Yader Sandoval

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).

Supply/Demand Type 2 Myocardial Infarction Should We Be Paying More Attention?

Supply/demand (type 2) myocardial infarction is a commonly encountered clinical challenge. It is anticipated that it will be detected more frequently once high-sensitivity cardiac troponin assays are approved for clinical use in the United States. We provide a perspective that is based on available data regarding the definition, epidemiology, etiology, pathophysiology, prognosis, management, and controversies regarding type 2 myocardial infarction. Understanding these basic concepts will facilitate the diagnosis and treatment of these patients as well as ongoing research efforts.

ViewpointSupply/Demand Type 2 Myocardial Infarction: Should We Be Paying More Attention?

Supply/demand (type 2) myocardial infarction is a commonly encountered clinical challenge. It is anticipated that it will be detected more frequently once high-sensitivity cardiac troponin assays are approved for clinical use in the United States. We provide a perspective that is based on available data regarding the definition, epidemiology, etiology, pathophysiology, prognosis, management, and controversies regarding type 2 myocardial infarction. Understanding these basic concepts will facilitate the diagnosis and treatment of these patients as well as ongoing research efforts.

Cardiac troponin changes to distinguish type 1 and type 2 myocardial infarction and 180-day mortality risk

Aims: To determine the ability of serial cardiac troponin (cTnI) changes (delta) to distinguish type 1 and type 2 myocardial infarction (MI) (excluding all ST-segment elevation MIs (STEMIs)) and describe the diagnostic accuracy and 180-day mortality in MI versus no-MI patients. Methods and results: Serial cTnIs were measured in 1112 consecutive patients without STEMI and within 6h of presentation to a United States emergency department: 856 (77%) with no MI, 66 (6%) type 1 MI, and 190 (17%) type 2 MI. Of the 0 to 3h and 0 to 6h absolute and relative cTnI changes, only the distribution of absolute change from 0 to 6h was significantly different between type 1 and type 2 MI: median (interquartile range) 311 (1430) ng/l vs. 80 (330) ng/l, p=0.03. Neither the absolute concentration change nor the absolute percent change from either 0 h to 3h (areas under the curves (AUCs) 0.57 and 0.54 respectively) or 0 h to 6h (AUCs 0.60 and 0.51) improved on the performance of the individual cTnI results at 3h (AUC 0.60) or 6h (AUC 0.62), respectively. After adjusting for age, and histories of heart failure and renal insufficiency, those with type 2 MI (hazard ratio 2.9, 95% confidence interval (CI) 1.4–5.9, p=0.004) and those with no index MI and cTnImax0–6h > 34 ng/l (2.5, CI 1.1–6.0, p=0.04) had increased risk of death within 180 days compared with those with no MI and cTnImax 0–6h ≤ 34 ng/l. Conclusion: Delta cTnI did not aid in distinguishing type 1 MI from the more common type 2 MI. Patients diagnosed with type 2 MIs, which represented more than half of all index MIs, had increased risk of death after discharge.

Present and Future of Cardiac Troponin in Clinical Practice: A Paradigm Shift to High-Sensitivity Assays.

Despite its wide utilization and central role in the evaluation of patients with potential ischemic symptoms, misconceptions and confusion about cardiac troponin (cTn) prevail. The implementation of high-sensitivity (hs) cTn assays in clinical practice has multiple potential advantages provided there is an education process tied to the introduction of these assays that emphasizes the appropriate utilization of the test. Several diagnostic strategies have been explored with hs-cTn assays, including the use of undetectable values, accelerated serial hs-cTn sampling, hs-cTn measurements in combination with a clinical-risk score, and the use of a single hs-cTn measurement with a concentration threshold tailored to meet a clinical need. In this document we discuss basic concepts that should facilitate the integration of hs-cTn assays into clinical care in years to come.

Diagnosis of Type 1 and Type 2 Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay with Sex-Specific 99th Percentiles Based on the Third Universal Definition of Myocardial Infarction Classification System

BACKGROUND The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. METHODS A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. RESULTS A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. CONCLUSIONS Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses.

Prognostic value of 12-lead electrocardiogram and peak troponin I level after vascular surgery

OBJECTIVE The aim of this investigation was to determine if the presence of ischemic electrocardiographic (ECG) changes in patients undergoing vascular surgery provides incremental prognostic information about the long-term risk of death compared with a single peak troponin level within 48 hours after surgery. METHODS This was a retrospective analysis of 337 patients undergoing moderate-risk to high-risk vascular surgery at our institution whose ECG and biomarker data were complete. Peak cardiac troponin (cTn) I values that exceeded the upper reference limit (URL) were categorized as low-positive (+), at or exceeding the URL but less than three times the URL, or high-positive (+), at or exceeding three times the URL. ECGs were classified as ischemic or nonischemic. The primary outcome was death at 1 year after the vascular operation. Independent predictors of long-term mortality were determined by Cox proportional hazards regression analysis. RESULTS The most common vascular problem was an expanding abdominal aortic aneurysm (n=185 [55%]). With regard to cTnI, 53 patients (16%) were classified as high (+) and 82 (24%) as low (+). The ECG in 21 patients (6%) showed evidence of myocardial ischemia. An increase in 1-year mortality of 3% for normal, 11% for low (+), and 17% for high (+) (P<.01) was seen with incremental cTn values. Independent predictors of long-term mortality were age (odds ratio [OR], 1.05, 95% confidence interval [CI], 1.02-1.07; P<.01), stratified troponin (OR, 1.62; 95% CI, 1.25-2.10; P<.01), tissue loss (OR, 3.30; 95% CI, 1.72-6.33; P<.01), stratified Revised Cardiac Risk Index (OR, 1.32; 95% CI, 0.97-1.81; P<.07), and statin use (OR, 0.62; 95% CI, 0.40-0.98; P=.04). The presence of ischemia on ECG was not a predictor of long-term mortality. CONCLUSIONS In the presence of an elevated cTn I, the ECG is not an independent predictor of long-term mortality after vascular surgery. These results support a strategy of routine surveillance of cTns after vascular surgery for the detection of cardiac events and postoperative risk stratification.

Myocardial Infarction Type 2 and Myocardial Injury.

BACKGROUND The development and implementation of sensitive and high-sensitivity cardiac troponin assays has not only expedited the early ruling in and ruling out of acute myocardial infarction, but has also contributed to the identification of patients at risk for myocardial injury with necrosis, as confirmed by the presence of cardiac troponin concentrations above the 99th percentile. Myocardial injury with necrosis may occur either in the presence of overt ischemia from myocardial infarction, or in the absence of overt ischemia from myocardial injury accompanying other conditions. Myocardial infarction type 2 (T2MI) has been a focus of attention; conceptually T2MI occurs in a clinical setting with overt myocardial ischemia where a condition other than an acute atherothrombotic event is the major contributor to a significant imbalance between myocardial oxygen supply and/or demand. Much debate has surrounded T2MI and its interrelationship with myocardial injury. CONTENT We provide a detailed overview of the current concepts and challenges regarding the definition, diagnosis, management, and outcomes of T2MI, as well as the interrelationship to myocardial injury, and emphasize several critical clinical concepts for both clinicians and researchers moving forward. SUMMARY T2MI and myocardial injury are frequently encountered in clinical practice and are associated with poor outcomes in both the short term and long term. Diagnostic strategies to facilitate the clinical distinction between ischemic myocardial injury with or without an acute atheroma-thrombotic event vs non-ischemic-mediated myocardial injury conditions are urgently needed, as well as evidence-based therapies tailored toward improving outcomes for patients with T2MI.

Incidence of Undetectable, Measurable, and Increased Cardiac Troponin I Concentrations Above the 99th Percentile Using a High-Sensitivity vs a Contemporary Assay in Patients Presenting to the Emergency Department

INTRODUCTION We compared the incidence of undetectable [below the limit of detection (LoD)], measurable (LoD to 99th percentile), and increased cardiac troponin I (cTnI) concentrations above the 99th percentile between Abbott high-sensitivity cTnI (hs-cTnI) and contemporary cTnI assays in a US emergency department population. METHODS Patients (n = 2100) presenting to the emergency department who had serial cTnI (0, 3, 6, 9 h) measurements ordered on clinical indication were enrolled. Contemporary cTnI [Abbott Architect used clinically; 99th percentile: 0.030 μg/L (30 ng/L)] and hs-cTnI [Abbott investigational; sex-specific 99th percentiles: female (F) 16 ng/L, male (M) 34 ng/L] assays simultaneously measured fresh EDTA plasma. RESULTS The hs-cTnI assay measured fewer undetectable cTnI concentrations compared to the contemporary cTnI assay across baseline (F: 31% vs 47%, M: 22% vs 40%) and serial (F: 21% vs 46%; M: 19% vs 54%) measurements. Conversely, the proportion of measurable cTnI concentrations was higher using hs-cTnI compared to contemporary cTnI assay across both baseline (F: 46% vs 31%; M: 60% vs 33%) and serial (F: 48% vs 28%; M: 83% vs 40%) measurements. The overall proportion of patients with increased cTnI concentrations above the 99th percentile was not significantly different between the contemporary (31%) and hs-cTnI (26%) assays (P = 0.09). CONCLUSIONS In patients presenting to the emergency department, the use of the Abbott hs-cTnI assay provides clinicians with more numeric cTnI concentrations. This occurs via a shift from results below the LoD to those between the LoD and the 99th percentile and does not increase in the number of cTnI concentrations above the 99th percentile.

Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients

INTRODUCTION Serial changes in cardiac troponin in hemodialysis (HD) patients have uncertain clinical implications. We evaluated associations of adverse outcomes in HD patients with reference change value (RCV) data and tertile concentrations for cardiac troponin I (cTnI) and cTnT measured by high-sensitivity (hs) assays. METHODS RCV data and tertiles for hs-cTnI and hs-cTnT were determined from plasma samples collected 3 months apart in 677 stable outpatient HD patients and assessed for their associations with adverse outcomes using adjusted Cox models. Primary outcomes were all-cause mortality and sudden cardiac death (SCD). RESULTS During a median follow-up of 23 months, 18.6% of patients died. RCVs were: hs-cTnI +37% and -30%; hs-cTnT +25% and -20%. Patients with serial hs-cTnI and hs-cTnT changes >RCV (increase or decrease) had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with changes ≤RCV [adjusted hazard ratios (aHRs): 1.9, P = 0.0003 and 1.7, P = 0.0066), respectively]. Only hs-cTnI changes >RCV were predictive of SCD (aHR 2.6, P = 0.005). hs-Cardiac troponin changes >RCV improved all-cause mortality prognostication compared to changes ≤RCV in tertile 2: hs-cTnI aHR, 2.70 (P = 0.003); hs-cTnT aHR, 1.98 (P = 0.043). The aHR of changes in hs-cTnI in tertile 2 >RCV for SCD was 5.62 (P = 0.039). CONCLUSIONS Changes over 3 months in hs-cTnI and hs-cTnT of >RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes >RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality.