Multicentre cross-sectional observational registry to monitor the safety of early discharge after rule-out of acute myocardial infarction by copeptin and troponin: the Pro-Core registry

Objectives: There is sparse information on the safety of early primary discharge from the emergency department (ED) after rule-out of myocardial infarction in suspected acute coronary syndrome (ACS). This prospective registry aimed to confirm randomised study results in patients at low-to-intermediate risk, with a broader spectrum of symptoms, across different institutional standards and with a range of local troponin assays including high-sensitivity cTn (hs-cTn), cardiac troponin (cTn) and point-of-care troponin (POC Tn). Design Prospective, multicentre European registry. Setting 18 emergency departments in nine European countries (Germany, Austria, Switzerland, France, Spain, UK, Turkey, Lithuania and Hungary) Participants: The final study cohort consisted of 2294 patients (57.2% males, median age 57 years) with suspected ACS. Interventions: Using the new dual markers strategy, 1477 patients were eligible for direct discharge, which was realised in 974 (42.5%) of patients. Main outcome measures: The primary endpoint was allcause mortality at 30 days. Results: Compared with conventional workup after dual marker measurement, the median length of ED stay was 60 min shorter (228 min, 95% CI: 219 to 239 min vs 288 min, 95% CI: 279 to 300 min) in the primary dual marker strategy (DMS) discharge group. All-cause mortality was 0.1% (95% CI: 0% to 0.6%) in the primary DMS discharge group versus 1.1% (95% CI: 0.6% to 1.8%) in the conventional workup group after dual marker measurement. Conventional workup instead of discharge despite negative DMS biomarkers was observed in 503 patients (21.9%) and associated with higher prevalence of ACS (17.1% vs 0.9%, p<0.001), cardiac diagnoses (55.2% vs 23.5%, p<0.001) and risk factors (p<0.01), but with a similar all-cause mortality of 0.2% (95% CI: 0% to 1.1%) versus primary DMS discharge (p=0.64). Conclusions Copeptin on top of cardiac troponin supports safe discharge in patients with chest pain or other symptoms suggestive of ACS under routine conditions with the use of a broad spectrum of local standard POC, conventional and high-sensitivity troponin assays. Trial registration number NCT02490969

Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes

Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture.; The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score.; This was a single-center cohort study, consecutively recruiting patients with adjudicated NSTE-ACS (n = 1,112) from the emergency department of an academic hospital. CTSS was measured in serum using enzyme-linked immunosorbent assay. All-cause mortality at 8 years was the primary endpoint. CV death was the secondary endpoint.; In total, 367 (33.0%) deaths were recorded. CTSS was associated with increased risk of all-cause mortality (HR for highest vs lowest quarter of CTSS: 1.89; 95% CI: 1.34-2.66; P < 0.001) and CV death (HR: 2.58; 95% CI: 1.15-5.77; P = 0.021) after adjusting for traditional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization and index diagnosis (unstable angina/ non-ST-segment elevation myocardial infarction). When CTSS was added to the GRACE score, it conferred significant discrimination and reclassification value for all-cause mortality (Delta Harrell's C: 0.03; 95% CI: 0.012-0.047; P = 0.001; and net reclassification improvement = 0.202; P = 0.003) and CV death (AUC: 0.056; 95% CI: 0.017-0.095; P = 0.005; and net reclassification improvement = 0.390; P = 0.001) even after additionally considering high-sensitivity troponin-T and left ventricular ejection fraction.; Circulating CTSS is a predictor of long-term mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score

Age- and gender-related reference values of cardiac morphology and function in cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) is the reference standard for the quantitative assessment of cardiac morphology and function. The aim of the study was to determine age- and gender-related reference values for cardiac morphology and function according to current recommendations. 454 healthy volunteers (235 men, median age 52.0 (44.0-59.0) years) underwent a standard CMR scan and were divided into six groups of nearly equal size with regard to sex (male, female) and age (21-47 years, 48-57 years, 58-84 years). Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were measured at end-diastole and end-systole in steady-state free precession series with including papillary muscles and trabecular tissue in the LV-M. Absolute and indexed volumetric parameters were significantly different between gender groups with higher values in men compared to women (all p &amp;lt; 0.001). Furthermore, a significant age-dependent decline could be observed for left ventricular and right ventricular volumes (all p &amp;lt; 0.001), while LV-M did not show differences between the different age-groups. Parameters of longitudinal function for the left and right ventricle were higher in female compared to male subjects with a significant age-dependent decline. We provided normal values for cardiac volumes, function, and mass derived in accordance with current guidelines from a large population of healthy subjects, which can be implemented in clinical routine as a standard of reference

Real‐World Evidence on Disparities on the Initiation of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome

Background Management of patients with non–ST‐segment–elevation acute coronary syndrome (NSTE‐ACS) is based on 2020 European Society of Cardiology guidelines, which recommend the preferential use of prasugrel over ticagrelor. Because the selection of the respective P2Y12 inhibitor has to consider label restrictions, we sought to evaluate the proportion of patients qualifying for either ticagrelor or prasugrel and reasons for noneligibility in an unselected cohort of patients with acute coronary syndrome. Methods and Results In this retrospective observational study, patients with ST‐segment–elevation myocardial infarction (STEMI) or NSTE‐ACS presenting consecutively during a 24‐month period were enrolled. The eligibility of patients for a dual antiplatelet therapy option was assessed retrospectively. A total of 1502 patients had confirmed acute coronary syndrome (287 STEMI and 1215 NSTE‐ACS). Eligibility for ticagrelor and full‐dose prasugrel differed significantly for STEMI and NSTE‐ACS (93% versus 51%, P<0.0001 versus 80% versus 31%, P<0.0001). Eligibility remained significantly lower (STEMI 78% versus NSTE‐ACS 52%) if low‐dose prasugrel was considered. Patients eligible for full‐dose prasugrel had lower ischemic risk per GRACE (Global Registry of Acute Coronary Events) score (109 points [90–129 points] versus 121 points [98–146 points], P<0.0001) and lower bleeding risk (14 points [13–15 points] versus 20 points [12–29 points], P<0.0001) per PRECISE‐DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score. Conclusions In real life, eligibility for prasugrel in patients requiring dual antiplatelet therapy is considerably lower than for ticagrelor, even in a cohort with high rates of coronary angiography and percutaneous coronary interventions. The recommended use of prasugrel over ticagrelor in current acute coronary syndrome guidelines contrasts with our observations of a substantial disparity on the eligibility. This important aspect has not received appropriate attention yet. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05774431

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study

Aims: We aimed to assess the prognostic role of copeptin in patients presenting to the emergency department with acute symptoms and increased high-sensitivity cardiac troponin T. Methods: A total of 3890 patients presenting with acute symptoms to the emergency department of Heidelberg University Hospital were assessed for increased hs-cTnT (&gt;14 ng/L) from three cohorts: the Heidelberg Acute Coronary Syndrome (ACS) Registry (n = 2477), the BIOPS Registry (n = 320), and the ACS OMICS Registry (n = 1093). In a pooled analysis, 1956 patients remained, comprising of 1600 patients with ACS and 356 patients with non-ACS. Results: Median follow-up was 1468 days in the ACS cohort and 709 days in the non-ACS cohort. Elevated copeptin levels (&gt;10 pmol/L) were found in 1174 patients (60.0%) in the entire cohort (58.1% in ACS and 68.5% in non-ACS, respectively) and mortality rates were significantly higher than in patients with normal copeptin levels (29.0% vs. 10.7%, p &lt; 0.001). In a multivariate Cox regression, elevated copeptin was independently associated with all-cause death in the ACS (HR = 1.7, 1.3&ndash;2.3, p = 0.002) and non-ACS cohort (HR = 2.7, 1.4&ndash;5.0, p = 0.0018). Conclusion: Copeptin may aid in identifying patients at risk for adverse outcomes in patients with increased levels of hs-cTnT in ACS patients and in non-ACS conditions

High-sensitivity cardiac troponin T as an independent predictor of stroke in patients admitted to an emergency department with atrial fibrillation.

AimsElevated levels of high-sensitivity cardiac troponin T (hsTnT) are associated with adverse outcomes in numerous patient populations. Their value in prediction of stroke risk in patients with atrial fibrillation (AF) is in debate.MethodsThe study population included 2898 consecutive patients presenting with AF to the emergency department of the Department of Cardiology, Heidelberg University Hospital. Associations between hsTnT and stroke risk were assessed using multivariable Cox regression.ResultsElevated hsTnT levels (>14 ng/L) were associated with increased risk of stroke. Even after adjustment for various risk factors, elevated hsTnT remained independently associated with stroke risk in patients with AF, adjusted hazard ratio 2.35 [95% confidence interval (CI): 1.26-4.36] (P = 0.007). These results were consistent across important subgroups (age, renal function, ejection fraction, CHA2DS2-VASc score and main admission diagnosis). For hsTnT, area under the receiver-operating-characteristic curve (AUC) was 0.659 [95% CI: 0.575-0.742], compared to 0.610 [95% CI: 0.526-0.694] for the CHA2DS2-VASc score. Inclusion of hsTnT in the multivariable model for stroke risk prediction consisting of all variables of the CHA2DS2-VASc score was associated with a significant improvement of its discriminatory power.ConclusionElevated hsTnT levels are significantly associated with higher risk of stroke and provide prognostic information independent of CHA2DS2-VASc score variables. Measurement of hsTnT may improve prediction of stroke risk in patients presenting to an emergency department with AF as compared to risk stratification based only on clinical variables

Prognostic value of changes in high-sensitivity cardiac troponin T beyond biological variation in stable outpatients with cardiovascular disease: a validation study

Objective!#!To evaluate the prognostic implications of longitudinal long-term changes beyond the biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in outpatients with stable or asymptomatic cardiovascular disease (CV) and to assess possible differences in the prognostic value while using reference change value (RCV) and minimal important differences (MID) as metric for biological variation.!##!Methods!#!Hs-cTnT was measured at index visit and after 12 months in outpatients presenting for routine follow-up. The prognostic relevance of a concentration change of hs-cTnT values exceeding the biological variation defined by RCV and MID of a healthy population within the next 12 months following the stable initial period was determined regarding three endpoints: all-cause mortality (EP1), a composite of all-cause mortality, non-fatal myocardial infarction and stroke (EP2), and a composite of all-cause mortality, non-fatal myocardial infarction, stroke, hospitalization for acute coronary syndrome (ACS) or decompensated heart failure, and planned and unplanned percutaneous coronary interventions (PCI, EP3).!##!Results!#!Change in hs-cTnT values exceeding the biovariability defined by MID but not by RCV discriminated a group with a higher cardiovascular risk profile. Changes within MID were associated with uneventful course (NPV 91.6-99.7%) while changes exceeding MID were associated with a higher occurrence of all endpoints within the next 365 days indicating a 5.5-fold increased risk for EP 1 (p = 0.041) a 2.4-fold increased risk for EP 2 (p = 0.049) and a 1.9-fold increased risk for EP 3 (p &amp;lt; 0.0001).!##!Conclusions!#!In stable outpatients MID calculated from hs-cTnT changes measured 365 ± 120 days apart are helpful to predict an uneventful clinical course.!##!Clinical trials identifier!#!NCT01954303

Validation of two severity scores as predictors for outcome in Coronavirus Disease 2019 (COVID-19).

BackgroundAn established objective and standardized reporting of clinical severity and disease progression in COVID-19 is still not established. We validated and compared the usefulness of two classification systems reported earlier-a severity grading proposed by Siddiqi and a system from the National Australian COVID-19 guideline. Both had not been validated externally and were now tested for their ability to predict complications.MethodsIn this retrospective, single-centre observational study, patients hospitalized with confirmed COVID-19 across all severity stages were enrolled. The clinical severity was graded at admission and during hospitalization. Multivariate Cox regression was used to identify independent risk factors for mortality, a composite primary (mortality, incident acute respiratory distress syndrome, incident mechanical ventilation), a secondary endpoint (mortality, incident acute myocardial injury, incident venous thrombosis, pulmonary embolism or stroke) and progression of severity grades.ResultsOf 109 patients 17 died, 31 and 48 developed the primary and secondary endpoint, respectively. Worsening of the severity grade by at least one stage occurred in 27 and 28 patients, respectively. Siddiqi and Australian classification were identified as independent predictors for the primary endpoint (adjusted hazard ratio (aHR) 2.30, pConclusionsStandardized and objective severity grading is useful to unequivocally stratify patients presenting with COVID-19 for their individual risk of complications

Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study.

OBJECTIVES: To evaluate the impact of age- and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI). METHODS: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14ng/L to previously proposed age- and gender-dependent hs-cTnT 99th percentile cut-offs (28ng/L for ≥65years, 9ng/L for female and 15.5ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS. RESULTS: For patients ≥65years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n=557) and 54.7% to 40.9% in the ACS subcohort (n=225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n=477) and 62.6% to 71.7% (ACS subcohort, n=99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n=805) and 48.8% to 45.9% (ACS, n=281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p<0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs. CONCLUSIONS: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation