Is high sensitivity troponin, taken regardless of a clinical indication, associated with 1 year mortality in critical care patients?

The aim of this study was to assess whether high sensitivity troponin (hs-cTnI) is associated with 1 year mortality in critical care (CC). One year mortality data were obtained from NHS Digital for a consecutive cohort of patients admitted to general CC unit (GCCU) and neuroscience CC unit (NCCU) who had hs-cTnI tests performed throughout their CC admission, regardless of whether the test was clinically indicated. Cox proportional hazards were used to estimate the risk of 1-year mortality. A landmark analysis was undertaken to assess whether any relationship at 1 year was driven by mortality within the first 30 days. A total of 1033 consecutive patients were included. At 1 year 254 (24.6%) patients had died. The admission log(10)hs-cTnI concentration in the entire cohort (HR 1.35 (95% CI 1.05-1.75) p = 0.009 with a bootstrap of 1000 samples) was independently associated with 1 year mortality. On landmark analysis the association with 1 year mortality was driven by 30 day mortality. These results indicate that admission hs-cTnI concentration is independently associated with 1 year mortality in CC and this relationship may be driven by differences in mortality at 30 days.

Rationale and study protocol for the BRITISH randomized trial (Using cardiovascular magnetic resonance identified scar as the benchmark risk indication tool for implantable cardioverter defibrillators in patients with nonischemic cardiomyopathy and severe systolic heart failure).

BACKGROUND: For patients with nonischemic cardiomyopathy (NICM), current guidelines recommend implantable cardioverter defibrillators (ICD) when left ventricular ejection fraction (LVEF) is ≤35%, but the DANISH trial failed to confirm that ICDs reduced all-cause mortality for such patients. Circumstantial evidence suggests that scar on CMR is predictive of sudden and arrhythmic death in this population. The presence of myocardial scar identified by cardiac magnetic resonance imaging (CMR) in patients with NICM and an LVEF ≤35% might identify patients at higher risk of sudden arrhythmic death, for whom an ICD is more likely to reduce all-cause mortality. METHODS/DESIGN: The BRITISH trial is a prospective, multicenter, randomized controlled trial aiming to enrol 1,252 patients with NICM and an LVEF ≤35%. Patients with a nonischemic scar on CMR will be randomized to either: (1) ICD, with or without cardiac resynchronization (CRT-D), or (2) implantable loop recorder (ILR) or cardiac resynchronization (CRT-P). Patients who are screened for the trial but are found not to be eligible, predominantly due to an absence of scar or those who decline to be randomized will be enrolled in an observational registry. The primary endpoint is all-cause mortality, which we plan to assess at 3 years after the last participant is randomized. Secondary endpoints include clinical outcomes, appropriate and inappropriate device therapies, symptom severity and well-being, device-related complications, and analysis of the primary endpoint by subgroups with other risk markers. CONCLUSION: The BRITISH trial will assess whether the use of CMR-defined scar to direct ICD implantation in patients with NICM and an LVEF ≤35% is associated with a reduction in mortality.

Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

Systematic coronary physiology improves level of agreement in diagnostic coronary angiography.

OBJECTIVE: The training of interventional cardiologists (ICs), non-interventional cardiologists (NICs) and cardiac surgeons (CSs) differs, and this may be reflected in their interpretation of invasive coronary angiography (ICA) and management plan. Availability of systematic coronary physiology might result in more homogeneous interpretation and management strategy compared with ICA alone. METHODS: 150 coronary angiograms from patients with stable chest pain were presented independently to three NICs, three ICs and three CSs. By consensus, each group graded (1) coronary disease severity and (2) management plan, using options: (a) optimal medical therapy alone, (b) percutaneous coronary intervention, (c) coronary artery bypass graft or (d) more investigation required. Each group was then provided with fractional flow reserve (FFR) from all major vessels and asked to repeat the analysis. RESULTS: There was only 'fair' level of agreement of management plan among ICs, NICs and CSs (kappa 0.351, 95% CI 0.295-0.408, p<0.001) based on ICA alone (complete agreement in 35% of cases), which almost doubled to 'good' level (kappa 0.635, 95% CI 0.572-0.697, p<0.001) when comprehensive FFR was available (complete agreement in 66% of cases). Overall, the consensus management plan changed in 36.7%, 52% and 37.3% of cases for ICs, NICs and CSs, respectively, when FFR data were available. CONCLUSIONS: Compared with ICA alone, the availability of systematic FFR of all major coronary arteries produced a significantly more concordant interpretation and more homogeneous management plan among IC, NIC and CS specialists. Comprehensive physiological assessment may be of value in routine care for Heart Team decision-making. TRIAL REGISTRATION NUMBER: NCT01070771.

Randomized comparison of chest pain evaluation with FFRCT or standard care: Factors determining US costs.

BACKGROUND: FFRCT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs. METHODS: Patients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFRCT), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs. RESULTS: Planned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI -12% to +26%, p â€‹= â€‹0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction â€‹= â€‹0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%). CONCLUSIONS: Initial evaluation of chest pain using CTCA with FFRCT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests. Registration at ClinicalTrials.gov (NCT03187639).

Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial.

BACKGROUND: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. METHODS: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. RESULTS: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64). CONCLUSIONS: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01070771.

Incidence and 1-year outcome of periprocedural myocardial infarction following cardiac surgery: are the Universal Definition and Society for Cardiovascular Angiography and Intervention criteria fit for purpose?

OBJECTIVES: The diagnosis and clinical implications of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) are contentious, especially the importance of PPMI in the interpretation of trial data. METHODS: Consecutive patients admitted to a cardiothoracic critical care unit over a 6-month period following open cardiac surgery had high-sensitivity cardiac troponin I assay performed on admission and every day for 48 h, regardless of whether there was a request by the supervising clinical team. Patients were categorized as PPMI using both the Universal Definition of Myocardial Infarction (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Multivariable Cox regression analysis was performed to assess whether any relationships between PPMI diagnoses and 1-year mortality were independent. RESULTS: There were 2 groups of consecutive patients: (i) after CABG (n = 245) and (ii) after non-CABG surgery (n = 243). Of the CABG patients, 20.4% met criteria for UDMI PPMI and 87.6% for SCAI PPMI. The diagnosis of UDMI PPMI was independently associated with 1-year mortality on multivariable Cox regression analysis [hazard ratio 4.16 (95% confidence interval 1.28-13.49)]. Of 243 patients who had non-CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI but neither were associated with 1-year mortality. CONCLUSIONS: The incidence of SCAI PPMI in a real-world cohort of cardiac surgery patients is so high as to be of limited clinical value. In contrast, a diagnosis of UDMI PPMI post-CABG is independently associated with 1-year mortality, so may have clinical (and research) utility.

Relation of High-Sensitivity Troponin to 1 Year Mortality in 20,000 Consecutive Hospital Patients Undergoing a Blood Test for Any Reason.

This was an observational study of the 1-year outcomes of the 20,000 patients included in the original CHARIOT study. The aim of the study was to assess the association between high sensitivity troponin I (hs-cTnI) concentration and 1 year mortality in this cohort. The original CHARIOT study included a consecutive cohort of in- and out-patients undergoing blood tests for any reason. Hs-cTnI concentrations were measured regardless of whether the clinician requested them. These results were nested and not revealed to the team unless requested for clinical reasons. One year mortality data was obtained from NHS Digital as originally planned. Overall, 1782 (8.9%) patients had died at 1 year. Multivariable Cox regression analysis showed that a hs-cTnI concentration above the upper limit of normal was independently associated with the hazard of mortality (HR 2.23; 95% confidence intervals 1.97 to 2.52). Furthermore, the log (10) hs-cTnI concentration was independently associated with the hazard of 1 year mortality (HR 1.77; 95% confidence intervals 1.64 to 1.91). In conclusion, in a large, unselected hospital population of both in- and out-patients, in 18,282 (91.4%) of whom there was no clinical indication for testing, hs-cTnI concentration was associated with 1 year mortality.

Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial.

AIMS: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care. METHODS AND RESULTS: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). CONCLUSION: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.

Distribution of High-Sensitivity Troponin Taken Without Conventional Clinical Indications in Critical Care Patients and Its Association With Mortality.

OBJECTIVES: To describe the distribution of high-sensitivity troponin in a consecutive cohort of patients in critical care units, regardless of clinical indication, and its association with clinical outcomes. DESIGN: Prospective observational study. SETTING: Single-center teaching hospital. PATIENTS: Consecutive patients admitted to two adult critical care units (general critical care unit and neuroscience critical care unit) over a 6-month period. INTERVENTIONS: All patients had high-sensitivity troponin tests performed at admission and tracked throughout their critical care stay, regardless of whether the supervising team felt there was a clinical indication. The results were not revealed to patients or clinicians unless clinically requested. MEASUREMENTS AND MAIN RESULTS: There were 1,033 patients in the study cohort (general critical care unit 750 and neuroscience critical care unit 283). The median high-sensitivity troponin was 21 ng/L (interquartile range, 7-86 ng/L), with 560 patients (54.2%) above the upper limit of normal as defined by the manufacturer. Admission high-sensitivity troponin concentrations above the upper limit of normal in general critical care unit and neuroscience critical care unit were associated with increasing age, comorbidity, markers of illness severity, and the need for organ support. On adjusted analysis, the high-sensitivity troponin concentration remained an independent predictor of critical care mortality in general critical care unit and neuroscience critical care unit. CONCLUSIONS: High-sensitivity troponin elevation, taken outside the context of conventional clinical indications, was common in the critically ill. Such elevations were associated with increasing age, comorbidity, illness severity, and the need for organ support. Admission high-sensitivity troponin concentration is an independent predictor of critical care mortality and as such may represent a novel prognostic biomarker at admission.

Distribution of contemporary sensitivity troponin in the emergency department and relationship to 30-day mortality: The CHARIOT-ED substudy.

BACKGROUND: Contemporary sensitivity troponin (cs-cTn) concentrations above the upper limit of normal (ULN) are seen in a wide range of clinical conditions and evidence is growing that suggests cs-cTn may be a biomarker of future morbidity and mortality. OBJECTIVES: Our aim was to test the hypothesis that cs-cTn, measured in the emergency department, may be a biomarker for 30-day mortality, irrespective of the patient's presentation. METHOD: In all 5,708 consecutive cases, contemporary sensitivity troponin I (cs-cTnI) was measured either as requested by the clinical team or as part of the study, in which case both the clinical team and the patient were unaware of the result. Basic demographics were available from the original study and 30-day mortality was derived from NHS Digital data. RESULTS: In patients whose cs-cTnI test was requested solely as part of the study, 30-day mortality increased with increasing cs-cTnI concentrations (0% with undetectable concentrations to 14.7% with concentrations above the ULN). Multivariable Cox regression analysis showed that log(10)cs-cTnI concentration was independently associated with 30-day mortality. CONCLUSION: Increasing cs-cTnI concentrations are associated with higher short-term mortality as well as length of stay. As such, cs-cTnI measurements may provide useful prognostic information.

Fractional Flow Reserve Derived from Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain: Rationale and Design of the FORECAST Trial.

BACKGROUND: Fractional flow reserve measurement based on computed tomography (FFRCT) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFRCT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFRCT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial. METHODS: The FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFRCT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment. CONCLUSION: The FORECAST randomized trial will assess the clinical and economic outcomes of using FFRCT as the primary test to evaluate patients presenting with stable chest pain.

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study.

OBJECTIVE: To determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital. DESIGN: Prospective, observational cohort study. SETTING: University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017. PARTICIPANTS: 20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons. MAIN OUTCOME MEASURES: Distribution of hs-cTnI concentrations of all study participants and specifically the 99th centile. RESULTS: The 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer's quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN. CONCLUSIONS: Of 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03047785.

Changes in platelet function with inflammation in patients undergoing vascular surgery.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesized, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured pre-procedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2, 12-HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as compared to baseline). Patients had negligible levels of TXB2 throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5 days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

A randomised controlled trial to compare two coronary pressure wires using simultaneous measurements in human coronary arteries: the COMET trial.

AIMS: We aimed to examine the relative performance of the new COMET wire from Boston Scientific (BS), and the established technology from St. Jude/Abbott Vascular (SJ). METHODS AND RESULTS: We compared simultaneous readings from pairs of wires. Patients were randomised to one of three groups: BS/BS, SJ/SJ, or SJ/BS. The last group was sub-randomised to specify the type of wire that would be passed first. After pressure equalisation at the guide catheter, we recorded paired observations in sequence: (a) distal to proximal pressure ratio at baseline, (b) FFR at maximum hyperaemia, and (c) pressure on withdrawal into the guide catheter to quantify "drift". We randomised 106 patients, yielding 288 sets of paired recordings (BS/BS=90; SJ/SJ=90; SJ/BS=108). Drift was recorded from 208 vessels (BS=105; SJ=103). All wires were successfully advanced to their desired positions in the coronary vasculature. The mean (±SD) differences for the randomised pairs were similar: BS/BS=0.0016 (0.023); SJ/SJ=0.002 (0.03); SJ/BS=0.0013 (0.028). The primary outcome tested the hypothesis that the absolute magnitude of the difference (irrespective of sign) observed in the SJ/BS pairing would be similar to that in the SJ/SJ group. The median (IQR) values were SJ/BS=0.015 (0.01-0.03); SJ/SJ=0.01 (0.00-0.03); p=0.61. The drift, expressed as the median (IQR) difference in Pd/Pa from 1.0 (irrespective of sign), was similar: BS=0.02 (0.01-0.05); SJ=0.02 (0.01-0.04); p=0.14. CONCLUSIONS: We found no significant difference between these wires in terms of safety and performance.

Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s.

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s. METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s. RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2  = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier. CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

Design and Rationale of the RIPCORD 2 Trial (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?): A Randomized Controlled Trial to Compare Routine Pressure Wire Assessment With Conventional Angiography in the Management of Patients With Coronary Artery Disease.

BACKGROUND: Investigation of anginal chest pain has traditionally involved either assessment of the coronary anatomy by angiography or noninvasive testing for reversible ischemia. Invasive pressure wire assessment at the time of angiography offers information on both anatomy and physiology. Fractional flow reserve-guided percutaneous coronary intervention is associated with lower resource utilization and improved clinical outcome compared with angiographic guidance alone. However, the value of routine fractional flow reserve of all major coronary vessels at the time of diagnostic angiography has not been established in a randomized trial despite persuasive observational data. A change in practice to routine fractional flow reserve assessment of all major vessels during diagnostic angiography would require evidence not just of clinical benefit but also of cost effectiveness. This randomized trial aims to test that strategy. METHODS AND RESULTS: RIPCORD 2 (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?) is an 1100 patient prospective, multicenter, randomized trial. Participants are randomized, after initial coronary angiography, and in equal proportion, to assessment and management according to (1) conventional angiography only or (2) additional routine pressure wire assessment in all epicardial vessels of sufficient size to be amenable to revascularization. The primary economic outcome measure will be a comparison of healthcare costs at 1 year. The primary quality-of-life outcome measure analysis will compare patient-reported quality-of-life scores at 1 year. Secondary outcome measures include clinical events at 1 year, management strategy (optimal medical therapy with or without revascularization), and angina status at 1 year according to Canadian Cardiovascular Society angina grade. CONCLUSIONS: The aim of the RIPCORD 2 trial is to assess whether a strategy of routine fractional flow reserve-guided assessment and management of all major coronary arteries will be associated with more effective resource utilization, improved quality of life, and better clinical outcome, compared with angiographic guidance alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02892903.

High sensitivity troponin in the management of tachyarrhythmias.

BACKGROUND: The introduction of the highly sensitive troponin (hs-trop) assays into clinical practice has allowed for the more rapid diagnosis or exclusion of type 1 myocardial infarctions (T1MI) by clinicians, in addition type 2 myocardial infarctions (T2MI) are now more frequently detected. Tachyarrhythmias are one of the common causes of T2MI, the medium and long term outcome for this cohort of T2MI is yet to be clarified. METHODS: Retrospective review of consecutive patients admitted with a diagnosis of either (a) non ST-elevation myocardial infarction (NSTEMI) or (b) tachyarrhythmia was performed. Data were collected on patient demographics and investigations. Patient mortality status was recorded through the Personal Demographics Service (PDS) via NHS Digital. RESULTS: A total of 704 patients were eligible for inclusion to the study. 264 patients were included in the study with a final discharge diagnosis of NSTEMI and 440 patients with a final discharge diagnosis of tachyarrhythmia. There was a significantly higher peak troponin in NSTEMI patients compared to the tachyarrhythmia troponin positive group (4552ng/L vs 571ng/L, p<0.001). Mortality was significantly higher in the troponin positive tachyarrhythmia patients than the troponin negative patients (54 vs 34, 26.2% vs 14.5%, log rank p=0.003), furthermore, the mortality of NSTEMI and troponin positive tachyarrhythmia patients was similar (55 vs 54, 20.8% vs 26.2%, log rank p=0.416). Only one patient (0.14%) was given a formal diagnosis of T2MI. CONCLUSIONS: These data suggest that troponin positive tachyarrhythmia is not a benign diagnosis, and has a mortality rate similar to NSTEMI. Formal labeling as T2MI is rare in real life practice. More investigation into the detection and management of T2MI and troponin positive arrhythmia patients is now warranted.

Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain?: the RIPCORD study.

BACKGROUND: The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined. METHODS AND RESULTS: Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA. CONCLUSIONS: Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.

Detection of regional myocardial ischaemia by a novel 80-electrode body surface Delta map in patients presenting to the emergency department with cardiac-sounding chest pain.

BACKGROUND: Presentation with acute chest pain is common, but the conventional 12-lead ECG has limitations in the detection of regional myocardial ischaemia. The previously described method of the body surface mapping system (BSM) Delta map, derived from an 80-electrode BSM, as well as a novel parameter total ischaemic burden (IB), may offer improved diagnostic sensitivity and specificity in patients with myocardial ischaemia. METHODS: The feasibility of using the novel BSM Delta map technique, and IB, for transient regional myocardial ischaemia was assessed in comparison with 12-lead ECG in 49 patients presenting to the emergency department (ED) with cardiac-sounding chest pain. RESULTS: The sensitivity and specificity of 12-lead ECG for the diagnosis of acute coronary syndrome (ACS) was 67 and 55%, respectively, positive likelihood ratio (+LR) 1.52 [95% confidence interval (CI) 0.86, 2.70] and negative likelihood ratio (-LR) 0.58 [95% CI 0.30, 1.12]. The sensitivity and specificity of the BSM Delta map for the diagnosis of ACS was 71 and 78%, +LR 3.19 [95% CI 1.31, 7.80], -LR 0.37 [95% CI 0.20, 0.68]. There was a significantly positive correlation between peak troponin-I concentration and IB (r=0.437; P<0.002). CONCLUSION: This pilot study confirms the feasibility of using the Delta map for the diagnosis of ACS in patients presenting to the ED with cardiac-sounding chest pain and suggests that it has promising diagnostic accuracy and has superior sensitivity and specificity to the 12-lead ECG. The novel parameter of IB shows a significant correlation with troponin-I and is a promising tool for describing the extent of ischaemia. The use of the BSM Delta map in the ED setting could improve the diagnosis of clinically important ischaemic heart disease and furthermore presents the result in an intuitive manner, requiring little specialist experience. Further larger scale study is now warranted.