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Systemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and risk stratification of patients with AHF.Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/L) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. 1-year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated Interleukin-6 concentrations (4.45ng/L). Interleukin-6 was significantly higher in AHF patients compared to patients with other causes of dyspnea (11.2 [6.1-26.5] ng/L vs 9.0 [3.2-32.3] ng/L, p0.0005). Elevated Interleukin-6 concentrations were independently predicted by increasing NT-proBNP and high-sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0-164.2] ng/L) and lowest in patients with hypertensive AHF (9.3 [4.8-21.6] ng/L, p=0.001). Inflammation as quantified by Interleukin-6 was a strong and independent predictor of 1-year mortality both in all AHF patients, as well as those without clinically overt infection at presentation [adjusted hazard ratio (95%CI): 1.45 (1.15-1.83) vs 1.48 (1.09-2.00), respectively]. The addition of Interleukin-6 significantly improved the discrimination of the BIOSTAT-CHF risk score.An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by Interleukin-6, which seems to contribute to AHF phenotype and to the risk of death.

Background Quantitative assessment of self-reported exercise capacity as provided by the Duke Activity Status Index (DASI) is a validated measure of exercise capacity in stable ambulatory patients. Objectives This study aimedto test whether the quantification of self-reported exercise capacityusing the DASI may aid physicians in the risk stratification of patients presenting with acute dyspnea to the emergency department (ED). Methods Basics in Acute Shortness of Breath EvaLuation (BASEL V) was a prospective cohort study recruiting dyspneic patients at the ED. The prognostic value and accuracy of theDASI assessed shortly after presentation were quantified using Cox regression analyses and the Area under the curve (AUC). Results Among 1019 patients eligible for this analysis 529 (51.9%) had an adjudicated final diagnosis of acute heart failure, 75 (7.4%) and 297 (29.1%) patients died within 90 and 720 days after presentation. Unadjusted hazard ratios (HR) and multivariable adjusted hazard ratios (aHR) for 90-day and 720-day mortality increased continuously from the fourth (best self-reported exercise capacity) to the first DASI-quartile (worst self-reported exercise capacity). For 720-day mortality in the first quartile theHR was 9.1 (95%-CI 5.5–14.9) (aHR 6.1 [95%-CI 3.7–10.1]), in the second quartile 6.4 (95%-CI 3.9–10.6) (aHR 4.4 [95%-CI 2.6–7.3]), while in the third quartile the HR was 3.2 (95%-CI 1.9–5.5) (aHR 2.4 [95%-CI 1.4–4.0]). The prognostic accuracy of the DASI was moderate-to-high and higher than that of B-type natriuretic peptide (BNP) and NT-proBNP (N-terminal pro-BNP) concentrations, e.g. for 720-day mortality prediction AUC 0.70 versus 0.64, p=0.020; 0.72 versus 0.68, p=0.074. Conclusions Quantification of self-reported subjective exercise capacityusing the DASI provides moderate-to-high prognostic accuracy in patients presenting with acute dyspnea to the ED and may aid physicians in further risk stratification. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union, the Swiss National Science Foundation. Duke Activity Status Index

Background Especially in patients with acute heart failure (AHF) the NYHA classification remains of uncertain representation of patients' actual health state. Alternatively, patient's subjective well-being, in terms of health-related quality of life (HRQL), showed to have an excellent prognostic ability in out clinic patients with chronic heart failure. Objectives It is unknown whether HRQL instruments can assess a more reliable prognostication in patients hospitalized due to AHF than the NYHA classification. Methods Goal Directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC) was a multicenter, randomized, open-label blinded-end-point trial that emphasized early intensive and sustained vasodilation in adult patients hospitalized due to AHF with NYHA functional class III/IV, however provided neutral findings. HRQL was assessed by the generic EQ-5D-3L which is a 3-leveled 5-item instrument and the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ). Unadjusted and adjusted Cox regression models were performed after patients were grouped into low (EQ-5D −0.074 Results 781 patients were enrolled in 10 centres in 5 countries over 2 continents among which 536 (69%) patientshad completed theEQ-5D and 419 (54%) the KCCQ shortly after admission. Within 180 days of follow-up69 (13%) and 54 (13%) patients died and 151 (28%) and 122 (29%) died or were rehospitalized due to AHF, respectively. Cumulative incidence as well as HRs in patients grouped according to NYHA (n=536) indicated a comparable or significantly lower risk in patients with NYHA IV: e.g. for the combined outcome HR 1.07 (95% CI 0.777–1.473) and aHR 0.463 (95% CI 0.245–0.875). Whereas HRs in patients grouped according to both, EQ-5D (n=536) and KCCQ (n=419), increased from the group with highest to the group with the lowest HRQL: e.g. aHR for moderately high 1.11 (95% CI 0.718–1.715), for moderately low 1.721 (95% CI 1.102–2.688) and for low EQ-5D index 1.891 (95% CI 1.136–3.149) referenced to high HRQL (EQ-5D index 0.75–1.0). Conclusions These findings corroborate and extend previous work suggesting that NYHA classification poorly discriminates AHF patients' prognosis and challenge its' extensive application. HRQL might be a possible alternative to easily assess these patients' heath state. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, the Swiss Heart Foundation A. 180-day mortality; B. composite outcome

Acute dyspnoea is a very common symptom in the acute cardiac care setting. In contrast to current beliefs, acute dyspnoea, as the leading symptom, is associated with about twice the mortality risk, compared to acute chest pain. Rapid and accurate identification of the cause of dyspnoea is critical to the initiation of specific and effective treatment. In most patients, a rapid and accurate diagnosis in the emergency department can be achieved by a combination of vital signs, including pulse oximetry, detailed patient history, physical examination, blood tests including B-type natriuretic peptide or N-terminal pro-B type natriuretic peptide, venous blood gases, and C-reactive protein in all patients, and D-dimers in selected patients, electrocardiograms, chest X-ray and pleural and/or lung ultrasound. It is key to remember that the prevalence of acute heart failure in unselected patients with acute dyspnoea is about 50%. Therefore, a high awareness for the presence of acute heart failure is mandatory. Acute heart failure, pneumonia, obstructive pulmonary diseases (chronic obstructive pulmonary disease and asthma), pulmonary embolism, and anxiety disorders represent more than 90% of all cases with acute dyspnoea in the emergency department. In about 10-15%, two acute causes (e.g. acute heart failure and pneumonia) may be present and require combined treatment. Transthoracic echocardiography should be immediately performed in all patients with acute dyspnoea and shock, and in those patients in whom the diagnosis remains uncertain, even after initial work-up

Background Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. Methods This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. Results Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values n = 764) (interaction p values p p Conclusions Quantifying the adrenomedullin’s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

BACKGROUND The diagnosis of cardiac syncope remains a challenge in the emergency department (ED). OBJECTIVE Assessing the diagnostic accuracy of the early standardized clinical judgement (ESCJ) including a standardized syncope-specific case report form (CRF) in comparison with a recommended multivariable diagnostic score. METHODS In a prospective international observational multicentre study, diagnostic accuracy for cardiac syncope of ESCJ by the ED physician amongst patients ≥ 40 years presenting with syncope to the ED was directly compared with that of the Evaluation of Guidelines in Syncope Study (EGSYS) diagnostic score. Cardiac syncope was centrally adjudicated independently of the ESCJ or conducted workup by two ED specialists based on all information available up to 1-year follow-up. Secondary aims included direct comparison with high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) concentrations and a Lasso regression to identify variables contributing most to ESCJ. RESULTS Cardiac syncope was adjudicated in 252/1494 patients (15.2%). The diagnostic accuracy of ESCJ for cardiac syncope as quantified by the area under the curve (AUC) was 0.87 (95% CI: 0.84-0.89), and higher compared with the EGSYS diagnostic score (0.73 (95% CI: 0.70-0.76)), hs-cTnI (0.77 (95% CI: 0.73-0.80)) and BNP (0.77 (95% CI: 0.74-0.80)), all P

Aims Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non‐cardiac causes. Methods and results Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all‐cause mortality in AHF and non‐AHF patients and those readmitted due to cardiovascular and non‐cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2–4.0), P

Background Acute heart failure (AHF) is the most common cause of hospital admission and continues to have unacceptable high rates of mortality and morbidity. In contrast to acute myocardial infarction, the pathophysiology of AHF is incompletely understood and risk-prediction is poorly defined. Aim We aimed to quantify systemic inflammation to assess its possible role in the pathophysiology and risk stratification of patients with AHF. Methods Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/l) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. Plasma concentrations of NT-proBNP (open label) and Interleukin-6 (blinded) were measured at presentation and at discharge. The final diagnosis of AHF and the AHF phenotype were adjudicated by two independent cardiologists. 1-year mortality was the prognostic endpoint. Results Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF. Interleukin-6 concentrations were significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1–26.5] ng/l vs 9.0 [3.2–32.3] ng/l, p4.45ng/l) in 83.7% of them. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0–164.2] ng/l) and lowest in patients with hypertensive HF (9.3 [4.8–21.6] ng/l, p=0.001). Inflammation as quantified by Interleukin-6 was a strong predictor of 1-year mortality both in AHF as well as in other causes of acute dyspnea (Figure). During in-hospital treatment Interleukin-6 concentrations significantly decreased in AHF patients. However, changes in the extend of systemic inflammation (delta Interleukin-6) were poorly correlated with changes in hemodynamic stress as quantified by NT-proBNP (delta NT-proBNP, Φc=0.11, p=0.004). Conclusions An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation that can be quantified by Interleukin-6, which seems to contribute to the AHF phenotype and to the risk of death. Kaplan Meier curves for mortality Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation, European Union, Stiftung für kardiovaskuläre Forschung Basel, University of Basel, University Hospital Basel

Background It is unclear whether BNP or NT-proBNP, their admission or discharge measurement or percentage change during hospitalization are preferable for mortality prediction in patients with acute dyspnea. Purpose To directly compare BNP and NT-proBNP regarding their potential in mortality prediction in patients with acute dyspnea and in patients with dyspnea due to AHF. Methods In a prospective multicenter diagnostic study the presence of AHF was centrally adjudicated by two independent cardiologists among patients presenting with acute dyspnea. The levels of BNP and NT-proBNP were measured at presentation and discharge. Patients were stratified according to their natriuretic peptide response (responders vs. non-responders: natriuretic peptide decrease ≥25% vs. Results Among 1156 patients presenting with acute dyspnea, 353 (30.5%) died within 720 days of follow-up. Prognostic accuracy for death at 720 days was significantly higher for discharge compared to admission measurements for BNP (AUC 0.750 vs. 0.711, p Conclusion Percentage change of NT-proBNP during hospitalization seems to be the strongest predictor for long-term mortality in patients with acute dyspnea in general and in those with dyspnea due to AHF in particular. ROC curve for direct comparison Funding Acknowledgement Type of funding source: None

Background Previous studies have shown the prognostic value of health-related quality of life (HRQL) in stable and ambulatory chronic heart failure patients. However, it is unknown whether HRQL can predict all-cause mortality in patients presenting to the emergency department (ED) after acute onset of symptoms. In order to address this unmet need, the aim of this study was to assess the prognostic value of HRQL in patients with acute dyspnea caused by acute heart failure (AHF) and other dyspnea aetiologies for 360-day mortality. Purpose To assess prognostic value of HRQL using the generic EQ-5D and visual analogue scale (EQ VAS) in patients with acute dyspnea. Methods Basics in Acute Shortness of Breath EvaLuation (BASEL V) is a prospective, multicenter, diagnostic study enrolling adult patients presenting with acute dyspnea to the ED. For this analysis, only patients with a complete set of variables necessary for calculation of EQ-5D (range 0–10; with higher score indicating worse HRQL) and EQ VAS (range 0–100; with 100 being the best imaginable health state) at baseline were included. The endpoint was the prognostic value of EQ-5D and EQ VAS at 360 days of follow-up regarding all-cause death. Prognostic accuracy was calculated using c-statistics. In a cox regression analysis EQ-5D was treated as both, a continuous and categorical variable. Adjustments were made for clinically relevant covariates (age, sex, orthopnoea, edema, level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at presentation, history of coronary artery disease and chronic obstructive pulmonary disease, diuretics, β-blockers and ACE-inhibitors at discharge). Results Among 2605 patients enrolled, 1141 (43,8%) had a complete set of variables allowing the calculation of EQ-5D and EQ VAS. Of these patients 594 (52.1%) had an adjudicated final diagnosis of AHF. 211 (18.5%) patients died within 360 days of follow-up. Median EQ-5D was 3 (interquartile range (IQR) 1.5–5) and median EQ VAS was 50 (IQR 40–70). The prognostic accuracy for 360-day mortality was 0.65 (95% confidence interval ((CI) 0.61–0.69) and 0.58 (95% CI 0.54–0.62) for EQ-5D and EQ VAS, respectively (p=0.002). After combining EQ-5D and EQ VAS in a logistic regression model c-statistics regarding all-cause mortality within 360 days did not improve. The prognostic accuracy of EQ-5D was comparable to that of NT-proBNP (c-statistics 0.69, p=0.385). In an adjusted cox regression analysis the hazard ratio for patients with EQ-5D >4 was 2.2 (95% CI 1.7–2.9; p Conclusions In patients presenting with acute dyspnea HRQL is a strong prognostic instrument. Independently of the aetiology of the dyspnea the prognostic value of the generic EQ-5D for 360-day mortality is comparable to NT-proBNP. Patients with an EQ-5D >4 are at significantly higher risk for mortality within 360 days. Figure 1. Prognostic value of HRQL Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms.This study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI).This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue-specific 0/1-h algorithm.MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p 0.001). A single cutoff concentration 3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication.The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587).

Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need.; The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE.; Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization.; Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI.; The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).

BACKGROUND The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94–0.96), higher than hs-cTnI Architect [0.92 (95% CI, 0.91–0.94; P < 0.001)] and comparable to hs-cTnT Elecsys [0.94 (95% CI, 0.93–0.95; P = 0.12)]. Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out [sensitivity, 98.9% (95% CI, 94.3–99.8)], and 15% of patients were ruled in [specificity, 95.9% (95% CI, 94.0–97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI. CONCLUSIONS Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays. ClinicalTrials.gov Identifier: NCT00470587.

BACKGROUND We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93–0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92–0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90–0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94–0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1–100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4–97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. ClinicalTrials.gov Identifier NCT00470587.

Prompt identification of acute myocardial infarction (AMI) may be particularly challenging in patients with prior coronary artery bypass grafting (CABG). The effect of prior CABG on the diagnostic performance of high-sensitivity cardiac troponin (hs-cTnT/I) concentrations and the European Society of

Background: The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. Methods: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding, or valvular surgery. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) served as the prognostic comparators. Results: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope versus other causes ( P P P Conclusions: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01548352.

Importance Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39];P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration ClinicalTrials.gov Identifier:NCT00512759