2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.

Interpreting High-Sensitive Troponins in Patients with Hypertension.

PURPOSE OF REVIEW: As the high-sensitivity cardiac troponin (hs-cTn) becomes more broadly used, physicians must understand the strengths and limitations of using the hs-cTn in the hypertensive population. RECENT FINDINGS: The most common cause of hs-cTn elevation is cardiac myocyte injury and death; alternate mechanisms for hs-cTn elevation in the absence of cardiac myocyte death are not clearly understood. Hs-cTn elevation has been found in significant proportions of patients with asymptomatic hypertension, in patients with acute hypertensive crisis, and has even been used to predict patients who will go on to develop hypertension. While the mechanisms remain undefined, there is evidence that elevations in hs-cTn are associated with both short- and long-term morbidity and mortality. While ongoing research further defines the relationship between hypertension and hs-cTn, the emergency medicine physician must make clinical decisions today regarding the utility of this increasingly used biomarker. Given the current evidence, clinical context must be utilized including a complete clinical picture, EKGs findings, and importantly serial hs-cTn when needed to establish whether myocardial injury or myocardial infarction is occurring.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

BACKGROUND: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. METHODS: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. RESULTS: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. CONCLUSIONS: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Risk Stratification of Older Adults Who Present to the Emergency Department With Syncope: The FAINT Score.

STUDY OBJECTIVE: Older adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes. METHODS: We performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome. RESULTS: We enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670). CONCLUSION: Among older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.

Clinical risk assessment of biotin interference with a high-sensitivity cardiac troponin T assay.

Objectives Biotin >20.0 ng/mL (81.8 nmol/L) can reduce Elecsys® Troponin T Gen 5 (TnT Gen 5; Roche Diagnostics) assay recovery, potentially leading to false-negative results in patients with suspected acute myocardial infarction (AMI). We aimed to determine the prevalence of elevated biotin and AMI misclassification risk from biotin interference with the TnT Gen 5 assay. Methods Biotin was measured using an Elecsys assay in two cohorts: (i) 797 0-h and 646 3-h samples from 850 US emergency department patients with suspected acute coronary syndrome (ACS); (ii) 2023 random samples from a US laboratory network, in which biotin distributions were extrapolated for higher values using pharmacokinetic modeling. Biotin >20.0 ng/mL (81.8 nmol/L) prevalence and biotin 99th percentile values were calculated. AMI misclassification risk due to biotin interference with the TnT Gen 5 assay was modeled using different assay cutoffs and test timepoints. Results ACS cohort: 1/797 (0.13%) 0-h and 1/646 (0.15%) 3-h samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 2.62 ng/mL (10.7 nmol/L; 0-h) and 2.38 ng/mL (9.74 nmol/L; 3-h). Using conservative assumptions, the likelihood of false-negative AMI prediction due to biotin interference was 0.026% (0-h result; 19 ng/L TnT Gen 5 assay cutoff). US laboratory cohort: 15/2023 (0.74%) samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 16.6 ng/mL (68.0 nmol/L). Misclassification risk due to biotin interference (19 ng/L TnT Gen 5 assay cutoff) was 0.025% (0-h), 0.0064% (1-h), 0.00048% (3-h), and <0.00001% (6-h). Conclusions Biotin interference has minimal impact on the TnT Gen 5 assay's clinical utility, and the likelihood of false-negative AMI prediction is extremely low.

The Accuracy of Interqual Criteria in Determining the Observation versus Inpatient Status in Older Adults with Syncope.

BACKGROUND: McKesson's InterQual criteria are widely used in hospitals to determine if patients should be classified as observation or inpatient status, but the accuracy of the criteria is unknown. OBJECTIVE: We sought to determine whether InterQual criteria accurately predicted length of stay (LOS) in older patients with syncope. METHODS: We conducted a secondary analysis of a cohort study of adults ≥60 years of age who had syncope. We calculated InterQual criteria and classified the patient as observation or inpatient status. Outcomes were whether LOS were less than or greater than 2 midnights. RESULTS: We analyzed 2361 patients; 1227 (52.0%) patients were male and 1945 (82.8%) were white, with a mean age of 73.2 ± 9.0 years. The median LOS was 32.6 h (interquartile range 24.2-71.8). The sensitivity of InterQual criteria for LOS was 60.8% (95% confidence interval 57.9-63.6%) and the specificity was 47.8% (95% confidence interval 45.0-50.5%). CONCLUSIONS: In older adults with syncope, those who met InterQual criteria for inpatient status had longer LOS compared with those who did not; however, the accuracy of the criteria to predict length of stay over 2 days is poor, with a sensitivity of 60% and a specificity of 48%. Future research should identify criteria to improve LOS prediction.

Clinical Benefit of Hospitalization for Older Adults With Unexplained Syncope: A Propensity-Matched Analysis.

STUDY OBJECTIVE: Many adults with syncope are hospitalized solely for observation and testing. We seek to determine whether hospitalization versus outpatient management for older adults with unexplained syncope is associated with a reduction in postdisposition serious adverse events at 30 days. METHODS: We performed a propensity score analysis using data from a prospective, observational study of older adults with unexplained syncope or near syncope who presented to 11 emergency departments (EDs) in the United States. We enrolled adults (≥60 years) who presented with syncope or near syncope. We excluded patients with a serious diagnosis identified in the ED. Clinical and laboratory data were collected on all patients. The primary outcome was rate of post-ED serious adverse events at 30 days. RESULTS: We enrolled 2,492 older adults with syncope and no serious ED diagnosis from April 2013 to September 2016. Mean age was 73 years (SD 8.9 years), and 51% were women. The incidence of serious adverse events within 30 days after the index visit was 7.4% for hospitalized patients and 3.19% for discharged patients, representing an unadjusted difference of 4.2% (95% confidence interval 2.38% to 6.02%). After propensity score matching on risk of hospitalization, there was no statistically significant difference in serious adverse events at 30 days between the hospitalized group (4.89%) and the discharged group (2.82%) (risk difference 2.07%; 95% confidence interval -0.24% to 4.38%). CONCLUSION: In our propensity-matched sample of older adults with unexplained syncope, for those with clinical characteristics similar to that of the discharged cohort, hospitalization was not associated with improvement in 30-day serious adverse event rates.

Comparison of 30-Day Serious Adverse Clinical Events for Elderly Patients Presenting to the Emergency Department With Near-Syncope Versus Syncope.

STUDY OBJECTIVE: Controversy remains in regard to the risk of adverse events for patients presenting with syncope compared with near-syncope. The purpose of our study is to describe the difference in outcomes between these groups in a large multicenter cohort of older emergency department (ED) patients. METHODS: From April 28, 2013, to September 21, 2016, we conducted a prospective, observational study across 11 EDs in adults (≥60 years) with syncope or near-syncope. A standardized data extraction tool was used to collect information during their index visit and at 30-day follow-up. Our primary outcome was the incidence of 30-day death or serious clinical events. Data were analyzed with descriptive statistics and multivariate logistic regression analysis adjusting for relevant demographic or historical variables. RESULTS: A total of 3,581 patients (mean age 72.8 years; 51.6% men) were enrolled in the study. There were 1,380 patients (39%) presenting with near-syncope and 2,201 (61%) presenting with syncope. Baseline characteristics revealed a greater incidence of congestive heart failure, coronary artery disease, previous arrhythmia, nonwhite race, and presenting dyspnea in the near-syncope compared with syncope cohort. There were no differences in the primary outcome between the groups (near-syncope 18.7% versus syncope 18.2%). A multivariate logistic regression analysis identified no difference in 30-day serious outcomes for patients with near-syncope (odds ratio 0.94; 95% confidence interval 0.78 to 1.14) compared with syncope. CONCLUSION: Near-syncope confers risk to patients similar to that of syncope for the composite outcome of 30-day death or serious clinical event.

QTc prolongation as a marker of 30-day serious outcomes in older patients with syncope presenting to the Emergency Department.

BACKGROUND: Syncope is a common chief complaint in the ED, and the electrocardiogram (ECG) is a routine diagnostic tool in the evaluation of syncope. We assessed whether increasingly prolonged QTc intervals are associated with composite 30-day serious outcomes in older adults presenting to the ED with syncope. METHODS: This is a secondary analysis of a prospective, observational study at 11 EDs in adults 60 years or older who presented with syncope or near syncope. We excluded patients presenting without an ECG, measurement of QTc, non-sinus rhythm, bundle branch block or those without 30-day follow-up. We categorized QTc cutoffs into values of <451; 451-470; 471-500, and >500 ms. We determined the rate of composite 30-day serious outcomes including ED serious outcomes and 30-day arrhythmias not identified in ED. RESULTS: The study cohort included 2609 patients. There were 1678 patients (64.3%) that had QTc intervals <451 ms; 544 (20.8%) were 451-470 ms; 302 (11.6%) were 471-500 ms, and 85 (3.3%) had intervals >500 ms. Composite 30-day serious outcomes was associated with increasingly prolonged QTc intervals (13.0%, 15.3%, 18.2%, 22.4%, p = 0.01), but this association did not persist in multivariate analysis. CONCLUSIONS: In a cohort of older patients presenting with syncope, increased QTc interval was a marker of but was not independently predictive of composite 30-day serious outcomes.

Recurrent syncope is not an independent risk predictor for future syncopal events or adverse outcomes.

Almost 20% of patients with syncope will experience another event. It is unknown whether recurrent syncope is a marker for a higher or lower risk etiology of syncope. The goal of this study is to determine whether older adults with recurrent syncope have a higher likelihood of 30-day serious clinical events than patients experiencing their first episode. METHODS: This study is a pre-specified secondary analysis of a multicenter prospective, observational study conducted at 11 emergency departments in the US. Adults 60 years or older who presented with syncope or near syncope were enrolled. The primary outcome was occurrence of 30-day serious outcome. The secondary outcome was 30-day serious cardiac arrhythmia. In multivariate analysis, we assessed whether prior syncope was an independent predictor of 30-day serious events. RESULTS: The study cohort included 3580 patients: 1281 (35.8%) had prior syncope and 2299 (64.2%) were presenting with first episode of syncope. 498 (13.9%) patients had 1 prior episode while 771 (21.5%) had >1 prior episode. Those with recurrent syncope were more likely to have congestive heart failure, coronary artery disease, previous diagnosis of arrhythmia, and an abnormal ECG. Overall, 657 (18.4%) of the cohort had a serious outcome by 30 days after index ED visit. In multivariate analysis, we found no significant difference in risk of events (adjusted odds ratio 1.09; 95% confidence interval 0.90-1.31; p = 0.387). CONCLUSION: In older adults with syncope, a prior history of syncope within the year does not increase the risk for serious 30-day events.

Orthostatic vital signs do not predict 30 day serious outcomes in older emergency department patients with syncope: A multicenter observational study.

BACKGROUND: Syncope is a common chief complaint among older adults in the Emergency Department (ED), and orthostatic vital signs are often a part of their evaluation. We assessed whether abnormal orthostatic vital signs in the ED are associated with composite 30-day serious outcomes in older adults presenting with syncope. METHODS: We performed a secondary analysis of a prospective, observational study at 11 EDs in adults ≥ 60 years who presented with syncope or near syncope. We excluded patients lost to follow up. We used the standard definition of abnormal orthostatic vital signs or subjective symptoms of lightheadedness upon standing to define orthostasis. We determined the rate of composite 30-day serious outcomes, including those during the index ED visit, such as cardiac arrhythmias, myocardial infarction, cardiac intervention, new diagnosis of structural heart disease, stroke, pulmonary embolism, aortic dissection, subarachnoid hemorrhage, cardiopulmonary resuscitation, hemorrhage/anemia requiring transfusion, with major traumatic injury from fall, recurrent syncope, and death) between the groups with normal and abnormal orthostatic vital signs. RESULTS: The study cohort included 1974 patients, of whom 51.2% were male and 725 patients (37.7%) had abnormal orthostatic vital signs. Comparing those with abnormal to those with normal orthostatic vital signs, we did not find a difference in composite 30-serious outcomes (111/725 (15.3%) vs 184/1249 (14.7%); unadjusted odds ratio, 1.05 [95%CI, 0.81-1.35], p = 0.73). After adjustment for gender, coronary artery disease, congestive heart failure (CHF), history of arrhythmia, dyspnea, hypotension, any abnormal ECG, physician risk assessment, medication classes and disposition, there was no association with composite 30-serious outcomes (adjusted odds ratio, 0.82 [95%CI, 0.62-1.09], p = 0.18). CONCLUSIONS: In a cohort of older adult patients presenting with syncope who were able to have orthostatic vital signs evaluated, abnormal orthostatic vital signs did not independently predict composite 30-day serious outcomes.

Management of Patients on Non-Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association.

Non-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

ECG Predictors of Cardiac Arrhythmias in Older Adults With Syncope.

STUDY OBJECTIVE: Cardiac arrhythmia is a life-threatening condition in older adults who present to the emergency department (ED) with syncope. Previous work suggests the initial ED ECG can predict arrhythmia risk; however, specific ECG predictors have been variably specified. Our objective is to identify specific ECG abnormalities predictive of 30-day serious cardiac arrhythmias in older adults presenting to the ED with syncope. METHODS: We conducted a prospective, observational study at 11 EDs in adults aged 60 years or older who presented with syncope or near syncope. We excluded patients with a serious cardiac arrhythmia diagnosed during the ED evaluation from the primary analysis. The outcome was occurrence of 30-day serous cardiac arrhythmia. The exposure variables were predefined ECG abnormalities. Independent predictors were identified through multivariate logistic regression. The sensitivities and specificities of any predefined ECG abnormality and any ECG abnormality identified on adjusted analysis to predict 30-day serious cardiac arrhythmia were also calculated. RESULTS: After exclusion of 197 patients (5.5%; 95% confidence interval [CI] 4.7% to 6.2%) with serious cardiac arrhythmias in the ED, the study cohort included 3,416 patients. Of these, 104 patients (3.0%; 95% CI 2.5% to 3.7%) had a serious cardiac arrhythmia within 30 days from the index ED visit (median time to diagnosis 2 days [interquartile range 1 to 5 days]). The presence of nonsinus rhythm, multiple premature ventricular conductions, short PR interval, first-degree atrioventricular block, complete left bundle branch block, and Q wave/T wave/ST-segment abnormalities consistent with acute or chronic ischemia on the initial ED ECG increased the risk for a 30-day serious cardiac arrhythmia. This combination of ECG abnormalities had a similar sensitivity in predicting 30-day serious cardiac arrhythmia compared with any ECG abnormality (76.9% [95% CI 67.6% to 84.6%] versus 77.9% [95% CI 68.7% to 85.4%]) and was more specific (55.1% [95% CI 53.4% to 56.8%] versus 46.6% [95% CI 44.9% to 48.3%]). CONCLUSION: In older ED adults with syncope, approximately 3% receive a diagnosis of a serious cardiac arrhythmia not recognized on initial ED evaluation. The presence of specific abnormalities on the initial ED ECG increased the risk for 30-day serious cardiac arrhythmias.