive activations. CONCLUSION: Pre-hospital activation of STEMI leads to reduced door to balloon times without a significant increase in inappropriate procedures, though false positive activation rates are unclear. The majority of STEMI patients transferred from non-PPCI centres failed to receive reperfusion therapy within 90 minutes of initial hospital presentation. Further studies are required to assess the benefits of thrombolysis in selected patients in inter-hospital transfer group.

Prehospital continuous positive airway pressure (CPAP) for acute respiratory distress: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of continuous positive airway pressure (CPAP) versus usual care for prehospital patients with severe respiratory distress. METHODS: We conducted a parallel group, individual patient, non-blinded randomised controlled trial in Western Australia between March 2016 and December 2018. Eligible patients were aged ≥40 years with acute severe respiratory distress of non-traumatic origin and unresponsive to initial treatments by emergency medical service (EMS) paramedics. Patients were randomised (1:1) to usual care or usual care plus CPAP. The primary outcomes were change in dyspnoea score and change in RR at ED arrival, and hospital length of stay. RESULTS: 708 patients were randomly assigned (opaque sealed envelope) to usual care (n=346) or CPAP (n=362). Compared with usual care, patients randomised to CPAP had a greater reduction in dyspnoea scores (usual care -1.0, IQR -3.0 to 0.0 vs CPAP -3.5, IQR -5.2 to -2.0), median difference -2.0 (95% CI -2.5 to -1.6); and RR (usual care -4.0, IQR -9.0 to 0.0 min-1 vs CPAP -8.0, IQR -14.0 to -4.0 min-1), median difference -4.0 (95% CI -5.0 to -4.0) min-1. There was no difference in hospital length of stay (usual care 4.2, IQR 2.1 to 7.8 days vs CPAP 4.8, IQR 2.5 to 7.9 days) for the n=624 cases admitted to hospital, median difference 0.36 (95% CI -0.17 to 0.90). CONCLUSIONS: The use of prehospital CPAP by EMS paramedics reduced dyspnoea and tachypnoea in patients with acute respiratory distress but did not impact hospital length of stay. TRIAL REGISTRATION NUMBER: ACTRN12615001180505.

Association of hypertension with mortality in patients hospitalised with COVID-19.

OBJECTIVE: To assess whether hypertension is an independent risk factor for mortality among patients hospitalised with COVID-19, and to evaluate the impact of ACE inhibitor and angiotensin receptor blocker (ARB) use on mortality in patients with a background of hypertension. METHOD: This observational cohort study included all index hospitalisations with laboratory-proven COVID-19 aged ≥18 years across 21 Australian hospitals. Patients with suspected, but not laboratory-proven COVID-19, were excluded. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs. RESULTS: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (adjusted OR (aOR) 1.09, 95% CI 1.07 to 1.12, p<0.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13 to 6.53, p=0.026), chronic kidney disease (aOR 2.33, 95% CI 1.02 to 5.32, p=0.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06 to 4.85, p=0.035). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48 to 1.77, p=0.81). Among patients with hypertension, ACE inhibitor (aOR 1.37, 95% CI 0.61 to 3.08, p=0.61) and ARB (aOR 0.64, 95% CI 0.27 to 1.49, p=0.30) use was not associated with mortality. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

Cardiac Complications in Patients Hospitalised With COVID-19 in Australia.

OBJECTIVES: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. DESIGN: Observational cohort study. SETTING: Twenty-one (21) Australian hospitals. PARTICIPANTS: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: Incidence of cardiac complications. RESULTS: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. CONCLUSIONS: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

Antithrombotic Therapy in Atrial Fibrillation Management in Western Australia: Temporal Trends and Evidence-Treatment Gaps.

OBJECTIVE: To describe temporal trends in appropriate antithrombotic therapy use in hospitalised atrial fibrillation (AF) patients and identify evidence-treatment gaps in clinical practice. DESIGN: Retrospective cohort study from January 2009-March 2016. SETTING: Tertiary and secondary teaching hospitals in Perth, Western Australia. PARTICIPANTS: Hospitalised adults with non-valvular AF. RESULTS: We identified 11,294 index AF admissions, with a mean age of 76.9 years, 45.8% women and 86.3% at high risk of stroke (CHA2DS2-VASc score ≥2 in men and ≥3 in women). In high risk subjects use of appropriate antithrombotic therapy improved over time with increasing oral anticoagulant (OAC) use and declining sole antiplatelet use (both trend p<0.001). However, by study end only 45.3% of high-risk patients were receiving OAC therapy. In low risk patients, receipt of OAC therapy was steady throughout the study at 40.5% (trend p=0.10). The gender gap in OAC use narrowed over time, with no significant difference between high risk men and women by study end. Use of OAC therapy in elderly patients (age ≥75 years) remained lower than younger patients (age <65 years) over the entire period, with only 31% of elderly patients receiving OAC therapy at study end. From 2012 onwards use of non-vitamin K oral anticoagulants (NOACs) doubled each year with declining warfarin use (both trend p<0.001). CONCLUSION: Despite substantial uptake of NOACs, OAC therapy in AF patients at high risk of stroke remains under-utilised in Western Australia and over-utilised in low risk patients. Further work is required to reduce treatment-risk mismatch for stroke prevention in AF patients.

Drivers of hospitalisation trends for non-valvular atrial fibrillation in Western Australia, 2000-2013.

OBJECTIVE: To determine if increasing hospitalisations for non-valvular atrial fibrillation (NVAF) in Western Australia (WA) was due to incident (first-ever) or repeat hospitalisations, an ageing population structure, changing procedural practice or a combination of these factors. METHODS: We conducted a longitudinal retrospective population study on all WA residents aged 25-94 years between 2000 and 2013, with a principal hospital discharge diagnosis of NVAF. Person-linked hospital morbidity and mortality records were used to measure annual rate ratios (RRs) and 95% confidence intervals (CIs) in the total and incident NVAF (25-94 years) hospitalisations, further stratified by sex and by age-specific standardised groups (25-44, 45-64, 65-75, 75-84, 85-94 years). RESULTS: There were 55,532 total hospitalisations for NVAF between 2000 and 2013, patient mean age 68.3 years, and 58% male. Annual age- and sex- standardised rates for total NVAF hospitalisation increased by 3.0%/year (RR 1.030; 95%CI; 1.028, 1.038), and in both men and women. The largest absolute increase in hospitalisation rate occurred in those aged 85-94 years (∆613/100,000 men and women combined). Incident NVAF hospitalisations showed a borderline decline of 0.5%/year (RR 0.99; 95%CI; 0.99, 1.0) with a statistically significant trend in women but not men. The rate of AF admissions associated with a catheter ablation increased by 13%/year (95%CI; 13.1%, 15.3%). CONCLUSION: The increasing rates of total hospitalisation for NVAF is driven more by repeat than incident admissions, escalating hospitalisations in the very elderly, and more frequent interventional procedures. These drivers have major economic and healthcare planning implications.

Ischaemic Stroke and the Echocardiographic "Bubble Study": Are We Screening the Right Patients?

BACKGROUND: Patent foramen ovale (PFO) is a potential mechanism for paradoxical embolism in cryptogenic ischaemic stroke or transient ischaemic attack (TIA). PFO is typically demonstrated with agitated saline ("bubble study", BS) during echocardiography. We hypothesised that the BS is frequently requested in patients that have a readily identifiable cause of stroke, that any PFO detected is likely incidental, and its detection often does not alter management. METHODS: This was a retrospective observational study of patients with recent ischaemic stroke/TIA referred for a BS. Patient demographics, stroke risk factors, vascular/cerebral imaging results and transoesophageal echocardiogram (TOE) reports were recorded. A "modified" Risk of Paradoxical Embolism (RoPE) score was calculated. Change in management was defined as antiplatelet/anticoagulant therapy alteration or referral for PFO closure. Bubble Study complications were recorded. RESULTS: Among 715 patients with ischaemic stroke/TIA referred for a BS, 8.7% had atrial fibrillation and 9.2% had carotid stenosis ≥70%. At least three stroke risk factors were present in 39.3% and only 47.1% of patients screened had a "modified" RoPE score of >5. A PFO was detected in 248 patients of whom only 31% (77/248) had a subsequent change in management. Of BS performed, 1/924 patients (0.1%) suffered a TIA as a complication. CONCLUSIONS: The echocardiographic BS is frequently performed in patients that have a readily identifiable cause of stroke and whose PFO unlikely relates to the stroke/TIA. Bubble Study findings resulted in a change in management in the minority. The procedure is safe but the complication rate warrants informed consent.

A 5α-reductase (SRD5A2) polymorphism is associated with serum testosterone and sex hormone-binding globulin in men, while aromatase (CYP19A1) polymorphisms are associated with oestradiol and luteinizing hormone reciprocally.

CONTEXT: Pituitary luteinizing hormone (LH) stimulates testicular production of testosterone (T) which is metabolized to dihydrotestosterone (DHT) by 5α-reductase and to oestradiol (E2) by aromatase. How the activity of population variants in these enzymes impacts on gonadal function is unclear. We examined whether polymorphisms in 5α-reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations. DESIGN: Cross-sectional analysis of 1865 community-dwelling men aged 50.4 ± 16.8 years. MEASUREMENTS: Early morning sera assayed for T, DHT and E2 (mass spectrometry), and SHBG and LH (immunoassay). Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR. Regression models were adjusted for age and cardiometabolic risk factors. RESULTS: SRD5A2 polymorphism rs9282858 GA vs. GG was associated with higher serum T (+1.5 nmol/L, P < 0.001) and higher SHBG (+3.3 nmol/L, P = 0.001). CYP19A1 polymorphisms were associated with higher serum E2 and lower LH in reciprocal fashion, from which the two-copy haplotype rs10046 = T/rs2899470 = G/rs11575899 = I/rs700518 = G/rs17703883 = T was associated with higher E2 (63.4 vs. 56.5 pmol/L, P = 0.001) and lower LH (3.9 vs. 4.5 IU/L, P = 0.001) compared to null copies. Conversely, rs10046 = C/rs2899470 = T/rs11575899 = D/rs700518 = A/rs17703883 = C was associated with lower E2 (51.8 vs. 62.0 pmol/L, P = 0.001) and higher LH (5.7 vs. 3.9 IU/L, P < 0.001). These haplotypes were associated primarily with differences in E2 in men <65 years and LH in men ≥65 years. CONCLUSIONS: A 5α-reductase polymorphism predicts circulating T and SHBG, while aromatase polymorphisms predict E2 and LH in reciprocal fashion. Age and aromatase polymorphisms interact to affect E2 and LH. How these functional polymorphisms impact on male reproductive and general health outcomes requires further study.

Lipoprotein(a) and apolipoprotein(a) isoform size: Associations with angiographic extent and severity of coronary artery disease, and carotid artery plaque.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an emerging genetic risk factor for cardiovascular disease (CVD). We examined whether plasma Lp(a) concentration and apolipoprotein(a) [apo(a)] isoform size are associated with extent and severity of coronary artery disease (CAD), and the presence of carotid artery plaque. METHODS: We included in our study male participants (n = 263) from a cohort with angiographically defined premature CAD (Carotid Ultrasound in Patients with Ischemic Heart Disease). The angiographic extent and severity of CAD were determined by the modified Gensini and Coronary Artery Stenosis≥20% (CAGE) scores. Carotid artery plaque was assessed by bilateral carotid B-mode ultrasound. Apo(a) isoform size was determined by LPA Kringle IV-2 copy number (KIV-2 CN). RESULTS: Lp(a) concentration, but not KIV-2 CN, was positively associated with the Gensini score. The association remained significant following adjustment for conventional CVD risk factors (all p < 0.05). Lp(a) concentration and elevated Lp(a) [≥50 mg/dL] were positively associated with the CAGE≥20 score, independent of conventional CVD risk factors. KIV-2 C N Q1 (lowest KIV-2 CN quartile) was associated with CAGE≥20 score and KIV-2 CN, with the CAGE≥20 score in those without diabetes. In multivariate models that included phenotypic familial hypercholesterolemia or low-density lipoprotein cholesterol, Lp(a) concentration, but not KIV-2 CN, was independently associated with the Gensini and CAGE≥20 scores. No significant associations between Lp(a) concentration and KIV-2 CN with carotid artery plaque were observed. CONCLUSIONS: Lp(a) concentration, but not apo(a) isoform size, is independently associated with angiographic extent and severity of CAD. Neither Lp(a) nor apo(a) isoform size is associated with carotid artery plaque.

REACTED - Reducing Acute Chest pain Time in the ED: A prospective pre-/post-interventional cohort study, stratifying risk using early cardiac multi-markers, probably increases discharges safely.

OBJECTIVE: ED chest pain assessments can be challenging, lengthy and contribute to overcrowding. Rapid accurate risk stratification strategies should improve ED length of stay (EDLOS). Emergency, Biochemistry and Cardiology implemented new guidelines using paired (<3 h) multiple cardiac markers to stratify patients. The intervention would reduce chest pain EDLOS. We observed for safety and disposition effects. METHODS: This is a single-site, prospective observational, before and after intervention study. In December 2009, paired multiple cardiac markers, the second at least 4 h from pain, replaced late troponins. The 4 h rule (ED flow improvement) started in April 2009 (unplanned confounder). Demographics, clinical features, risk assessment and disposition; preferably prospective. Administrative datasets provided disposition outcomes, 4 months pre-/post-intervention. Follow up with partially blinded adjudications assessed for 45 day major adverse cardiac events (MACE). Before intervention, consecutive patients were enrolled with mixed prospective/retrospective data. After, sampling occurred whenever prospective data were collected. RESULTS: Adjudicated patients were n = 1029 (14.2% MI, 14.9% MACE), 426 before, 603 after. EDLOS reduced 87 min (416-329; P < 0.001), similar to triage 2 patients without chest pain. Possibly, avoidable MACE occurred in five of 598 discharges (0.8%, CI 0.3-1.8%) with non-significant decreases (0.5%, CI 0.1-1.8%) post-intervention. Disposition changes included greater observation ward use (3.8-12.3%; P < 0.001), more discharges (47.4-52.9%, P = 0.002), less transfers (9.3-6.9%, P = 0.014) and less late inpatient discharge decisions (15.2-8.7%, P = 0.001). CONCLUSION: Paired cardiac markers performed adequately for avoidable MACE, and disposition improved significantly. A confounding system change meant the reduced EDLOS (primary outcome) was unable to be associated with the intervention.

Neutral associations of testosterone, dihydrotestosterone and estradiol with fatal and non-fatal cardiovascular events, and mortality in men aged 17-97 years.

CONTEXT: Lower testosterone (T) is associated with poorer health outcomes in older men, however, the relationship between T, dihydrotestosterone (DHT) and estradiol (E2) with cardiovascular disease (CVD) in younger to middle-aged men remains unclear. OBJECTIVES: We assessed associations between endogenous sex hormones with mortality (all-cause and CVD) and CVD events, in a cohort of men aged 17-97 years. PARTICIPANTS AND METHODS: Sex hormones were assayed using mass spectrometry in 2143 men from the 1994/5 Busselton Health Survey. Outcomes to December 2010 were analysed. RESULTS: Of the 1804 men included in the analysis, mean age was 50·3 ± 16·8 years and 68·9% of men were aged <60. Mean follow-up period was 14·9 years. There were 319 deaths, 141 CVD deaths and 399 CVD events. Compared to the full cohort, men who died had lower baseline T (12·0 ± 4·4 vs 13·6 ± 4·9 nmol/l), free T (181·9 ± 52·9 vs 218·3 ± 63·8 pmol/l) and DHT (1·65 ± 0·64 vs 1·70 ± 0·72 nmol/l), but higher E2 (64·0 ± 32 vs 60·1 ± 30·2 pmol/l). After adjustment for risk factors, T was not associated with mortality (adjusted HR = 0·90, 95% CI 0·79-1·04; P = 0·164 for every increase in 1 SD of T), CVD deaths (adjusted HR = 1·04, 95% CI 0·84-1·29; P = 0·708) or CVD events (adjusted HR = 1·03, 95% CI 0·92-1·15, P = 0·661). No associations were found for free T, DHT or E2. Results were similar for men older and younger than 60 years. CONCLUSIONS: In predominantly middle-aged men, T, DHT and E2 do not influence mortality or CVD outcomes. This neutral association of hormones with CVD contrasts with prior studies of older men.

Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men.

CONTEXT: Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is metabolized to DHT by 5α-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro. OBJECTIVE: The objective of the study was to establish whether circulating T or its metabolites, DHT or E2, and single-nucleotide polymorphisms in SRD5A2 or CYP19A1 associate with leucocyte telomere length (LTL) in men. PARTICIPANTS AND METHODS: Early-morning serum T, DHT, and E2 were assayed using mass spectrometry, and SRD5A2 and CYP19A1 single-nucleotide polymorphisms and LTL analyzed by PCR in 980 men from the Western Australian Busselton Health Survey who participated in the study. LTL was expressed as the T/S ratio. RESULTS: Men were aged (mean ± SD) 53.7 ± 15.6 years. LTL decreased linearly with age, from the T/S ratio of 1.89 ± 0.41 at younger than 30 years to 1.50 ± 0.49 at 70 to younger than 80 years (r = -0.225, P < .0001). After adjustment for age, DHT and E2 were positively correlated with LTL (DHT, r = 0.069, P = .030; E2, r = 0.068, P = .034). The SRD5A2 rs9282858 polymorphism was associated with serum DHT but not with LTL. Three dominant alleles of CYP19A1 were each associated with lower serum E2 and shorter LTL: rs2899470 T (E2, 59.3 vs 68.6 pmol/L, P < .0001; T/S ratio, 1.54 vs 1.62, P = .045), rs10046 C (60.5 vs 68.1 pmol/L, P = .0005, 1.54 vs 1.62, P = .035), and rs700518 A (59.9 vs 68.9 pmol/L, P < .0001, 1.54 vs 1.63, P = .020). A single-copy haplotype C/T/I/A/T rs10046/rs2899470/rs11575899/rs700518/rs17703883 (52% prevalence) was associated with both lower E2 and shorter LTL. CONCLUSIONS: In men, serum DHT and E2 correlate with LTL independently of age. Aromatase gene polymorphisms include three dominant alleles that are associated with both lower serum E2 and shorter LTL. E2 influences telomere length in vivo, thus warranting further studies to examine whether hormonal interventions might slow biological aging in men.

Trends in incidence and prevalence of hospitalization for atrial fibrillation and associated mortality in Western Australia, 1995-2010.

OBJECTIVE: Hospitalization for atrial fibrillation (AF) is a large and growing public health problem. We examined current trends in the incidence, prevalence, and associated mortality of first-ever hospitalization for AF. METHODS: Linked hospital admission data were used to identify all Western Australia residents aged 35-84 years with prevalent AF and incident (first-ever) hospitalization for AF as a principal or secondary diagnosis during 1995-2010. RESULTS: There were 57,552 incident hospitalizations, mean age 69.8 years, with 41.4% women. Over the calendar periods, age- and sex-standardized incidence of hospitalization for AF as any diagnosis declined annually by 1.1% (95% CI; 0.93, 1.29), while incident AF as a principal diagnosis increased annually by 1.2% (95% CI; 0.84, 1.50). Incident AF hospitalization was higher among men than women, and 15-fold higher in the 75-84 compared with 35-64 year age group. The age- and sex-standardized prevalence of AF increased annually by 2.0% (95% CI; 1.88, 2.03) over the same period. Comorbidity trends were mixed with diabetes and valvular heart disease increasing, and hypertension, coronary artery disease, heart failure, cerebrovascular disease, and chronic kidney disease decreasing. The 1-year all-cause mortality after incident AF hospitalization declined from 17.6% to 14.6% (trend P<0.001), with an adjusted hazard ratio of 0.86 (95% CI; 0.81, 0.91). CONCLUSION: This contemporary study shows that incident AF hospitalization is not increasing except for AF as a principal diagnosis, while population prevalence of hospitalized AF has risen substantially. The high 1-year mortality following incident AF hospitalization has improved only modestly over the recent period.

Transient occlusion of the right coronary artery by a calcific bicuspid aortic valve mass - An interesting case of inferior STEMI.

Calcified bicuspid aortic valves are a commonly encountered clinical problem. Less common and possibly underreported, however, are embolic events secondary to a calcified valve. Events, including stroke and myocardial infarction, have been documented in the literature. We report the case of a myocardial infarction caused by transient occlusion of the right coronary artery, secondary to a mobile calcified lesion attached to a bicuspid aortic valve. .