Validation of a 0/1 h Algorithm for Rapid Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I Assay.

BACKGROUND: Current guidelines recommend 0/1 h algorithms using high-sensitivity cardiac troponin (hs-cTn) for fast diagnosis of myocardial infarction (MI). Yet, for some assays, existing data is limited. We aimed to evaluate the diagnostic performance and the prognostic value of a rapid 0/1 h algorithm for the Access hs-cTnI assay. METHODS: In consecutive patients presenting with suspected MI, we measured concentrations of Access hs-cTnI at presentation and after 1 hour. Final diagnosis was adjudicated independently by 2 cardiologists. Parameters for diagnostic performance were calculated, applying the recently derived European Society of Cardiology (ESC) 0/1 h algorithm for Access hs-cTnI. Additionally, we assessed the prognostic utility of Access hs-cTnI for the composite end point of all-cause mortality and incident MI at 3 years. RESULTS: In 1879 patients, 257 non-ST-elevation MIs occurred. Application of the 0/1 h algorithm classified 44.5% as rule-out, 20.3% as rule-in, and triaged 35.1% to the observe group. High rule-out safety was confirmed with a sensitivity of 97.7% (95% CI, 95.0%-99.1%) and a negative predictive value of 99.3% (95% CI, 98.4%-99.7%). Rule-in capacity was moderate with a specificity of 88.0% (95% CI, 86.3%-89.6%) and a positive predictive value of 50.8% (95% CI, 45.7%-55.9%). After exclusion of patients with ST-elevation MI the results showed strong prognostic value, even after adjustment for cardiovascular risk factors and comorbidities, with adjusted hazard ratios of 2.51 (95% CI, 1.56-4.04) in the observe and 3.55 (95% CI, 2.18-5.79) in the rule-in group for the composite end point of all-cause mortality and incident MI at 3 years, compared to ruled-out patients. CONCLUSION: The ESC 0/1 h algorithm for Access hs-cTnI allows safe and efficient triage of patients with suspected MI and has strong prognostic utility up to 3 years after the initial evaluation.

Clinical application of the 4th Universal Definition of Myocardial Infarction.

AIMS: The recently released 4th version of the Universal Definition of Myocardial Infarction (UDMI) introduces an increased emphasis on the entities of acute and chronic myocardial injury. We applied the 4th UDMI retrospectively in patients presenting to the emergency department with symptoms potentially indicating myocardial infarction (MI) to investigate its effect on diagnosis and prognosis. METHODS AND RESULTS: We included 2302 patients presenting to the emergency department with symptoms suggestive of MI. The final diagnosis was adjudicated sequentially according to the 3rd and 4th UDMI. Reclassification after readjudication was assessed. Established diagnostic algorithms for patients with suspected MI were applied to compare diagnostic accuracy. All patients were followed to assess mortality, recurrent MI, revascularization, and rehospitalization to investigate the effect of the 4th UDMI on prognosis. After readjudication, 697 patients were reclassified. Most of these patients were reclassified as having acute (n = 78) and chronic myocardial injury (n = 585). Four hundred and thirty-four (18.9%) patients were diagnosed with MI, compared with 501 (21.8%) MIs when adjudication was based on the 3rd UDMI. In the non-MI population, patients with myocardial injury (n = 663) were older, more often female and had worse renal function compared with patients without myocardial injury (n = 1205). Application of diagnostic algorithms for patients with suspected MI revealed a high accuracy after readjudication. Reclassified patients had a substantially higher rate of cardiovascular events compared with not-reclassified patients, particularly patients reclassified to the category of myocardial injury. CONCLUSION: By accentuating the categories of acute and chronic myocardial injury the 4th UDMI succeeds to identify patients with higher risk for cardiovascular events and poorer outcome and thus seems to improve risk assessment in patients with suspected MI. Application of established diagnostic algorithms remains safe when using the 4th UDMI.

Diagnostic and prognostic value of the sex-specific 99th percentile of four high-sensitivity cardiac troponin assays in patients with suspected myocardial infarction.

AIMS: High-sensitivity cardiac troponin (hs-cTn) assays are used for detection of myocardial infarction (MI). Ninety-ninth percentiles show wide inter-assay variation. The use of sex-specific cut-offs is recommended as definitory cut-off for MI. We compared diagnostic performance and prognostic value of sex-specific 99th percentiles of four hs-cTn assays in patients with suspected MI. METHODS AND RESULTS: Concentrations of four hs-cTn assays were measured at presentation and after 3 h in patients with suspected MI. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. Unisex and sex-specific 99th percentiles were evaluated as diagnostic cut-offs following the ESC 0/3 h algorithm. These cut-offs were used in Cox-regression analyses to investigate the association with a composite endpoint of MI, revascularization, cardiac rehospitalization, and death. Non-ST-elevation MI was diagnosed in 368 of 2718 patients. Applying the unisex 99th percentile, Elecsys hs-cTnT provided highest negative predictive value (NPV) of 99.7 and a positive predictive value (PPV) of 75.9. The analysed hs-cTnI assays showed slightly lower NPVs and comparable PPVs [Architect (NPV 98.0, PPV of 71.4); Atellica (NPV 97.7, PPV of 76.1); Pathfast (NPV 97.7, PPV of 66.6)]. Application of sex-specific 99th percentiles did not significantly affect diagnostic performance. Concentrations above 99th percentile were independent predictors for impaired long-term outcome (hazard ratios 1.2-1.5, P < 0.001). CONCLUSION: We describe a good diagnostic accuracy of four hs-cTn assays using the assay-specific 99th percentile for detection of MI. Application of sex-specific 99th percentiles did neither affect diagnostic performance nor prognostic value significantly. Finally, values above the 99th percentile were associated with poor long-term outcome.

The association of anaemia and high-sensitivity cardiac troponin and its effect on diagnosing myocardial infarction.

AIMS: Anaemia is common in patients with acute myocardial infarction (MI). We investigated the association of high-sensitivity cardiac troponin (hs-cTn) and haemoglobin (Hb) and the influence of anaemia on the performance of diagnostic protocols for suspected MI. METHODS AND RESULTS: Patients with suspected MI were consecutively enrolled at a tertiary centre. Final diagnoses were independently adjudicated by two cardiologists. Performance measures of hs-cTn-based algorithms were compared for anaemic and non-anaemic patients (Hb <12 g/dL in women and <13 g/dL in men). The influence of anaemia on survival (median follow-up 1.7 years) was investigated using multivariable cox-regression analysis and the association of Hb and hs-cTn by multivariable linear regression analysis. Overall, 2223 patients were included, of whom 415 (18.7%) had anaemia. In anaemic patients, the incidence of MI was similar; however, chronic myocardial injury was significantly more prevalent (20.1% vs. 48.2%). The negative predictive value to rule-out MI was similar for both algorithms and all assays in patients with anaemia, although the positive predictive value to rule-in MI was partly reduced for the 0/3-h algorithm. Fewer anaemic patients were triaged after 1 h. Anaemia was an independent predictor of death. Adjusted for patient characteristics, Hb was significantly associated with hs-cTn. By providing a point-based tool, the Hb-associated hs-cTn concentration and thus chronic myocardial injury may be predicted. CONCLUSION: Anaemia partly affects the rule-in, but not the rule-out of MI in hs-cTn-based diagnostic protocols. Hs-cTn concentrations and thus chronic myocardial injury may be predicted by clinical variables and Hb. TRIAL REGISTRATION: clinicaltrials.gov (NCT02355457 and NCT03227159).

Predictors of transportation delay in patients with suspected ST-elevation-myocardial infarction in the VIENNA-STEMI network.

OBJECTIVE: The emergency medical service (EMS) provides rapid pre-hospital diagnosis and transportation in ST-elevation myocardial infarction (STEMI) systems of care. Aim of the study was to assess temporal and regional characteristics of EMS-related delays in a metropolitan STEMI network. METHODS: Patient call-to-arrival of EMS at site (call-to-site), transportation time from site to hospital (site-to-door), call-to-door, patient's location, month, weekday, and hour of EMS activation were recorded in 4751 patients referred to a tertiary center with suspicion of STEMI. RESULTS: Median call-to-site, site-to-door, and call-to-door times were 9 (7-12), 39 (31-48), and 49 (41-59) minutes, respectively. The shortest transportation times were noted between 08:00 and 16:00 and in general on Sundays. They were significantly prolonged between midnight and 04:00, whereby the longest difference did not exceed 4 min in median. Patient's site of call had a major impact on transportation times, which were shorter in Central and Western districts as compared to Southern and Eastern districts of Vienna (p < 0.001 between-group difference for call-to-site, site-to-door, and call-to-door). After multivariable adjustment, patient's site of call was an independent predictor of call-to-site delay (p < 0.001). Moreover, age and hour of EMS activation were the strongest predictors of call-to-site, site-to-door, and call-to-door delays (p < 0.05). CONCLUSION: In our Viennese STEMI network, the strongest determinants of pre-hospital EMS-related transportation delays were patient's site of call, patient's age, and hour of EMS activation. Due to the significant but small median time delays, which are within the guideline-recommended time intervals, no impact on clinical outcome can be expected.

Predictive Value of Serial ECGs in Patients with Suspected Myocardial Infarction.

The electrocardiogram (ECG) is an important diagnostic tool for patients with suspected acute myocardial infarction (AMI). Current guidelines recommend serial ECGs in case of persisting symptoms. We aimed to analyze the predictive value of ischemic ECG-signs in patients with suspected AMI. Patients presenting to the emergency department with suspected AMI were included. All patients with ST-elevation AMI were excluded from analyses. Patients received 12-lead-ECG and high-sensitive Troponin T (hs-TnT)-measurement at admission and after 3 h. Four groups were defined: no ischemic signs in either ECG; new ischemic signs in the second ECG; resolved ischemic signs in the second ECG; and persistent ischemic signs in both ECGs. Patients were followed for 2 years to assess the composite endpoint of all-cause-mortality, AMI, and coronary revascularization. Using a 30-day landmark analysis, a Cox regression with ischemic signs as the variable of interest, adjusted by cardiovascular risk factors, was calculated. Of 1675 patients, 1321 showed no ischemic signs, in 25 new-, in 92 resolved- and in 237 patients, persistent ischemic signs were documented. Patients with persistent ischemic signs had significantly worse outcomes, compared to those without. Compared to no ischemic signs, adjusted hazard ratios for the combined endpoint were 0.81 (95% CI 0.20, 3.31; p-value = 0.77) for new-, 0.59 (95% CI 0.26, 1.34; p-value = 0.21) for resolved-, and 1.47 (95% CI 1.102, 2.13; p-value = 0.041) for persistent ischemic signs. In patients with suspected AMI, persistent ischemic ECG-signs are predictive of a higher rate of all-cause-mortality, AMI, and revascularization.

Increased platelet reactivity in dyslipidemic patients with coronary artery disease on dual anti-platelet therapy.

INTRODUCTION: The optimal duration of dual anti-platelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still a matter of debate. Biomarkers may help to identify patients who will benefit from extended DAPT. The aim of the study was to test the interaction between lipid parameters and platelet function in patients with coronary artery disease (CAD) on DAPT. MATERIAL AND METHODS: Overall, 58 patients on DAPT were prospectively included following PCI in stable CAD. Platelet markers, i.e. mean platelet volume (MPV), platelet distribution width (PDW), fraction of reticulated thrombocytes (RT) and ADP-induced multiple electrode aggregometry (MEA), as well as serum lipids, i.e. high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG) and remnant cholesterol (RC), were assessed after intake of a maintenance dose of ASA and P2Y12 inhibitor. RESULTS: A significant inverse correlation was found for HDL-C levels and markers of platelet activation: MPV (r = -0.351, p = 0.009), PDW (r = -0.391, p = 0.003), fraction of RT (r = -0.402, p = 0.003) and ADP-induced MEA (r = -0.345, p = 0.011). Only a weak or no association was found between other lipid parameters and platelet markers. After multivariable adjustment, HDL-C levels served as a strong and significant predictor of MPV (95% CI: -0.039 to -0.009; p = 0.002), PDW (95% CI: -0.094 to -0.034; p < 0.0001), RT (95% CI: -0.107 to -0.031; p = 0.001) and MEA (95% CI: -0.540 to -0.170; p < 0.0001), while TG, LDL-C, RC and TC were not significantly associated with platelet function. CONCLUSIONS: Within lipid parameters, only HDL-C levels are strongly associated with markers of platelet activation in CAD patients on DAPT. Accordingly, detection of dyslipidemia might indicate the need for prolongation of DAPT.

Impact of age on short- and long-term mortality of patients with ST-elevation myocardial infarction in the VIENNA STEMI network.

BACKGROUND AND AIM: Our senescent society includes a growing number of elderly people suffering from ST-elevation myocardial infarction (STEMI); however, exactly this population is often underrepresented in randomized trials. Hence, our aim was to investigate the influence of age on patient characteristics, as well as short- and long-term outcome in the Vienna STEMI registry. METHODS: We included all patients of the Vienna STEMI registry (2003-2009). Patients were stratified into age cohorts (≤45, 46-59, 60-79 and ≥80 years, respectively). Differences between cohorts were investigated by descriptive statistics and regression models. Crude and adjusted mortality rates were investigated using log rank test and Cox regression models, respectively. The influence of treatment on mortality was further investigated using propensity score matching. RESULTS: A total of 4579 patients fulfilled the criteria for further investigation. With rising age of cohorts, the number of females, diabetes mellitus (DM), hypertension (HTN), previous myocardial infarction (MI), shock, no reperfusion therapy and anterior wall infarction significantly increased. In contrast, the number of patients with a positive family history, smoking and hyperlipidemia (HLP) significantly declined. Log rank analysis showed significant differences between age cohorts for short- and long-term mortality. Cox regression analysis for short-term mortality revealed an independent association for age at the event, HTN and shock, while age, smoking, DM, HTN, HLP, previous MI and shock independently influenced long-term mortality after correction for confounders. Also, we found a significant association of age and total ischemic time (TIT), which however had no influence on long-term mortality (interaction term p = 0.236). Propensity score matching revealed reduced mortality rates for patients who received reperfusion therapy compared to conservative management, irrespective of age. CONCLUSIONS: Increasing age independently influenced short- and long-term mortality in patients with STEMI in the Vienna STEMI network. The TIT significantly increased with baseline age, but had no impact on mortality. Furthermore, reperfusion therapy exerted beneficial effects irrespective of the patients' age.