Consequences of different cut-off values for high-sensitivity cardiac troponin for risk stratification of patients suspected for NSTE-ACS with a modified HEART score.

Aim: This study aims to enhance prehospital risk assessment for suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) patients using the HEART-score. By incorporating novel point-of-care high-sensitivity cardiac troponin devices, a modified HEART-score was developed and compared with the conventional approach. Patients & methods: Troponin points within the modified HEART-score are based on values below the limit of quantitation (LoQ), between the LoQ and 99th percentile and above the 99th percentile of the used device. A total HEART-score of three or lower is considered low-risk for major adverse cardiac events. Results & conclusion: The number of low-risk patients decreased based on the modified HEART-score. The sensitivity and negative predictive value increased which suggests increasing safety in ruling out patients with suspected NSTE-ACS.

Referral decisions based on a pre-hospital HEART score in suspected non-ST-elevation acute coronary syndrome: final results of the FamouS Triage study.

AIMS: Although pre-hospital risk stratification of patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) by ambulance paramedics is feasible, it has not been investigated in daily practice whether referral decisions based on this risk stratification is safe and does not increase major adverse cardiac events (MACE). In Phase III of the FamouS Triage study, it was investigated whether referral decisions by ambulance paramedics based on a pre-hospital HEART score, is non-inferior to routine management. METHODS AND RESULTS: FamouS Triage Phase III is a non-inferiority study, comparing the occurrence of MACE before (Phase II) and after (Phase III) implementation of referral decisions based on a pre-hospital HEART score. In Phase II, all patients were risk-stratified and referred to the hospital; in Phase III, low-risk patients (HEART score ≤ 3) were not referred. Primary endpoint was MACE (acute coronary syndrome, revascularization, or death) within 45 days. A total of 1236 patients were included. Mean age was 63 years, 43% were female, 700 patients were included in the second phase and 536 in the third phase in which 149 low-risk patients (28%) were not transferred to the hospital. Occurrence of 45 days MACE was 16.6% in Phase II and 15.7% in Phase III (P = 0.67). Percentage MACE in low-risk patients was 2.9% in Phase II and 1.3% in Phase III. After adjustments for differences in baseline variables, the hazard ratio of 45 days MACE in Phase III was 0.88 (95% confidence interval 0.63-1.25) as compared to Phase II. CONCLUSION: Pre-hospital risk stratification of patients with suspected NSTE-ACS, avoiding hospitalization of a substantial number of low-risk patients, seems feasible and non-inferior to transferring all patients to the hospital.

Pre-hospital versus hospital acquired HEART score for risk classification of suspected non ST-elevation acute coronary syndrome.

INTRODUCTION: Although increasing evidence shows that in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) both hospital and pre-hospital acquired HEART (History, ECG, Age, Risk factors, Troponin) scores have strong predictive value, pre-hospital and hospital acquired HEART scores have never been compared directly. METHODS: In patients with suspected NSTE-ACS, the HEART score was independently prospectively assessed in the pre-hospital setting by ambulance paramedics and in the hospital by physicians. The hospital HEART score was considered the gold standard. Low-risk (HEART score ≤3) was considered a negative test. Endpoint was occurrence of major adverse events within 45 days. RESULTS: A total of 699 patients were included in the analyses. In 516 (74%) patients pre-hospital and hospital risk classification was similar, in 50 (7%) pre-hospital risk classification was false negative (45 days mortality 0%) and in 133 (19%) false positive (45 days mortality 1.5%). False negative risk classifications were caused by differences in history (100%), risk factor assessment (66%) and troponin (18%) and were more common in older patients. Occurrence of major adverse events was comparable in pre-hospital and hospital low-risk patients (2.9% vs. 2.7%, p = 0.9). Incidence of major adverse events was 0% in the true negative group, 26% in the true positive group, 10% in the false negative group and 5% in the false positive group. Predictive value of both pre-hospital and hospital acquired HEART scores was high, although the 'area under the curve' of hospital acquired HEART score was higher (0.84 vs. 0.74, p < 0.001). CONCLUSION: In approximately 25% of patients hospital and pre-hospital HEART score risk classifications disagree, mainly by risk overestimation in the pre-hospital group. Since disagreement is primarily caused by different scoring of history and risk factors, additional training may improve pre-hospital scoring.

Referral decisions based on a prehospital HEART score in suspected non-ST-elevation acute coronary syndrome: design of the FamouS Triage 3 study.

Background: It is not yet investigated whether referral decisions based on prehospital risk stratification of non-ST-elevation Acute Coronary Syndrome (NSTE-ACS) by the complete History, ECG, Age, Risk factors and initial Troponin (HEART) score are feasible and safe. Hypothesis: Implementation of referral decisions based on the prehospital acquired HEART score in patients with suspected NSTE-ACS is feasible and not inferior to routine management in the occurrence of major adverse cardiac events within 45 days. Study design & methods: FamouS Triage 3 is a feasibility study with a before-after sequential design. The aim is to assess whether prehospital HEART-score management including point-of-care troponin measurement is feasible and noninferior to routine management. Primary end point is the occurrence of major adverse cardiac events within 45 days. Conclusion: If referral decisions based on prehospital acquired risk stratification are feasible and noninferior this can become the new prehospital management in suspected NSTE-ACS.

Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study.

BACKGROUND: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). METHODS: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. RESULTS: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group (p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group (p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk (p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). CONCLUSIONS: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

Accuracy of pre-hospital HEART score risk classification using point of care versus high sensitive troponin in suspected NSTE-ACS.

INTRODUCTION: Pre-hospital risk classification by the HEART score is performed with point of care troponin assessment. However, point of care troponin is less sensitive than high sensitive troponin measurement which is used in the hospital setting. In this study we compared pre-hospital HEART-score risk classification using point of care troponin versus high sensitive troponin. METHODS: In 689 consecutive patients with suspected NSTE-ACS, point of care troponin and laboratory high-sensitive troponin were measured in pre-hospital derived blood. For every patient the HEART score with both point of care troponin (HEART-POC) and high sensitive troponin (HEART-hsTnT) was determined. Endpoint was MACE within 45 days. RESULTS: Mean age was 64 (SD ±â€¯14), 163 (24%) patients were considered low-risk by HEART-hsTnT and 170 (25%) by HEART-POC. MACE was observed in 17%. Although high sensitive versus POC troponin scoring was different in 130 (19%) of patients, in 678 (98%) patients risk classification in low versus intermediate-high risk was similar. The predictive values of HEART-POC versus HEART-HsTnT was similar (AUC 0.75 versus 0.76, p = 0.241). CONCLUSION: Although high sensitive versus POC troponin scoring was dissimilar in one fifth of patients, this resulted in different patient risk classification in only 2 percent of patients. Therefore POC troponin measurement suffices for pre-hospital risk stratification of suspected NSTE-ACS.

Value of Prehospital Troponin Assessment in Suspected Non-ST-Elevation Acute Coronary Syndrome.

There is an increasing awareness that prehospital risk stratification in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) is important. The HEART score accurately identifies patients at low risk and is nowadays fully assessable outside the hospital after the development of point-of-care (POC) troponin tests. However, the added value of the troponin component to the prehospital HEART score has not yet been assessed. This is a prospective cohort study including 700 patients with suspected NSTE-ACS in which prehospital risk stratification using the HEART score was performed by paramedics. Low risk was defined as HEAR or HEART score ≦3. Troponin was measured by a POC troponin T Test device (Roche Cobas h232). Troponin <40 ng/l scored 0 point, troponin ≥40 ng/l scored 2 points. Primary end point was major adverse cardiac events (MACE) within 45 days after inclusion. Mean HEAR score was 4.5 ± 1.6, mean HEART score was 4.7 ± 1.7. Using the HEAR score, a total of 183 patients (26%) were stratified as low risk, whereas using the HEART score, 172 patients (25%) were stratified as low risk (p = 0.001). In both low-risk groups, there were no deaths within 45 days. Using HEAR, MACE occurred in 13 patients (7%) in the low-risk group, whereas using HEART, MACE occurred in 5 patients in the low-risk group (3%, p <0.001). The use of HEART (Area under the curve 0.74) obtained a higher predictive value compared to HEAR (Area under the curve 0.65, p <0.001) for MACE. In conclusion, in patients with suspected NSTE-ACS, the prehospital troponin component of the HEART score has important added predictive value.

Comparison of Outcomes and Intervention Among Patients With Non-ST-Segment Elevation Acute Myocardial Infarction of Those With a Left Circumflex Versus Those With a Non-Left Circumflex-Related Coronary Artery (From the ELISA-3 Trial).

Previous studies found that patients with an acute coronary syndrome (ACS) due to occlusion of the left circumflex (LC) coronary artery often present without ST-elevation, leading to a delay in diagnosis and revascularization, a larger infarct size, and a worse prognosis. In this subgroup analysis of the ELISA-3 study (early or late intervention in high-risk non-ST-segment elevation acute coronary syndromes [NSTE-ACS]) incidence, characteristics and prognosis of LC-related NSTE-ACS was investigated, and the outcome of early versus late invasive strategy was compared. In 383 of 542 patients the culprit vessel could be identified, with the LC artery in 112 (29%) of them. Patients with LC-related ACS had more often single vessel disease and underwent percutaneous coronary intervention more and CABG less frequently. The primary end point of the combined incidences of death, myocardial infarction, and recurrent ischemia at 30-day follow-up occurred in 9.0% of LC versus 16.5% of non-LC-related ACS (p = 0.057). Enzymatic infarct size and incidence of bleeding were comparable. Of patients with LC-related ACS, 62 were assigned to an early and 50 to a late invasive treatment with a median time from admission to angiography of 5.5 and 65.7 hours, respectively. The primary end point occurred in 9.7% and 8.0%, respectively (p = 1.00) with comparable enzymatic infarct size and bleeding. In conclusion, no significant differences in outcome were found between patients with an LC- and a non-LC-related NSTE-ACS. In LC-related NSTE-ACS, angiography within 12 hours of admission is feasible but not superior to angiography after more than 48 hours.

Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.

BACKGROUND: A routine invasive strategy is recommended for patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). However, optimal timing of invasive strategy is less clearly defined. Individual clinical trials were underpowered to detect a mortality benefit; we therefore did a meta-analysis to assess the effect of timing on mortality. METHODS: We identified randomised controlled trials comparing an early versus a delayed invasive strategy in patients presenting with NSTE-ACS by searching MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. We included trials that reported all-cause mortality at least 30 days after in-hospital randomisation and for which the trial investigators agreed to collaborate (ie, providing individual patient data or standardised tabulated data). We pooled hazard ratios (HRs) using random-effects models. This meta-analysis is registered at PROSPERO (CRD42015018988). FINDINGS: We included eight trials (n=5324 patients) with a median follow-up of 180 days (IQR 180-360). Overall, there was no significant mortality reduction in the early invasive group compared with the delayed invasive group HR 0·81, 95% CI 0·64-1·03; p=0·0879). In pre-specified analyses of high-risk patients, we found lower mortality with an early invasive strategy in patients with elevated cardiac biomarkers at baseline (HR 0·761, 95% CI 0·581-0·996), diabetes (0·67, 0·45-0·99), a GRACE risk score more than 140 (0·70, 0·52-0·95), and aged 75 years older (0·65, 0·46-0·93), although tests for interaction were inconclusive. INTERPRETATION: An early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients. FUNDING: None.

Two-year outcome after early or late Intervention in non-ST elevation acute coronary syndrome.

OBJECTIVE: To compare long-term outcome of an early to a delayed invasive strategy in high-risk patients with non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: This prospective, multicentre trial included patients with NSTE-ACS and at least two out of three of the following high-risk criteria: (1) evidence of extensive myocardial ischaemia on ECG, (2) elevated biomarkers for myocardial necrosis and (3) age above 65 years. Patients were randomised to either an early (angiography and revascularisation if appropriate <12 hours) or a delayed invasive strategy (>48 hours after randomisation). Endpoint for this prespecified long-term follow-up was the composite incidence of death or reinfarction after 2 years. Data collection was performed by telephone contact with the patients, their relatives or general practitioner and by review of hospital records. RESULTS: Endpoint status after 2-year follow-up was collected in 521 of 542 initially enrolled patients. Incidence of death or reinfarction was 11.8% in the early and 13.1% in the delayed treatment group (relative risk (RR)=0.90, 95% CI 0.57 to 1.42). No significant differences were found in occurrence of the individual components of the primary endpoint: death 6.1% vs 8.9%, RR 0.69 (95% CI 0.37 to 1.27), reinfarction 6.5% vs 5.4%, RR 1.20 (95% CI 0.60 to 2.38). Post-hoc subgroup analysis showed statistical significant interaction between age and treatment strategy on outcome (p=0.02). CONCLUSIONS: After 2 years follow-up, no difference in incidence of death or reinfarction was seen between early to late invasive strategy. These findings are in line with results of other studies with longer follow-up. Older patients seem to benefit more from early invasive treatment.

Randomised comparison of drug-eluting versus bare-metal stenting in patients with non-ST elevation myocardial infarction.

OBJECTIVE: The superiority of drug-eluting stents (DES) over bare-metal stents (BMS) in patients with ST elevation myocardial infarction (STEMI) is well studied; however, randomised data in patients with non-ST elevation myocardial infarction (NSTEMI) are lacking. The objective of this study was to investigate whether stenting with everolimus-eluting stents (EES) safely reduces restenosis in patients with NSTEMI as compared to BMS. METHODS: ELISA-3 patients were asked to participate in the angiographic substudy and were randomised to DE (Xience V) or BM (Vision) stenting (ELISA-3 group). The primary end point was minimal luminal diameter (MLD) at 9-month follow-up angiography. In addition, 296 patients with NSTEMI who were excluded or did not want to participate in the ELISA-3 trial (RELI group) were randomised to DE or BM stenting and underwent clinical follow-up only (major adverse cardiac events (MACE), stent thrombosis (ST)). A pooled analysis was performed to assess an effect on clinical outcome. RESULTS: 178 of 540 ELISA-3 patients participated in the angiographic substudy. MLD at 9 months angiography was 2.37±0.63 mm (DES) versus 1.84±0.62 mm (BMS), p<0.001. Binary restenosis occurred in 1.9% in the DES group versus 16.7% in the BMS group (RR 0.11, 95% CI 0.02 to 0.84, p=0.007). In the pooled analysis, the incidence of MACE, target vessel revascularisation and ST at 2 years follow-up in the DES versus BMS group was 12.5% versus 16.0% (p=0.28), 4.0% versus 10.4% (p=0.009) and 1.3% versus 3.0% (p=0.34), respectively. CONCLUSIONS: In patients with NSTEMI, use of EES is safe and decreases both angiographic and clinical restenosis as compared to BMS http://www.isrctn.com/search?q=39230163. TRIAL REGISTRATION NUMBER: 39230163; Post-results.

Early or late intervention in patients with transient ST-segment elevation acute coronary syndrome: Subgroup analysis of the ELISA-3 trial.

OBJECTIVES: To investigate incidence and patient characteristics of transient ST-segment elevation (TSTE) ACS and to compare outcome of early versus late invasive treatment. BACKGROUND: Optimal timing of treatment in TSTE-ACS patients is not outlined in current guidelines and no prospective randomized trials have been done so far. METHODS: Post hoc subgroup analysis of patients with TSTE randomized in the ELISA 3 trial. This study compared early (<12 h) versus late (>48 h) angiography and revascularization in 542 patients with high-risk NSTE-ACS. Primary endpoint was incidence of death, reinfarction, or recurrent ischemia at 30 days follow-up. RESULTS: TSTE was present in 129 patients (24.2%) and associated with male gender, smoking and younger age. The primary endpoint occurred in 8.9% of patients with and 13.0% of patients without TSTE (RR = 0.681, P = 0.214). Incidence of death or MI after 2 year follow-up was 5.7 and 14.6% respectively (RR = 0.384, P = 0.008). Within the group of patients with TSTE, incidence of the primary endpoint was 5.8% in the early and 12.7% in the late treatment group (RR = 0.455, P = 0.213), driven by reduction in recurrent ischemia. Enzymatic infarct size, bleeding and incidence of death or recurrent MI at 2 years follow-up was comparable between the treatment groups. CONCLUSIONS: In high-risk patients with NSTE-ACS, TSTE is frequently seen. Similar to findings in patients with high-risk NSTE-ACS, immediate angiography and revascularization in these patients is feasible but not superior to later treatment. Prospective randomized trials are needed to provide more evidence in the optimal timing of treatment in patients with TSTE-ACS. © 2016 Wiley Periodicals, Inc.

Early or late intervention in high-risk non-ST-elevation acute coronary syndromes: results of the ELISA-3 trial.

AIMS: To compare an early to a delayed invasive strategy in high-risk patients with NSTE-ACS. METHODS AND RESULTS: In this prospective multicentre trial, 542 patients hospitalised with NSTE-ACS were randomised to either an immediate (angiography and revascularisation if appropriate <12 hr) or a delayed invasive strategy (>48 hr after randomisation). Patients were eligible if they had two of the following three high-risk characteristics: evidence of extensive myocardial ischaemia on ECG, elevated biomarkers for myocardial necrosis (TropT >0.10 µg/L), and an age above 65 years. Primary endpoint of the study was the combined incidence of death, reinfarction and/or recurrent ischaemia at 30-day follow-up. Secondary endpoints were enzymatic infarct size as assessed by a single cardiac troponin T, at 72-96 hours after admission or at discharge, and the percentage of patients without a rise in CKMB during admission. Median age was 71.9 (interquartile range [IQR] 64.5-78.4) years. Median time between randomisation and start of angiography was 2.6 (IQR 1.2-6.2) hours in the immediate and 54.9 (44.2-74.5) hours in the delayed intervention group. The composite of death, reinfarction and/or recurrent ischaemia at 30 days occurred in 12% of patients and was not significantly different between the two groups (9.9% and 14.2%, respectively, p=0.135). All secondary endpoints and bleeding complications were comparable. Hospital duration was two days shorter in the immediate intervention group (4 days [IQR 2-10] vs. 6 days [IQR 4-12]). CONCLUSIONS: Although no definitive conclusion can be drawn due to a lower than expected prevalence of the primary endpoint, an immediate invasive strategy was safe and feasible but not superior to a delayed invasive strategy in terms of the combined primary endpoint of death, reinfarction and/or recurrent ischaemia at 30 days. These results are consistent with previous randomised trials which studied the effect of timing of angiography in patients with NSTE-ACS. TRIAL REGISTRATION: ISRCTN Register 9230163.

Strategies to detect abnormal glucose metabolism in people at high risk of cardiovascular disease from the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial population.

BACKGROUND: To investigate whether the combination of HbA1c and fasting plasma glucose (FPG) can be used for the diagnosis of diabetes and impaired glucose tolerance (IGT) in people at high risk of cardiovascular disease (CVD). METHODS: A cross-sectional study was performed on 2907 people at high risk of cardiovascular events but without a previous diagnosis of diabetes. Optimal cut-off points and the diagnostic potential of FPG, HbA1c, and their combination were determined. RESULTS: The sensitivity of the usually applied FPG cut-off point of 7.0 mmol/L to diagnose diabetes mellitus was low (59.0%). Receiver operating characteristic (ROC) curve analysis indicated that the optimal cut-off points for the diagnosis of diabetes using FPG and HbA1c were 6.4 mmol/L (sensitivity 75.7%; specificity 77.5%; likelihood ratio 3.37) and 5.9% (41 mmol/mol; sensitivity 68.7%; specificity 67.1%; likelihood ratio 2.09), respectively. To diagnose IGT, the optimal cut-off points for FPG and HbA1c were 6.1 mmol/L (sensitivity 57.1%; specificity 57.9%) and 5.7% (39 mmol/mol; sensitivity 63.8%; specificity 60.3%), respectively. For diabetes, combining cut-off points for FPG and HbA1c identified four categories with likelihood ratios ranging from 5.59 to 0.21, and post-test probabilities between 69.3% and 7.8%. For IGT, likelihood ratios varied between 2.05 and 0.56, whereas post-test probabilities ranged from 84.0% to 58.8%. CONCLUSIONS: Using FPG alone results in the underdiagnosis of glucometabolic abnormalities in people at high risk of CVD. Using an algorithm with both HbA1c and FPG improves the detection of diabetes, but not IGT, and could be easily implemented in patient care.

Obesity and Clomiphene Challenge Test as predictors of outcome of in vitro fertilization and intracytoplasmic sperm injection.

One hundred and sixty-two consecutive patients undergoing in vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection (ICSI) were studied to determine the effect of obesity on the outcome of this treatment and to evaluate the prognostic value of the Clomiphene Challenge Test (CCT) in controlled ovarian hyperstimulation. In this prospective clinical study, we assessed the mean number of stimulation days, the mean gonadotropin level/day, cancellation rate, the mean thickness of the endometrium, the mean number of oocytes retrieved, the fertilization rate, the clinical pregnancy rate/embryo transfer and the abortion rate. Obese women had a doubled risk of cancellation due to poor response, although this was not statistically significant. Furthermore, they showed up to 45% lower fertilization rates compared to women of normal weight. The CCT was a good predictor of IVF and IVF/ICSI outcome. Women with an abnormal CCT needed more days of stimulation and higher doses of gonadotropins to reach an adequate stimulation, but still overall results were less than in women with a normal CCT. We conclude that obesity negatively affects IVF and IVF/ICSI outcome, and that CCT is a useful prognosticator of response to ovarian stimulation. Obese patients show a tendency to experience more cancellation due to poor response and lower fertilization rates. Obese women should be counseled on their possible poor performance in IVF and IVF/ICSI programs.