Luciano Babuin

Troponin: the biomarker of choice for the detection of cardiac injury

It has been known for 50 years that transaminase activity increases in patients with acute myocardial infarction. With the development of creatine kinase (CK), biomarkers of cardiac injury began to take a major role in the diagnosis and management of patients with acute cardiovascular disease. In 2000 the European Society of Cardiology and the American College of Cardiology recognized the pivotal role of biomarkers and made elevations in their levels the “cornerstone” of diagnosis of acute myocardial infarction. At that time, they also acknowledged that cardiac troponin I and T had supplanted CK-MB as the analytes of choice for diagnosis. In this review, we discuss the science underlying the use of troponin biomarkers, how to interpret troponin values properly and how to apply these measurements to patients who present with possible cardiovascular disease.

Elevated cardiac troponin is an independent risk factor for short- and long-term mortality in medical intensive care unit patients

Background:Troponin elevations are common in critically ill patients. Whether they are predictors of mortality independent of the severity of the underlying disease is unclear. Objective:To determine whether troponin elevations predict in-hospital, short-term, and long-term mortality in medical intensive care unit patients independent of the severity of the underlying disease as measured by Acute Physiology and Chronic Health Evaluation III prognostic system. Design:Retrospective study. Setting:We examined the Acute Physiology and Chronic Health Evaluation III database and cardiac troponin T levels of medical intensive care unit patients at Mayo Clinic, Rochester, MN. Patients:In all, 1,657 patients consecutively admitted to medical intensive care units between August 2000 and December 2001. Measurements:In-hospital, short-term (30-day), and long-term all-cause mortality. Results:During hospitalization, 12.5% of patients with a cardiac troponin T < 0.01 &mgr;g/L suffered deaths compared with 29.5% among those with cardiac troponin T ≥0.01 &mgr;g/L (p < .001). At 30 days, mortality was 13.7% without and 34.6% with elevations (p < .001). The expected probability of survival at 1-, 2-, and 3-yr follow-up was 43.7%, 33.8%, and 25.7% among patients with cardiac troponin T ≥0.01 &mgr;g/L and 75.3%, 67.6%, and 62.9% in those with cardiac troponin T < 0.01 &mgr;g/L, respectively (p < .001). After adjustment for the severity of disease and baseline characteristics, cardiac troponin levels were still associated with in-hospital, short-term, and long-term mortality (p = .006, p = .007, and p = .001, respectively). Limitations:This is a single-site retrospective study that included only patients in whom a troponin level was obtained on admission. Conclusions:In medical intensive care unit patients, admission troponin levels are independently associated with short- and long-term mortality, even after adjustment for severity of disease.

Long-term prognostic significance of elevated cardiac troponin levels in critically ill patients with acute gastrointestinal bleeding.

Background:Elevations in troponin level have prognostic importance in critically ill patients, including those with gastrointestinal (GI) bleeding. However, there are no data addressing the independent association of troponin levels and mortality, adjusted for the severity of the underlying disease, in patients with GI bleeding. Objective:This study was designed to determine whether troponin T elevations are independently associated with in-hospital, short-term (30 days), and long-term mortality in medical intensive care unit patients with GI bleeding after adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation score prognostic system. Design:Retrospective study. Setting:We examined the Acute Physiology, Age, and Chronic Health Evaluation III database and cardiac troponin T levels from patients consecutively admitted to the medical intensive care unit at Mayo Clinic, Rochester, MN, with acute GI bleeding. Patients:Between August 2000 and July 2005, 1076 patients with acute GI bleeding consecutively admitted to the medical intensive care units. Measurements:In-hospital, short-term (30 days), and long-term all-cause mortality. Results:During hospitalization, 8.0% of deaths occurred in patients with troponin T <0.01% and 11.9% with troponin T ≥0.01 (p = 0.083). At 30 days, mortality was 10.1% and 18.8% in patients without and with elevations of troponins, respectively (p < 0.001). The Kaplan-Meier expected probability of survival at 1-, 2-, and 3-yr follow-up was 54.2%, 40.8%, and 30.4% with troponin T ≥0.01 &mgr;g/L and 78.3%, 69.3%, and 61.5% with troponin T <0.01 &mgr;g/L (p < 0.001). After adjustment for severity of disease and baseline characteristics, cardiac troponin levels were associated only with long-term mortality (p < 0.001). Limitations:This is a retrospective, single-center study which included only patients in whom troponin level was determined upon admission. Conclusions:In patients with GI bleeding severe enough to require admission to the medical intensive care unit, admission troponin T elevations are associated with long-term but not short-term mortality.

Relationship of MRI-Determined Infarct Size and cTnI Measurements in Patients with ST-Elevation Myocardial Infarction

The extent of myocardial infarction (MI) is related to patient outcomes (1), and clinicians often wish to have a sense for this critical measure. Imaging methods, although accurate, have limited accessibility and high cost. Thus clinicians often use biomarkers to provide such an estimate. Measurement of cardiac troponin T (cTnT) at 96 h after onset of MI was observed to correlate with MRI-determined infarct size in both ST-elevation MI (STEMI) and non-STEMI (2). We tested the hypothesis that cardiac troponin I (cTnI), another myocardium-specific biomarker, would provide an equivalent estimation in the subset of STEMI patients previously described (2). The 28 patients with STEMI had sufficient sample remaining to allow for determination of cTnI (2). The characteristics of this group have previously been reported (2), but in brief the mean age (SD) was 56 (11) years, and 17.4% of patients were women. Mean (SD) body mass index was 26.46 (3.5) kg/m2, and 71.4% of patients were hypertensive, 64.3% were current smokers, 60.7% had hypercholesterolemia, and 14.3% had diabetes. Blood samples were available at admission and at 24, 48, …

Design and Methodologies of the POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) Trial

Background: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. Study Design: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 ± 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. Conclusion: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.

Defining Myocardial Infarction

The diagnosis of acute myocardial infarction (AMI) as defined by the World Health Organization (WHO) was based for many years on the presence of two of three possible criteria: clinical symptoms compatible with AMI, typical electrocardiogram changes, and increases in markers of cardiac injury. However, because of the very good sensitivity and specificity of creatine kinase-MB (CK-MB), it eventually became rare to diagnose AMI in the absence of elevations of this biomarker. Thus, although never formally embraced by WHO, the clinical diagnosis of AMI became dependent on elevation of a biomarker of myocardial injury in the appropriate clinical setting. This approach evolved further with the development of cardiac troponin and its integration into the definition of MI by the European Society of Cardiology and the American College of Cardiology. The present diagnostic standard for MI is thus based on the following biomarker criteria: Maximal concentration of troponin T or I exceeding the decision limit (99th percentile of the values for a reference control group) manifesting a dynamic pattern on at least one occasion during the first 24 h after the index clinical event; if the value is between the 99th percentile and the 10% coefficient of variation level, caution is warranted because analytic false-positive results can occur. In the unusual situation in which troponin assays are not available, the value of CK-MB (preferably CK-MB mass) exceeding the 99th percentile of the value for a reference control group and manifesting a dynamic pattern can be used for diagnosis.