Seoung Mann Sou

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin

BACKGROUND We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). METHODS AND RESULTS In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. CONCLUSIONS Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays.

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays

AIMS Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. METHODS AND RESULTS In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. CONCLUSION High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.

Normal presenting levels of high-sensitivity troponin and myocardial infarction

Objective To analyse whether levels of high-sensitivity cardiac troponin (hs-cTn) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infarction (AMI) at presentation. Design Prospective, multicentre study. Main outcome measures We measured hs-cTn using four different methods (hs-cTnT Roche, hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting to the emergency department with acute chest pain. Two independent cardiologists adjudicated the final diagnosis. Patients were followed for death or AMI during a mean period of 24 months. Results Among 2072 consecutive patients with hs-cTnT measurements available, 21.4% had an adjudicated diagnosis of AMI (sensitivity 89.6%, 95% CI 86.4% to 92.3%, negative predictive value (NPV): 96.5%, 95% CI 95.4% to 97.4%). Among 1180 consecutive patients with hs-cTnI Siemens measurements available, 20.0% had AMI (sensitivity 94.1%, 95% CI 90.3% to 96.7%, NPV: 98.0%, 95% CI: 96.6% to 98.9%). Among 1151 consecutive patients with hs-cTnI Beckman Coulter measurements available, 19.7% had AMI (sensitivity 92.1%, 95% CI 87.8% to 95.2%, NPV: 97.5%, 95% CI 96.0% to 98.5%). Among 1567 consecutive patients with hs-cTnI Abbott measurements available, 20.0% had AMI (sensitivity 77.2%, 95% CI 72.1% to 81.7%, NPV: 94.3%, 95% CI 92.8% to 95.5%). Conclusions Normal hs-cTn levels at presentation should not be used as a single parameter to rule out AMI as 6%–23% of adjudicated AMI cases had normal levels of hs-cTn levels at presentation. Our data highlight the lack of standardisation among hs-cTnI assays resulting in substantial differences in sensitivity and NPV at the 99th percentile.

Prevalence, extent, and independent predictors of silent myocardial infarction.

BACKGROUND The phenomenon of silent myocardial infarction is poorly understood. METHODS We aimed to evaluate the prevalence, extent, and independent predictors of silent myocardial infarction in 2 large independent cohorts of consecutive patients without a history of myocardial infarction referred for rest/stress myocardial perfusion single photon emission computed tomography. There were 1621 patients enrolled in the derivation cohort and 338 patients in the validation cohort. Silent myocardial infarction was diagnosed in patients with a myocardial scar ≥5% of the left ventricle. RESULTS In the derivation cohort, the prevalence of silent myocardial infarction was 23.3% (n = 377). The median infarct size was 10% (interquartile range [IQR] 5%-15%) of the left ventricle. The prevalence of silent myocardial infarction was 28.5% in diabetics and 21.5% in nondiabetics (P = .004). Diabetes mellitus was an independent predictor for the presence of silent myocardial infarction (odds ratio 1.5; 95% confidence interval, 1.1-1.9; P = .004). These findings were confirmed in the independent validation cohort. In the validation cohort, the prevalence of silent myocardial infarction was 26.3% (n = 89), while the prevalence was higher in diabetics (35.8%) than in nondiabetics (24%; P = .049). The median infarct size was 11.8% (IQR 5.9%-17.6%) of the left ventricle. Again, in logistic regression analysis, diabetes mellitus was a significant predictor of the presence of silent myocardial infarction. CONCLUSION Silent myocardial infarctions are more common than previously thought. One of 4 patients with suspected coronary artery disease had experienced a silent myocardial infarction; the extent in average is 10% of the left ventricle, and it is more common in diabetics.

Early Diagnosis of Myocardial Infarction Using Absolute and Relative Changes in Cardiac Troponin Concentrations

BACKGROUND Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. METHODS In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. CONCLUSIONS Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI.

Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction

BACKGROUND Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high-sensitivity cTnI assays. METHODS In a prospective international multicentre study, we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre-commercial high-sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI. The final diagnosis of AMI was adjudicated using all available data including serial hs-cTnT levels by two independent cardiologists. RESULTS The diagnostic accuracy of absolute changes in the diagnosis of AMI as quantified by the area under the receiver operating characteristics curve (AUC) was very high (e.g. at 2 h, Siemens high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96; Beckman Coulter high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96) and superior to relative changes at all time points (p < 0.001). The results were consistent in clinically important subgroups. Direct comparison of the absolute changes in the two high-sensitivity cTnI assays showed similar accuracy. When combined with the baseline cTnI levels, the difference between absolute and relative changes became much smaller and remained statistically significant only for the Siemens assay. CONCLUSIONS As single variables early absolute changes in high-sensitivity cTnI levels have significantly higher diagnostic accuracy than relative changes. When combined with the baseline cTn level, reflecting clinical practice, both absolute and relative changes provided very high accuracy with much smaller differences between both approaches.

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea

Objectives Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). Design Prospective cohort study. Setting University hospital, emergency department. Patients 632 consecutive patients presenting with acute dyspnoea. Main outcome measures MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. Results AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258–598) versus 201 (89–375) pmol/l for MR proANP, p<0.001 and 4916 (2169–10285) versus 1177 (258–5166) pg/ml, p<0.001 for NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90, 95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off levels in AF patients were significantly higher compared with the optimal cut-off levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500 pg/ml respectively). After adjustment in multivariable Cox proportional hazard analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13 (1.09–1.17), per 100 pmol/l increase, p<0.001). Conclusion In AF patients, NT proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

Direct comparison of cardiac troponin I and cardiac troponin T in the detection of exercise-induced myocardial ischemia

BACKGROUND It is unknown, whether cardiac troponin (cTn) I or cTnT is the preferred biomarker in the detection of exercise-induced myocardial ischemia. METHODS We investigated patients with suspected myocardial ischemia referred for exercise or pharmacological rest/stress myocardial perfusion single-photon emission computed tomography (SPECT) to directly compare the diagnostic accuracy of high-sensitivity cTnI (hs-cTnI) and hs-cTnT. Diagnostic performance was analyzed separately according to stress modality. Hs-cTnI and hs-cTnT were measured before, immediately after, as well as 2h and 4h after maximal exercise in a blinded fashion. Further, all clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of myocardial ischemia using a visual analog scale twice: once prior and once after stress-testing. The presence of stress-induced myocardial ischemia was adjudicated using SPECT combined with coronary angiography findings. RESULT A total of 403 consecutive patients were enrolled in our study, of which 229 underwent exercise stress and 174 patients pharmacological stress. Exercise-stress-induced myocardial ischemia was detected in 90 patients (39.3% of 229). Levels of hs-cTnI and hs-cTnT were both significantly higher at all time-points examined in patients with exercise-induced myocardial ischemia as compared to patients without myocardial ischemia (all p<0.001). Correlation of hs-cTnI and hs-cTnT was high in direct comparison of time-points (Spearmans rho all ≥0.7). The AUCs for baseline/peak/2h/4h for hs-cTnI and hs-cTnT were 0.71/0.71/0.72/0.69 vs. 0.74/0.73/0.71/0.72, respectively (all p=ns for hs-cTnI versus hs-cTnT). In patients undergoing pharmacological stress, the AUCs for baseline/peak/2h/4h for hs-cTnI and hs-cTnT were 0.66/0.66/0.68/0.67 and 0.61/0.62/0.64/0.59, respectively (all p=ns for hs-cTnI versus hs-cTnT). Also the combinations including clinical judgment or changes during serial sampling were similar for hs-cTnI and hs-cTnT (all p=ns). CONCLUSIONS Hs-cTnI and hs-cTnT provide comparable diagnostic information regarding exercise-induced myocardial ischemia. Overall, their diagnostic accuracy seems moderate. UNIQUE IDENTIFIER NCT01838148.

B-type Natriuretic Peptide and Clinical Judgment in the Detection of Exercise-induced Myocardial Ischemia

BACKGROUND Myocardial ischemia has been shown to be associated with increased levels of B-type natriuretic peptide (BNP). However, it remains unclear whether and how BNP levels could be used clinically in patients with suspected exercise-induced myocardial ischemia. METHODS We enrolled 274 consecutive patients with suspected exercise-induced myocardial ischemia referred for evaluation by rest/bicycle myocardial perfusion single-photon emission computed tomography (SPECT). All clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of myocardial ischemia using a visual analogue scale twice: once before and once after bicycle exercise stress testing. BNP measurements were obtained before, immediately after, and 2 hours after stress testing in a blinded manner. The presence of myocardial ischemia was adjudicated on the basis of perfusion SPECT combined with coronary angiography findings. RESULTS Exercise-induced myocardial ischemia was adjudicated to be present in 103 patients (38%). BNP levels were significantly higher at all time points in patients with myocardial ischemia compared with those without (P < .01 for all). The accuracy of BNP levels as quantified by the area under the receiver operating characteristic curve (AUC) was similar among the time points evaluated (AUC, 0.677-0.697). Combining clinical judgment before exercise testing with BNP levels at rest increased diagnostic accuracy from AUC 0.708 to 0.754 (P = .018). When combining clinical judgment after exercise testing with BNP levels, AUC increased from 0.741 to 0.771 (P = .055). CONCLUSIONS Combining clinical judgment with BNP levels increased the diagnostic accuracy regarding the presence of myocardial ischemia.

Delayed release of brain natriuretic peptide to identify myocardial ischaemia

A recent pilot study suggested that exercise‐induced myocardial ischaemia may lead to a delayed release of cardiac biomarkers, so that later sampling, for example, at 4 h after exercise could be used for diagnostic purpose.