Role of high sensitivity cardiac troponin assays in the assessment and experience of patients presenting to the Emergency Department with suspected acute coronary syndrome

The improved precision of high-sensitivity cardiac troponin (hs-cTnI) assays has enabled two advances in the assessment of patients with suspected acute coronary syndrome; 1) the use of sex-specific criteria for the diagnosis of myocardial infarction, and 2) the development of pathways to identify low risk patients in the Emergency Department setting, who may be suitable for immediate discharge. This thesis had two overarching aims: to explore the gendered dimensions of the new assessment process and to examine how patient experience of chest pain may be shaped by the implementation of an early rule-out pathway for myocardial infarction. In order to achieve these, the study had two components: a quantitative analysis of the presenting characteristics of men and women diagnosed with myocardial infarction using sex-specific criteria, and a qualitative interview study with patients who experienced assessment either before or after implementation of an early rule-out pathway. In the quantitative element of this thesis, I aimed to determine the frequency and predictive value of presenting characteristics in patients with myocardial infarction by evaluating patient reported symptoms in 1,941 patients (39% women) with suspected acute coronary syndrome. Typical symptoms were more common in women than men with myocardial infarction (77% [69/90] versus 59% [109/184], P=0.007), and were similar in those women and men who were reclassified with myocardial infarction due to the use of sex-specific criteria (74% [20/27] versus 44% [4/9], P=0.22). In women, the combination of three or more typical features was associated with a significantly positive likelihood ratio for a diagnosis of myocardial infarction (LR+1.18, 95% CI 1.03 to 1.31), but this relationship was not observed in men (LR+ 1.09, 95% CI 0.96 to 1.24). The improved precision of the hs-cTnI assay has enabled the diagnosis of myocardial infarction to be excluded in the Emergency Department without requiring hospital admission. Understanding the patient experience of earlier clinical decisions will ensure these new diagnostic pathways benefit both the healthcare system and patients themselves. The qualitative element was designed to explore how patient experience of chest pain may be shaped by the implementation of an early rule-out pathway. Patients attending the Emergency Department who had myocardial infarction ruled out were eligible for inclusion. Purposive sampling was used to ensure representation across age and sex categories. 23 participants were interviewed before, and 26 participants were interviewed after implementation of the early rule-out pathway one week following discharge. The content of participant accounts did not appear to be dictated by whether they were assessed before or after implementation of the early rule-out pathway with many common themes arising from both pathways. Patient experience of chest pain extended both before and after the in-hospital period revealing a phased illness episode. Participants described how they appraised their symptoms involving a complex process of interpretation and evaluation of the appropriate action. Patient accounts also revealed the differing priorities of the clinical pathway (the rule-out of myocardial infarction) to the holistic patient view desired by participants themselves. The confirmation of the absence of disease did not provide all patients with the reassurance that they desired. Providing pre-test information regarding the troponin test, in addition to active listening and the building of a trustful clinician-patient relationship appeared to relate to positive expressions of reassurance within participant accounts. Following discharge, participants had to continue to make sense of their chest pain experience. The way in which some participants made use of their acute chest pain presentation to hospital as an opportunity to consider their future heart health emerged as an unelicited theme. Participants assessed using the early rule-out pathway appeared to have a lesser orientation to use the episode of chest pain as a cue to action to appraise their future health status. The findings of this thesis suggest that high-sensitivity cardiac troponin assays will aid the assessment of patients with suspected acute coronary syndrome in two important ways. Firstly, the clinical significance of typical symptom clusters and their correlation to myocardial infarction in women is highlighted. Secondly, the successful implementation of early rule-out pathways into the Emergency Department will be aided by the addition of simple communication interventions during the chest pain assessment process. Extending the focus of assessment beyond the rule-out of myocardial infarction may enhance the care experience of patients. This thesis has also demonstrated how qualitative research has provided a mechanism through which to explore how the biochemical evidence of the early rule-out pathway may be applied in a clinical environment, enabling the application of trial data into a real-life clinical context that responds to patients’ needs

Cardiovascular risk communication strategies in primary prevention. A systematic review with narrative synthesis

Aim: To evaluate the effectiveness of cardiovascular risk communication strategies to improve understanding and promote risk factor modification. Design: Systematic review with narrative synthesis. Data sources: A comprehensive database search for quantitative and qualitative studies was conducted in five databases, Cumulative Index to Nursing and Allied health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, Applied Social Sciences Index and Abstracts (ASSIA) and Web of Science. The searches were conducted between 1980 and July 2019. Review methods: The systematic review was conducted in accordance with Cochrane review methods. Data were extracted and a narrative synthesis of quantitative and qualitative results was undertaken. Results: The abstracts of 16,613 articles were assessed and 210 underwent in‐depth review, with 31 fulfilling the inclusion criteria. We observed significant heterogeneity across study designs and outcomes. Nine communication strategies were identified including numerical formats, graphical formats, qualitative information, infographics, avatars, game interactions, timeframes, genetic risk scores and cardiovascular imaging. Strategies that used cardiovascular imaging had the biggest impact on health behaviour change and risk factor modification. Improvements were seen in diet, exercise, smoking, risk scores, cholesterol and intentions to take preventive medication. Conclusion: A wide range of cardiovascular risk communication strategies has been evaluated, with those that employ personalized and visual evidence of current cardiovascular health status more likely to promote action to reduce risk. Impact: Future risk communication strategies should incorporate methods to provide individuals with evidence of their current cardiovascular health status

High-sensitivity troponin and the application of risk stratification thresholds in patients with suspected acute coronary syndrome

Background: Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTnl) for risk stratification and the early rule-out of myocardial infarction, but multiple thresholds have been described. We evaluate the safety and effectiveness of risk stratification thresholds in patients with suspected acute coronary syndrome. Methods: Consecutive patients with suspected acute coronary syndrome (n=48 282) were enrolled in a multicenter trial across 10 hospitals in Scotland. In a prespecified secondary and observational analysis, we compared the performance of the limit of detection (<2 ng/L) and an optimized risk stratification threshold (<5 ng/L) using the Abbott high-sensitivity troponin I assay. Patients with myocardial injury at presentation, with ≤2 hours of symptoms or with ST-segment elevation myocardial infarction were excluded. The negative predictive value was determined in all patients and in subgroups for a primary outcome of myocardial infarction or cardiac death within 30 days. The secondary outcome was myocardial infarction or cardiac death at 12 months, with risk modeled using logistic regression adjusted for age and sex. Results: In total, 32 837 consecutive patients (61±17 years, 47% female) were included, of whom 23 260 (71%) and 12,716 (39%) had hs-cTnl concentrations of <5 ng/L and <2 ng/L at presentation. The negative predictive value for the primary outcome was 99.8% (95% CI, 99.7%–99.8%) and 99.9% (95% CI, 99.8%–99.9%) in those with hs-cTnl concentrations of <5 ng/L and <2 ng/L, respectively. At both thresholds, the negative predictive value was consistent in men and women and across all age groups, although the proportion of patients identified as low risk fell with increasing age. Compared with patients with hs-cTnl concentrations of ≥5 ng/L but <99th centile, the risk of myocardial infarction or cardiac death at 12 months was 77% lower in those <5 ng/L (5.3% vs 0.7%; adjusted odds ratio, 0.23 [95% CI, 0.19–0.28]) and 80% lower in those <2 ng/L (5.3% vs 0.3%; adjusted odds ratio, 0.20 [95% CI, 0.14–0.29]). Conclusions: Use of risk stratification thresholds for hs-cTnl identify patients with suspected acute coronary syndrome and at least 2 hours of symptoms as low risk at presentation irrespective of age and sex

Influence of age on the diagnosis of myocardial infarction

The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction. METHODS: In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50–74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds. RESULTS: In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5–82.9), 80.6% (95% CI, 79.2–82.1), and 81.6% (95% CI, 79.8–83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1–98.5) to 95.5% (95% CI, 95.2–95.8), and 82.6% (95% CI, 81.9–83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%–91.9%] versus 82.6% [95% CI, 81.9%–83.4%]) and positive predictive value (59.3% [57.0%–61.5%] versus 51.5% [49.9%–53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%–57.9%] versus 81.6% [79.8%–83.3%]. CONCLUSIONS: Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population

Implementation of high-sensitivity cardiac troponin and risk of myocardial infarction or death at 5 years: stepped-wedge, cluster-randomised controlled trial

AbstractObjective: To evaluate the impact of implementing a high-sensitivity cardiac troponin I assay on long-term outcomes in patients with suspected acute coronary syndromeDesign: Secondary observational analysis of a stepped-wedge cluster-randomised controlled trial.Setting: Ten secondary and tertiary care centresParticipants: Consecutive patients with suspected acute coronary syndrome (n=48,282; 47% women) were included in this trial. Myocardial injury was defined as any high-sensitivity cardiac troponin I concentration &gt;99th centile of 16 ng/L in women and 34 ng/L in men.Intervention: Hospital sites were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation of a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds.Main Outcome Measures: Subsequent myocardial infarction or death at 5 years.Results: Overall, 10,360 patients had cardiac troponin concentrations greater than the 99th centile of whom 1,771 (17%) were reclassified by the high-sensitivity assay. The 5-year incidence of subsequent myocardial infarction or death before and after implementation of the high-sensitivity assay was 29% (5,588/18,978) versus 26% (7,591/29,304), respectively, in all patients (adjusted hazard ratio [aHR] 0.97 [95% CI 0.93 to 1.01]), and 63% (456/720) versus 54% (567/1,051) in those reclassified by the high-sensitivity assay (aHR 0.82 [0.72-0.94]). Following implementation, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischemic myocardial injury (aHR 0·83 [0·75-0·91]), but not in those with type 1 or type 2 myocardial infarction (aHR 0·92 [0·83-1·01] and 0·98 [0·84-1·14]).Conclusions: In patients with suspected acute coronary syndrome, implementation of a high-sensitivity cardiac troponin assay reduced the risk of subsequent myocardial infarction or death at 5 years in those reclassified by the high-sensitivity assay. Improvements in outcome were greatest in patients with non-ischemic myocardial injury suggesting a broader benefit beyond the identification of myocardial infarction.<br/

Implementation of a high sensitivity cardiac troponin i assay and risk of myocardial infarction or death at five years:Observational analysis of a stepped wedge, cluster randomised controlled trial

Abstract:Objective: To evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome. Design: Secondary observational analysis of a stepped wedge, cluster randomised controlled trial. Setting: 10 secondary and tertiary care centres in Scotland, UK. Participants: 48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I &gt;99th centile of 16 ng/L in women and 34 ng/L in men. Intervention: Hospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds. Main outcome measure: The main outcome was myocardial infarction or death at five years. Results: 10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978) v 25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720) v 53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14). Conclusions: Implementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction. Trial registration: ClinicalTrials.gov NCT01852123.</p

Improving Risk Stratification for Patients with Type 2 Myocardial Infarction

BACKGROUND: Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. OBJECTIVES: The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction. METHODS: The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe. RESULTS: There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts. CONCLUSIONS: The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123

When Microrheology, Bulk Rheology, and Microfluidics Meet: Broadband Rheology of Hydroxyethyl Cellulose Water Solutions

In this work, we present new insights related to a debate on the morphological structure of hydroxyethyl cellulose (HEC) molecules when dissolved in water, i.e., whether HEC adopts a linear-flexible or a rod-like fibrillar configuration. We have employed “seven” rheological techniques to explore the viscoelastic properties of HEC solutions at different time and length scales. This work demonstrates an excellent convergence between various rheological techniques over a broad range of frequencies and concentrations, allowing us to derive microstructural information for aqueous HEC solutions without the use of complex optical imaging techniques. We find that when dissolved in water unmodified HEC behaves like a linear uncharged polymer, with an entangled mass concentration of ce = 0.3 wt%. Moreover, for the first time we provide the concentration scaling laws (across ce) for the longest relaxation time λ of HEC solutions, obtained from direct readings and not inferred from fitting procedures of fluids shear flow curves