High-sensitivity troponin assays in the evaluation of patients with acute chest pain in the emergency department

Evaluating patients with acute chest pain presenting to the emergency department remains an ongoing challenge. The spectrum of etiologies in acute chest pain ranges from minor disease entities to life-threatening diseases, such as pulmonary embolism, acute aortic dissection or acute myocardial infarction (MI). The diagnosis of acute MI is usually made integrating the triad of patient history and clinical presentation, readings of 12-lead ECG and measurement of cardiac troponins (cTn). Introduction of high-sensitivity cTn assays substantially increases sensitivity to identify patients with acute MI even at the time of presentation to the emergency department at the cost of specificity. However, the proportion of patients presenting with cTn positive, non-vascular cardiac chest pain triples with the implementation of new sensitive cTn assays increasing the difficulty for the emergency physician to identify those patients who are at need for invasive diagnostics. The main objectives of this mini-review are 1) to discuss elements of disposition decision made by the emergency physician for the evaluation of chest pain patients, 2) to summarize recent advances in assay technology and relate these findings into the clinical context, and 3) to discuss possible consequences for the clinical work and suggest an algorithm for the clinical evaluation of chest pain patients in the emergency departmen

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation The influence of collateral function and coronary hemodynamics

AbstractObjectivesThe goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO).BackgroundCollaterals may have an adverse effect on TVF.MethodsIn 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured.ResultsAngiographic follow-up after 5 ± 1.4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR ≥2.0, and only 18% a CFVR ≥2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 ± 0.07 vs. 0.86 ± 0.08, p < 0.05) but not with restenosis (0.87 ± 0.06).ConclusionsThis study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BACKGROUND: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo. METHODS: We perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes. RESULTS: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r(2 )> 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments. CONCLUSION: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making

Multiple biomarker strategy for improved diagnosis of acute heart failure in older patients presenting to the emergency department

Aim: Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED. Methods: 302 non-surgical patients aged ≥ 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach. Results: AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI. Conclusion: In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP

Prognostic value of different biomarkers for cardiovascular death in unselected older patients in the emergency department

Background: Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED. Methods: We consecutively enrolled 302 non-surgical patients ⩾70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models. Results: Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156–319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62–4.48) vs. 1.11 nmol/L (IQR 0.83–1.80), P<0.001 and 81 ng/L (IQR 38–340) vs. 17 ng/L (IQR 0.9–38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61–2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97–10.68, P=0.056). Conclusion: Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR). Methods A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital. A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview. Results Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy. Conclusion INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin. Practice implications Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life