Multiple Cardiac Biomarker Testing Among Patients With Acute Dyspnea From the ICON-RELOADED Study.

BACKGROUND: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown. METHODS AND RESULTS: Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P < .001), and 12.6 (95% CI, 4.54-35.0, P < .001) fold increased risk of 180-day mortality or HF rehospitalization. CONCLUSIONS: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

Sex-related differences in D-dimer levels for venous thromboembolism screening.

BACKGROUND: D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels. METHODS: This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on Wells criteria ≤ 6 for pulmonary embolism (PE) and ≤ 2 for deep vein thrombosis (DVT). VTE diagnoses were based on computed tomography, ventilation perfusion scanning, or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from receiver operating characteristic analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cutoff corresponding to 95% sensitivity were calculated. Statistical difference for cutoffs was tested via 95% confidence intervals from 2,000 bootstrapped samples. RESULTS: We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% White, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE-positive group and the DVT-negative group, but males had significantly lower D-dimer levels than females in the PE-negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden thresholds for PE patients were 0.97 (95% CI = 0.64 to 1.79) mg/L and 1.45 (95% CI = 1.36 to 1.95) mg/L for females and males, respectively; 95% sensitivity cutoffs for this group were 0.64 (95% CI = 0.20 to 0.89) and 0.55 (95% CI = 0.29 to 1.61). For DVT, the Youden thresholds were 0.98 (95% CI = 0.84 to 1.56) mg/L for females and 1.25 (95% CI = 0.65 to 3.33) mg/L for males with 95% sensitivity cutoffs of 0.33 (95% CI = 0.2 to 0.61) and 0.32 (95% CI = 0.18 to 0.7), respectively. CONCLUSION: Differences in D-dimer levels between males and females are diagnosis specific; however, there was no significant difference in optimal cutoff values for excluding PE and DVT between the sexes.

Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure.

AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P < 0.001), lower left ventricular ejection fraction (r = -0.27, P < 0.001), lower right ventricular fractional area change (r = -0.31, P < 0.001), and higher tissue Doppler E/e' ratio (r = 0.44, P < 0.001). In multivariable linear regression analyses, increased LAVi (P = 0.01), lower estimated glomerular filtration rate (P = 0.008), higher body mass index (P = 0.001), diabetes (P = 0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P = 0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio = 12.08, 95% confidence interval 2.42-60.15, P = 0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis. CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

UNIFIED: Understanding New Information from Emergency Departments Involved in the San Bernardino Terrorist Attack.

INTRODUCTION: Emergency departments (ED) are on the front line for treating victims of multi-casualty incidents. The primary objective of this study was to gather and detail the common experiences from those hospital-based health professionals directly involved in the response to the San Bernardino terrorism attack on December 2, 2015. Secondary objectives included gathering information on experiences participants found were best practices. METHODS: We undertook a qualitative study using Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines by performing semi-structured interviews with physicians, nurses, and incident management staff from multiple institutions responding to the San Bernardino terrorist attack. We coded transcripts using qualitative analysis techniques and we delineated and agreed upon a refined list with code definitions using a negotiated group process. Final themes were developed and analyzed. RESULTS: A total of 26 interviews were completed; 1172 excerpts were coded and categorized into 66 initial themes. Six final categories of communication, training, unexpected help, process bypassed, personal impact/emotions, and practical advice resulted. CONCLUSION: Our study provides context regarding the response of healthcare personnel from multiple institutions to a singular terrorist attack in the United States. It elucidates several themes to help other institutions prepare for similar events. Understanding these common experiences provides opportunity to prepare for future incidents and develop questions to study in future events.

N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study.

BACKGROUND: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. OBJECTIVES: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. METHODS: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF. RESULTS: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13). CONCLUSIONS: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.

Does emergency physician empathy reduce thoughts of litigation? A randomised trial.

BACKGROUND: We hypothesised the addition of brief empathetic statements to physician-patient interaction might decrease thoughts regarding litigation. METHODS: We enrolled a convenience sample of adults in our emergency department (ED) waiting room into a randomised, double-blind controlled trial. Subjects watched videos of simulated discharge conversations between physicians and patient actors; half of the videos differed only by the inclusion of two brief empathetic statements: verbalisations that (1) the physician recognises that the patient is concerned about their symptoms and (2) the patient knows their typical state of health better than a physician seeing them for the first time and did the right thing by seeking evaluation. After watching the video subjects were asked to score a five-point Likert scale their thoughts regarding suing this physician in the event of a missed outcome leading to lost work (primary outcome), and four measures of satisfaction with the physician encounter (secondary outcomes). RESULTS: We enrolled and randomised 437 subjects. 213 in the empathy group and 208 in the non-empathy group completed the trial. Sixteen subjects did not complete the trial due to computer malfunction or incomplete data sheets. Empathy group subjects reported statistically significant less thoughts of litigation than the non-empathy group (mean Likert scale 2.66 vs 2.95, difference -0.29, 95% CI -0.04 to -0.54, p=0.0176). All four secondary measures of satisfaction with the physician encounter were better in the empathy group. CONCLUSIONS: In this study, the addition of brief empathetic statements to ED discharge scenarios was associated with a statistically significant reduction in thoughts regarding litigation. CLINICAL TRIAL REGISTRATION: NCT01837706.

Emergency department provider preferences related to clinical practice guidelines for tobacco cessation: a multicenter survey.

OBJECTIVES: The objective was to assess current emergency department (ED) provider practices and preferences for tobacco cessation interventions. The ED is an opportune place to initiate smoking cessation interventions. However, little is known about ED provider current practices and preferences for cessation counseling in the ED. METHODS: This was a survey of ED providers conducted in 2008-2009 (including physicians, nurse practitioners, physician assistants, and nurses), working at least half-time at 10 U.S. academic EDs, regarding adherence to clinical practice guidelines ("5 As") and preferences for cessation interventions/styles. Data analysis occurred in 2012-2013. RESULTS: The response rate was 64% (800 out of 1,246 completed surveys). Providers reported strongest adherence to asking about patient smoking status, followed by advising, with significant variance by clinical role. Assessing, assisting, and arranging support for patients was low overall. Most frequently used interventions were to provide patients with a list of telephone numbers for stop-smoking counseling (87%), pamphlets on smoking health risks and the benefits of stopping (85%), and referrals to the National Toll-Free Smoker's Quitline (84%). Most providers (80%) were supportive of personally conducting brief (less than 3 minutes) smoking cessation counseling sessions during the ED visit, emphasizing education and encouragement. The least appealing intervention was writing a prescription for nicotine replacement therapies or medications to stop smoking (35%). CONCLUSIONS: Interventions most likely to be used were brief and delivered with a positive tone and included referral to external resources. The logical next step is to design and test interventions that ED providers find acceptable.

Acute Aortic Dissection in Third Trimester Pregnancy without Risk Factors.

Spontaneous aortic dissection in pregnancy is rare and life threatening for both the mother and the fetus. Most commonly, it is associated with connective tissue disorders, cardiac valve variants, or trauma. We present the case of a 23-year-old previously healthy woman, 36 weeks pregnant with a syncopal episode after dyspnea and vomiting. She subsequently developed cardiac arrest and underwent aggressive resuscitation, emergent thoracotomy, and cesarean delivery without recovery. On autopsy, she was found to have an aortic dissection of the ascending aorta. This case is presented to raise awareness and review the literature and the clinical approach to critical care for pregnant patients.