Limitations of using COX proportional hazards model in cardiovascular research.

The article by Zhao et al. titled "Associations of Triglyceride-Glucose (TyG) Index with Chest Pain Incidence and Mortality among the U.S. Population" provides valuable insights into the positive correlation between the TyG index and chest pain incidence, as well as a nonlinear relationship with mortality. However, the use of the COX proportional hazards model in their analysis presents several limitations. The assumption of constant hazard ratios over time may not hold, potentially leading to biased estimates. The model's struggle with time-dependent covariates and the possibility of residual confounding are notable concerns. Additionally, the study's subgroup analyses might suffer from reduced statistical power, and potential interactions with other metabolic markers were not explored. Considering these limitations, future research should adopt alternative approaches, such as time-varying covariate models, to provide a more comprehensive understanding of the relationship between the TyG index and cardiovascular outcomes.

Effect of transitioning from conventional cardiac troponin to high-sensitivity cardiac troponin on resource utilization- a single center experience.

BACKGROUND: Compared to conventional cardiac troponin (cTn), the high-sensitivity cardiac troponin (hs-cTn) assay is associated with improved detection of myocardial infarction (MI). METHODS: We performed a descriptive retrospective analysis of resource utilization at Rush University Medical Center over the transition period (July 1, 2021) from a cTn to a hs-cTn assay. Inclusion criteria included emergency department (ED) encounters between January 1 to December 31, 2021, with chief complaints of "chest pain" or "dyspnea" with associated troponin orders. The primary endpoint was the percentage of ED discharges. Secondary endpoints included the number of cardiac studies ordered. Univariable comparisons of these endpoints were performed using Student's t-test for continuous variables and Chi-square tests for binary/categorical variables. RESULTS: A total of 5113 encounters were analyzed. Hs-cTn was associated with an overall increase in ED patient discharges with negative troponin tests (44.1% vs. 29.9%, P < 0.01). In terms of cardiac testing per encounter, hs-cTn was associated with significant increases in the number of troponin tests (1.9 vs. 1.6, P < 0.01), electrocardiograms (3.0 vs. 2.9, P = 0.01), and echocardiograms (0.5 vs. 0.4, P < 0.01). There was a significant decrease in the utilization of stress testing (0.21 vs. 0.26, P < 0.01). There was a significant increase in total coronary angiography use during the hs-cTn period compared to cTn (227/2471 (9.2%) vs. 195/2642 (7.4%), P = 0.02). CONCLUSION: Transitioning from cTn to hs-cTn was associated with significantly increased ED discharges and an increase in troponin tests, ECG, echocardiograms, and coronary angiograms. There was a decrease in the number of stress tests.

Performance analysis considering endpoints for three accelerated diagnostic protocols for chest pain.

INTRODUCTION: The modified accelerated diagnostic protocol (ADP) to assess patients with chest pain symptoms using troponin as the only biomarker (mADAPT), the History, ECG, Age, Risk factors, and Troponin (HEART) pathway, and the Emergency Department Assessment of Chest Pain Rule (EDACS)-ADP, are the three most well-known ADPs for patients with chest pain. These ADPs define major adverse cardiac event (MACE) as components of acute myocardial infarction, revascularization, and death; unstable angina is not included as an endpoint. METHODS: We performed a single-center prospective observational study comparing the performance of these 3 ADPs for patients with 30-day MACE with and without unstable angina. We hypothesized that these ADPs will have high sensitivities for MACE without unstable angina, a definition used for score derivation studies. However, when unstable angina is included in the MACE, their performances would be lower than the acceptable rate of >99% sensitivity. RESULTS: A total of 1,214 patients were included in the analysis. When unstable angina was not included in the endpoint, sensitivities for MACE were 99.1% (95% confidence interval [CI]: 96.7-99.9%), 99.5% (95% CI: 97.4-100%), and 100% (95% CI: 98.3-100%) for mADAPT, EDACS-ADP, and HEART pathway, respectively. The HEART pathway had the highest proportion of patients classified as low risk (39.2%, 95% CI: 35.8-42.9%), followed by EDACS-ADP (31.3%, 95% CI: 28.2-34.6%) and mADAPT (29.3%, 95% CI: 26.4-32.5%). However, when unstable angina was included in the MACE, sensitivities were 96.6% (95% CI: 94.4-98.1%) for mADAPT, 97.3% (95% CI: 95.3-98.6%) for EDACS-ADP, and 97.3% (95% CI: 95.3-98.6%) for the HEART pathway, respectively. There were 15 false-negative cases with mADAPT, and 12 false-negative cases each for EDACS-ADP and HEART pathway. CONCLUSION: All three ADPs-mADAPT, EDACS-ADP, and HEART pathway-were similarly accurate in their discriminatory performance for the risk stratification of ED patients presenting with possible ACS when unstable angina was not included in the endpoint. The HEART pathway showed the best combination of sensitivity and proportion of patients that can be classified as safe for early discharge. However, when unstable angina was added to the endpoint, all three ADPs did not show appropriate safety levels and their performances were lower than the acceptable risk of MACE.

Development of a prehospital prediction model for risk stratification of patients with chest pain.

INTRODUCTION: Chest pain is one of the most common reasons for contacting the emergency medical services (EMS). About 15% of these chest pain patients have a high-risk condition, while many of them have a low-risk condition with no need for acute hospital care. It is challenging to at an early stage distinguish whether patients have a low- or high-risk condition. The objective of this study has been to develop prediction models for optimising the identification of patients with low- respectively high-risk conditions in acute chest pain early in the EMS work flow. METHODS: This prospective observational cohort study included 2578 EMS missions concerning patients who contacted the EMS in a Swedish region due to chest pain in 2018. All the patients were assessed as having a low-, intermediate- or high-risk condition, i.e. occurrence of a time-sensitive diagnosis at discharge from hospital. Multivariate regression analyses using data on symptoms and symptom onset, clinical findings including ECG, previous medical history and Troponin T were carried out to develop models for identification of patients with low- respectively high-risk conditions. Developed models where then tested hold-out data set for internal validation and assessing their accuracy. RESULTS: Prediction models for risk-stratification based on variables mutual for both low- and high-risk prediction were developed. The variables included were: age, sex, previous medical history of kidney disease, atrial fibrillation or heart failure, Troponin T, ST-depression on ECG, paleness, pain debut during activity, constant pain, pain in right arm and pressuring pain quality. The high-risk model had an area under the receiving operating characteristic curve of 0.85 and the corresponding figure for the low-risk model was 0.78. CONCLUSIONS: Models based on readily available information in the EMS setting can identify high- and low-risk conditions with acceptable accuracy. A clinical decision support tool based on developed models may provide valuable clinical guidance and facilitate referral to less resource-intensive venues.

EMS blood collection from patients with acute chest pain reduces emergency department length of stay.

BACKGROUND: Expediting the measurement of serum troponin by leveraging EMS blood collection could reduce the diagnostic time for patients with acute chest pain and help address Emergency Department (ED) overcrowding. However, this practice has not been examined among an ED chest pain patient population in the United States. METHODS: A prospective observational cohort study of adults with non-traumatic chest pain without ST-segment elevation myocardial infarction was conducted in three EMS agencies between 12/2016-4/2018. During transport, paramedics obtained a patient blood sample that was sent directly to the hospital core lab for troponin measurement. On ED arrival HEART Pathway assessments were completed by ED providers as part of standard care. ED providers were blinded to troponin results from EMS blood samples. To evaluate the potential impact on length of stay (LOS), the time difference between EMS blood draw and first clinical ED draw was calculated. To determine the safety of using troponin measures from EMS blood samples, the diagnostic performance of the HEART Pathway for 30-day major adverse cardiac events (MACE: composite of cardiac death, myocardial infarction (MI), coronary revascularization) was determined using EMS troponin plus arrival ED troponin and EMS troponin plus a serial 3-h ED troponin. RESULTS: The use of EMS blood samples for troponin measures among 401 patients presenting with acute chest pain resulted in a mean potential reduction in LOS of 72.5 ± SD 35.7 min. MACE at 30 days occurred in 21.0% (84/401), with 1 cardiac death, 78 MIs, and 5 revascularizations without MI. Use of the HEART Pathway with EMS and ED arrival troponin measures yielded a NPV of 98.0% (95% CI: 89.6-100). NPV improved to 100% (95% CI: 92.9-100) when using the EMS and 3-h ED troponin measures. CONCLUSIONS: EMS blood collection used for core lab ED troponin measures could significantly reduce ED LOS and appears safe when integrated into the HEART Pathway.

Impact of coronary risk scores on disposition decision in emergency patients with chest pain.

BACKGROUND: Coronary risk scores (CRS) including History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score and Emergency Department Assessment of Chest pain Score (EDACS) can help identify patients at low risk of major adverse cardiac events. In the emergency department (ED), there are wide variations in hospital admission rates among patients with chest pain. OBJECTIVE: This study aimed to evaluate the impact of CRS on the disposition of patients with symptoms suggestive of acute coronary syndrome in the ED. METHODS: This retrospective cohort study included 3660 adult patients who presented to the ED with chest pain between January and July in 2019. Study inclusion criteria were age > 18 years and a primary position International Statistical Classification of Diseases and Related Health Problems-10th revision coded diagnosis of angina pectoris (I20.0-I20.9) or chronic ischemic heart disease (I25.0-I25.9) by the treating ED physician. If the treating ED physician completed the electronic structured variables for CRS calculation to assist disposition planning, then the patient would be classified as the CRS group; otherwise, the patient was included in the control group. RESULTS: Among the 2676 patients, 746 were classified into the CRS group, whereas the other 1930 were classified into the control group. There was no significant difference in sex, age, initial vital signs, and ED length of stay between the two groups. The coronary risk factors were similar between the two groups, except for a higher incidence of smokers in the CRS group (19.6% vs. 16.1%, p = 0.031). Compared with the control group, significantly more patients were discharged (70.1% vs. 64.6%) directly from the ED, while fewer patients who were hospitalized (25.9% vs. 29.7%) or against-advise discharge (AAD) (2.6% vs. 4.0%) in the CRS group. Major adverse cardiac events and mortality at 60 days between the two groups were not significantly different. CONCLUSIONS: A higher ED discharge rate of the group using CRS may indicate that ED physicians have more confidence in discharging low-risk patients based on CRS.

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.

N-acety-b-D-glucosaminidase: A potential biomarker for early detection of acute kidney injury in acute chest pain.

AIM: Acute kidney injury (AKI) is often underdiagnosed due to several limitations of the renal marker creatinine. Tubular urinary biomarkers may substantially contribute to diagnose AKI early. For early detection of AKI, we evaluated for the first time N-acetyl-ß-d-glucosaminidase (NAG), Kidney-injury-molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in acute chest pain. METHODS: We included 402 chest pain patients aged 18 to 95 years seen in the emergency department. From 311 subjects, blood and urine samples were collected. RESULTS: Thirty-three patients developed an AKI and showed a significant increase in all three tubular markers compared to patients without AKI (each P < .001). According to receiver operating characteristic (ROC) analysis, combining NAG and creatinine showed a significantly increased area under the curve (AUC) compared to creatinine alone (AUC: 0.75 vs 0.87; P < .001). KIM-1, NGAL and cystatin C showed no significant differences in AUC compared to creatinine. In 120 individuals with blood and urine sampling before contrast media exposure, ROC analysis showed a significantly improved diagnostic performance for the combination of both (AUC: 0.83 vs creatinine AUC: 0.66; P = .004). AKI occurrence showed no dependency from CM volume. NAG presented as an independent AKI predictor beside creatinine, age, the diagnosis of myocardial infarction and mean arterial pressure. Regarding the prognostic value for renal replacement therapy, the combination of NAG and creatinine showed a significantly lager AUC than creatinine (AUC: 0.95 vs AUC: 0.85; P < .001). CONCLUSION: NAG presented as a promising marker of impending AKI and the necessity of renal replacement therapy.

Performance of cardiac troponins within the HEART score in predicting major adverse cardiac events at the emergency department.

BACKGROUND: This study compared the performance of a single blood draw of high-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI) and conventional troponin I (cTnI) within a modified HEART score for predicting 30-day MACE at Emergency Department (ED) presentation, and established local reference norms for all three assays by determining the cut-off point which yielded the highest sensitivity and negative predictive value for acute myocardial infarction and 30-day MACE. METHODS: This single-center prospective cohort study recruited chest pain patients at the ED, whose hsTnT, hsTnI and cTnI were taken on admission. Subjects were classified into low and non-low risk group according to their modified HEART score, with MACE as the primary endpoint. Receiver-operating characteristic (ROC) curves were generated, area under the curves (AUCs) were calculated; the performance characteristics were determined. RESULTS: The performance of modified HEART scores was comparable among the three assays for 30-day MACE (84.9-87.0% sensitivity, 95.6-96.0% NPV, 95%CI) and none of these had very high AUC and specificity (AUC 0.70-0.71, 53.7-56.7% specificity, 95% CI). The modified HEART score using a single blood draw of either hsTnT (3.9ng/L), hsTnI (0.9ng/L) or cTnI (0.0ng/L) at presentation yielded a sensitivity of 100% for 30-day MACE. CONCLUSION: The modified HEART score using a single blood draw of either hsTnT, hsTnI or cTnI was equally effective in risk-stratifying chest pain patients for safe discharge. The theoretical cut-off points yielding 100% sensitivity are potentially useful (when achieved) for safely discharging low risk patients with undifferentiated chest pain in the ED.

Emergency medicine misconceptions: Utility of routine coagulation panels in the emergency department setting.

BACKGROUND: Coagulation panels are ordered for a variety of conditions in the emergency department (ED). OBJECTIVE: This narrative review evaluates specific conditions for which a coagulation panel is commonly ordered but has limited utility in medical decision-making. DISCUSSION: Coagulation panels consist of partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR). These tests evaluate the coagulation pathway which leads to formation of a fibrin clot. The coagulation panel can monitor warfarin and heparin therapy, evaluate for vitamin K deficiency, evaluate for malnutrition or severe systemic disease, and assess hemostatic function in the setting of bleeding. The utility of coagulation testing in chest pain evaluation, routine perioperative assessment, prior to initiation of anticoagulation, and as screening for admitted patients is low, with little to no change in patient management based on results of these panels. Coagulation testing should be considered in systemically ill patients, those with a prior history of bleeding or family history of bleeding, patients on anticoagulation, or patients with active hemorrhage and signs of bleeding. Thromboelastography and rotational thromboelastometry offer more reliable measures of coagulation function. CONCLUSIONS: Little utility for coagulation assessment is present for the evaluation of chest pain, routine perioperative assessment, initiation of anticoagulation, and screening for admitted patients. However, coagulation panel assessment should be considered in patients with hemorrhage, patients on anticoagulation, and personal history or family history of bleeding.

60-day major adverse cardiac events in emergency department patients with non-low modified HEART scores.

BACKGROUND: A low (0-3) History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score reliably identifies ED chest pain patients who are low risk for near-term major adverse cardiac events (MACE). To optimize sensitivity, many clinicians employ a modified HEART score by repeating troponin measurements and excluding patients with abnormal troponin values or ischemic electrocardiograms (ECGs). The residual MACE risk among patients with otherwise non-low (≥4) modified HEART scores is thus likely much lower than with non-low original HEART scores. OBJECTIVE: To explore residual 60-day MACE risks among patients with non-low modified HEART scores. METHODS: Secondary analysis of a retrospective cohort of ED patients presenting with chest pain to an integrated healthcare system between 2013 and 2015. Patients with serial troponin measurements within 6 h of ED arrival were considered for inclusion. Exclusions included an ischemic ECG, troponin values above the 99th percentile or a lack of continuous health plan coverage through the 60-day follow-up period. MACE was defined as a composite of myocardial infarction, cardiac arrest, cardiogenic shock or death. RESULTS: There were 22,976 study eligible patients encounters, 13,521 (59%) of which had non-low (≥4) modified HEART scores. The observed 60-day MACE risk among non-low HEART score patients was 2.0% (95% CI 1.8-2.3). When including all coronary revascularizations (MACE-R), the risk was 4.4% (95% CI 4.1-4.4). CONCLUSION: Risk of near-term MACE among patients with non-low modified HEART scores (excluding those with abnormal troponin or ischemic ECGs) appears to be much lower than in the original HEART score validation studies.

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.

Diagnostic accuracy of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid with a point-of-care cardiac troponin assay.

OBJECTIVE: Point-of-care (POC) cardiac troponin (cTn) assays have a rapid turnaround time but are generally less sensitive than laboratory-based assays. Previous research found that the Abbott i-Stat cardiac troponin I (cTnI) assay has good diagnostic accuracy when used with the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid and serial sampling over 3 hours. Accuracy of other assays may differ. We therefore evaluated the diagnostic accuracy of a different POC cTnI assay with serial sampling over 3 hours, both with T-MACS and when used alone. METHODS: In a prospective diagnostic accuracy study at eight EDs in England (July 2015-October 2017), we collected clinical data from consenting adults with suspected ACS at the time of assessment in the ED. Blood samples were drawn on arrival and 3 hours later for POC cTnI (Cardio 3 Triage, Alere). The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI), based on reference standard serial laboratory-based cTn testing. We calculated test characteristics for POC cTnI using the limit of detection (LoD, 0.01 µg/L) and the T-MACS decision aid. RESULTS: Of 347 participants, 59 (14.9%) had AMI. With serial POC cTnI testing over 3 hours, POC cTnI at the LoD cut-off ruled out AMI in 193 (55.6%) patients with 98.1% sensitivity (95% CI 89.9% to 100.0%) and 99.5% negative predictive value (NPV, 95% CI 96.5% to 99.9%). T-MACS ruled out AMI in 117 (33.7%) patients with 98.1% sensitivity (95% CI 89.9% to 100%) and 99.2% NPV (95% CI 94.3% to 99.9%). T-MACS ruled in AMI with 97.9% specificity (95% CI 95.8% to 99.5%) and 83.7% positive predictive value (95% CI 70.6% to 91.7%). CONCLUSIONS: With serial sampling over 3 hours, the Alere Cardio 3 Triage cTnI assay has relatively high NPV for AMI using either the LoD cut-off alone or the T-MACS decision aid. However, wide CIs around the measures of diagnostic accuracy mean that further prospective testing of this strategy is required before clinical implementation. TRIAL REGISTRATION NUMBER: UKCRN 18000.

Transfusion-associated chest pain.

BACKGROUND: Chest pain is a common clinical dilemma and is rarely reported as part of suspected adverse events in transfusion recipients. The aim of this study is to describe and characterize the clinical presentation of transfusion-associated chest pain and how it relates to currently defined National Healthcare Safety Network hemovigilance entities. STUDY DESIGN AND METHODS: This is a retrospective chart review at a single large academic institution of patients who reported chest pain during or after a transfusion that resulted in a transfusion reaction investigation during the period January 2004 to December 2016. RESULTS: Of approximately 500,000 transfusions occurring during the study period and 3220 suspected transfusion reactions reported, 23 (0.7%) reactions involving chest pain were identified, of which 20 had medical records available for analysis. Ninety percent of cases presented with chest pain within 2.5 hours of the start of transfusion, with a mean time of onset of 92.2 minutes. Fourteen RBC units and 6 platelet units were implicated, and all transfusions were ABO identical. All posttransfusion workups were negative for hemolysis or agglutination on direct antiglobulin testing. Twenty percent of cases showed evidence of acute coronary ischemia that was first detected during transfusion with rising troponins or electrocardiographic abnormalities, all in association with RBC transfusion for anemia. For most reactions, the signs and symptoms did not fit any hemovigilance definitions for transfusion reactions. CONCLUSION: Chest pain is an infrequently reported chief complaint for transfusion reactions. Increased circulatory volume due to transfusion may be an important contributor to myocardial demand ischemia in at-risk patients. Additional studies are necessary to determine the clinical significance of chest pain during transfusion and to elucidate potential mechanisms.

Association of 25-hydroxyvitamin D with HDL-cholesterol and other cardiovascular risk biomarkers in subjects with non-cardiac chest pain.

BACKGROUND: Chest pain is a serious symptom that is routinely investigated as a sign of coronary artery disease. Non-cardiac chest pain (NCCP) is indistinguishable from ischemic chest pain and both are considered serious and receive similar medical investigations. Although NCCP is not associated with cardiovascular diseases (CVDs), patients with NCCP may become anxious and frightened from developing coronary events. So, it will be valuable to improve modifiable cardiovascular risk factors in such subjects to reduce fear from CVDs. Because vitamin D deficiency was considered as a possible modifiable cardiovascular risk factor, our aim was to investigate association between serum vitamin D and cardiovascular risk variables in subjects with NCCP. METHODS: A cross-sectional study involved 104 subjects who underwent cardiac catheterization that did not reveal any cardiac origin for their chest pain. 25-hydroxyvitamin D was measured by electrochemiluminescence immunoassay, glucose was measured by hexokinase method, hemoglobin A1c (HbA1c) was measured by turbidimetric inhibition immunoassay and lipid profile was measured by enzymatic colorimetric assays. RESULTS: High density lipoprotein cholesterol (HDL-C) was significantly higher in subjects with sufficient vitamin D compared to those with insufficient or deficient vitamin D (p-value< 0.01). 25-hydroxyvitamin D was positively associated with HDL-C (p-value< 0.01) and inversely associated with HbA1c (p-value = 0.02). 25-hydroxyvitamin D was not significantly correlated with other cardiovascular biomarkers including blood pressure, glucose, and other components of lipid profile (p-values> 0.05). CONCLUSIONS: low serum vitamin D could be involved in reducing HDL-C and increasing HbA1c and thus it may increase cardiovascular risk in subjects with NCCP.

CCTA in patients with positive troponin and low clinical suspicion for ACS: a useful diagnostic option to exclude obstructive CAD.

PURPOSE: It is uncertain whether patients with elevated troponin and non-classical presentation of acute coronary syndrome (ACS) should receive coronary CT angiography (CCTA). A proportion of these patients will have no coronary artery disease (CAD) and would benefit from non-invasive investigations and expedited discharge. Objectives were to determine most common diagnoses and rate of ACS among patients with positive troponin and low clinical suspicion of ACS who received CCTA. METHODS: IRB approved retrospective analysis of 491 consecutive patients in a level I trauma center ED referred for CCTA between April 4, 2015 to April 2, 2017. Patients were included if there was an elevated troponin (TnI > 0.045 µg/L) and atypical chest pain within 24 h prior to imaging. One hundred one patients met inclusion criteria; 17 excluded due to technical factors or history. Scans performed on dual-source CT. RESULTS: Eighty-four patients (47 men, 37 women) with median TnI of 0.11 ± 0.21 µg/L underwent CCTA 8.20 ± 6.41 h after first elevated Tn. Mean age was 53.2 ± 14.6 years. CCTA demonstrated absence of CAD in 39 patients (46.4%; 20 M, 19 F). CAD < 25% stenosis was observed in 24 (28.6%; 9 M, 15 F). CAD with 25-50% stenosis was observed in seven (8.3%; six M, one F). CAD > 50% stenosis was observed in 11 (13.1%; 9 M, 2 F), and non-diagnostic in three (3.6%, 3 M, 0 F). Forty-six (56.8%) were discharged directly from ED with median stay 15.82 ± 6.41 h. CONCLUSIONS: Use of CCTA in ED patients with elevated troponin and low clinical suspicion for ACS allowed obstructive CAD to be excluded in 83%.

Non-cardiac Chest Pain and Anxiety: A Possible Link to Vitamin D and Calcium.

This study was performed to check the hypothesis that low serum vitamin D and reduced calcium intake may contribute to the comorbidity of psychological symptoms (anxiety and depression) and non-cardiac chest pain (NCCP). The design was a case-control study that involved 40 subjects with NCCP and 40 age and gender-matched healthy controls. Serum vitamin D was assessed using electrochemiluminescence immunoassay; anxiety and depression symptoms were assessed using Hospital Anxiety and Depression Scale, and dietary calcium intake was assessed by self-reporting. Subjects with NCCP had higher anxiety and depression scores and lower vitamin D and dietary calcium intake compared to healthy controls (p < .05). NCCP was associated with anxiety score (odds ratio = 1.40, p < .01). Prevalence of abnormal anxiety score was much higher in subjects with NCCP (47.5%) compared to healthy controls (7.5%). Anxiety score was inversely correlated with vitamin D level and dietary calcium intake (p < .01). Anxiety score was inversely associated with vitamin D level (R2 = .32, p < .05). In conclusion, development of NCCP can be predicted from increased anxiety score which in turn can be predicted from low vitamin D levels. This suggests physicians to consider anxiety and vitamin D deficiency as possible causes for NCCP.

Treating the troponin: adverse consequences of over-treatment of elevated troponin in non-coronary presentations.

BACKGROUND AND AIMS: Anti-platelet and anti-thrombotic therapy are well-established treatments in acute coronary syndromes. Highly sensitive assays have diminished the positive predictive value of troponin in acute coronary syndromes and increased the importance of the clinical assessment in interpreting positive results. This cohort study sought to investigate over-treatment of non-coronary troponin rises and associated adverse outcomes. METHODS AND RESULTS: We reviewed 223 consecutive patients presenting to Queen Elizabeth University Hospital, Glasgow, with suspected acute coronary syndromes over a six-week period. Of these, 27 (12%) met our 'inappropriate therapy' criteria. This group had a low ischaemic risk (HEART score: 4.2 ± 1.4) (GRACE score: 117 ± 30.8) but an intermediate-high bleeding risk (CRUSADE score: 34 ± 14.5). Approximately half of the patients (14/27, 52%) reported chest pain, with only 4/27 (15%) having ischaemic ECG changes. There were three intracranial haemorrhages, each after the patient had received a single dose of aspirin, ticagrelor and fondaparinux. CONCLUSION: The combination of injudicious high-sensitivity troponin testing with potent anti-platelet and anti-thrombotic therapy was associated with possible over-treatment of patients and associated harm. Emphasis on interpretation of troponin in the context of clinical presentation and improved awareness of type 2 myocardial infarction are essential to limit iatrogenic pharmacological harm.

Clinical implications of high-sensitivity cardiac troponins.

Cardiac troponin assays have become more sensitive over the years leading to the clinical introduction of high-sensitivity cardiac troponin assays in 2010. Their use has revolutionized the assessment of patients with chest pain in the emergency department by allowing earlier rule-in and rule-out of myocardial infarction leading to shorter stays in the emergency department and reduced admissions for chest pain. The incidence of myocardial infarction has increased slightly, and patients with myocardial infarction diagnosed with high-sensitivity cardiac troponins have been found to have a reduced risk of reinfarction, though without an impact on survival. High-sensitivity cardiac troponins are powerful predictors of long-term mortality and cardiovascular disease in the general population as well as in patients with chest pain with or without cardiovascular disease. The increase in risk for death and cardiovascular disease associated with high-sensitivity cardiac troponins is graded and starts already at detectable levels, well below the upper normal level. The aim of this review was to describe the clinical use and consequences of the introduction of high-sensitivity cardiac troponins. In addition, the importance of persistently elevated troponin levels for prognosis and what investigations may be appropriate to perform in patients with stable troponin elevations are discussed.

High-Sensitivity Cardiac Troponin-Based Strategies for the Assessment of Chest Pain Patients-A Review of Validation and Clinical Implementation Studies.

BACKGROUND: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays has improved the early assessment of chest pain patients. A number of hs-cTn-based algorithms and accelerated diagnostic protocols (ADPs) have been developed and tested subsequently. In this review, we summarize the data on the performance and clinical utility of these strategies. CONTENT: We reviewed studies investigating the diagnostic and prognostic performance of hs-cTn algorithms [level of detection (LoD) strategy, 0/1-h, 0/2-h, and 0/3-h algorithms) and of hs-cTn-based ADPs, together with the implications of these strategies when implemented as clinical routine. The LoD strategy, when combined with a nonischemic electrocardiogram, is best suited for safe rule-out of myocardial infarction and the identification of patients eligible for early discharge from the emergency department. The 0/1-h algorithms appear to identify most patients as being eligible for rule-out. The hs-cTn-based ADPs mainly focus on prognostic assessment, which is in contrast with the hs-cTn algorithms. They identify smaller proportions of rule-out patients, but there is increasing evidence from prospective studies on their successful clinical implementation. Such information is currently lacking for hs-cTn algorithms. CONCLUSIONS: There is a trade-off between safety and efficacy for different hs-cTn-based strategies. This trade-off should be considered for the intended strategy, along with its user-friendliness and evidence from clinical implementation studies. However, several gaps in knowledge remain. At present, we suggest the use of an ADP in conjunction with serial hs-cTn results to optimize the early assessment of chest pain patients.