α1-Antichymotrypsin Complex (SERPINA3) Is an Independent Predictor of All-Cause but Not Cardiovascular Mortality in Patients Hospitalized for Chest Pain of Suspected Coronary Origin.

INTRODUCTION: SERPINA3 is an acute-phase protein triggered by inflammation. It is upregulated after an acute myocardial infarction (AMI). Data on its long-term prognostic value in MI patients are scarce. We aimed to assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin. METHODS: A total of 871 consecutive patients, 386 diagnosed with AMI, were included. Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for the biomarker with all-cause mortality and cardiac death within 2 years or all-cause mortality within the median 7 years as dependent variables. An analysis of MI and stroke, and combined endpoints, respectively, was added. The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model. RESULTS: Plasma samples from 847 patients were available. By 2-year follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a significant association between SERPINA3 and all-cause mortality (HR 1.41 [95% 1.19-1.68], p < 0.001) but not for cardiac death. Associations after adjustment were non-significant. By 7-year follow-up, 332 (38.1%) patients had died. SERPINA3 was independently associated with all-cause mortality from the third year onward. The HR was 1.14 (95% CI, 1.02-1.28), p = 0.022. Similar results applied to combined endpoints, but not for MI and stroke, respectively. The prognostic value of SERPINA3 was limited to non-AMI patients. No independent associations were noted among AMI patients. CONCLUSIONS: SERPINA3 predicts long-term all-cause mortality but fails to predict outcome in AMI patients.

Increased short-term mortality among patients presenting with altered mental status to the emergency department: A cohort study.

OBJECTIVES: To evaluate the short-term mortality of adult patients presenting to the emergency department (ED) with altered mental status (AMS) as compared to other common chief complaints. METHODS: Observational cohort study of adult patients (age ≥ 40) who presented to an academic ED over a 1-year period with five pre-specified complaints at ED triage: AMS, generalized weakness, chest pain, abdominal pain, and headache. Primary outcomes included 7 and 30-day mortality. Hazard ratios (HR) were calculated with 95% confidence intervals (CI) using Cox proportional hazards models adjusted for age, acuity level, and comorbidities. RESULTS: A total of 9850 ED visits were included for analysis from which 101 (1.0%) and 295 (3.0%) died within 7 and 30 days, respectively. Among 683 AMS visits, the 7-day mortality rate was 3.2%. Mortality was lower for all other chief complaints, including generalized weakness (17/1170, 1.5%), abdominal pain (32/3609, 0.9%), chest pain (26/3548, 0.7%), and headache (4/840, 0.5%). After adjusting for key confounders, patients presenting with AMS had a significantly higher risk of death within 7 days of ED arrival than patients presenting with chest pain (HR 3.72, 95% CI 2.05 to 6.76, p < .001). Similarly, we found that patients presenting with AMS had a significantly higher risk of dying within 30 days compared to patients with chest pain (HR 3.65, 95% CI 2.49 to 5.37, p < .001), and headache (HR 2.09, 95% CI 1.09 to 4.01, p = .026). Differences were not statistically significant for comparisons with abdominal pain and generalized weakness, but confidence intervals were wide. CONCLUSION: Patients presenting with AMS have worse short-term prognosis than patients presenting to the ED with chest pain or headache. AMS may indicate an underlying brain dysfunction (delirium), which is associated with adverse outcomes and increased mortality.

The Average Effect of Emergency Department Admission on Readmission and Mortality for Older Adults With Chest Pain.

BACKGROUND: Many older adults (65+) present to the Emergency Department (ED) with chest pain, but do not have otherwise clear clinical indication of whether they should be admitted or discharged. This uncertainty leads to decisions that are highly variable-in addition to already being costly-which could have adverse consequences, since older adults are particularly vulnerable from hospitalization. OBJECTIVE: The objective of this study was to determine whether admitting versus discharging an older adult presenting to the ED with chest pain reduces risk of mortality and readmission. STUDY DESIGN: Electronic health records were curated from an academic hospital system between January 1, 2014, and September 27, 2018. Average effects of admission on 30-day readmission and mortality were estimated using a new causal inference approach based on a latent-variable model of the admission process. Additional analyses assessed moderators and robustness of estimates. SUBJECTS: Older patients (n=3090) presenting to University of Wisconsin Hospital ED. MEASURES: Readmission and mortality within 25, 30, and 35 days of discharge from the ED for discharged patients or the hospital for admitted patients RESULTS:: For older chest pain patients, admission is estimated to lower the 30-day risk of readmission by 42.8% (95% confidence interval: 41.0%-44.6%) but increase the 30-day risk of mortality by 0.8% (95% confidence interval: 0.4%-1.2%). Individuals with higher hierarchical conditional category scores or diabetes with complications have both lower 30-day risk of readmission and higher 30-day risk of mortality compared with their counterparts (P≤0.02). CONCLUSIONS: Our findings suggest ED admission may prevent readmission at the cost of increasing mortality risk for older chest pain patients, especially those with comorbidity. Additional studies are needed to validate these findings.

HEART Pathway Implementation Safely Reduces Hospitalizations at One Year in Patients With Acute Chest Pain.

STUDY OBJECTIVE: We determine whether implementation of the HEART (History, ECG, Age, Risk Factors, Troponin) Pathway is safe and effective in emergency department (ED) patients with possible acute coronary syndrome through 1 year of follow-up. METHODS: A preplanned analysis of 1-year follow-up data from a prospective pre-post study of 8,474 adult ED patients with possible acute coronary syndrome from 3 US sites was conducted. Patients included were aged 21 years or older, evaluated for possible acute coronary syndrome, and without ST-segment elevation myocardial infarction. Accrual occurred for 12 months before and after HEART Pathway implementation, from November 2013 to January 2016. The HEART Pathway was integrated into the electronic health record at each site as an interactive clinical decision support tool. After integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or nonlow risk (appropriate for further inhospital evaluation). Safety (all-cause death and myocardial infarction) and effectiveness (hospitalization) at 1 year were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3,713 and 4,761 patients, respectively. The HEART Pathway identified 30.7% of patients as low risk; 97.5% of them were free of death and myocardial infarction within 1 year. Hospitalization at 1 year was reduced by 7.0% in the postimplementation versus preimplementation cohort (62.1% versus 69.1%; adjusted odds ratio 0.70; 95% confidence interval 0.63 to 0.78). Rates of death or myocardial infarction at 1 year were similar (11.6% versus 12.4%; adjusted odds ratio 1.00; 95% confidence interval 0.87 to 1.16). CONCLUSION: HEART Pathway implementation was associated with decreased hospitalizations and low adverse event rates among low-risk patients at 1-year follow-up.

Factors influencing physician risk estimates for acute cardiac events in emergency patients with suspected acute coronary syndrome.

BACKGROUND: Emergency physicians frequently assess risk of acute cardiac events (ACEs) in patients with undifferentiated chest pain. Such estimates have been shown to have moderate to high sensitivity for ACE but are conservative. Little is known about the factors implicitly used by physicians to determine the pretest probability of risk. This study sought to identify the accuracy of physician risk estimates for ACE in patients presenting to the ED with chest pain and to identify the demographic and clinical information emergency physicians use in their determination of patient risk. METHODS: This study used data from two prospective studies of consenting adult patients presenting to the ED with symptoms of possible acute coronary syndrome. ED physicians estimated the pretest probability of ACE. Multiple linear regression analysis was used to identify predictors of physician risk estimates. Logistic regression was used to determine whether there was a correlation between physicians' estimated risk and ACE. RESULTS: Increasing age, male sex, abnormal ECG features, heavy/crushing chest pain and risk factors were correlated with physician risk estimates. Physician risk estimates were consistently found to be higher than the expected proportion of ACE from the sampled population. CONCLUSION: Physicians systematically overestimate ACE risk. A range of factors are associated with physician risk estimates. These include factors strongly predictive of ACE, such as age and ECG characteristics. They also include other factors that have been shown to be unreliable predictors of ACE in an ED setting, such as typicality of pain and risk factors.

Comparison of four decision aids for the early diagnosis of acute coronary syndromes in the emergency department.

OBJECTIVES: To directly compare the diagnostic accuracy of four decision aids (Troponin-only Manchester Acute Coronary Syndromes (T-MACS), History, ECG, Age, Risk factors and Troponin (HEART), Thrombolysis in Myocardial Infarction (TIMI) and Emergency Department Assessment of Chest Pain (EDACS)) used to expedite the early diagnosis of acute coronary syndromes (ACS) in the ED. METHODS: We prospectively included patients who presented to 14 EDs in England (February 2015 to June 2017) with suspected ACS within 12 hours of symptom onset. Data to enable evaluation of the T-MACS, HEART, TIMI and EDACS decision aids (without recalibration) were prospectively collected, blinded to patient outcome. We tested admission blood samples for high-sensitivity cardiac troponin I (hs-cTnI; Siemens ADVIA Centaur). Patients also underwent serial cardiac troponin testing over 3-12 hours. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We also evaluated the incidence of major adverse cardiac events (including death, AMI or coronary revascularisation) at 30 days. Diagnostic accuracy of each decision aid and hs-cTnI alone (using the limit of quantification cut-off, 3 ng/L) was evaluated by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Of 999 included patients, 132 (13.2%) had AMI. C-statistics were 0.96 for T-MACS, 0.78 for HEART and 0.69 for TIMI. The sensitivities of T-MACS, HEART, TIMI, EDACS and hs-cTnI <3 ng/L for AMI were 99.2% (95% CI 95.7% to 100.0%), 91.8% (85.0% to 96.2%), 97.5% (92.9% to 99.5%), 96.2% (92.2% to 99.4%) and 99.2% (95.9% to 100.0%), respectively. The respective strategies would have ruled out 46.5%, 34.9%, 19.4%, 48.3% and 28.8% patients. PPVs for the decision aids that identify 'high-risk' patients were 80.4% (T-MACS), 51.9% (TIMI) and 37.2% (HEART). CONCLUSIONS: In this study, T-MACS could rule out AMI in 46.5% patients with 99.2% sensitivity. EDACS could rule out AMI in 48.3% patients with lower sensitivity, although the difference was not statistically significant. The HEART and TIMI scores had lower diagnostic accuracy.

Hospitalised patients with unexplained chest pain: incidence and prognosis.

BACKGROUND: The prognosis of unexplained chest pain patients provides valuable information for evaluation of health services. OBJECTIVE: To examine prognosis of unexplained chest pain. METHODS: Using data from in- and outpatient hospital visits in Norway of patients discharged with a main diagnosis of unexplained chest pain (ICD-10: R072-R074) in 2010-2012, the 1-year incidence of coronary heart disease (CHD), any cardio-vascular disease (CVD) and mortality was evaluated. Cases with prior 2-year history of CVD or chest pain were excluded. Cox proportional hazards evaluated outcomes by patient characteristics and standardized mortality ratios evaluated observed versus expected mortality. RESULTS: Of 59 569 patients identified (20-89 years of age), the majority (86%) were referred to hospital by out-of-hours emergency care centres. Subsequent CHD was noted for 12.5%, 19.5% and 25.0% of men and 7.2%, 11.0%, 14.0% of women aged 45-64, 65-74 and 75-89 years, respectively. The per cent of deaths attributed to CVD were greatest within the first 2 months of postdischarge. Total mortality rates (per 1000 person-years) were 6.6 in men and 4.7 in women aged 45-64 and 69.2 in men and 39.5 in women aged 75-89 years. Relative to the general population, mortality was 53% and 45% higher for men and women under 65 years of age, respectively, attributed primarily to non-CVD causes. CONCLUSION: Patients in Norway discharged with unexplained chest pain are an at-risk group in terms of incident CHD, any CVD and mortality, including non-CVD mortality during the first-year postdischarge. The results suggest that unexplained chest pain patients may benefit from greater healthcare coordination between medical disciplines.

Associations Between Crowding and Ten-Day Mortality Among Patients Allocated Lower Triage Acuity Levels Without Need of Acute Hospital Care on Departure From the Emergency Department.

STUDY OBJECTIVE: We describe the association between emergency department (ED) crowding and 10-day mortality for patients triaged to lower acuity levels at ED arrival and without need of acute hospital care on ED departure. METHODS: This was a registry study based on ED visits with all patients aged 18 years or older, with triage acuity levels 3 to 5, and without need of acute hospital care on ED departure during 2009 to 2016 (n=705,699). The sample was divided into patients surviving (n=705,076) or dying (n=623) within 10 days. Variables concerning patient characteristics and measures of ED crowding (mean length of stay and ED occupancy ratio) were extracted from the hospital's electronic health records. ED length of stay per ED visit was estimated by the average length of stay for all patients who presented to the ED during the same day and shift and with the same acuity level. The 10-day mortality after ED discharge was used as the outcome measure. Multivariable logistic regression analyses were conducted. RESULTS: The 10-day mortality rate was 0.09% (n=623). The event group had larger proportions of patients aged 80 years or older (51.4% versus 7.7%) and triaged with acuity level 3 (63.3% versus 35.6%), and greater comorbidity (age-combined Charlson comorbidity index median interquartile range 6 versus 0). We observed an increased 10-day mortality for patients with a mean ED length of stay greater than or equal to 8 hours versus less than 2 hours (adjusted odds ratio 5.86; 95% confidence interval [CI] 2.15 to 15.94) and for elevated ED occupancy ratio. Adjusted odds ratios for ED occupancy ratio quartiles 2, 3, and 4 versus quartile 1 were 1.48 (95% CI 1.14 to 1.92), 1.63 (95% CI 1.24 to 2.14), and 1.53 (95% CI 1.15 to 2.03), respectively. CONCLUSION: Patients assigned to lower triage acuity levels when arriving to the ED and without need of acute hospital care on departure from the ED had higher 10-day mortality when the mean ED length of stay exceeded 8 hours and when ED occupancy ratio increased.

Non-traumatic chest pain in patients presenting to an urban emergency Department in sub Saharan Africa: a prospective cohort study in Tanzania.

BACKGROUND: Non-traumatic chest pain (NTCP) is a common reason for emergency department (ED) attendance in high-income countries, with the primary concern focused on life threatening cardiovascular diseases. There is general lack of data on aetiologies, diagnosis and management of NTPC in Sub Sahara African (SSA) countries. We aimed to describe evaluation, diagnosis and outcomes of adult patients presenting with NTCP to an urban ED in Tanzania. METHOD: This was a prospective observational cohort study of consecutive adult (≥18 years) patients presenting with non-traumatic chest pain to the Emergency Medicine Department (EMD) of Muhimbili National Hospital (MNH) in Dar es salaam from September 2017 to April 2018. Structured case report form was used to collected demographics, clinical presentation, investigations, diagnosis, and EMD disposition and in hospital mortality. We determined frequency of NTCP among our patients, aetiologies, 24-h and 7-day in-hospital mortality, and predictors for mortality. RESULTS: We screened 29,495 adults attending EMD-MNH during the study and 389 (1.3%) presented with NTCP of these, 349 (90%) were enrolled. The median age was 45 (IQR 29-60) years and 177 (50.7%) were female. Overall, 69.1% patients received electrocardiography (ECG) in the EMD and 34.1% had a troponin test. Heart failure and pulmonary tuberculosis (PTB) were the leading hospital diagnoses (12.6% each), followed by chronic kidney disease (10%) and acute coronary syndrome (ACS) (9.6%). Total of 167 (48%) patients were admitted, and the 24-h and 7-day in-hospital mortality were 5 (3%) and 16 (9.6%) respectively. Univariate risk factors for mortality were a Glasgow Coma Scale of < 15 [RR = 3.4 (95%CI 3.2-23)], Acute Coronary Syndrome [RR = 5.7 (95% CI 1.7-11.8) and Troponin > 0.04 ng/ml [RR 2.9 (95%CI 1.2-7.3)]. Features distinguishing cardiovascular from other causes were: bradycardia [RR = 2.6 (95%CI 2.1-3.2)], heart beat awareness [RR = 2.3 (95%CI 1.7-3.2)] and history of diabetic mellitus [RR = 2.2 (95% CI 1.6-3.0)]. CONCLUSION: In this ED of SSA country, heart failure and pulmonary tuberculosis were the leading causes of NCTP, and ACS was present in 9.6%. NTCP in this setting carries high mortality, and ACS was the leading risk factor for death. ED providers in SSA must increasingly consider cardiovascular causes of NTCP.

Long Term Prognostic Value of a Negative Work-Up for Acute Coronary Disease in Emergency Department Chest Pain Patients Without Known Coronary Artery Disease: A Cohort Study.

BACKGROUND: To determine the rate of all cause and cardiac death, new myocardial infarction (MI) or coronary revascularisation at over three years from index visit in emergency department chest pain patients without known coronary artery disease (CAD) at index presentation who had a negative electrocardiogram (ECG) and biomarker workup for acute coronary syndrome (ACS). METHODS: An unplanned sub-study of a prospective observational study of consecutive adult patients presenting to the ED with atraumatic chest pain (or equivalents). The primary outcome of interest was the predictive performance of a negative ECG and biomarker work-up for ACS for all cause and cardiac mortality over more than three years' follow-up in patients not known to have pre-existing CAD presenting to the ED with chest pain. Secondary outcomes were rate of new MI or revascularisation not related to the index visit. RESULTS: 237 patients were studied. Median age was 52 years (IQR 42 - 62) and 55.3% were male. Median follow-up was 48 months. There were seven deaths (3%, 95% CI 1.4 - 6%), one of which was potentially cardiac in origin with cause of death given as pulmonary hypertension and cardiac failure (0.4%, 95% CI 0.02 - 2.3%). There was one confirmed MI (0.6%, 95% CI 0.03 - 3.8%). The rate of revascularisation not related to the index visit was 3.1% (95% CI 1.1 - 7.4%). CONCLUSION: Patients who present to ED with potentially cardiac chest pain but who do not have known CAD, and have non-ischaemic ECGs and troponin assays below the 99th percentile are at low risk of cardiac death or MI in long-term follow-up. This challenges the recommendation for routine functional or anatomic testing.

Coronary Computed Tomography Angiography Versus Traditional Care: Comparison of One-Year Outcomes and Resource Use.

STUDY OBJECTIVE: Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial. METHODS: Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use. RESULTS: One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI -5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference -2.1%; 95% CI -7.9% to 3.7%), hospital admissions (16% versus 17%; difference -0.9%; 95% CI -6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference -0.4%; 95% CI -6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%). CONCLUSION: A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing.

Guideline-conforming timing of invasive management in troponin-positive or high-risk ACS without persistent ST-segment elevation in German chest pain units. Urban university maximum care vs. rural regional primary care.

AIM: This study aimed to analyze guideline adherence in the timing of invasive management for myocardial infarction without persistent ST-segment elevation (NSTEMI) in two exemplary German centers, comparing an urban university maximum care facility and a rural regional primary care facility. METHODS: All patients diagnosed as having NSTEMI during 2013 were retrospectively enrolled in two centers: (1) site I, a maximum care center in an urban university setting, and (b) site II, a primary care center in a rural regional care setting. Data acquisition included time intervals from admission to invasive management, risk criteria, rate of intervention, and medical therapy. RESULTS: The median time from admission to coronary angiography was 12.0 h (site I) or 17.5 h (site II; p = 0.17). Guideline-adherent timing was achieved in 88.1 % (site I) or 82.9 % (site II; p = 0.18) of cases. Intervention rates were high in both sites (site I-75.5 % vs. site II-75.3 %; p = 0.85). Adherence to recommendations of medical therapy was high and comparable between the two sites. CONCLUSION: In NSTEMI or high-risk acute coronary syndromes without persistent ST-segment elevation, guideline-adherent timing of invasive management was achieved in about 85 % of cases, and was comparable between urban maximum and rural primary care settings. Validation by the German Chest Pain Unit Registry including outcome analysis is required.

Non-coronary chest pain does not affect long-term mortality: a prospective, observational study using a matched population control.

BACKGROUND: Chest pain assumed to be of non-coronary origin (NCCP) may be linked to enhanced mortality due to coronary heart disease (CHD). The aim of this study was to follow NCCP patients, as defined in primary care, with respect to mortality and long-term morbidity of CHD. We further examined if NCCP associates with risk factors for CHD. METHODS: Patients consulting general practitioners (GPs) in 1998-2000 in three primary care centers in the southeast Sweden for chest pain regarded as NCCP were compared with controls matched for age, gender and residential area. Causes of death were gathered from registry data and death certificates. In 2005 a postal questionnaire was distributed to the survivors to collect demographic and clinical data. If participants had CHD diagnosed by a physician prior to inclusion they were excluded. RESULTS: Patients with NCCP (n = 382) and population controls (n = 746) did not differ with respect to mortality and incidence of CHD. The NCCP group reported more ongoing chest pain (OR 3.34 95 % CI 2.41-4.62), they more often had elevated blood pressure (OR 1.86 95 % CI 1.32-2.60), consumed more ß-blockers (p < 0.001), aspirin (p = 0.013), thiazides (p = 0.004) and long-acting nitrates (p = 0.002). They further had more remedies for acid-related disorders (p = 0.014) and obstructive pulmonary disease (p < 0.001). CONCLUSIONS: The study suggests that individuals with chest pain judged by GPs to be NCCP do not develop CHD more frequently than population controls. It is evident that NCCP often lasts for many years and that the condition associates with hypertension.

Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia. METHODS: We categorized 876 women from the Women's Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ≥90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild CKD], ≤59 mL/min per 1.73 m(2) [severe CKD]). Time to death from all-cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates. RESULTS: Obstructive coronary artery disease (CAD) was present only in few patients (39%). Even after adjusting for CAD severity, renal function remained a strong independent predictor of all-cause and cardiac mortality (P < .001). Every 10-unit decrease in eGFR was associated with a 14% increased risk of all-cause mortality (adjusted hazard ratio [AHR] 1.14 [1.08-1.20], P < .0001), 16% increased risk of cardiovascular mortality (AHR 1.16 [1.09-1.23], P < .0001), and 9% increased risk of adverse cardiovascular events (AHR 1.09 [1.03-1.15], P = .002). CONCLUSIONS: Even mild CKD is a strong independent predictor of all-cause and cardiac mortality in women with symptoms/signs of ischemia, regardless of underlying obstructive CAD severity, underscoring the need to better understand the interactions between ischemic heart disease and CKD.

Unexplained acute chest pain in young adults: disease patterns and medication use 25 years later.

BACKGROUND: Patients with unexplained chest pain are commonly revisiting an emergency department with various symptoms, but comprehensive long-term studies are lacking. METHODS: A total of 150 young adults (aged 18-40 years) with unexplained chest pain who presented at an emergency unit for 16 weeks in mid-1980s were included in a prospective cohort study. An age- and sex-matched control group was randomly selected from the same area. Data were retrieved from registers that recorded death, income, education, country of birth, diagnoses, hospitalizations, outpatient visits, and medications dispensed. RESULTS: Patients with unexplained acute chest pain had lower levels of education and income and were more often immigrants. Long-term mortality rates did not differ between cases (4%) and controls (5%) during 25 years of follow-up, nor were there differences in diagnosis of ischemic heart disease. Patients with unexplained acute chest pain had more outpatient visits (median, 5 versus 2; p < .0001) and had more often been hospitalized (61.6% ever versus 41.8%; p < .001) during the follow-up period. Several disorders were more common among patients 20 to 25 years later, including atrial fibrillation, esophageal/gastric disorders, chest pain, palpitations, abdominal discomfort, musculoskeletal symptoms, sleeping disturbance, and stress reactions (p values < .05). More patients had been given antihypertensives, anticoagulants, antidepressants, analgesics, and hypnotics/tranquilizers (p values < .05). CONCLUSIONS: Young patients admitted to the emergency department with unexplained acute chest pain showed no increased risk of mortality or ischemic heart disease during 25 years of follow-up, but they had higher incidence of a wide range of disorders and used more medications. Early identification and preventive interventions may improve health outcomes in these patients.

A Clinical Decision Instrument for 30-Day Death After an Emergency Department Visit for Atrial Fibrillation: The Atrial Fibrillation in the Emergency Room (AFTER) Study.

STUDY OBJECTIVE: The high volume of patients treated in an emergency department (ED) for atrial fibrillation is predicted to increase significantly in the next few decades. Currently, 11% of these patients die within a year. We sought to derive and validate a complex model and a simplified model that predicts mortality in ED patients with atrial fibrillation. METHODS: This population-based, retrospective cohort study included 3,510 adult patients with a primary diagnosis of atrial fibrillation who were treated at 24 hospital EDs in Ontario, Canada, between April 2008 and March 2009. The main outcome was 30-day all-cause mortality. RESULTS: In the derivation cohort (n=2,343; mean age 68.8 years), 2.6% of patients died within 30 days of the ED visit versus 2.7% in the validation cohort (n=1,167; mean age 68.3 years). Variables associated with mortality in the complex model included age, presenting pulse rate and systolic blood pressure, presence of chest pain, 2 laboratory results (positive troponin result and creatinine level greater than 200 µmol [2.26 mg/dL]), 4 comorbidities (smoking, chronic obstructive pulmonary disease, cancer, and dementia), an increased bleeding risk, and a second acute ED diagnosis (in addition to atrial fibrillation). Observed 30-day mortality in the 5 risk strata that were defined by the predicted probability of death were 0.44%, 0.41%, 0.23%, 1.61%, and 10.3%. The c statistics were 0.88 and 0.87 in the derivation and validation cohorts, respectively. The a priori-selected 6-variable model, TrOPs-BAC, included a positive Troponin result, Other acute ED diagnosis, Pulmonary disease (chronic obstructive pulmonary disease), Bleeding risk, Aged 75 years or older, and Congestive heart failure. The c statistic for the simplified model was 0.81 in both the derivation and validation cohorts. CONCLUSION: Using a population-based sample, we derived and validated both a complex and a simplified instrument that predicts mortality after an emergency visit for atrial fibrillation. These may aid clinicians in identifying high-risk patients for hospitalization while safely discharging more patients home.

Dual imaging stress echocardiography versus computed tomography coronary angiography for risk stratification of patients with chest pain of unknown origin.

BACKGROUND: Dual imaging stress echocardiography, combining the evaluation of wall motion and coronary flow reserve (CFR) on the left anterior descending artery (LAD), and computed tomography coronary angiography (CTCA) are established techniques for assessing prognosis in chest pain patients. In this study we compared the prognostic value of the two methods in a cohort of patients with chest pain having suspected coronary artery disease (CAD). METHODS: A total of 131 patients (76 men; age 68 ± 9 years) with chest pain of unknown origin underwent dipyridamole (up to 0.84 mg/kg over 6 min) stress echo with CFR assessment of LAD by Doppler and CTCA. A CFR ≤ 1.9 was considered abnormal, while > 50% lumen diameter reduction was the criterion for significant CAD at CTCA. RESULTS: Of 131 patients, 34 (26%) had ischemia at stress echo (new wall motion abnormalities), and 56 (43%) had reduced CFR on LAD. Significant coronary stenosis at CTCA was found in 69 (53%) patients. Forty-six patients (84%) with abnormal CFR on LAD showed significant CAD at CTCA (p < 0.001). Calcium score was higher in patients with reduced than in those with normal CFR (265 ± 404 vs 131 ± 336, p = 0.04). During a median follow-up of 7 months (1st to 3rd quartile: 5-13 months), there were 45 major cardiac events (4 deaths, 11 nonfatal myocardial infarctions, and 30 late [≥6 months] coronary revascularizations). At Cox analysis, independent prognostic indicators were calcium score > 100 (HR 2.84, 95% CI 1.33-6.07, p = 0.007), significant CAD at CTCA (HR 2.68, 95% CI 1.23-5.82, p = 0.013), and inducible ischemia or CFR <1.9R on LAD on dual imaging stress echo (HR 2.25, 95% CI 1.05-4.84, p = 0.038). CONCLUSIONS: Functional and anatomical evaluation using, respectively, dual imaging stress echocardiography and CTCA are both effective modalities to risk stratify patients with chest pain of unknown origin, yielding independent and comparable prognostic value. Compared to CTCA, however, stress echocardiography has the advantage of lower cost and of being free of radiations.

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays.

AIMS: Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. METHODS AND RESULTS: In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. CONCLUSION: High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.

Retrospective Evaluation of Two Fast-track Strategies to Rule Out Acute Coronary Syndrome in a Real-life Chest Pain Population.

BACKGROUND: The European Society of Cardiology (ESC) guideline on non-ST-elevation acute coronary syndrome (N-STE ACS) proposed a new ACS rule-out protocol. OBJECTIVES: To evaluate this new tool, which uses diagnostic levels of high-sensitivity troponin T (hs-TnT; > 14 ng/L) in a slightly modified version and compare this to a recently proposed approach using undetectable levels of hs-TnT to rule out patients. METHODS: There were 534 consecutive patients with suspected ACS included. Protocol 1: symptom duration, hs-TnT at 0 and 6-9 h, Global Registry of Acute Coronary Events (GRACE) score, and symptom status at 6-9 h. Protocol 2: a single blood sample of hs-TnT. The primary endpoint was a discharge diagnosis of ACS by blinded adjudication. Secondary endpoints were ACS re-admission < 30 days and 1-year mortality. RESULTS: Protocol 1 classified 434/534 (81%) patients, with 27.9% being ruled out. All myocardial infarctions were correctly ruled in, but 15 cases of unstable angina were missed, resulting in a sensitivity and negative predictive value of 87.3% (79.6-92.5%) and 87.6% (80.4-92.9%), respectively. Protocol 2 ruled out 17.5% of the population, yielding a sensitivity and negative predictive value of 94.1% (88.2-97.6%) and 90.8% (81.9-96.2%), respectively. Both protocols correctly ruled in 2/3 patients with ACS re-admission < 30 days and 55/56 1-year fatalities. CONCLUSION: The present study confirms the diagnostic value of a modified version of the ESC rule-out protocol (Protocol 1) in N-STE ACS patients, but also suggests that a simpler protocol using undetectable levels of hs-TnT (Protocol 2) could provide a similar or even superior sensitivity.

Characteristics and Outcomes of MI Patients with and without Chest Pain: A Cohort Study.

INTRODUCTION: There are conflicting data on patient characteristics and outcomes of myocardial infarction (MI) patients presenting with and without the symptom of chest pain. OBJECTIVES: Compare the characteristics and survival of patients stratified by the symptom chest pain. METHODS: This retrospective cohort study identified patients with an emergency department discharge diagnosis of MI, who arrived by ambulance at a teaching hospital in Perth, Western Australia, between January 2008 to October 2009. The cohort was linked to hospital data and the state-based death register; clinical data were extracted by medical record review. Patient characteristics were compared using logistic regression models and survival analysis using Kaplan-Meier curves and Cox regression models. RESULTS: Of 382 patients, 26% presented without chest pain. The odds of presenting without chest pain were increased if aged 80+ (OR 7.54; 95%CI 2.81-20.3) and aged 70-79 years (OR 4.33; 95% CI 1.50-12.5), and female (OR 1.67; 95%CI 0.99-2.82). The adjusted hazard (median follow-up time 2.2 years) of presenting without chest pain was not significantly associated with survival (HR 1.03; 95%CI 0.71-1.48). CONCLUSION: Characteristics differed between patients with and without chest pain. However, the symptom of chest pain was not associated with survival.