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Background: Pulsed-field ablation (PFA) using a pentaspline-catheter for the treatment of atrial fibrillation (AF) is performed in a standardized fashion. Whether a reduced number of applications results in similar clinical outcomes has not been fully investigated., Objectives: To assess a simplified PFA-dosing protocol for pulmonary vein isolation (PVI) compared to a standard protocol., Method: consecutive Patients undergoing their first PVI using PFA were enrolled. In the simple PFA-group, patients received 4 applications/PV (2x basket and 2x flower configuration) whereas 8 applications/PV (4x basket and 4x flower configuration) were used in the standard PFA-group., Results: We included 245 patients (32% female, median age 66 years): 96 patients were in the simple PFA-group (39%) and 149 in the standard PFA-group (61%). Median procedure duration, left atrial dwell time and fluoroscopy time were significantly shorter in the simple-PFA group compared to the standard PFA-group with 40 [25-55] min vs. 53 [41-67] min (p<0.001); 22 [13-37] min vs. 37 [27-50] min (p<0.001); 9 [7-12] min vs. 11 [9-14] min (p<0.001), respectively. First pass isolation was similar for the simple PFA and the standard PFA-group (95% vs. 95%, p>0.999). Overall, 4 procedural complications were observed, all in the standard PFA-group (p=0.303). During a median follow-up of 373 days, freedom from atrial arrhythmias was 79% in the simple PFA-group and 77% in the standard PFA-group (p=0.767), respectively. Findings were confirmed when only comparing patients who received PVI with/without EAM., Conclusion: In conclusion, the novel simplified PFA-protocol was associated with increased procedural efficiency while maintaining non-inferior efficacy and safety compared to the standard PFA-protocol., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. Prediction of left ventricular ejection fraction (LVEF) recovery after catheter ablation (CA) for AF remains difficult., Objectives: To evaluate the value of biomarkers, alone and in conjunction with the Antwerp score to predict LVEF recovery after CA for AF., Methods: Patients undergoing CA for AF with depressed LVEF(<50%) were included. Plasma levels of 13 biomarkers were measured immediately prior to CA. Patients were categorized into "responders" and "non-responders" in similar fashion to the Antwerp score derivation and validation cohorts. The predictive power of the biomarkers alone and combined in outcome prediction was evaluated., Results: 208 patients with depressed LVEF were included (median age 63 years, 19% female, median LAVI 42 ml/m2, median LVEF 43%). At a median follow-up time of 30 months, 161 (77%) were responders and 47 (23%) were non-responders. Of 13 biomarkers, four (ANG2, GDF15, FGF23 and MyBPC3) were significantly different between responders and non-responders (p ≤0.001) and combined could predict the endpoint with an AUC of 0.72 (95%CI 0.64-0.81) overall, 0.69 (95%CI 0.59-0.78) in HFmrEF and 0.88 (95%CI 0.77-0.98) in HFrEF. Only ANG2 and GDF15 remained significantly associated with LVEF recovery after adjustment for age, sex and Antwerp score and significantly improved the accuracy of the Antwerp score predictions (p<0.001). The AUC of the Antwerp score in the outcome prediction improved from 0.75 (95% CI 0.67-0.83) to 0.78 (95% CI 0.70-0.86) CONCLUSION: A biomarker panel (ANG2, GDF15) significantly improved the accuracy of the Antwerp Score., (Copyright © 2024. Published by Elsevier Inc.)

Study Objective: Study the clinical outcomes associated with the number of concomitant vasopressors used in critically ill COVID-19 patients., Design: A single-center retrospective cohort study was conducted on patients admitted with COVID-19 to the intensive care unit (ICU) between March and October 2020., Setting: Rush University Medical Center, United States., Participants: Adult patients at least 18 years old with COVID-19 with continuous infusion of any vasopressors were included., Main Outcome Measures: 60-day mortality in COVID-19 patients by the number of concurrent vasopressors received., Results: A total of 637 patients met our inclusion criteria, of whom 338 (53.1 %) required the support of at least one vasopressor. When compared to patients with no vasopressor requirement, those who required 1 vasopressor (V1) (adjusted odds ratio [aOR] 3.27, 95 % confidence interval (CI) 1.86-5.79, p < 0.01) (n = 137), 2 vasopressors (V2) (aOR 4.71, 95 % CI 2.54-8.77, p < 0.01) (n = 86), 3 vasopressors (V3) (aOR 26.2, 95 % CI 13.35-53.74 p < 0.01) (n = 74), and 4 or 5 vasopressors(V4-5) (aOR 106.38, 95 % CI 39.17-349.93, p < 0.01) (n = 41) were at increased risk of 60-day mortality. In-hospital mortality for patients who received no vasopressors was 6.7 %, 22.6 % for V1, 27.9 % for V2, 62.2 % for V3, and 78 % for V4-V5., Conclusion: Critically ill patients with COVID-19 requiring vasopressors were associated with significantly higher 60-day mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope., Objective: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies., Methods: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE)., Results: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines., Conclusion: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients with pre-existing cardiovascular disease may carry a higher risk for mortality from COVID-19. This study examined the association between individuals with pre-existing cardiovascular disease admitted for COVID-19 and their clinical outcomes., Methods: A retrospective cohort study was conducted on patients admitted with COVID-19 to Rush University System for Health (RUSH) to identify cardiovascular risk factors associated with increased mortality and major adverse cardiovascular events (MACE; a composite of cardiovascular death, stroke, myocardial injury, and heart failure exacerbation). Multivariable logistic regression was used to adjust for demographic data and comorbid conditions., Results: Of the 1682 patients who met inclusion criteria, the median age was 59. Patients were predominantly African American (34.4 %) and male (54.5 %). Overall, 202 (12 %) patients suffered 60-day mortality. In the multivariable model that assessed risk factors for 60-day mortality, age 60-74 (adjusted odds ratio [aOR] 3.30 [CI: 1.23-10.62]; p < 0.05) and age 75-100 (aOR 4.52 [CI: 1.46-16.15]; p < 0.05) were significant predictors when compared to those aged 19 to 39. This model also showed that those with past medical histories of atrial fibrillation (aOR 2.47 [CI: 1.38-4.38]; p < 0.01) and venous thromboembolism (aOR 2.00 [CI: 1.12-3.50]; p < 0.05) were at higher risk of 60-day mortality., Conclusion: In this cohort, patients over 60 years old with a pre-existing history of atrial fibrillation and venous thromboembolism were at increased risk of mortality from COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Study Objective: To compare the characteristics and outcomes of COVID-19 patients with a hyperdynamic LVEF (HDLVEF) to those with a normal or reduced LVEF., Design: Retrospective study., Setting: Rush University Medical Center., Participants: Of the 1682 adult patients hospitalized with COVID-19, 419 had a transthoracic echocardiogram (TTE) during admission and met study inclusion criteria., Interventions: Participants were divided into reduced (LVEF < 50%), normal (≥50% and <70%), and hyperdynamic (≥70%) LVEF groups., Main Outcome Measures: LVEF was assessed as a predictor of 60-day mortality. Logistic regression was used to adjust for age and BMI., Results: There was no difference in 60-day mortality between patients in the reduced LVEF and normal LVEF groups (adjusted odds ratio [aOR] 0.87, p  = 0.68). However, patients with an HDLVEF were more likely to die by 60 days compared to patients in the normal LVEF group (aOR 2.63 [CI: 1.36-5.05]; p  < 0.01). The HDLVEF group was also at higher risk for 60-day mortality than the reduced LVEF group (aOR 3.34 [CI: 1.39-8.42]; p < 0.01)., Conclusion: The presence of hyperdynamic LVEF during a COVID-19 hospitalization was associated with an increased risk of 60-day mortality, the requirement for mechanical ventilation, vasopressors, and intensive care unit., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Study Objective: This study sought to assess the predictive value of H 2 FPEF score in patients with COVID-19., Design: Retrospective study., Setting: Rush University Medical Center., Participants: A total of 1682 patients had an echocardiogram in the year preceding their COVID-19 admission with a preserved ejection fraction (≥50%). A total of 156 patients met inclusion criteria., Interventions: Patients were divided into H 2 FPEF into low (0-2), intermediate (3-5), and high (6-9) score H 2 FPEF groups and outcomes were compared., Main Outcome Measures: Adjusted multivariable logistic regression models evaluated the association between H 2 FPEF score group and a composite outcome for severe COVID-19 infection consisting of (1) 60-day mortality or illness requiring (2) intensive care unit, (3) intubation, or (4) non-invasive positive pressure ventilation., Results: High H 2 FPEF scores were at increased risk for severe COVID-19 infection when compared intermediate to H 2 FPEF score groups (OR 2.18 [CI: 1.01-4.80]; p  = 0.049) and low H 2 FPEF score groups (OR 2.99 [CI: 1.22-7.61]; p  < 0.05). There was no difference in outcome between intermediate H 2 FPEF scores (OR 1.34 [CI: 0.59-3.16]; p  = 0.489) and low H 2 FPEF score., Conclusions: Patients with a high H 2 FPEF score were at increased risk for severe COVID-19 infection when compared to patients with an intermediate or low H 2 FPEF score regardless of regardless of coronary artery disease and chronic kidney disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Study Objective: Chest computed tomography (chest CT) is routinely obtained to assess disease severity in COVID-19. While pulmonary findings are well-described in COVID-19, the implications of cardiovascular findings are less well understood. We evaluated the impact of cardiovascular findings on chest CT on the adverse composite outcome (ACO) of hospitalized COVID-19 patients., Setting/participants: 245 COVID-19 patients who underwent chest CT at Rush University Health System were included., Design: Cardiovascular findings, including coronary artery calcification (CAC), aortic calcification, signs of right ventricular strain [right ventricular to left ventricular diameter ratio, pulmonary artery to aorta diameter ratio, interventricular septal position, and inferior vena cava (IVC) reflux], were measured by trained physicians., Interventions/main Outcome Measures: These findings, along with pulmonary findings, were analyzed using univariable logistic analysis to determine the risk of ACO defined as intensive care admission, need for non-invasive positive pressure ventilation, intubation, in-hospital and 60-day mortality. Secondary endpoints included individual components of the ACO., Results: Aortic calcification was independently associated with an increased risk of the ACO (odds ratio 1.86, 95% confidence interval (1.11-3.17) p  < 0.05). Aortic calcification, CAC, abnormal septal position, or IVC reflux of contrast were all significantly associated with 60-day mortality and major adverse cardiovascular events. IVC reflux was associated with in-hospital mortality ( p  = 0.005)., Conclusion: Incidental cardiovascular findings on chest CT are clinically important imaging markers in COVID-19. It is important to ascertain and routinely report cardiovascular findings on CT imaging of COVID-19 patients as they have potential to identify high risk patients., Competing Interests: The authors have no conflicts of interest to disclose. The authors have no competing interests. The Conflict of Interest Form is attached., (© 2021 Published by Elsevier Inc.)

Background: In the coronavirus disease 2019 (COVID-19) global pandemic, patients with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. However, the relationship between COVID-19 and heart failure (HF) is unclear, specifically whether HF is an independent risk factor for severe infection or if other accompanying comorbidities are responsible for the increased risk., Methods: This is a retrospective analysis of 1331 adult patients diagnosed with COVID-19 infection between March and June 2020 admitted at Rush University System for Health (RUSH) in metropolitan Chicago, Illinois, USA. Patients with history of HF were identified by International Classification of Disease, Tenth Revision (ICD-10) code assignments extracted from the electronic medical record. Propensity score matching was utilized to control for the numerous confounders, and univariable logistic regression was performed to assess the relationship between HF and 60-day morbidity and mortality outcomes., Results: The propensity score matched cohort consisted of 188 patients in both the HF and no HF groups. HF patients did not have lower 60-day mortality (OR 0.81; p  = 0.43) compared to patients without HF. However, those with HF were more likely to require readmission within 60 days (OR 2.88; p  < 0.001) and sustain myocardial injury defined as troponin elevation within 60 days (OR 3.14; p  < 0.05)., Conclusions: This study highlights the complex network of confounders present between HF and COVID-19. When balanced for these numerous factors, those with HF appear to be at no higher risk of 60-day mortality from COVID-19 but are at increased risk for morbidity., Competing Interests: None., (© 2021 The Author(s).)

Background: Atrial fibrillation (AF) is a growing health burden, and pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represents an attractive therapeutic option. Sex-specific differences in the epidemiology, pathophysiology, and clinical presentation of AF and PVI are recognized., Objective: We aimed at comparing the efficacy, safety, and procedural characteristics of CB and RF in women and men undergoing a first PVI procedure., Methods: We searched for randomized controlled trials and prospective observational studies comparing CB and RF ablation with at least 1 year of follow-up. After merging individual patient data from 18 data sets, we investigated the sex-specific (procedure failure defined as recurrence of atrial arrhythmia, reablation, and reinitiation of antiarrhythmic medication), safety (periprocedural complications), and procedural characteristics of CB vs RF using Kaplan-Meier and multilevel models., Results: From the 18 studies, 4840 men and 1979 women were analyzed. An analysis stratified by sex correcting for several covariates showed a better efficacy of CB in men (hazard ratio for recurrence 0.88; 95% confidence interval 0.78-0.98, P = .02) but not in women (hazard ratio 0.98; 95% confidence interval 0.83-1.16; P = .82). For women and men, the energy source had no influence on the occurrence of at least 1 complication. For both sexes, the procedure time was significantly shorter with CB (-22.5 minutes for women and -27.1 minutes for men)., Conclusion: CB is associated with less long-term failures in men. A better understanding of AF-causal sex-specific mechanisms and refinements in CB technologies could lead to higher success rates in women., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: To assess the prognostic performance of Growth differentiation factor-15 (GDF-15) concentrations in unselected patients presenting with suspected acute myocardial infarction (AMI) and adjudication based on high-sensitivity cardiac troponin (hs-cTn)., Methods and Results: In an ongoing prospective multicenter diagnostic study, consecutive patients presenting with suspected AMI to the emergency department and available GDF-15 and hs-cTnT concentrations were included. Adjudication of AMI was performed central by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations. Overall, 718 patients were included, with 23% (162/718) having an adjudicated diagnosis of AMI. The cumulative incidence of death within 2 years was 19% in patients with AMI (30 deaths in 162 patients) versus 5% in patients without AMI (25 deaths in 556 patients; P < 0.001). In AMI patients, GDF-15 provided an AUC of 0.89 (95% confidence interval [CI] 0.83-0.94) for 2-year death versus 0.55 (95% CI 0.44-0.66) for hs-cTnT (P < 0.001). A GDF-15 cutoff of ≤1560 ng/L predicted 2-year survival in 47% (76/162) of AMI patients and had 100% sensitivity (95% CI 88-100%) for 2-year death. In patients without AMI, GDF-15 provided an AUC of 0.83 (95% CI 0.76-0.89) versus 0.76 (95% CI 0.67-0.85) for hs-cTnT (P = 0.096). A GDF-15 cutoff of ≤886 ng/L predicted 2-year survival in 37% (203/556) of non-AMI patients and had 100% sensitivity (95% CI 86-100%) for 2-year death., Conclusions: GDF-15 concentrations at emergency department presentation have a high predictive accuracy for all-cause death in patients with suspected AMI and allow the identification of a large proportion of AMI patients with very low mortality risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Rapid and reliable diagnosis of ST-elevation myocardial infarction (STEMI) as a surrogate for acute coronary occlusion is critical for early reperfusion therapy., Objectives: We aimed to examine the diagnostic performance of current guideline-recommended Electrocardiogram (ECG) STEMI criteria., Methods: In a prospective diagnostic multicenter study, we objectively quantified the extent of ST-segment elevation in all ECG leads using an automated software-based analysis of the digital 12-lead-ECG in adult patients presenting to the emergency department (ED) with suspected myocardial infarction (MI). Classification according to current guideline-recommended ECG criteria for STEMI at ED presentation was compared against a final diagnosis adjudicated by two independent cardiologists after reviewing all available medical records including serial ECGs, cardiac imaging and coronary angiograms., Results: Among 2486 patients, 52 (2%) were found to have significant ST-segment elevation on ECG at ED presentation according to current guideline-recommended ECG criteria for STEMI. Eighty-one (3%) patients received a final adjudicated diagnosis of STEMI. Only 35% (28 of 81) of all patients with a final diagnosis of STEMI were correctly identified (PPV 54% (95% CI 41-66%), sensitivity 35% (95% Cl 24-46%), NPV 97.8% (95% CI 97.5-98.1%). Four reasons for missing STEMIs emerged: timing (significant STE at an earlier/later time point) in 25%, incorrect measurement points in 30%, non or borderline-significant STE in 36% and inferoposterior MI localisation in 9%., Conclusions: A computerized analysis of current guideline-recommended ECG criteria for STEMI showed suboptimal diagnostic performance when applied to a single 12‑lead ECG performed at ED presentation., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact of relative hypochromia in acute heart failure (AHF)., Methods: We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points., Results: Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4-2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3-1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21-1.76) and eGFR (HR 1.5, 95% CI 1.3-1.8, p < 0.001)., Conclusions: Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Noncardiac surgery early after coronary stenting has been associated with a high rate of stent thrombosis and catastrophic outcomes. However, those outcomes were mostly seen when dual antiplatelet therapy (DAPT) was discontinued before surgery. This observational study sought to estimate the risk of major adverse cardiac events (MACEs) after femoral artery repair following recent stent-percutaneous coronary intervention under continued DAPT and to explore potential risk factors. We suspect that in this setting, the risk of MACEs is lower than previously reported., Methods: This retrospective cohort study included all consecutive patients who underwent femoral artery repair because of puncture site complications (bleeding or occlusion) within 28 days after coronary stenting at a tertiary referral center in Switzerland from 2005 to 2015. The primary end point consisted of the MACEs death, cardiac arrest, stent thrombosis, and myocardial infarction., Results: There were 12,960 patients who underwent coronary stenting. Seventy patients (0.5%) required repair of the femoral vessels, which was performed under continued DAPT in all cases. Eight patients (11.4%; 95% confidence interval [CI], 5.4-21.8) experienced a total of 17 MACEs within 30 days after surgery, including 5 deaths (7.1%; 95% CI, 2.7-16.6). Factors significantly associated with postoperative MACEs were cardiogenic shock on admission before coronary stenting (hazard ratio, 6.9; 95% CI, 1.8-29.6; P = .035) and limb ischemia as an indication for surgery compared with bleeding (hazard ratio, 10.5; 95% CI, 2.7-40.7; P = .008)., Conclusions: In our series, femoral artery repair under DAPT for access site complications early after stent-percutaneous coronary intervention is associated with only a modest MACE rate and therefore a much better outcome than previously reported., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging., Methods: In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations., Results: AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8-100% and 99.5-100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7-100% and 98.9-100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7-26.8%)., Conclusion: All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice., Clinical Trial Registration: NCT00470587, http://clinicaltrials.gov/show/NCT00470587., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The value of the 12-lead ECG in the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is limited due to insufficient sensitivity and specificity of standard ECG criteria. The QRS-T angle reflects depolarization-repolarization heterogeneity and might assist in detecting patients with a NSTEMI (diagnosis) as well as predicting patients with an increased mortality risk (prognosis)., Methods: We prospectively enrolled 2705 consecutive patients with symptoms suggestive of NSTEMI. The QRS-T angle was automatically derived from the standard 10 s 12-lead ECG recorded at presentation to the ED. Patients were followed up for all-cause mortality for 2 years., Results: NSTEMI was the final diagnosis in 15% (n = 412) of patients. QRS-T angles were significantly greater in patients with NSTEMI compared to those without (p < 0.001). The use of the QRS-T angle in addition to standard ECG criteria indicative of ischemia improved the diagnostic accuracy for NSTEMI as quantified by the area under the ROC curve from 0.68 to 0.72 (p < 0.001). An algorithm for the combined use of standard ECG criteria and the QRS-T angle improved the sensitivity of the ECG for NSTEMI from 45% to 78% and the specificity from 86% to 91% (p < 0.001 for both comparisons). The 2-year survival rates were 98%, 97% and 87% according to QRS-T angle tertiles (p < 0.001)., Conclusion: In patients with suspected NSTEMI, the QRS-T angle derived from the standard 12-lead ECG provides incremental diagnostic accuracy on top of standard ECG criteria indicative of ischemia, and independently predicts all-cause mortality during 2 years of follow-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD)., Methods: We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations., Results: Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years., Conclusion: Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Various scores have been derived for the assessment of syncope patients in the emergency department (ED) but stay inconsistently validated. We aim to compare their performance to the one of a common, easy-to-use CHADS 2 score., Methods: We prospectively enrolled patients ≥ 40 years old presenting with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of the treating ED-physician regarding the probability of cardiac syncope was quantified. Two independent physicians adjudicated the final diagnosis after 1-year follow-up. Major cardiovascular events (MACE) and death were recorded during 2 years of follow-up. Nine scores were compared by their area under the receiver-operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac syncope., Results: 1490 patients were available for score validation. The CHADS 2 -score presented a higher or equally high accuracy for death in the long- and short-term follow-up than other syncope-specific risk scores. This score also performed well for the prediction of MACE in the long- and short-term evaluation and stratified patients with accuracy comparative to OESIL, one of the best performing syncope-specific risk score. All scores performed poorly for diagnosing cardiac syncope when compared to the ECJ., Conclusions: The CHADS 2 -score performed comparably to more complicated syncope-specific risk scores in the prediction of death and MACE in ED syncope patients. While better tools incorporating biochemical and electrocardiographic markers are needed, this study suggests that the CHADS 2 -score is currently a good option to stratify risk in syncope patients in the ED., Trial Registration: NCT01548352., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Exercise ECG stress testing is the most widely available method for evaluation of patients with suspected myocardial ischemia. Its major limitation is the relatively poor accuracy of ST-segment changes regarding ischemia detection. Little is known about the optimal method to assess ST-deviations., Methods: A total of 1558 consecutive patients undergoing bicycle exercise stress myocardial perfusion imaging (MPI) were enrolled. Presence of inducible myocardial ischemia was adjudicated using MPI results. The diagnostic value of ST-deviations for detection of exercise-induced myocardial ischemia was systematically analyzed 1) for each individual lead, 2) at three different intervals after the J-point (J+40ms, J+60ms, J+80ms), and 3) at different time points during the test (baseline, maximal workload, 2min into recovery)., Results: Exercise-induced ischemia was detected in 481 (31%) patients. The diagnostic accuracy of ST-deviations was highest at +80ms after the J-point, and at 2min into recovery. At this point, ST-amplitude showed an AUC of 0.63 (95% CI 0.59-0.66) for the best-performing lead I. The combination of ST-amplitude and ST-slope in lead I did not increase the AUC. Lead I reached a sensitivity of 37% and a specificity of 83%, with similar sensitivity to manual ECG analysis (34%, p=0.31) but lower specificity (90%, p<0.001)., Conclusion: When using ECG stress testing for evaluation of patients with suspected myocardial ischemia, the diagnostic accuracy of ST-deviations is highest when evaluated at +80ms after the J-point, and at 2min into recovery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned "rule-out" or "rule-in" of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25-30% of patients assigned to "observe". We aimed to better characterize these patients., Methods: In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm., Results: Twenty-four percent (n=523) of patients were assigned to "observe" by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from "rule-out" and "rule-in" patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to "rule-out" (p<0.001) and comparable to "rule-in" (p=ns). Findings were similar for the hs-cTnI "observe" zone., Conclusion: "Observe" patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)