Automatically computed ECG algorithm for the quantification of myocardial scar and the prediction of mortality

Myocardial scar is associated with adverse cardiac outcomes. The Selvester QRS-score was developed to estimate myocardial scar from the 12-lead ECG, but its manual calculation is difficult. An automatically computed QRS-score would allow identification of patients with myocardial scar and an increased risk of mortality.; To assess the diagnostic and prognostic value of the automatically computed QRS-score.; The diagnostic value of the QRS-score computed automatically from a standard digital 12-lead was prospectively assessed in 2742 patients with suspected myocardial ischemia referred for myocardial perfusion imaging (MPI). The prognostic value of the QRS-score was then prospectively tested in 1151 consecutive patients presenting to the emergency department (ED) with suspected acute heart failure (AHF).; Overall, the QRS-score was significantly higher in patients with more extensive myocardial scar: the median QRS-score was 3 (IQR 2-5), 4 (IQR 2-6), and 7 (IQR 4-10) for patients with 0, 5-20 and > 20% myocardial scar as quantified by MPI (p < 0.001 for all pairwise comparisons). A QRS-score ≥ 9 (n = 284, 10%) predicted a large scar defined as > 20% of the LV with a specificity of 91% (95% CI 90-92%). Regarding clinical outcomes in patients presenting to the ED with symptoms suggestive of AHF, mortality after 1 year was 28% in patients with a QRS-score ≥ 3 as opposed to 20% in patients with a QRS-score < 3 (p = 0.001).; The QRS-score can be computed automatically from the 12-lead ECG for simple, non-invasive and inexpensive detection and quantification of myocardial scar and for the prediction of mortality. TRIAL-REGISTRATION: http://www.clinicaltrials.gov . Identifier, NCT01838148 and NCT01831115

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction.

AIMS: High-sensitivity cardiac troponin (hs-cTn) assays provide higher diagnostic accuracy for acute myocardial infarction (AMI) when compared with conventional assays, but may result in increased use of unnecessary coronary angiographies due to their increased detection of cardiomyocyte injury in conditions other than AMI. METHODS AND RESULTS: We evaluated the impact of the clinical introduction of high-sensitivity cardiac troponin T (hs-cTnT) on the use of coronary angiography, stress testing, and time to discharge in 2544 patients presenting with symptoms suggestive of AMI to the emergency department (ED) within a multicentre study either before (1455 patients) or after (1089 patients) hs-cTnT introduction. Acute myocardial infarction was more often the clinical discharge diagnosis after hs-cTnT introduction (10 vs. 14%, P < 0.001), while unstable angina less often the clinical discharge diagnosis (14 vs. 9%, P = 0.007). The rate of coronary angiography was similar before and after the introduction of hs-cTnT (23 vs. 23%, P = 0.092), as was the percentage of coronary angiographies showing no stenosis (11 vs. 7%, P = 0.361). In contrast, the use of stress testing was substantially reduced from 29 to 19% (P < 0.001). In outpatients, median time to discharge from the ED decreased by 79 min (P < 0.001). Mean total costs decreased by 20% in outpatients after the introduction of hs-cTnT (P = 0.002). CONCLUSION: The clinical introduction of hs-cTn does not lead to an increased or inappropriate use of coronary angiography. Introduction of hs-cTn is associated with an improved rule-out process and thereby reduces the need for stress testing and time to discharge.R.T. reports speaker honoraria from B.R.A.H.M.S. and Roche. T.R. reports grants from Swiss National Science Foundation (PASMP3-136995) as well as personal fees from Swiss Heart Foundation and from Goldschmidt-Jacobson Foundation. C.M. reports research grants from the Swiss National Science Foundation, the European Union, the KTI, and the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, 8sense, Abbott, ALERE, Astra Zeneca, Beckman Coulter, Biomerieux, Brahms, Critical Diagnostics,Nanosphere, Roche, Siemens, Singulex, and the University Hospital Basel, as well as speaker honoraria from Abbott, ALERE, Astra Zeneca, BG medicine, Biomerieux, BMS, Brahms, Cardiorentis, Daiichi Sankyo, Novartis, Radiometer, Roche, Sanofi, Siemens, and Singulex

Prevalence and determinants of exercise‐induced left ventricular dysfunction in patients with coronary artery disease

The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD).; We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively.; Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD.; One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD

Prevalence and determinants of exercise-induced left ventricular dysfunction in patients with coronary artery disease

The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD).; We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively.; Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD.; One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD

Direct Comparison of Cardiac Troponin T and I Using a Uniform and a Sex-Specific Approach in the Detection of Functionally Relevant Coronary Artery Disease.

BACKGROUND We aimed to directly compare high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the detection of functionally relevant coronary artery disease (fCAD). METHODS Consecutive patients referred with clinical suspicion of fCAD and no structural heart disease other than coronary artery disease were included. The presence of fCAD was based on rest/stress myocardial perfusion single-photon emission computed tomography/computed tomography and coronary angiography. hs-cTnI and hs-cTnT concentrations were measured in a blinded fashion. Diagnostic accuracy was quantified using the area under the ROC curve (AUC) and evaluated both for uniform use in all patients and for sex-specific use in women and men separately. The prognostic end point was major adverse cardiac events (MACEs; cardiovascular death or myocardial infarction) within 2 years. For the prognostic performance, we used a multivariable model comparison with the Akaike information criterion (AIC). RESULTS fCAD was detected in 613 of 2062 patients (29.7%) overall, 112 of 664 of women (16.9%), and 501 of 1398 of men (35.8%). hs-cTnI and hs-cTnT had comparable diagnostic accuracy when assessed for uniform use in all patients (AUC, 0.68 vs 0.66; = 0.107) and separately in women (AUC, 0.68 vs 0.63; = 0.068) and men (AUC, 0.65 vs 0.64; = 0.475). However, women required lower rule-out cutoffs to achieve high sensitivity, and men needed higher rule-in cutoffs to achieve high specificity. hs-cTnI and hs-cTnT were strongly and independently associated with MACE within 2 years ( < 0.001), with comparable prognostic accuracies by the AIC. CONCLUSIONS hs-cTnI and hs-cTnT provide moderate and comparable diagnostic accuracy. Sex-specific cutoffs may be preferred. The prognostic utility of both troponins is comparable

Combining high-sensitivity cardiac troponin and B-type natriuretic peptide in the detection of inducible myocardial ischemia.

BACKGROUND Single biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP). METHODS Consecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints. RESULTS Among 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63-0.69), hs-cTnI 0.70 (95%CI 0.67-0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62-0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72-0.77 vs AUC 0.74, 95%CI 0.71-0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3-1.9), and BNP for death (HR 1.6, 95%CI 1.3-2.1). CONCLUSION A dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone. SUMMARY AND HIGHLIGHTS We included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment. CLINICAL TRIAL REGISTRATION Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148

Prospective Validation of a Biomarker-Based Rule Out Strategy for Functionally Relevant Coronary Artery Disease.

BACKGROUND This study aimed to prospectively advance a rule-out strategy for functionally significant coronary artery disease (CAD) by use of high-sensitivity cardiac troponin I (hs-cTnI) from bench to bedside, by application of a 3-step approach: validation in serum, correlation in plasma, and application on a clinical platform. METHODS Patients without known CAD referred for rest/stress myocardial perfusion single-photon emission tomography/computer tomography (MPI-SPECT/CT) were assigned to 3 consecutive cohorts: validation, correlation, and application. Functionally relevant CAD was adjudicated with the use of expert interpretation of MPI-SPECT/CT and, if available, coronary angiography. In the validation cohort resting hs-cTnI was measured in serum before stress testing with the research Erenna system, in serum and plasma in the correlation cohort with the research Erenna system, and in plasma in the application cohort with the clinical Clarity system. RESULTS Overall, functionally relevant CAD was adjudicated in 21% (304/1478) of patients. In the validation cohort (n = 613), hs-cTnI concentrations were significantly higher in patients with functionally relevant CAD (median 2.8 ng/L vs 1.9 ng/L, < 0.001) as compared to patients without functionally relevant CAD and allowed a rule out with 95% sensitivity in 14% of patients. In the correlation cohort (n = 606), hs-cTnI concentrations in serum and plasma strongly correlated (Spearman = 0.921) and had similar diagnostic accuracy as quantified by the area under the receiver operating characteristic curve (0.686 vs 0.678, = 0.425). In the application cohort (n = 555), very low hs-cTnI plasma concentrations (< 0.5 ng/L) ruled out functionally relevant CAD with 95% sensitivity in 10% of patients. CONCLUSIONS A single resting plasma hs-cTnI measurement can safely rule out functionally relevant CAD in around 10% of patients without known CAD