Jaffe, Allan S.

Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and elimination from the human circulation are incompletely understood. Myocardial injury may be caused by a variety of different mechanisms, for example, myocardial ischaemia, inflammatory and immunological processes, trauma, drugs and toxins, and myocardial necrosis is preceded by a substantial reversible prelethal phase. Recent experimental data in a pig model of myocardial ischaemia demonstrated cardiac troponin release into the circulation from apoptotic cardiomyocytes as an alternative explanation for clinical situations with increased cardiac troponin without any other evidence for myocardial necrosis. However, the comparably lower sensitivities of all currently available imaging modalities, including cardiac magnetic resonance imaging for the detection of particularly non-focal myocardial necrosis in patients, has to be considered for cardiac troponin test result interpretation in clinical settings without any other evidence for myocardial necrosis apart from increased cardiac troponin concentrations as well.

Background: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. Methods: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation Results: There were 11 529 participants in the preimplementation phase (range, 284–3465) and 19 803 in the postimplementation phase (range, 395–5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%–37.7%) to 18.4% (6.8%–43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3–2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4–3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P =0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. Conclusions: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. Clinical Trial Registration: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

Background Current American Heart Association/American College of Cardiology guidelines recommend the GRACE (Global Registry of Acute Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction) scores to assess myocardial infarction ( MI ) prognosis. Changes in the epidemiological characteristics of MI and the availability of new biomarkers warrant an assessment of the performance of these scores in contemporary practice. We assessed the following: (1) the performance of GRACE and TIMI to predict 1‐year mortality in a cohort of patients stratified by ST ‐segment elevation MI (STEMI) and non‐STEMI ( NSTEMI ) and (2) the incremental discriminatory power of soluble suppression of tumorigenicity‐2, a myocardial fibrosis biomarker. Methods and Results Olmsted County, Minnesota, residents with incident MI (N=1401) were recruited prospectively from November 1, 2002 to December 31, 2012 (mean age, 67 years; 61% men; 79% with NSTEMI ). Baseline data were used to calculate risk scores; soluble suppression of tumorigenicity‐2 was measured in stored plasma samples obtained at index MI . C ‐statistics adapted to survival data were used to assess the discriminatory power of the risk scores and the improvement gained by adding other markers. During the first year of follow‐up, 190 patients (14%) died. The discriminatory performance to predict death was reasonable for GRACE and poor for TIMI , and was generally worse in those with NSTEMI versus those with STEMI. In people with NSTEMI , sequential addition of comorbidities and soluble suppression of tumorigenicity‐2 substantially improved the c ‐statistic over GRACE (from 0.78 to 0.80 to 0.84) and TIMI (from 0.61 to 0.73 to 0.81), respectively (all P ≤0.05). Conclusions Guideline‐recommended scores for risk assessment after MI underperform in contemporary community patients, particularly those with NSTEMI, which now represents most infarcts. Incorporating comorbidities and soluble suppression of tumorigenicity‐2 substantially improves risk prediction, thereby delineating opportunities to improve clinical care.

Background Troponin‐T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin‐T testing in the prognostication of these patients. Methods and Results This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin‐T and significant delta troponin‐T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in‐hospital mortality. Secondary outcomes included 1‐year mortality and lengths of stay. During this 8‐year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin‐T ≥0.01 ng/mL. Serial troponin‐T values were available in 732 (78%) patients. Elevated admission troponin‐T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin‐T was associated with higher severity of illness. Admission log 10 troponin‐T was associated with unadjusted in‐hospital (odds ratio 1.6; P =0.003) and 1‐year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin‐T and log 10 delta troponin‐T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin‐T remained an independent predictor of in‐hospital mortality (odds ratio 1.4; P =0.04) and 1‐year survival (hazard ratio 1.3; P =0.008). Conclusions In patients with sepsis and septic shock, elevated admission troponin‐T was associated with higher short‐ and long‐term mortality. Routine serial troponin‐T testing did not add incremental prognostic value in these patients.

Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.

High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischaemia are detected than with previous cardiac troponin assays. Increased troponin concentrations that do not fit with the clinical presentation are seen in the daily routine, mainly as a result of a variety of pathologies, and if tested in the same sample, even discrepancies between high-sensitivity cardiac troponin I and troponin T test results may sometimes be found as well. In addition, analytically false-positive test results occasionally may occur since no assay is perfect. In this review, we summarise the biochemical, pathophysiological and analytical background of the work-up for such a clinical setting.