Amy Ferry

High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study.

Objective To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary syndrome. Design Prospective cohort study. Setting Regional cardiac centre, United Kingdom. Participants Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care. Main outcome measure Diagnosis of myocardial infarction. Results The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 for both). At 12 months, women with undisclosed increases in troponin concentration (17-49 ng/L) and those with myocardial infarction (≥50 ng/L) had the highest rate of death or reinfarction compared with women without (≤16 ng/L) myocardial infarction (25%, 24%, and 4%, respectively; P<0.001). Conclusions Although having little effect in men, a high sensitivity troponin assay with sex specific diagnostic thresholds may double the diagnosis of myocardial infarction in women and identify those at high risk of reinfarction and death. Whether use of sex specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention.

High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study

Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers. Funding British Heart Foundation and Chief Scientist Office (Scotland).

Comparison of the Efficacy and Safety of Early Rule Out Pathways for Acute Myocardial Infarction

Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients. Methods: Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease. Results: The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9–98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0–99.9; P<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (P<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease. Conclusions: Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT01852123.

Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome

Importance High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain. Objective To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome. Data Sources Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017. Study Selection Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction. Data Extraction and Synthesis The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model. Main Outcomes and Measures The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. Results Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death. Conclusions and Relevance Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.

Cardiac Biomarkers and the Diagnosis of Myocardial Infarction in Women

Purpose of reviewWomen with suspected acute coronary syndrome are less likely to undergo investigation or receive treatment than men, and women consistently have poorer outcomes. This review summarises how the latest development in cardiac biomarkers could improve both diagnosis and outcomes in women.Recent findingsNovel high-sensitivity cardiac troponin assays have identified differences in the reference range and therefore diagnostic threshold for myocardial infarction in men and women. These differences are present across multiple populations with different ethnic backgrounds and for a range of assays. The use of a uniform threshold for cardiac troponin does not provide equivalent prediction in men and women, with lower thresholds needed for women to provide comparable risk stratification.SummarySex differences in cardiac troponin concentrations are not widely recognised in clinical practice and may be contributing to the under-diagnosis of myocardial infarction in women and discrepancies in patient care and outcomes.

HIGH-SENSITIVITY CARDIAC TROPONIN AND THE CLASSIFICATION OF MYOCARDIAL INFARCTION

Background: Guidelines recommend classification of myocardial infarction due to plaque rupture (type 1) or myocardial oxygen supply-demand mismatch (type 2). Whether more sensitive cardiac troponin assays can help to differentiate between subtypes is uncertain. Methods: Consecutive patients (n=4,

58 Optimal risk stratification pathways for patients with suspected acute coronary syndrome

Background Novel pathways utilise low concentrations of cardiac troponin and a normal ECG to risk stratify patients with suspected acute coronary syndrome. However, clinical risk scores incorporating additional cardiovascular risk factors or physiological parameters are commonly used in practice. Whether such clinical risk scores are safer than novel pathways is uncertain. Methods Patients with suspected acute coronary syndrome (n=1,139) underwent high-sensitivity cardiac troponin I testing at presentation, 3 and 6 or 12 hours. We applied the HighSTEACS pathway, which rules out myocardial infarction in those without ischaemia on the ECG if troponin concentrations are <5 ng/L at presentation and symptom duration is 2 hours. Early presenters and those 5 ng/L are ruled out if absolute change is <3 ng/L at 3 hours and they remain 99th centile. We compared the HighSTEACS pathway with the HEART score (low risk 3), or a TIMI score of 0 with a normal ECG. We compared the negative predictive value (NPV) and efficacy of each approach for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. Results The primary outcome occurred in 15.5% (177/1,139). The HighSTEACS pathway ruled out 61.9% (705/1,139) of patients by three hours, with a NPV of 99.6% [95%CI 99.1%–99.9%]. The NPV of both the HEART and the TIMI score was similar (Figure 1A) , however, they identified a significantly lower proportion of patients as eligible for discharge (HEART 18% (205/1,139), TIMI 26.3% (299/1,139); Figure 1B ). Conclusions The HighSTEACS pathway identifies patients at very low risk of index myocardial infarction, or myocardial infarction or cardiac death at 30 days, and rules out acute coronary syndrome in over half of patients presenting to the Emergency Department. Whilst the HEART and the TIMI scores have a comparable safety profile, they identify a significantly lower proportion of patients as low risk.Abstract 58 Figure 1