External validation of the 0/1h-algorithm and derivation of a 0/2h-algorithm using a new point-of-care Hs-cTnI assay.

BACKGROUND: The high-sensitivity cardiac troponin (hs-cTn) I point-of-care (POC) hs-cTnI-PATHFAST assay has recently become clinically available. METHODS: We aimed to externally validate the hs-cTnI-PATHFAST 0/1h-algorithm recently developed for the early diagnosis of non-ST-segment-elevation myocardial infarction (NSTEMI) and derive and validate a 0/2-algorithm in patients presenting to the emergency department with acute chest discomfort included in a multicenter diagnostic study. Two independent cardiologists centrally adjudicated the final diagnoses using all the clinical and study-specific information available including serial measurements of hs-cTnI-Architect. RESULTS: Among 1,532 patients (median age 60 years, 33% [n = 501] women), NSTEMI was the final diagnosis in 13%. External validation of the hs-cTnI-PATHFAST 0/1h-algorithm showed very high negative predictive value (NPV; 100% [95%CI, 99.5%-100%]) and sensitivity 100% (95%CI, 98.2%-100%) for rule-out of NSTEMI. Positive predictive value (PPV) and specificity for rule-in of NSTEMI were high (74.9% [95%CI, 68.3%-80.5%] and 96.4% [95%CI, 95.2%-97.3%], respectively). Among 1,207 patients (median age 61 years, 32% [n = 391] women) available for the derivation (n = 848) and validation (n = 359) of the hs-cTnI-PATHFAST 0/2h-algorithm, a 0h-concentration <3 ng/L or a 0h-concentration <4 ng/L with a 2h-delta <4ng/L ruled-out NSTEMI in 52% of patients with a NPV of 100% (95%CI, 98-100) and sensitivity of 100% (95%CI, 92.9%-100%) in the validation cohort. A 0h-concentration ≥90ng/L or a 2h-delta ≥ 55ng/L ruled-in 38 patients (11%): PPV 81.6% (95%CI, 66.6-90.8), specificity 97.7% (95%CI, 95.4-98.9%). CONCLUSIONS: The POC hs-cTnI-PATHFAST assay allows rapid and effective rule-out and rule-in of NSTEMI using both a 0/1h- and a 0/2h-algorithm with high NPV/sensitivity for rule-out and high PPV/specificity for rule-in. CLINICAL TRIAL REGISTRATION: NCT00470587.

Diagnostic discrimination of a novel high-sensitivity cardiac troponin I assay and derivation/validation of an assay-specific 0/1h-algorithm.

BACKGROUND: We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. METHODS: 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. RESULTS: 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 were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587.

Hyperacute T Wave in the Early Diagnosis of Acute Myocardial Infarction.

STUDY OBJECTIVE: The diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap. METHODS: T-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity. RESULTS: Myocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction, and T-wave amplitude exceeding the 95th percentile had positive and negative lr close to 1 or with confidence intervals (CIs) crossing 1. The exceptions were leads III, aVR, and V1, which had positive lrs of 3.8 (95% CI, 2.7 to 5.3), 4.3 (95% CI, 3.1 to 6.0) and 2.0 (95% CI, 1.4 to 2.9), respectively. These leads normally have inverted T waves, so T-wave amplitude exceeding the 95th percentile reflects upright rather than increased-amplitude hyperacute T waves. CONCLUSION: Hyperacute T waves, when defined as increased T-wave amplitude exceeding the 95th percentile, did not provide useful information in diagnosing myocardial infarction in this sample.

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation. OBJECTIVE: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score. DESIGN: Prospective cohort study. SETTING: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents. PARTICIPANTS: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope. MEASUREMENTS: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome). RESULTS: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome). LIMITATION: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge. CONCLUSION: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain. PRIMARY FUNDING SOURCE: Swiss National Science Foundation & Swiss Heart Foundation.

Very early risk modeling in patients with chest pain based on the pattern on admission ECG.

OBJECTIVES: The aim was to investigate the prognostic accuracy of admission ECG and its usefulness in determining the population at the highest risk of worse outcomes. BACKGROUND: Fast and accurate assessment of chest pain patients remains a challenge for clinicians. Electrocardiogram (ECG) is performed in each case of suspicion of the cardiac origin of chest pain. METHODS: Consecutive adult chest pain patients with suspicion of acute myocardial infarction (AMI) were enrolled in the study. The prognostic value of admission ECG changes alone and in combination with other clinical variables (cardiac troponin, diagnosis of AMI) were analyzed for the incidence of major adverse cardiac events (MACE) in a one­year observation. RESULTS: The ischemic pattern on admission ECG was a single risk factor of MACE (HR 2.996 95% CI 1.31-6.86, p = 0.009), contrary to the single admission high-sensitivity cardiac troponin T assay (hs-cTnT) (HR 1.79 95% CI 0.695-4.61). The highest risk of MACE was identified in case of the presence of both ischemic-ECG and positive hs-cTnT (HR 3.19 95% CI 1.496-6.81, p = 0.003). CONCLUSIONS: The presence of ischemic changes in ECG in chest pain population with AMI suspicion increases the risk of MACE. The group at highest risk of MACE can by identified by the additional stratification with the admission single hs-TnT measurement (Tab. 2, Fig. 4, Ref. 40). Text in PDF www.elis.sk Keywords: acute coronary syndromes, cardiac troponin, electrocardiogram, emergency department, chest pain.

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. METHODS: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. RESULTS: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]). CONCLUSIONS: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.

Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction.

BACKGROUND: We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93-0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92-0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90-0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94-0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1-100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS: The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. CLINICALTRIALSGOV IDENTIFIER: NCT00470587.

Circadian, weekly, seasonal, and temperature-dependent patterns of syncope aetiology in patients at increased risk of cardiac syncope.

AIMS: It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns. METHODS AND RESULTS: We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P < 0.01). While reflex and orthostatic syncope showed a broad peak of prevalence with 80.9% of these events occurring between 4 am and 4 pm, cardiac syncope showed a narrow peak of prevalence with 70.1% of all events occurring between 8 am and 2 pm. A weekly pattern was present for most syncope aetiologies, with events occurring mainly from Monday to Friday (P < 0.01). Reflex syncope displayed a seasonal rhythm and was more common in winter (P < 0.01), while cardiac syncope stayed constant over the year. Syncope occurred most often when the outside temperature was coldest. Overall the patterns observed for cardiac syncope were similar to the patterns observed for its differential diagnosis. CONCLUSION: Syncope aetiologies in patients >40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies.

Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I.

BACKGROUND: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. METHODS: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. RESULTS: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (P<0.01 for LOD versus each of the other strategies). CONCLUSIONS: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Gender differences and bleeding complications after PCI on first and second generation DES.

BACKGROUND: The aim of this study was to evaluate gender differences in the long-term clinical outcomes and safety of patients treated with first- and second generation DES. METHODS: The Katowice-Zabrze Registry included 1916 consecutive patients treated with either first or second generation DES. We evaluated major adverse cardiac and cerebrovascular events (MACCE) [composite of death, myocardial infarction (MI), stroke and target vessel revascularization (TVR)] at 12-month follow-up. Safety end point was bleeding complications and stent thrombosis. RESULTS: Registry included [unstable angina (UA) 1500(78%), non-ST-segment elevation myocardial infarction (NSTEMI) 285 (15%), ST-segment elevation myocardial infarction/left bundle branch block (STEMI/LBBB) 131 (7%)]. There were 35.5% females and 64.5% males. Women were older and had higher prevalence of comorbidities. Males more often had multivessel disease and higher Syntax score when comparable to females. We did not observed difference in acute and subacute stent thrombosis in our data, however, females had more in-hospital bleeding complications. Univariable Cox regression analysis revealed that women had similar outcomes when compared to men in terms of a risk of death, MI, TVR, stroke and MACCE at 1-year follow-up. There were no differences between males and females in MACCE when first- and second generation DES were analyzed separately. CONCLUSION: Despite higher risk profile, women treated with DES have similar outcomes as males in 1-year follow-up. However there is, an increased risk of in-hospital bleedings in women.

Second-generation drug-eluting stents in the elderly patients with acute coronary syndrome: the in-hospital and 12-month follow-up of the all-comer registry.

BACKGROUND: Katowice-Zabrze registry provides data that can be used to evaluate clinical outcomes of percutaneous coronary interventions in elderly patients (≥70 y/o) treated with either first- (DES-I) or second-generation (DES-II) drug-eluting stents (DES). METHODS: The registry consisted of data from 1916 patients treated with coronary interventions using either DES-I or DES-II stents. For our study, we defined patients ≥70 years of age as elderly. We evaluated any major adverse cardiac and cerebral events (MACCE) at 12-month follow-up. RESULTS: Coronary angiography revealed a higher incidence of multivessel coronary artery disease in this elderly patient population. There were no differences in acute and subacute stent thrombosis (0.4 vs. 0.6%, p = 0.760; 0.4 vs. 0.4%; p = 0.712). Elderly patients experienced more in-hospital bleeding complications requiring blood transfusion (2.0 vs. 0.9%; p = 0.003). Resuscitated cardiac arrests (2.0 vs. 0.9%; p = 0.084) were observed more often in this elderly patients during hospitalization. The composite in-hospital MACCE rates did not differ statistically between both groups (1.4 vs. 1.1%; p = 0.567). Data from a twelve-month follow-up disclosed that mortality was higher (7.1 vs. 1.8%; p < 0.001) in the elderly, with no difference in TVR (7.2 vs. 9.9%, p = 0.075), MI (6.0 vs. 4.8%, p = 0.300), stroke (0.8 vs. 0.6%, p = 0.600) and composite MACCE (15.0 vs. 13.4%, p = 0.324). The age of 70 years or over was an independent predictor of death [HR = 2.55 (95% CI 1.49-4.37); p < 0.001]. The use of DES-II reduced the risk of MI [HR = 0.40 (95% CI 0.19-0.82); p = 0.012] in the elderly. CONCLUSION: This elderly patient population had an increased risk of in-hospital bleeding complications requiring blood transfusion and a higher risk of death at 12-month follow-up. The use of new-generation DES reduced the risk of MI in the elderly population.

Clinical Significance of Viral Genome Persistence in the Myocardium of Patients with Dilated Cardiomyopathy.

BACKGROUND: The impact of myocardial viral persistence on the clinical outcome of patients with dilated cardiomyopathy (DCM) is still open to question. METHODS: Fifty-two patients with DCM were enrolled and followed for a median of 3.8 years with respect to death or heart transplantation. Studied patients were clinically stable for at least 6 months before hospitalization. They underwent coronary angiography and endomyocardial biopsy. Specimens were examined by histo- and immunohistochemistry, and the viral genomes of parvovirus B19, cytomegalovirus (CMV), Coxsackie B virus (CVB), and hepatitis B and C viruses were studied by real-time polymerase chain reaction. RESULTS: Forty-two out of 52 patients were available for clinical follow-up. The viral genome was detected in the myocardium of 32 out of 42 patients. Among the viruses studied, CMV and CVB were the most frequently found. Nine out of 42 patients achieved the predefined study end point. No statistically significant correlation was found between the presence of a persistent viral genome and study end point. No statistically significant relationship between viral genomes studied and immunohistology results was detected. CONCLUSIONS: High prevalence of a viral genome in the myocardium of patients with DCM did not have an influence on their long-term clinical outcome.

Comparison of First- and Second-Generation Drug-Eluting Stents in an All-Comer Population of Patients with Diabetes Mellitus (from Katowice-Zabrze Registry).

BACKGROUND: This study compared safety and efficacy of first- and second-generation DES in an unrestricted, real-life population of diabetic patients undergoing PCI. MATERIAL AND METHODS: The study was a subanalysis of diabetic patients from the all-comer Katowice-Zabrze Registry of patients undergoing PCI with the implantation of either first- (Paclitaxel-, Sirolimus-eluting stents) or second-generation DES (Zotarolimus-, Everolimus-, Biolimus-eluting stents). Efficacy defined as major adverse cardiac and cerebrovascular events (MACCE: death, myocardial infarction, target vessel revascularization, stroke) and safety defined as stent thrombosis (ST) were evaluated at 1 year. RESULTS: From the total of 1916 patients, 717 were diabetics. Among them, 257 (36%) were treated with first-generation DES (230 [89%] Paclitaxel-eluting stents, 27 [11%] Sirolimus-eluting stents), 460 with second-generation DES (171 [37%] Zotarolimus-eluting stents, 243 [53%] Everolimus-eluting stents, 46 [10%] Biolimus-eluting stents). Rate of MACCE was equal in both groups (p=0.54). Second-generation DES had a better safety profile than first-generation DES (log-rank for cumulative ST at 1 year p<0.001). First-generation DES was a risk factor for ST (HR 5.75 [1.16-28.47], p=0.03) but not for MACCE (HR 0.89 [0.6-1.32], p=0.57). CONCLUSIONS: In a real-life setting of diabetic patients undergoing PCI, second-generation DES had lower risk of ST and similar MACCE rate compared to first-generation DES.

Diagnostic contribution of cardiac magnetic resonance in patients with acute coronary syndrome and culprit-free angiograms.

BACKGROUND: In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. MATERIAL/METHODS: Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. RESULTS: Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. CONCLUSIONS: The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.

Role of copeptin in dual-cardiac marker strategy for patients with chest pain presented to ED.

OBJECTIVE: The objective of the study is to evaluate the role of copeptin in the diagnosis of acute coronary syndrome (ACS) and its role in dual-cardiac marker diagnostic strategy with troponin. DESIGN: A prospective cohort study was carried out from May 2012 to October 2012. SETTING: The study was conducted at the emergency department (ED) of a public hospital in a cluster of Hong Kong. METHODS: Patients aged at least 18 years presented with chest pain to ED who have intermediate or high likelihood of ACS were included. All patients had blood taken in the ED for copeptin and troponin I. The adjudicated diagnoses of ACS were made by 2 independent physicians based on the universal definition. Diagnostic characteristics were calculated. Receiver operating characteristic curves were created. Areas under the curves were compared for copeptin, troponin I, and dual-marker strategy with copeptin and troponin I. RESULTS: A total of 637 patients were recruited. Seventy-eight had been diagnosed to be ACS. The negative predictive value of copeptin for ACS was 0.881 (0.849-0.907) compared with troponin I, 0.937 (0.913-0.956). The areas under the receiver operating characteristic curves of copeptin, troponin I, and dual-marker strategy were 0.68, 0.859, and 0.880, respectively. CONCLUSIONS: Addition of copeptin to troponin does not have significant improvement of the diagnostic accuracy of ACS in patients presented with chest pain.

Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay.

BACKGROUND: Point-of-care (POC) high-sensitivity cardiac troponin assays may further accelerate the diagnosis of myocardial infarction (MI). OBJECTIVES: This study sought to assess the clinical and analytical performance of the novel high-sensitivity cardiac troponin I (hs-cTnI)-SPINCHIP POC test. METHODS: Adult patients presenting with acute chest discomfort to the emergency department were enrolled in an international, diagnostic, multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all clinical information. We compared the discriminatory performance of hs-cTnI-SPINCHIP with current established central laboratory assays and derived an assay-specific hs-cTnI-SPINCHIP 0/1-hour algorithm. Secondary analyses included sample type comparisons (whole blood, fresh/frozen plasma, and capillary finger prick) and precision analysis. RESULTS: MI was the adjudicated final diagnosis in 214 (19%) of 1,102 patients. Area under the receiver-operating characteristic curve was 0.94 (95% CI: 0.92-0.95) for hs-cTnI-SPINCHIP vs 0.94 (95% CI: 0.92-0.95) for hs-cTnI-Architect (P = 0.907) and 0.93 (95% CI: 0.91-0.95) for high-sensitivity cardiac troponin T Elecsys (P = 0.305). A cutoff <7 ng/L at presentation (if chest pain onset was >3 hours) or <7 ng/L together with a 0/1-hour delta of <4 ng/L ruled out 51% with a sensitivity and negative predictive value of 100% (95% CI: 97.7%-100%) and 100% (95% CI: 99.0%-100%), respectively. A hs-cTnI-SPINCHIP concentration ≥36 ng/L or a 0/1-hour delta ≥11 ng/L ruled in 27% with a specificity and positive predictive value of 90.9% (95% CI: 88.3%-92.9%) and 72.9% (95% CI: 66.4%-78.6%), respectively. Bootstrap internal validation confirmed excellent diagnostic performance. High agreement was observed between different sample types. CONCLUSIONS: The SPINCHIP hs-cTnI POC test has very high diagnostic accuracy. Its assay-specific 0/1-hour algorithm achieved very high sensitivity/negative predictive value and specificity/positive predictive value for rule-out/in MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study [APACE]; NCT00470587).

Combining glucose and high-sensitivity cardiac troponin in the early diagnosis of acute myocardial infarction.

Glucose is a universally available inexpensive biomarker, which is increased as part of the physiological stress response to acute myocardial infarction (AMI) and may therefore help in its early diagnosis. To test this hypothesis, glucose, high-sensitivity cardiac troponin (hs-cTn) T, and hs-cTnI were measured in consecutive patients presenting with acute chest discomfort to the emergency department (ED) and enrolled in a large international diagnostic study (NCT00470587). Two independent cardiologists centrally adjudicated the final diagnosis using all clinical data, including serial hs-cTnT measurements, cardiac imaging and clinical follow-up. The primary diagnostic endpoint was index non-ST-segment elevation MI (NSTEMI). Prognostic endpoints were all-cause death, and cardiovascular (CV) death or future AMI, all within 730-days. Among 5639 eligible patients, NSTEMI was the adjudicated final diagnosis in 1051 (18.6%) patients. Diagnostic accuracy quantified using the area under the receiver-operating characteristics curve (AUC) for the combination of glucose with hs-cTnT and glucose with hs-cTnI was very high, but not higher versus that of hs-cTn alone (glucose/hs-cTnT 0.930 [95% CI 0.922-0.937] versus hs-cTnT 0.929 [95% CI 0.922-0.937]; glucose/hs-cTnI 0.944 [95% CI 0.937-0.951] versus hs-cTnI 0.944 [95% CI 0.937-0.951]). In early-presenters, a dual-marker strategy (glucose < 7 mmol/L and hs-cTnT < 5/hs-cTnI < 4 ng/L) provided very high and comparable sensitivity to slightly lower hs-cTn concentrations (cTnT/I < 4/3 ng/L) alone, and possibly even higher efficacy. Glucose was an independent predictor of 730-days endpoints. Our results showed that a dual marker strategy of glucose and hs-cTn did not increase the diagnostic accuracy when used continuously. However, a cutoff approach combining glucose and hs-cTn may provide diagnostic utility for patients presenting ≤ 3 h after onset of symptoms, also providing important prognostic information.

Comparing the utility of clinical risk scores and integrated clinical judgement in patients with suspected acute coronary syndrome.

AIMS: The utility of clinical risk scores regarding the prediction of major adverse cardiac events (MACE) is uncertain. We aimed to directly compare the prognostic performance of five established clinical risk scores as well as an unstructured integrated clinical judgement (ICJ) of the treating emergency department (ED) physician. METHODS AND RESULTS: Thirty-day MACE including all-cause death, life-threatening arrhythmia, cardiogenic shock, acute myocardial infarction (including the index event), and unstable angina requiring urgent coronary revascularization were centrally adjudicated by two independent cardiologists in patients presenting to the ED with acute chest discomfort in an international multicentre study. We compared the prognostic performance of the HEART score, GRACE score, T-MACS, TIMI score, and EDACS, as well as the unstructured ICJ of the treating ED physician (visual analogue scale to estimate the probability of acute coronary syndrome, ranging from 0 to 100). Among 4551 eligible patients, 1110/4551 patients (24.4%) had at least one MACE within 30 days. Prognostic accuracy was high and comparable for the HEART score, GRACE score, T-MACS, and ICJ [area under the receiver operating characteristic curve (AUC) 0.85-0.87] but significantly lower and only moderate for the TIMI score (AUC 0.79, P < 0.001) and EDACS (AUC 0.74, P < 0.001), resulting in sensitivities for the rule-out of 30-day MACE of 93-96, 87 (P < 0.001), and 72% (P < 0.001), respectively. CONCLUSION: The HEART score, GRACE score, T-MACS, and unstructured ICJ of the treating physician, not the TIMI score or EDACS, performed well for the prediction of 30-day MACE and may be considered for routine clinical use. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00470587.

[The diagnostic value of virus serology in patients with non-ischemic systolic heart failure and parvovirus B19 infection]. / Wartosc diagnostyczna testów serologicznych u chorych ze skurczowa nie-niedokrwienna niewydolnoscia serca i zakazeniem parwowirusem B19.

INTRODUCTION: We determined retrospective analysis of the diagnostic value of virus serology in patients with non-ischemic systolic heart failure and parvovirus B19 infection. MATERIAL AND METHODS: Virus serology and endomyocardial biopsy were performed in 31 patients with non-ischemic systolic heart failure hospitalized from 2001 to 2006 in our clinic. RESULTS: The serum specimens from 31 patients were tested for IgM and IgG antibody against parvovirus B19. IgM antibodies were identified in 3 patients and IgG antibodies were identified in 23 patients. All of the patients underwent endomyocardial biopsy which revealed chronic active myocarditis in 10 patients (32.4%), chronic persistent myocarditis in 14 patients (45.1%) and no myocarditis in 7 patients (22.5%). CONCLUSIONS: Virus serology has no relevance for the diagnosis of non-ischemic systolic heart failure caused by parvovirus B19 infection. The result of serological tests are positive more frequently than the biopsy specimens results.

Direct comparison of high-sensitivity cardiac troponin T and I in the early differentiation of type 1 vs. type 2 myocardial infarction.

AIMS: To directly compare the diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn) T vs. hs-cTnI in the early non-invasive differentiation of Type 1 myocardial infarction (T1MI) due to plaque rupture and atherothrombosis from Type 2 myocardial infarction (T2MI) due to supply-demand mismatch. METHODS AND RESULTS: In a prospective multicentre diagnostic study, two independent cardiologists centrally adjudicated the final diagnosis of T1MI vs. T2MI according to the fourth universal definition of myocardial infarction (MI), using all available clinical information including cardiac imaging in patients presenting with acute chest pain. Diagnostic accuracy was quantified by the area under the receiver operating characteristics curve (AUC). The most extensively validated hs-cTnT-Elecsys and hs-cTnI-Architect assays were measured at presentation, 1 h, and 2 h. Among 5887 patients, 1106 (19%) had a final diagnosis of MI, including 860 (78%) T1MI and 246 (22%) T2MI. The AUC of hs-cTnT-Elecsys to differentiate T1MI from T2MI was moderate and comparable to that provided by hs-cTnI-Architect: hs-cTnT-Elecsys AUC-presentation 0.67 [95% confidence interval (CI) 0.64-0.71], AUC-1 h 0.70 (95% CI 0.66-0.74), and AUC-2 h 0.71 (95% CI 0.66-0.75) vs. hs-cTnI-Architect AUC-presentation 0.71 (95% CI 0.67-0.74), AUC-1 h 0.72 (95% CI 0.68-0.76), and AUC-2 h 0.74 (95% CI 0.69-0.78), all P = not significant (NS). Similarly, the AUC of absolute changes was moderate and comparable for hs-cTnT-Elecsys and hs-cTnI-Architect (all P = NS). Cut-off concentrations achieving at least 90% specificity for the differentiation of T1MI vs. T2MI were >114 ng/L for hs-cTnT-Elecsys [odds ratio (OR) 4.2, 95% CI 2.7-6.6] and >371 ng/L for hs-cTnI-Architect (OR 4.0, 95% CI 2.6-6.2). CONCLUSION: hs-cTnT-Elecsys and hs-cTnI-Architect provided comparable, albeit only moderate, diagnostic accuracy for the early differentiation of T1MI vs. T2MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.