To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without ...acute myocardial infarction (AMI).
In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays.
Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value.
Abstract Background The early and accurate diagnosis of AMI is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new ESC rapid 0 h/3 h-rule-out ...protocol for AMI. Methods We enrolled 2727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study. The final diagnosis was adjudicated by two independent cardiologists. The performance of the 0 h/3 h-rule-out protocol was evaluated using four high-sensitivity (primary analysis) and three sensitive cardiac troponin (cTn) assays). Results AMI was the final diagnosis in 473 patients (17.3%). Using the four high-sensitivity cTn assays, the 0 h-rule-out protocol correctly ruled-out 99.8% (95%CI, 98.7–100%), 99.6% (95%CI, 98.5–99.9%), 100% (95%CI, 97.9–100%) and 100% (95%CI, 98.0–100%) of late presenters (>6 h from chest pain onset). The 3 h-rule-out protocol correctly ruled-out 99.9% (95%CI, 99.1–100%), 99.5% (95%CI, 98.3–99.9%), 100% (95%CI, 98.1–100%) and 100% (95%CI, 98.2–100%) of early presenters (<6 h from chest pain onset). Using the three sensitive cTn assays, the 0 h-rule-out protocol correctly ruled-out 99.6% (95%CI, 98.6–99.9%), 99.0% (95%CI, 96.9–99.7%) and 99.1% (95%CI, 97.2–99.8%) of late presenters, and the 3 h-rule-out protocol correctly ruled-out 99.4% (95%CI, 98.3–99.8%), 99.2% (95%CI, 97.3–99.8%) and 99.0% (95%CI, 97.2–99.7%) of early presenters. Overall, the 0 h/3 h-rule-out protocol assigned 40–60% of patients to rule-out. None of the patients assigned rule-out died during 3-months follow-up. Conclusions The 0 h/3 h-rule-out protocol seems to allow the accurate rule-out of AMI using both high-sensitivity and sensitive cTn measurements in conjunction with clinical assessment. Additional studies are warranted for external validation.
Abstract Objective The study objective was to compare the incidence and prognosis of acute myocardial infarction when using high-sensitivity cardiac troponin assays instead of a standard cardiac ...troponin assay for the diagnosis of acute myocardial infarction. Methods In a prospective international multicenter study, we enrolled 1124 consecutive patients presenting with suspected acute myocardial infarction. Final diagnoses were adjudicated by 2 independent cardiologists 2 times using all available clinical information: first using standard cardiac troponin levels and second using high-sensitivity cardiac troponin T levels for adjudication. Patients were followed up for a mean of 19 ± 9 months. Results The use of high-sensitivity cardiac troponin T instead of standard cardiac troponin resulted in an increase in the incidence of acute myocardial infarction from 18% to 22% (242 vs 198 patients), a relative increase of 22%. Of the 44 additional acute myocardial infarctions, 35 were type 1 acute myocardial infarctions and 9 were type 2 acute myocardial infarctions. This was accompanied by a reciprocal decrease in the incidence of unstable angina (unstable angina, 11% vs 13%). The most pronounced increase was observed in patients adjudicated with cardiac symptoms of origin other than coronary artery disease with cardiomyocyte damage (83 vs 31 patients, relative increase of 268%). Cumulative 30-month mortality rates were 4.8% in patients without acute myocardial infarction, 16.4% in patients with a small acute myocardial infarction detected only by high-sensitivity cardiac troponin T but not standard cardiac troponin, and 23.9% in patients with a moderate/large acute myocardial infarction according to standard cardiac troponin assays and high-sensitivity cardiac troponin T ( P < .001). Conclusions The introduction of high-sensitivity cardiac troponin assays leads to only a modest increase in the incidence of acute myocardial infarction. The novel sensitive assays identify an additional high-risk group of patients with increased mortality, therefore appropriately classified with acute myocardial infarction (Advantageous Predictors of Acute Coronary Syndromes Evaluation; NCT00470587 ).
Objective We aimed to prospectively derive and validate a novel 0-/1-hour algorithm using high-sensitivity cardiac troponin I (hs-cTnI) for the early “rule-out” and “rule-in” of acute myocardial ...infarction (AMI). Methods In a prospective multicenter diagnostic study, we enrolled 1,500 patients presenting with suspected AMI to the emergency department. The final diagnosis was centrally adjudicated by 2 independent cardiologists blinded to hs-cTnI concentrations. The hs-cTnI (Siemens Vista) 0-/1-hour algorithm incorporated measurements performed at baseline and absolute changes within 1 hour, was derived in the first 750 patients (derivation cohort), and then validated in the second 750 (validation cohort). Results Overall, AMI was the final diagnosis in 16% of patients. Applying the hs-cTnI 0-/1-hour algorithm developed in the derivation cohort to the validation cohort, 57% of patients could be classified as “rule-out”; 10%, as “rule-in”; and 33%, as “observe.” In the validation cohort, the sensitivity and the negative predictive value for AMI in the “rule-out” zone were 100% (95% CI 96%-100%) and 100% (95% CI 99%-100%), respectively. The specificity and the positive predictive value (PPV) for AMI in the “rule-in” zone were 96% (95% CI 94%-97%) and 70% (95% CI 60%-79%), respectively. Negative predictive value and positive predictive value of the 0-/1-hour algorithm were higher compared to the standard of care combining hs-cTnI with the electrocardiogram (both P < .001). Conclusion The hs-cTnI 0-/1-hour algorithm performs very well for early rule-out as well as rule-in of AMI. The clinical implications are that used in conjunction with all other clinical information, the 0-/1-hour algorithm will be a safe and effective approach to substantially reduce time to diagnosis.
The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due ...to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging.
In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations.
AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8–100% and 99.5–100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7–100% and 98.9–100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7–26.8%).
All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice.
NCT00470587, http://clinicaltrials.gov/show/NCT00470587.
•All examined hs-cTn-based rapid rule-out strategies, except for the dual-marker strategy and the NICE-algorithm using hs-cTnI, provide high and comparable safety.•The efficacy of the different hs-cTn-based rapid rule-out strategies varied substantially among the different strategies.•The incidence of 30-day MACE among patients triaged towards rule-out was very low and comparable among the different strategies.•Findings in the subgroup of early presenters overall were similar to those obtained for the whole cohort for the different strategies.•No systematic difference was shown between the rule-out strategies according to the applied hs-cTn assay, except for the NICE algorithm.
To investigate the diagnostic and prognostic role of heart-type fatty acid-binding protein (hFABP) compared with copeptin and in addition to high-sensitivity cardiac troponin T (hs-cTnT) in patients ...with chest pain suspected of acute myocardial infarction (AMI).
Diagnostic and prognostic performances of hFABP, copeptin and hs-cTnT were evaluated and compared. The final diagnosis was adjudicated by two independent cardiologists.
This prospective observational multicentre study took place in four primary and one secondary hospital from April 2006 to September 2009.
We enrolled 1247 consecutive patients with suspected AMI to the emergency department. For analysis, patients were included, if baseline levels for hs-cTnT and hFABP were available (n=1074), patients with ST-segment elevation myocardial infarction (STEMI) were excluded for the diagnostic analysis (n=43).
Treatment was left to the discretion of the emergency physician.
AMI and mortality.
4% of the patients had STEMI and 16% of the patients had non-STEMI. Patients with AMI had significantly higher levels of hFABP at presentation (p<0.001). Neither the combination with hFABP nor with copeptin increased the diagnostic accuracy of hs-cTnT at admission, quantified by the area under the receiver operating characteristic curve (AUC) (p>0.05). The negative predictive value regarding 90-day, 1-year and 2-year mortality was 100% (99-100), 99% (98-100) and 98% (96-99), respectively, for hFABP levels below the median (p<0.001). The accuracy of hFABP to predict 90-day mortality was moderate (AUC 0.83; 95% CI 0.77 to 0.90).
hFABP and copeptin do not improve the diagnosis of patients with chest pain without ST-segment elevation, but may be useful for risk stratification beyond hs-TnT.
We compared 2 high-sensitivity cardiac troponin (hs-cTn)-based 2-h strategies in patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED): the 2-h ...accelerated diagnostic protocol (2h-ADP) combining hs-cTn, electrocardiogram, and a risk score, and the 2-h algorithm exclusively based on hs-cTn concentrations and their absolute changes.
Analyses were performed in 2 independent diagnostic cohorts European Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study, Australian-New Zealand 2-h Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker (ADAPT) study employing hs-cTnT (Elecsys) and hs-cTnI (Architect). The final diagnosis was adjudicated by 2 independent cardiologists.
AMI was the final diagnosis in 16.5% (95% CI, 14.6%-18.6%) of the 1372 patients in APACE, and 12.6% (95% CI, 10.7%-14.7%) of 1153 patients in ADAPT. The negative predictive value (NPV) and sensitivity for AMI were very high and comparable with both strategies using either hs-cTnT or hs-cTnI in both cohorts (all statistical comparisons nonsignificant). The percentage of patients triaged toward rule-out was significantly lower with the 2h-ADP (36%-43%) vs the 2-h algorithm (55%-68%) with both assays and in both cohorts (
< 0.001). The sensitivity of the 2h-ADP was higher for 30-day major adverse cardiovascular events.
Both algorithms provided very high and comparable safety as quantified by the NPV and sensitivity for AMI and major adverse cardiac events (MACE) at 30 days in patients triaged toward rule-out, although sensitivity for MACE at 30 days was lower with both algorithms in cohort 2. Although the 2-h algorithm was more efficacious, not all patients ruled out for AMI by this algorithm were appropriate candidates for early discharge. The 2h-ADP seems superior in the selection of patients for early discharge from the ED.
APACE: http://clinicaltrials.gov/show/NCT00470587ADAPT: Australia-New Zealand Clinical Trials Registry ACTRN12611001069943.
Background A pilot study using a novel high-sensitivity cardiac troponin I (hs-cTnI) assay suggested that cTnI might be released into blood during exercise-induced myocardial ischemia. We ...investigated the potential clinical value of this signal. Methods We included 819 patients with suspected exercise-induced myocardial ischemia referred for rest/bicycle myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischemia using a visual analog scale twice: prior and after stress testing. High-sensitivity cTnI measurements were obtained before, immediately after peak stress, and 2 hours after stress testing in a blinded manner. Myocardial ischemia was adjudicated using perfusion single-photon emission computed tomography and coronary angiography findings. Results Exercise-induced myocardial ischemia was detected in 278 (34%) patients. High-sensitivity cTnI levels were significantly higher at all time points in patients with myocardial ischemia as compared with those without ( P < .001 for all). Combining clinical judgment prior exercise testing with baseline hs-cTnI levels increased diagnostic accuracy as quantified by the area under the receiver operating characteristics curve (AUC) from 0.672 to 0.757 ( P < .001). Combining clinical judgment after exercise testing (AUC 0.704) with baseline or poststress hs-cTnI levels also increased the diagnostic accuracy (AUC 0.761-0.771, P < .001 for all). In contrast, exercise-induced changes in hs-cTnI during exercise did not seem useful, as they were small and similar in patients with or without myocardial ischemia. Conclusions High-sensitivity cTnI concentrations at rest and after exercise, but not its exercise-induced changes, provide substantial incremental value to clinical judgment including exercise electrocardiography regarding the presence of myocardial ischemia.
The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown.
Ninety-eight patients from the randomized ...controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (
=0.046) and -0.381 (
=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively.
Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.
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