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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.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.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).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.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.

Given the concern that beta-blocker use may be associated with an increased risk for heart failure (HF) in populations with normal left ventricular systolic function, we evaluated the association between beta-blocker use and incident HF events, as well as loop diuretic initiation in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT demonstrated that a blood pressure target of120 mm Hg reduced cardiovascular outcomes compared with140 mm Hg in adults with at least one cardiovascular risk factor and without HF. The lower rate of the composite primary outcome in the 120 mm Hg group was primarily driven by a reduction in HF events. Subjects on a beta blocker for the entire trial duration were compared with subjects who never received a beta blocker after 1:1 propensity score matching. A competing risk survival analysis by beta-blocker status was performed to estimate the effect of the drug on incident HF and was then repeated for a secondary end point of cardiovascular disease death. Among the 3,284 propensity score-matched subjects, beta-blocker exposure was associated with an increased HF risk (hazard ratio 5.86; 95% confidence interval 2.73 to 13.04; p0.001). A sensitivity analysis of propensity score-matched cohorts with a history of coronary artery disease or atrial fibrillation revealed the same association (hazard ratio 3.49; 95% confidence interval 1.15 to 10.06; p = 0.028). In conclusion, beta-blocker exposure in this secondary analysis was associated with increased incident HF in subjects with hypertension without HF at baseline.

The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

Background Premature ventricular complexes (PVCs) are a potentially reversible cause of heart failure. However, the characteristics of patients most likely to develop impaired left ventricular function are unclear. Hence, the objective of this study is to systematically assess risk factors for the development of PVC-induced cardiomyopathy. Methods We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). We investigated the reporting of PVC-CM risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis. Results A total of 26 studies (9 prospective and 17 retrospective studies) involving 16,764,641 patients were analyzed (mean age 55 years, 58% women, mean PVC burden 17%). Eleven RF were suitable for quantitative analysis (≥ 3 occurrences in multivariable model assessing a binary change in left ventricular (LV) function). Among these, age (OR 1.02 per increase in the year of age, 95% CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95% CI [0.05, 0.64]), non-sustained ventricular tachycardias (VT) (OR 3.01, 95% CI [1.39, 6.50]), LV origin (OR 2.20, 95% CI [1.14, 4.23]), epicardial origin (OR 4.72, 95% CI [1.81, 12.34]), the presence of interpolation (OR 4.93, 95% CI [1.66, 14.69]), PVC duration (OR 1.05 per ms increase in QRS-PVC duration [1.004; 1.096]), and PVC burden (OR 1.06, 95% CI [1.04, 1.08]) were all significantly associated with PVC-CM. Conclusions In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VT, LV, epicardial origin, interpolation, and PVC burden, whereas the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up of patients presenting with frequent PVCs and normal LV function.

Introduction and objectives: Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in early AMI is near linear. Methods: In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2 hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2 hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values. Results: Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P

We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay.This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm.Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n = 813), optimal criteria for rule-out of MI were9ng/L at presentation (if chest pain onset3h) or9ng/L and 0h-1h-change5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n = 345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings.The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI.ClinicalTrials.gov number, NCT00470587.

Background: Recent advances in digital electrocardiography technology allow evaluating ST-segment deviations in all 12 leads as quantitative variables and calculating summed ST-segment deviation scores. The diagnostic and prognostic utility of summed ST-segment deviation scores is largely unknown. Methods: We aimed to explore the diagnostic and prognostic utility of the conventional and the modified ST-segment deviation score (Better Analysis of ST-segment Elevations and Depressions in a 12- Lead-ECG-Score (BASEL-Score): sum of elevations in the augmented voltage right - lead (aVR) plus absolute, unsigned ST-segment depressions in the remaining leads) in patients presenting with suspected non-ST-segment elevation myocardial infarction. The diagnostic endpoint was non-ST-segment elevation myocardial infarction, adjudicated by two independent cardiologists. Prognostic endpoint was mortality during two-year follow up. Results: Among 1330 patients, non-ST-segment elevation myocardial infarction was present in 200 (15%) patients. Diagnostic accuracy for non-ST-segment elevation myocardial infarction as quantified by the area under the receiver-operating-characteristics curve was significantly higher for the BASEL-Score (0.73; 95% confidence interval 0.69–0.77) as compared to the conventional ST-segment deviation score (0.53; 95% confidence interval 0.49–0.57, p Conclusions: The modified ST-segment deviation score BASEL-Score focusing on ST-segment elevation in aVR and ST-segment depressions in the remaining leads provides incremental diagnostic and prognostic information.

Aim: Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy. Methods and results: Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled. Presence of myocardial ischaemia, the primary diagnostic endpoint, was adjudicated using MPI and coronary angiography. Automated high-frequency QRS analysis was performed in a blinded fashion. The prognostic endpoint was major adverse cardiac events (MACEs) during two years of follow-up. Exercise-induced ischaemia was detected in 147/662 patients (22%). The sensitivity of high-frequency QRS was similar to ST-deviations (46% vs. 43%, p=0.59), while the specificity was lower (75% vs. 87%, p Conclusion: The use of high-frequency QRS analysis in addition to ST-deviation analysis improves the diagnostic accuracy during exercise stress testing and adds independent prognostic information.

Graphical abstract Fig. 1 Diagnostic performance of D-dimer using two different assays in patients presenting with syncope. A Left: Receiver-operating characteristic curves quantifying the diagnostic performance of Innovance® D-dimer (blue) and hs-Loci-Innovance® D-dimer (red) for the diagnosis of venous thromboembolism (VTE). Right: Clinical application of D-dimer using the 2-level Wells-score with age-adjusted1 or fixed cutoffs versus the YEARS-algorithm with probability-adjusted cut offs2. B Left: Specificity for different cufoffs of Innovance® D-dimer (blue) and hs-Loci-Innovance® D-dimer (red) for the diagnosis of venous thromboembolism (VTE). Right: Percentage of patients ruled-in and correctly identified VTE patients for different cutoffs of Innovance® D-dimer (blue) and hs-Loci-Innovance® D-dimer (red). 1In patients 50 years or younger, D-dimer concentration 2YEARS-algorithm: assessment of only three items from the Wells-score (clinical signs of deep vein thrombosis, hemoptysis, pulmonary embolism the most likely diagnosis) and using a D-dimer test threshold of 0.5 mg/l in presence, and 1.0 mg/l in absence of one of the YEARS-items

Background: Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs). Methods: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT–Elecsys) and 3 hs-cTnI assays (hs-cTnI–Architect, hs-cTnI–Access, hs-cTnI–Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. Results: Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P P P TNNT2 , encoding cTnT (but none for TNNI3 , encoding cTnI) versus control subjects (n=16, P Wald R =0.59, P t-statistic R =0.26, P t-statistic =0.031). Conclusions: In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03660969.

BACKGROUND The clinical utility of procalcitonin in the diagnosis and management of pneumonia remains controversial. METHODS We assessed the clinical utility of procalcitonin in 2 prospective studies: first, a multicenter diagnostic study in patients presenting to the emergency department with acute dyspnea to directly compare the diagnostic accuracy of procalcitonin with that of interleukin 6 and C-reactive protein (CRP) in the diagnosis of pneumonia; second, a randomized management study of procalcitonin guidance in patients with acute heart failure and suspected pneumonia. Diagnostic accuracy for pneumonia as centrally adjudicated by 2 independent experts was quantified with the area under the ROC curve (AUC). RESULTS Among 690 patients in the diagnostic study, 178 (25.8%) had an adjudicated final diagnosis of pneumonia. Procalcitonin, interleukin 6, and CRP were significantly higher in patients with pneumonia than in those without. When compared to procalcitonin (AUC = 0.75; 95% CI, 0.71–0.78), interleukin 6 (AUC = 0.80; 95% CI, 0.77–0.83) and CRP (AUC = 0.82; 95% CI, 0.79–0.85) had significantly higher diagnostic accuracy (P = 0.010 and P < 0.001, respectively). The management study was stopped early owing to the unexpectedly low AUC of procalcitonin in the diagnostic study. Among 45 randomized patients, the number of days on antibiotic therapy and the length of hospital stay were similar (both P = 0.39) in patients randomized to the procalcitonin-guided group (n = 25) and usual-care group (n = 20). CONCLUSIONS In patients presenting with dyspnea, diagnostic accuracy of procalcitonin for pneumonia is only moderate and lower than that of interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. SUMMARY Pneumonia has diverse and often unspecific symptoms. As the role of biomarkers in the diagnosis of pneumonia remains controversial, it is often difficult to distinguish pneumonia from other illnesses causing shortness of breath. The current study prospectively enrolled unselected patients presenting with acute dyspnea and directly compared the diagnostic accuracy of procalcitonin, interleukin 6, and CRP for the diagnosis of pneumonia. In this setting, diagnostic accuracy of procalcitonin for pneumonia was lower as compared to interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. ClinicalTrials.gov Identifier NCT01831115.

ObjectiveTo develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.MethodsIn a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.ResultsIn the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.ConclusionIn patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.Trial registration numberNCT01548352 (BASEL IX), NCT01802398 (SRS study).

This study sought to assess the predictive value of HRetrospective study.Rush University Medical Center.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.Patients were divided into HAdjusted multivariable logistic regression models evaluated the association between HHigh HPatients with a high H

Background: The non–ST-segment–elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/L) was proposed, warranting external validation. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort. Results: Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule out or rule in NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of Conclusions: A combination of a 3h-hs-cTnT concentration ( Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT00470587.

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 

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 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.

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.

ObjectiveAssess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI).DesignTwo independent prospective multicentre diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year.Results8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0).ConclusionsThe relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.

Background β-Blockers have an uncertain effect in heart failure with a preserved ejection fraction of 50% or higher (heart failure with preserved ejection fraction [HFpEF]). Methods and Results We included patients with HFpEF from the Swedish Heart Failure Registry (SwedeHF) enrolled from 2011 through 2018. In a 2:1 propensity-score matched analysis (β-blocker use vs nonuse), we assessed the primary outcome first HF hospitalization, the coprimary outcome cardiovascular (CV) death, and the secondary outcomes of all-cause hospitalization and all-cause death. We performed intention-to-treat and a per-protocol consistency analyses. There were a total of 14,434 patients (median age 79 years, IQR 71–85 years, 51% women); 80% were treated with a β-blocker at baseline. Treated patients were younger and had higher rates of atrial fibrillation and coronary artery disease, and higher N-terminal pro-B-type natriuretic peptide levels. In the 4412:2206 patient matched cohort, at 5 years, 42% (95% CI 40%–44%) vs 44% (95% CI 41%–47%) had a HF admission and 38% (IQR 36%–40%) vs 40% (IQR 36%–42%) died from CV causes. In the intention-to-treat analysis, β-blocker use was not associated with HF admissions (hazard ratio 0.95 [95% CI 0.87–1.05, P = .31]) or CV death (hazard ratio 0.94 [95% CI 0.85–1.03, P = .19]). In the subgroup analyses, men seemed to have a more favorable association between β-blockers and outcomes than did women. There were no associations between β-blocker use and secondary outcomes. Conclusions In patients with HFpEF, β-blocker use is common but not associated with changes in HF hospitalization or cardiovascular mortality. In the absence of a strong rational and randomized control trials the case for β-blockers in HFpEF remains inconclusive. Bullet points ● The effect of β-blockers with heart failure with preserved ejection fraction of 50% or greater is uncertain.● In a propensity score–matched heart failure with preserved ejection fraction analysis in the SwedeHF registry, β-blockers were not associated with a change in risk for heart failure admissions or cardiovascular deaths. Lay summary The optimal treatment for heart failure with a preserved pump function remains unknown. Despite the lack of scientific studies, β-blockers are very commonly used. When matching patients with a similar risk profile in a large heart failure registry, the use of β-blockers for the treatment of heart failure with a preserved pump function was not associated with any changes in heart failure hospital admissions or cardiovascular death.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has killed hundreds of thousands worldwide. Those with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. Congestive heart failure (CHF) may lead to worsening COVID-19 symptoms. However, it is unclear if CHF is an independent risk factor for severe COVID-19 infection or if other accompanying comorbidities are responsible for the increased risk. Methods: From March to June 2020, data was obtained from adult patients diagnosed with COVID-19 infection who were admitted in the Rush University System for Health (RUSH) in Illinois. Heart failure patients, determined by ICD code assignments extracted from the electronic medical records, were identified. Multivariable logistic regression was performed between predictor variables and a composite outcome of severe infection consisting of Intensive Care Unit (ICU) admission, intubation, or in-hospital mortality. Results: In this cohort (n=1136), CHF [odds ratio (OR) 1.02] alone did not predict a more severe illness. Prior myocardial infarction [(MI), OR 3.55], history of atrial fibrillation [(AF), OR 2.14], and male sex (OR 1.55) were all significantly (p Conclusions: Prior MI, history of AF, and male sex predicted more severe COVID-19 illness course in our cohort, but pre-existing heart failure alone did not. However, CHF patients who are females and older in age are at risk for severe infection. These findings help clinicians identify patients with comorbidities early at risk for severe COVID-19 illness.

Background: Computed tomography (CT) chest is routinely used for the diagnosis and management of COVID-19 patients. Though COVID-19 disease-specific pulmonary findings have been well described, the significance of concomitant cardiovascular findings on chest CT are less studied. We examined the presence of various cardiovascular findings as markers for predicting significant outcomes in COVID-19. Methods: A retrospective cohort study was conducted on 163 patients with confirmed COVID-19 who underwent chest CT. In addition to the reported pulmonary findings, specific cardiovascular CT variables were collected, including right and left ventricular dimensions, pulmonary artery and aortic size, reflux of contrast into the IVC, septal position, coronary artery and aortic calcifications. Multivariable analysis was used to determine whether cardiovascular findings predict a composite outcome consisting of in-hospital and 30-day mortality, Intensive Care Unit admission, intubation, extracorporeal membrane oxygenation, proning, and renal replacement therapy. Results: Among our cohort, aortic calcification significantly predicted an increased risk of the composite outcome (odds ratio (OR) 4.73, p < 0.0001). Larger RV diameter predicted composite outcome (OR 1.08, p < 0.01). RV/LV ratio > 0.9 (normal ratio < 0.9) showed borderline significant trend towards 30-day mortality (OR 1.12, p < 0.05). A combination of cardiac findings to discriminate between patients at higher or lower risk of a negative outcome (AUC 0.67, 95% CI 0.57 - 0.76) was non-inferior to a combination of pulmonary CT findings (AUC 0.68, 95% CI 0.6 - 0.76, p = 0.81). Discussion: Our data suggest that cardiovascular findings such as a dilated right ventricle and aortic calcification are important imaging markers in symptomatic patients with COVID-19. These findings highlight the importance of right ventricular parameters and vascular disease in predicting adverse clinical outcomes in these patients. Conclusions: Cardiovascular findings should be recognized and reported when imaging patients with COVID-19. Future, higher-power analyses of long-term outcomes in our cohort are anticipated to yield further results.

Introduction: Recent investigation has identified that discontinuation of beta-blockers in subjects with normal left ventricular ejection fraction (LVEF) leads to a reduction in natriuretic peptide levels. We investigated whether a similar trend would be seen in a hypertension clinical trial cohort. Methods: In 9,012 subjects hypertensive subjects without a history of symptomatic heart failure, known LVEF Results: Among the 9,012 subjects analyzed, the incidence of anti-hypertensive initiation and loop diuretic initiation was greatest following start of a beta-blocker (16.6%) compared with other antihypertensive medication classes (calcium channel blocker 13.8%, angiotensin converting enzyme-inhibitor/angiotensin receptor blocker 12.9% and thiazide diuretic 10.2%; p Conclusion: Compared to other major classes of hypertensive agents, starting beta-blockers was associated with more common and earlier initiation of a loop diuretics in a population without heart failure at baseline. This finding may suggest beta-blocker induced heart failure in a population with a predominantly normal ejection fraction.

Introduction: The coronavirus disease 2019 (COVID-19) led to a global pandemic. Comorbidities such as hypertension, diabetes mellitus, elevated cholesterol, cardiac/pulmonary diseases, and obesity were postulated as prognostic factors for a worse outcome. Hypothesis: Obese COVID-19 patients have a worse prognosis. Methods: From March to June 2020, we obtained data on all patients ≥18 y.o. who were admitted with a positive COVID-19 test at the Rush System, Chicago. Multivariable logistic regression analysis was performed between predictors and a composite outcome of intubation and in-hospital mortality. Results: Among the 1345 admitted patients, 69 (5%) were underweight (BMI40kg/m2). In a multivariable model assessing the risk for the in-hospital death or intubation, underweight patients showed decreased risk (odds ratio (OR) 0.31) while obesity class III patients showed increased risk (OR 1.68, Figure 1) when compared to normal BMI. When accounting for obesity classes, male sex, atrial fibrillation and coronary artery disease were also independent predictors adverse outcomes. Conclusions: Consistent with previous research, morbidly obese patients had a higher risk for a worse outcome, even when accounting for numerous comorbidities. Underweight patients appeared to be protected. Higher body mass leads to inherent changes in lung function, increased risk of thrombosis, greater viral replication, higher release of adipokines and higher inflammation. Inversely, fewer adipocytes could possibly limit the risk for cytokine storm by reducing the amount of proinflammatory factors released. Figure: Odds ratios with 95% confidence intervals for the outcome of death or intubation in all COVID-19 positive admitted patients.

Background European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines inform cardiac workup before noncardiac surgery based on an algorithm. Our primary hypotheses were that there would be associations between (i) the groups stratified according to the algorithms and major adverse cardiac events (MACE), and (ii) over- and underuse of cardiac testing and MACE. Methods This is a secondary analysis of a multicentre prospective cohort. Major adverse cardiac events were a composite of cardiac death, myocardial infarction, acute heart failure, and life-threatening arrhythmia at 30 days. For each cardiac test, pathological findings were defined a priori. We used multivariable logistic regression to measure associations. Results We registered 359 MACE at 30 days amongst 6976 patients; classification in a higher-risk group using the ESC/ESA algorithm was associated with 30-day MACE; however, discrimination of the ESC/ESA algorithms for 30-day MACE was modest; area under the curve 0.64 (95% confidence interval: 0.61–0.67). After adjustment for sex, age, and ASA physical status, discrimination was 0.72 (0.70–0.75). Overuse or underuse of cardiac tests were not consistently associated with MACE. There was no independent association between test recommendation class and pathological findings (P=0.14 for stress imaging; P=0.35 for transthoracic echocardiography; P=0.52 for coronary angiography). Conclusions Discrimination for MACE using the ESC/ESA guidelines algorithms was limited. Overuse or underuse of cardiac tests was not consistently associated with cardiovascular events. The recommendation class of preoperative cardiac tests did not influence their yield. Clinical trial registration NCT02573532.

Aims The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE). Methods and results We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18–22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11–2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54–2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64–2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26–2.77) and MACE (HR 2.69, 95% CI 2.02–3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation. Conclusion Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE. Trial registration BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).

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.