High-sensitivity cardiac troponin T and copeptin assays to improve diagnostic accuracy of exercise stress test in patients with suspected coronary artery disease

Background: The average diagnostic sensitivity of exercise stress tests (ESTs) is lower than that of other non-invasive cardiac stress tests. The aim of the study was to examine whether high-sensitivity cardiac troponin T (hs-cTnT) or copeptin concentrations rise in response to inducible myocardial ischaemia and may improve the diagnostic accuracy of ESTs. Methods and results: An EST was performed stepwise on a bicycle ergometer by 383 consecutive patients with suspected or progression of coronary artery disease (CAD). In addition venous blood samples for measurement of hs-cTnT and copeptin were collected prior to EST, at peak exercise, and 4 h after EST. Coronary angiography was assessed for all patients. Patients with significant CAD (n=224) were more likely to be male and older compared to patients with non-significant CAD (n=169). Positive EST was documented in 125 (55.8%) patients with significant CAD and in 69 (43.4%) patients with non-significant CAD. Copeptin and hs-cTnT concentrations at baseline were higher in patients with significant CAD (copeptin: 10.8 pmol/l (interquartile range (IQR) 8.1–15.6) vs 9.4 pmol/l (IQR 7.1–13.9); p=0.04; hs-cTnT: 3.0 ng/l (IQR <3.0–5.4) vs <3.0 ng/l (IQR <3.0); p=0.006). Hs-cTnT improved sensitivity (61.6% vs 55.8%), specificity (67.7% vs 56.6%) and the positive predictive value (PPV) (72.3% vs 64.4%) and negative (55.2% vs 47.6%) predictive value (NPV) of EST. Copeptin could not improve sensitivity (55.4% vs 55.8%) and reduced specificity, PPV and NPV. Conclusions: The measurement of hs-cTnT during EST improves sensitivity, specificity, and positive and negative predictive values. In contrast, measurement of copeptin does not improve diagnostic sensitivity and reduces specificity

Kinetics of Olivine Weathering in Seawater: An Experimental Study

Enhanced weathering of mafic and ultra-mafic minerals has been suggested as a strategy for carbon dioxide removal (CDR) and a contribution to achieve a balance between global CO2 sources and sinks (net zero emission). This study was designed to assess CDR by dissolution of ultramafic sand (UMS) in artificial seawater (ASW). Fine grained UMS with an olivine content of ~75% was reacted in ASW for up to 134 days at 1 bar and 21.5–23.9°C. A decline in total alkalinity (TA) was observed over the course of the experiments. This unexpected result indicates that TA removal via precipitation of cation-rich authigenic phases exceeded the production of TA induced by olivine dissolution. The TA decline was accompanied by a decrease in dissolved inorganic carbon and Ca concentrations presumably induced by CaCO3 precipitation. Temporal changes in dissolved Si, Ca, Mg, and TA concentrations observed during the experiments were evaluated by a numerical model to identify secondary mineral phases and quantify rates of authigenic phase formation. The modeling indicates that CaCO3, FeOOH and a range of Mg-Si-phases were precipitated during the experiments. Chemical analysis of precipitates and reacted UMS surfaces confirmed that these authigenic phases accumulated in the batch reactors. Nickel released during olivine dissolution, a potential toxic element for certain organisms, was incorporated in the secondary phases and is thus not a suitable proxy for dissolution rates as proposed by earlier studies. The overall reaction stoichiometry derived from lab experiments was applied in a box model simulating atmospheric CO2 uptake in a continental shelf setting induced by olivine addition. The model results indicate that CO2 uptake is reduced by a factor of 5 due to secondary mineral formation and the buffering capacity of seawater. In comparable natural settings, olivine addition may thus be a less efficient CDR method than previously believed

RV SONNE 241 Cruise Report / Fahrtbericht, Manzanillo, 23.6.2015 – Guayaquil, 24.7.2015 : SO241 - MAKS: Magmatism induced carbon escape from marine sediments as a climate driver – Guaymas Basin, Gulf of California

SO241 set out to test the hypothesis that rift-related magmatism is able to increase carbon emissions from sedimentary basins to the extent that they can actively force climate. To this end we investigated a study area in the Guaymas Basin in the Gulf of California which is one of very few geological settings where rift-related magmatism presently leads to magmatic intrusions into a sediment basin. During the cruise we collected 1100 km of 2D seismic lines to image the extent and volume of magmatic intrusions as well as the extent of metamorphic overprinting of the surrounding sediments and associated subsurface sediment mobilization. We selected three typical seep sites above magmatic intrusions for detailed geochemical studies using gravity corers, multicorers and TV grab. With these samples we will be able to determine the pore water composition to assess the amount and composition of hydrocarbon compounds that are released from these systems. Detailed ocean bottom seismometer measurements at a seep site in the center of the Guaymas Basin will provide further insights into effects of magmatic intrusions on carbon release and diagenetic overprinting of the sediments. It will be possible to reconstruct its long-term seepage history from big carbonate blocks that we have collected with a TV-grab. The northeastern margin of the Guaymas Basin is known for the presence of gas hydrates. During the cruise we collected several seismic lines, which show a clear but unusually shallow BSR indicating high heat flow in the region. Using the seismic data we discovered a previously unknown geological structure on the flank of the northern rift segment: a large mound that seems to consist entirely of black smoker deposits. It seems to be the result of a recent intrusion into the underlying sediments and changes the view how such systems function. The structure was investigated with a comprehensive geochemical, geothermal, and video surveying program which revealed at least seven vents that are active simultaneously. These vents inject methane and helium-rich vent fluids several hundred meters up into the water column. These findings suggest that large-scale magmatism, for example during the opening of an ocean basin under the influence of a hot spot, can be an effective way of liberating large amounts of carbon high up into the water column. The data collected during SO241 will allow us to constrain the amount of carbon that can escape into the atmosphere during LIP emplacement and their relevance on a global scale can be assessed. In addition to reaching the main objectives of the project we discovered a large landslide complex that was probably associated with a tsunami

Incremental value of high-sensitive troponin T in addition to the revised cardiac index for peri-operative risk stratification in non-cardiac surgery

Aims We aimed to evaluate the incremental value of high-sensitive troponin T (hsTnT) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index. Methods and results In this prospective, international multicentre observational study, 979 patients prior to non-cardiac surgery were enrolled. The endpoints were in-hospital mortality, the combination of death, acute myocardial infarction, cardiac arrest, cardio-pulmonary resuscitation, and acute decompensated heart failure. Twenty-five patients (2.6%) deceased and 36 (3.7%) of the patients experienced the combined endpoint. Cardiac markers were elevated in those patients who died when compared with survivors (hsTnT: 21 ng/L vs. 7 ng/L; P < 0.001; NT-proBNP: 576 pg/mL vs. 166 pg/mL; P < 0.001). Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL, those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2% (P < 0.001) and with elevated NT-proBNP 4.8 vs. 1.4% (P = 0.002). The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809. In a multivariate Cox regression analyses, hsTnT was the strongest independent predictor for the combined endpoint [HR 2.6 (95% CI: 1.3-5.3); P = 0.01]. Conclusion High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac inde

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30-7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32-7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38-7.97%) in the standard group, and 3.01% (95% CI 1.51-5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagate

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims: This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results: A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30–7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32–7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38–7.97%) in the standard group, and 3.01% (95% CI 1.51–5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion: After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagated

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

Rifting under steam – how rift magmatism triggers methane venting from sedimentary basins

During opening of a new ocean magma intrudes into the surrounding sedimentary basins. Heat provided by the intrusions matures the host rock creating metamorphic aureoles potentially releasing large amounts of hydrocarbons. These hydrocarbons may migrate to the seafloor in hydrothermal vent complexes in sufficient volumes to trigger global warming, e.g. during the Paleocene Eocene Thermal Maximum (PETM). Mound structures at the top of buried hydrothermal vent complexes observed in seismic data off Norway were previously interpreted as mud volcanoes and the amount of released hydrocarbon was estimated based on this interpretation. Here, we present new geophysical and geochemical data from the Gulf of California suggesting that such mound structures could in fact be edifices constructed by the growth of black-smoker type chimneys rather than mud volcanoes. We have evidence for two buried and one active hydrothermal vent system outside the rift axis. The vent releases several hundred degrees Celsius hot fluids containing abundant methane, mid-ocean-ridge-basalt (MORB)-type helium, and precipitating solids up to 300 m high into the water column. Our observations challenge the idea that methane is emitted slowly from rift-related vents. The association of large amounts of methane with hydrothermal fluids that enter the water column at high pressure and temperature provides an efficient mechanism to transport hydrocarbons into the water column and atmosphere, lending support to the hypothesis that rapid climate change such as during the PETM can be triggered by magmatic intrusions into organic-rich sedimentary basins

Evaluation of optimal medical therapy in acute myocardial infarction patients with prior stroke

Background: Treatment of acute myocardial infarction (AMI) patients with prior stroke is a common clinical dilemma. Currently, the application of optimal medical therapy (OMT) and its impact on clinical outcomes are not clear in this patient population. Methods: We retrieved 765 AMI patients with prior stroke who underwent percutaneous coronary intervention (PCI) during the index hospitalization from the international multicenter BleeMACS registry. All of the subjects were divided into two groups based on the prescription they were given prior to discharge. Baseline characteristics and procedural variables were compared between the OMT and non-OMT groups. Mortality, re-AMI, major adverse cardiovascular events (MACE), and bleeding were followed-up for 1 year. Results: Approximately 5% of all patients presenting with AMI were admitted to the hospital for ischemic stroke. Although the prescription rate of each OMT medication was reasonably high (73.3%-97.3%), 47.7% lacked at least one OMT medication. Patients receiving OMT showed a significantly decreased occurrence of mortality (4.5% vs 15.1%, p < 0.001), re-AMI (4.2% vs 9.3%, p = 0.004), and the composite endpoint of death/re-AMI (8.6% vs 20.5%, p < 0.001) compared to those without OMT. No significant difference was observed between the groups regarding bleeding. After adjusting for confounding factors, OMT was the independent protective factor of 1-year mortality, while age was the independent risk factors. Conclusions: OMT at discharge was associated with a significantly lower 1-year mortality of patients with AMI and prior stroke in clinical practice. However, OMT was provided to just half of the eligible patients, leaving room for substantial improvement