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.

Technical and clinical validation of the Greiner FC-Mix glycaemia tube.

BACKGROUND: Measurement of adequate glucose concentrations is complicated by in vitro breakdown of glucose due to glycolysis. Unlike the commonly used NaF-EDTA and NaF-oxalate phlebotomy tubes, citrated NaF-EDTA tubes are reported to directly and thereby completely inhibit glycolysis. Recently, Greiner introduced the Vacuette® FC-Mix NaF-EDTA-citrate tube, currently the only NaF-citrate tube without volume-disturbing liquid additions available on the European market. Here we present its potential as alternative for the laborious and therefore unfeasible conditions for glucose sampling as recommended by the World Health Organization (WHO). METHODS: The FC-Mix tube was tested against the WHO recommended method of optimal laboratory conditions, both in healthy volunteers and pregnant woman undergoing oral glucose tolerance test (oGTT) for screening of gestational diabetes mellitus (GDM). Glucose concentrations were measured after different incubation times (0-48 h) and temperatures (room temperature, 37 °C), both in uncentrifuged whole blood and centrifuged material. RESULTS: Deming regression analysis shows that glucose concentrations measured in the FC-Mix tube correlate to the WHO recommended method. Stability is maintained at room temperature for 48 h and at least 24 h at 37 °C. The use of the FC-Mix tube was also validated in screening for GDM and proved comparable to the WHO recommended method in diagnostic outcome. CONCLUSIONS: The new Greiner FC-Mix tube combines the easy handling of a routine tube with dry additive with the ability to immediately inhibit glycolysis as in the WHO method for optimal pre-analytical and analytical conditions and performs equally to those conditions when screening for GDM.

Management of patients suspected for non-ST elevation-acute coronary syndrome in the prehospital phase.

The management of patients with suspected acute coronary syndrome, especially in prehospital settings, is challenging. This Special Report focuses on studies in emergency medical services concerning chest pain patients' triage and risk stratification. In addition, it emphasizes advancements in point-of-care cardiac troponin testing. These developments are compared with in-hospital guidelines, proposing an initial framework for a new acute care pathway. This pathway integrates a risk stratification tool with high-sensitivity cardiac troponin testing, aiming to deliver optimal care and collaboration within the acute care chain. It has the potential to contribute to a significant reduction in hospital referrals, reduce observation time and overcrowding at emergency departments and hospital admissions.

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.

Two-year use of flash glucose monitoring is associated with sustained improvement of glycemic control and quality of life (FLARE-NL-6).

INTRODUCTION: The FreeStyle Libre (FSL) is a flash glucose monitoring (FGM) system. The Flash Monitor Register in the Netherlands (FLARE-NL-4) study previously demonstrated the positive effects of FSL-FGM use during 1 year on glycemic control, quality of life and disease burden among persons with diabetes mellitus (DM). The present follow-up study assesses the effects of FSL-FGM after 2 years. RESEARCH DESIGN AND METHODS: Patients included in the FLARE-NL-4 study who continued FSL-FGM during the 1-year study period were invited to participate (n=687). Data were collected using questionnaires (the 12-Item Short Form Health Survey version 2 (SF-12v2) and the EuroQol 5-Dimension 3-Level (EQ-5D-3L) for quality of life), including self-reported hemoglobin A1c (HbA1c). RESULTS: A total of 342 patients agreed to participate: mean age 48.0 (±15.6) years, 52% men and 79.5% with type 1 DM. HbA1c decreased from 60.7 (95% CI 59.1 to 62.3) mmol/mol before use of FSL-FGM to 57.3 (95% CI 55.8 to 58.8) mmol/mol after 1 year and 57.8 (95% CI 56.0 to 59.5) mmol/mol after 2 years. At the end of the 2-year follow-up period, 260 (76%) persons were still using the FSL-FGM and 82 (24%) had stopped. The main reason for stopping FSL-FGM was financial constraints (55%). Concerning the whole 2-year period, there was a significant decrease in HbA1c among persons who continued use of FSL-FGM (-3.5 mmol/mol, 95% CI -6.4 to -0.7), while HbA1c was unaltered compared with baseline among persons who stopped FSL-FGM (-2.4 mmol/mol, 95% CI -7.5 to 2.7): difference between groups 2.2 (95% CI -1.3 to 5.8) mmol/mol. After 2 years, persons who continued use of FSL-FGM had higher SF-12 mental component score and higher EQ-5D Dutch tariff score and felt less often anxious or depressed compared with persons who discontinued FSL-FGM. CONCLUSIONS: Although the considerable number of non-responders limits generalizability, this study suggests that persons who continue to use FSL-FGM for 2 years may experience sustained improvement in glycemic control and quality of life.

Flash Glucose Monitoring in the Netherlands: Increased monitoring frequency is associated with improvement of glycemic parameters.

AIMS: To evaluate the association between Flash Glucose Monitoring (FLASH) frequency and glycemic parameters during real-life circumstances in the Netherlands. METHODS: Obtained glucose readings were de-identified and uploaded to a dedicated database when FLASH reading devices were connected to internet. Data between September 2014 and March 2020, comprising 16,331 analyzable readers (163,762 sensors) were analyzed. Scan rate per reader was determined and each reader was sorted into 20 equally sized rank ordered groups (n = 817 each). RESULTS: Users performed a median of 11.5 [IQR 7.7-16.7] scans per day. Those in the lowest and highest ventiles scanned on average 3.7 and 40.0 times per day and had an eHbA1c of 8.6% (71 mmol/mol) and 6.9% (52 mmol/mol), respectively. Increasing scan rates were associated with more time in target range (3.9-10 mmol/L), less time in hyperglycemia (>10 mmol/L), and a lower standard deviation of glucose. An eHbA1c of 7.0% (53 mmol/mol) translated in approximately 65% time in target range, 30% time in hyperglycemia and 5% time in hypoglycemia (<3.9 mmol/L). CONCLUSIONS: These outcomes among Dutch FLASH users suggest that with higher scan rate glycemic control improves.

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.

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.

Fast assessment and management of chest pain patients without ST-elevation in the pre-hospital gateway (FamouS Triage): ruling out a myocardial infarction at home with the modified HEART score.

BACKGROUND: The first study of the FamouS Triage project investigates the feasibility of ruling out a myocardial infarction in pre-hospital chest pain patients without electrocardiographic ST-segment elevation by using the modified HEART score at the patient's home, incorporating only a single highly sensitive troponin T measurement. METHODS: A venous blood sample was drawn in the ambulance from 1127 consecutive chest pain patients for measurement of the pre-hospital highly sensitive troponin T levels, in order to establish a pre-hospital HEART score (i.e. the modified HEART score) and evaluate the possibility of triage at the patient's home. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) i.e. acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting or death within 30 days after initial presentation. RESULTS: Two hundred and six patients (18%) developed a MACE during 30 days of follow-up. Thirty-six per cent of the patients ( n=403) had a low modified HEART score (0-3 points) and none of them developed a MACE during follow-up. Forty-four per cent of the patients ( n=494) had an intermediate modified HEART score (4-6 points) and 18% of them developed a MACE. Twenty per cent of the patients ( n=230) had a high modified HEART score (7-10 points) of which 52% developed a MACE during follow-up. CONCLUSION: It seems feasible to rule out a myocardial infarction at home in chest pain patients without ST-segment elevation by using the modified HEART score. TRIAL ID: NTR4205. Dutch Trial Register [ http://www.trialregister.nl ]: trial number 4205.

A multi-site coronary sampling study on CRP in non-STEMI: Novel insights into the inflammatory process in acute coronary syndromes.

BACKGROUND AND AIMS: Inflammation has become a key element in cardiovascular disease, and recently, new anti-inflammatory interventions have shown promising results. In this context, CRP levels have been thoroughly studied in vitro and in animals, but studies in humans are scarce and insights into its release, site(s) of production and uptake are not uniform. METHODS: We performed a biomarker study with multi-site sampling in the coronary circulation, in non-ST elevation MI (NSTEMI) patients with coronary angiography and right-sided catheterisation. Trans-lesional gradients were obtained by sampling distal to the culprit lesion, in patients with a suitable anatomy. To asses trans-cardiac gradients, blood was sampled from the systemic circulation, coronary sinus (CS) and great cardiac vein. Concentrations of CRP were measured with a high-sensitivity assay. RESULTS: In 42 patients, a median systemic venous CRP concentration of 4.97 mg/L was observed. There was no evidence of a trans-lesional gradient (4.59 mg/L versus 4.56 mg/L, p = 0.278; n = 14). A significant decrease in CRP concentration was observed between systemic arterial and CS samples (4.88 mg/L versus 4.44 mg/L; p < 0.001; n = 42). This trans-cardiac gradient was irrespective of time of presentation, infarct size and culprit lesion location. The gradient was not only driven by blood that ran through the injured myocardium, but also by lower CRP concentrations in the coronary veins that drain non-infarcted myocardium. CONCLUSIONS: In the context of NSTEMI, we observed a trans-cardiac decrease in CRP, which may indicate the first human in vivo proof of a net CRP uptake by the myocardium, with a role for CRP both in the injured and adjacent myocardium.

Fast assessment and management of chest pain without ST-elevation in the pre-hospital gateway: rationale and design.

BACKGROUND: For chest pain patients without ST-segment elevation in the pre-hospital setting, current clinical guidelines merely offer in-hospital risk stratification and management, as opposed to chest pain patients with ST-segment elevation for whom there is a straightforward pre-hospital strategy for diagnosis, medication regimen and logistics. The FAMOUS TRIAGE study will assess the effects of introducing a pre-hospital triage system that reliably stratifies chest pain patients without ST-segment elevation into 1) patients at high risk for NSTEMI requiring a direct transfer to a PCI-hospital; 2) patients at intermediate risk for a major adverse cardiac event (MACE) who could be evaluated at the nearest non-PCI hospital; and 3) patients at low risk for MACE (benign non-cardiac chest pain) who could have further evaluation at home or in a primary care setting. METHODS: The FAMOUS TRIAGE study will be performed in three phases. In the first phase an appropriate pre-hospital risk stratification tool will be designed for chest pain patients without ST-segment elevation by means of a retrospective and a prospective study. The second phase of the project represents the external validation of the risk stratification models, and in the third and final phase an optimal risk stratification tool will be implemented into clinical practice. Clinical and economical endpoints before and after implementation of the pre-hospital risk stratification tool will be compared to assess clinical benefit and cost-effectiveness. CONCLUSION: The FAMOUS TRIAGE project is a triple phase study that aims to optimize the pre-hospital management of chest pain patients without ST-segment elevation by providing tools for pre-hospital identification of NSTEMI or exclusion of acute coronary syndrome at home. TRIAL ID: NTR4205. Dutch Trial Register [http://www.trialregister.nl]: trial number 4205.

Raman spectroscopy as a promising tool for noninvasive point-of-care glucose monitoring.

Self-monitoring of glucose is important for managing diabetes. Noninvasive glucose monitors are not yet available, but patients would benefit highly from such a device. We present results that may lead to a novel, point-of-care noninvasive system to measure blood glucose based on Raman spectroscopy. A hospitalized cohort of 111 subjects was measured using a custom-made Raman spectrometer system. Blood glucose reference samples were used to correlate Raman data to glucose levels, using advanced preprocessing and analysis algorithms. A correlation coefficient (R (2)) of .83 was found correlating independent Raman-based predictions on reference blood glucose for the full cohort. Stratification of the cohort in gender-specific groups raised correlation levels to .88 (females) and .94 (males). Glucose could be measured noninvasively with average errors as low as 0.9 mM. We conclude that this novel system shows promising results for the advance of noninvasive, point-of-care glucose monitoring.

Metabolic effects of high altitude trekking in patients with type 2 diabetes.

OBJECTIVE: Limited information is available regarding the metabolic effects of high altitude trekking in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirteen individuals with type 2 diabetes took part in a 12-day expedition to the summit of Mount Toubkal (altitude, 4,167 m), Morocco, after 6 months of exercise training. Energy expenditure, body weight, blood glucose, fasting insulin, lipids, and HbA(1c) were assessed. RESULTS: Training reduced fasting glucose (-0.7 ± 0.9 mmol/L, P = 0.026) and increased exercise capacity (+0.3 ± 0.3 W/kg, P = 0.005). High altitude trekking decreased fasting insulin concentrations (-3.8 ± 3.2 µU/L, P = 0.04), total cholesterol (-0.7 ± 0.8 mmol/L, P = 0.008), and LDL cholesterol (-0.5 ± 0.6 mmol/L, P = 0.007). CONCLUSIONS: High altitude trekking preceded by exercise training is feasible for patients with type 2 diabetes. It improves blood glucose, lipids, and fasting insulin concentrations, while glucose control is maintained.

Accuracy of handheld blood glucose meters at high altitude.

BACKGROUND: Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs. METHODOLOGY/PRINCIPAL FINDINGS: Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude. CONCLUSION: At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.