Cardiac Troponins For The Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease PDF
Cardiac Troponins For The Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease PDF
Cardiac Troponins For The Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease PDF
Background-—Patients with chronic kidney disease (CKD) are at high risk of myocardial infarction. Cardiac troponins are the
biomarkers of choice for the diagnosis of acute myocardial infarction (AMI) without ST-segment elevation (NSTE). In patients with
CKD, troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE-AMI is suspected. The aim of
this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE-AMI.
Methods and Results-—Two cohorts, 1494 patients from a prospective cohort study with high-sensitivity troponin I (hs-cTnI)
measurements and 7059 cases from a clinical registry with high-sensitivity troponin T (hs-cTnT ) measurements, were analyzed.
The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2). The registry data
set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE-AMI than non-CKD
patients. The specificities of hs-cTnI and hs-cTnT to detect NSTE-AMI were reduced with CKD (0.82 versus 0.91 for hs-cTnI and
0.26 versus 0.73 for hs-cTnT) but could be restored by applying optimized cutoffs to either the first or a second measurement after
3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or
out AMI in 69% (hs-cTnI) and 55% (hs-cTnT) of CKD patients.
Conclusions-—The diagnostic performance of high-sensitivity cardiac troponins in patients with CKD with suspected NSTE-AMI is
improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration. ( J Am Heart
Assoc. 2018;7:e008032. DOI: 10.1161/JAHA.117.008032.)
Key Words: biomarker • chronic kidney disease • cohort study • decision aids • non-ST-segment elevation acute coronary
syndrome
From the Division of Nephrology, 1st Department of Medicine (D.K., C.D., C.W.) and Department for Artificial Intelligence and Applied Computer Science (G.F.),
University of W€urzburg, Germany; Division of Cardiology, Department of Internal Medicine III, Goethe University Frankfurt, Frankfurt, Germany (B.v.J., L.P., A.M.Z., T.K.);
3rd Department of Cardiology, Ιppokrateio Hospital, Aristotle University of Thessaloniki, Greece (S.T.); Clinic for General and Interventional Cardiology, University Heart
Center Hamburg, Hamburg, Germany (T.Z., J.T.N., S. Blankenberg); Department of Internal Medicine, Federal Armed Forces Hospital, Koblenz, Germany (C.B.);
Departments of Laboratory Medicine (K.J.L.) and Internal Medicine II (T.M.), University Medical Center, Johannes Gutenberg University, Mainz, Germany; Department of
Internal Medicine III, University of Cologne, Germany (S. Baldus); German Centre for Cardiovascular Research (DZHK), partner site RheinMain, Frankfurt, Germany
(B.v.J., A.M.Z., T.K.); German Centre for Cardiovascular Research (DZHK), partner site Hamburg/L€ubeck/Kiel, Hamburg, Germany (T.Z., J.T.N., S. Blankenberg);
Comprehensive Heart Failure Center (CHFC), University Hospital, W€urzburg, Germany (C.W.); Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad
Nauheim, Germany (T.K.).
Accompanying Tables S1 through S8 and Figures S1 through S5 are available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.117.008032
Correspondence to: Till Keller, MD, FESC, Kerckhoff Klinik, Abteilung f€ur Kardiologie, Benekestr 2-61231 Bad Nauheim, Germany. E-mail: keller@chestpain.de
Received November 9, 2017; accepted July 11, 2018.
ª 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-
commercial and no modifications or adaptations are made.
ORIGINAL RESEARCH
2008, the stenoCardia study enrolled adult patients who
Clinical Perspective presented with acute chest pain to 1 of 3 German study
centers. The study was approved by institutional review
What Is New?
boards, and all patients provided informed consent. Primary
• The current study proposes algorithms to help make the exclusion criteria included major surgery or trauma in the
diagnosis of non–ST-elevation myocardial infarction in previous 4 weeks, pregnancy, intravenous drug abuse, and
patients with impaired renal function on the basis of anemia (hemoglobin <10 g/dL). Dialysis patients were not
changes in high-sensitivity cardiac troponin levels.
eligible to participate. A total of 1818 patients with
suspected AMI were eligible for the current analysis.
What Are the Clinical Implications?
Estimated glomerular filtration rate (eGFR) could not be
• The algorithms may assist clinical decision making in the assessed in 9 patients, and 211 patients did not have hs-cTnI
emergency department, when a decision has to be made measured; 104 patients with ST-segment elevation were
whether or not to prescribe antiplatelet medication or to excluded because we were interested in those cases with
perform percutaneous intervention in these high-risk
suspected NSTE-AMI (Figure 1A). The final diagnosis of AMI
patients.
was adjudicated by 2 independent cardiologists, based on a
complete chart review as described earlier.5,6 Myocardial
comes at the cost of decreased sensitivity, that is, a greater infarction was assumed when there was at least 1 abnormal
risk of missing the diagnosis. Given the progressive nature conventional troponin measurement in conjunction with a
of myocardial damage in acute infarction, dynamic changes rise or fall of 20% or more in the first 6 hours, together with
in cTn levels may be more informative, specifically in clinical symptoms of ischemia or ECG changes consistent
patients with potential chronic cTn elevation. Serial cTn with new ischemia (new ST-segment or T-wave changes or
testing is indeed recommended in evaluation of suspected new left bundle-branch block) or imaging evidence of new
NSTE-AMI, but dedicated algorithms for CKD patients are loss of viable myocardium or detection of a culprit lesion on
lacking.1 coronary angiography.
In the current study we hypothesized that the performance
of hs-cTnI and hs-cTnT to diagnose NSTE-AMI is reduced when
Clinical Data Set
CKD is present and that dynamic changes may outperform
static cutoffs for the diagnosis of NSTE-AMI in CKD patients. The clinical data set was obtained retrospectively from the
We propose an algorithm incorporating changes in hs-cTn University of W€urzburg’s Clinical Data Warehouse, which
levels that increases the diagnostic confidence in CKD collects all inpatient and outpatient cases in a deidentified
patients. fashion.7 The Data Warehouse continuously acquires all
patient-related data for all inpatient and outpatient cases and
provides tools to retrospectively query the data, including
algorithms that employ artificial intelligence to extract
Methods information from texts such as reports and discharge
Two cohorts with a total of more than 8500 patients were letters.7 The Data Warehouse is approved by the Ethics
analyzed in this study. The first cohort came from a Committee of W€urzburg University, and patients have given
prospective multicenter biomarker study, stenoCardia (study written informed consent.
data set NCT03227159).5 The second data set was a The Data Warehouse was queried for all cases in the 1st
retrospective cohort of patients with potential AMI in a Medical Department (Cardiology Department) with at least 2
university hospital (clinical data set). The first and measurements of hs-cTnT between May 2011 and January
corresponding authors had full access to all the data in 2018. Per local policy, hs-cTnT is measured only if there is a
the study and take responsibility for its integrity and clinically suspected AMI.
data analysis. The data, analytic methods, and study Out of 7836 cases in the initial query, 11 were
materials will not be made available to other researchers disregarded due to obviously erroneous data, 556 patients
for purposes of reproducing the results or replicating the due to ST-segment elevation AMI, and we excluded 210
procedure. dialysis patients (Figure 1B). Adjudication of the clinical
diagnosis of AMI was based on the final judgments of the
attending physicians as stated in the patient discharge letter,
Study Data Set which incorporated all available data over the course of the
Details of the prospective study data set have been published patient’s treatment and overall assessment, and which
previously.5,6 Briefly, between January 2007 and December determines subsequent medical care. Comorbidities such
ORIGINAL RESEARCH
The hs-cTnT assay (Elecsys, Roche Diagnostics, Risch-
Rotkreuz, Switzerland) that was used in the clinical data set
has an assay range of 3 to 10 000 ng/L and a 99th-
percentile diagnostic cutoff of 14 ng/L.
Creatinine in both cohorts was measured enzymatically in
the respective central laboratories. The eGFR was computed
with the CKD Epidemiology Collaboration equation.
Statistical Analyses
Variables with normal distribution were characterized by
arithmetic mean and SD; skewed variables were described by
median and interquartile range.
Changes in serial cTn measurements were analyzed in 2
ways, either by selecting only those cases with an increase or
by using the absolute (unsigned) difference. The former
reflects clinical practice, where AMI in acutely symptomatic
patients is suspected only if there is a concomitant increase
in cTn levels; the latter satisfies the criterion of a rise or fall
that is proposed in the guidelines to accommodate situations
in which the patient presents some time after the acute
event.1
Sensitivity, specificity, positive (PPV) and negative predic-
tive values, and positive and negative likelihood ratios were
computed from a 292 table in the usual way with 95%
confidence limits for binomially distributed variables using the
epiR library in R. The statistical significance of the difference
between diagnostic tests was determined using the McNemar
test for paired samples (DTComPair package for R), and 292
contingency tables with chi-squared tests for the sensitivities
and specificities of unpaired samples.
To investigate the diagnostic performance of cTn in
patients with CKD, the area under the receiver-operator
characteristic curve was derived in patients with and without
Figure 1. Flow charts for the inclusion of study subjects. Flow CKD. Confidence intervals were computed from estimated
charts for subjects from (A) the prospective study cohort and (B) respective covariance matrices.8 In the study data set,
the clinical registry. ACS indicates acute coronary syndrome; AMI,
acute myocardial infarction; CKD, chronic kidney disease; NSTE,
optimized cutoffs for CKD patients were defined so that their
non–ST-segment elevation; STE, ST-segment elevation; TnI, specificity was the same specificity as the 99th-percentile
troponin I; TnT, troponin T. cutoffs in the non-CKD population. In the clinical data set, an
upper gray-zone limit of the assay of 50 ng/mL9 was used as
as hypertension and diabetes mellitus were based on the optimized cutoff. Specificity-optimized change thresholds
final discharge letters. were computed based on the Youden index.
For subsequent analyses we selected the subgroups of
patients from both cohorts who had an increase in hs-cTn
Blood Sampling and Laboratory Methods levels, and we performed additional analyses with the
In the study data set, blood was drawn directly on presen- absolute (unsigned) changes, which include both increases
tation and 3 hours after admission. The investigational hs- and decreases in troponin levels.
cTnI was determined in thawed samples using a troponin I Youden-optimized change thresholds were computed for
assay (ARCHITECT STAT hs Troponin I, Abbott Diagnostics, the absolute and for the relative increases of the serial
Abbott Park, IL) with an assay range of 0 to 50 000 ng/L, a troponin measurements in CKD patients. After optimization,
limit of detection of 1.9 ng/L, and a 99th-percentile diagnos- we divided our data sets into patients with initial troponin
tic cutoff of 30 ng/L.6 below or above the 99th percentile.
ORIGINAL RESEARCH
Table 1. Study Data Set Characteristics
Characteristics All Patients Patients Without CKD Patients With CKD P Value
Baseline characteristics of the study data set. Data are presented as cases/number (percentage), mean (SD), or median (IQR), as indicated. CAD indicates coronary artery disease; CKD,
chronic kidney disease; eGFR, estimated glomerular filtration rate; hs-cTnI, high-sensitive cardiac troponin I; IQR, interquartile range; NSTE-AMI, non–ST-segment elevation myocardial
infarction.
To develop diagnostic algorithms that incorporate dynamic these algorithms is expressed as the percentage of patients for
changes in hs-cTn levels, we computed sensitivities and whom AMI can be ruled in or out if these algorithms are applied.
specificities for optimized hs-cTn cutoffs at baseline alone as P values less than 0.05 were considered significant. All
well as for the combination of normal or abnormal baseline and analyses were carried out using R, versions 3.1.1 or 3.2.3 (R
second measurements. The overall diagnostic performance of Foundation for Statistical Computing, Vienna, Austria).
Characteristics All Patients Patients Without CKD Patients With CKD P Value
Baseline characteristics of the clinical data set. Data presented as cases/number (percentage), mean (SD), or median (IQR), as indicated. CKD indicates chronic kidney disease; eGFR,
estimated glomerular filtration rate; hs-cTnT, high-sensitivity cardiac troponin T; IQR, interquartile range; NSTE-AMI, non–ST-segment elevation acute myocardial infarction.
ORIGINAL RESEARCH
Results
Data Set Characteristics
In the study data set, 19% of patients had impaired renal
function (eGFR <60 mL/min/1.73 m2). AMI was diagnosed in
15% of non-CKD patients and in 26% of CKD patients (P<0.001).
Causes of noncoronary chest pain included pulmonary
embolism, acute decompensated heart failure, myocarditis,
aortic dissection, and aortic valve stenosis. A second hs-cTnI
measurement was available in 1385 patients (1139 without
and 246 with CKD).
In the clinical data set, 22% of patients had impaired renal
function (eGFR <60 mL/min/1.73 m2). In both data sets the
majority of CKD patients presented with CKD stage 3 (88% in
the study data set and 84% in the clinical data set [Tables S1
and S2]).
The mean eGFR in CKD patients was 46 mL/min/1.73 m2
in the study dataset and 44 mL/min/1.73 m2 in the clinical data
set. CKD patients were older than non-CKD patients, had a higher
prevalence of hypertension and diabetes mellitus and a higher
risk of NSTE-AMI (P<0.001 for all) (Tables 1 and 2). CKD patients
were less likely to receive percutaneous coronary interventions,
even when NSTE-AMI was diagnosed (Tables S3 and S4).
ORIGINAL RESEARCH
Table 3. Diagnostic Performances of Conventional and Optimized Cutoffs for Initial Troponin Measurements
hs-cTnI
No CKD 30 ng/L 0.88 (0.82, 0.92) 0.91 (0.89, 0.93) 10.09 (8.22, 12.38) 0.14 (0.09, 0.20) 0.63 (0.57, 0.69) 0.98 (0.97, 0.99)
CKD 30 ng/L 0.92 (0.83, 0.97) 0.82 (0.76, 0.87) 5.00 (3.72, 6.72) 0.10 (0.05, 0.22) 0.64 (0.54, 0.73) 0.97 (0.93, 0.99)
54.0 ng/L 0.82 (0.71, 0.9) 0.9* (0.85, 0.94) 8.10 (5.33, 12.32) 0.20 (0.12, 0.33) 0.74 (0.63, 0.83) 0.93 (0.89, 0.96)
hs-cTnT
No CKD 14 ng/L 0.85 (0.83, 0.88) 0.73 (0.71, 0.74) 3.11 (2.95, 3.29) 0.2 (0.17, 0.24) 0.39 (0.37, 0.41) 0.96 (0.95, 0.97)
CKD 14 ng/L 0.94 (0.92, 0.96) 0.26 (0.23, 0.29) 1.27 (1.22, 1.33) 0.22 (0.15, 0.33) 0.33 (0.31, 0.36) 0.92 (0.88, 0.95)
50 ng/L 0.66† (0.61, 0.7) 0.8† (0.78, 0.83) 3.34 (2.92, 3.82) 0.42 (0.37, 0.48) 0.57 (0.52, 0.61) 0.82 (0.8, 0.84)
Study data set: n=1494 patients with suspected NSTE-AMI; NSTE-AMI in n=251 patients. Clinical data set: n=7059 patients with suspected NSTE-AMI; NSTE-AMI in n=1375 patients. CKD
indicates chronic kidney disease; hs-cTnI, high-sensitivity troponin I; hs-cTnT, high-sensitivity troponin T; LR , negative likelihood ratio; LR+, positive likelihood ratio; NPV, negative
predictive value; NSTE-AMI, non–ST-segment elevation acute myocardial infarction; PPV, positive predictive value.
*This was the condition for which the optimized threshold was derived.
†
P<0.001 compared with the 99th-percentile cutoff.
ORIGINAL RESEARCH
Figure 3. Algorithms for the diagnosis of NSTE-AMI in patients with CKD. Diagnostic algorithms for
patients with CKD, suspected myocardial infarction, and nonspecific ECGs with the (A) hs-cTnI and (B) hs-
cTnT assays. Numbers indicate how many patients were affected in the corresponding cohorts. AMI
indicates acute myocardial infarction; CKD, chronic kidney disease; D, change; ECG, electrocardiogram; hs-
cTnI and hs-cTnT, high-sensitivity cardiac troponin I and T, respectively; NSTE-AMI, non–ST-segment
elevation acute myocardial infarction.
imaging techniques that are not nephrotoxic, such as Our study incorporates a large number of CKD patients
echocardiography or single-photon emission computed from 2 cohorts with high-sensitivity cTn measurements and
tomography and possibly coronary angiography after reno- arrives at comparable results for both cohorts despite the use
protective treatment. Despite our improved algorithm, of different hs-cTn assays. Nonetheless, our study has several
patients with CKD and suspected NSTE-AMI represent high- limitations.
risk, complex patients, and a decision for or against treating A critical issue is the adjudication of the final diagnosis. In
an NSTE-AMI in such a patient must carefully balance the the prospective study cohort, 2 independent cardiologists
individual risk and benefit. adjudicated the final diagnosis based on a complete review of
Previous attempts to optimize the diagnostic performance clinical, laboratory, and imaging findings.5 In the retrospective
of troponins in patients with CKD have proposed adjusted data set from the Clinical Data Warehouse, the final diagnosis
higher static cutoffs at the cost of decreased sensitivity,3,4 was made by the physician who discharged the patient. This
have analyzed small numbers of CKD patients,4,15,16 or have final clinical diagnosis was based on the entire course of the
used non–high-sensitivity assays16 and elected not to provide treatment and includes laboratory, other diagnostic examina-
performance estimates.15 One recent retrospective study tions, and the overall impression and informs subsequent
proposed a graded cutoff system for CKD stages G3 to G5. medical care. Still, CKD patients with NSTE-AMI for whom the
This study also included patients with STE-AMI in whom the diagnosis was ruled out despite elevated troponin levels might
decision for immediate invasive imaging is primarily based on be misclassified in the retrospective data set. However, it
the pathognomonic ECG changes.17 should be noted that the proportion of patients with CKD who
ORIGINAL RESEARCH
Table 4. Diagnostic Performance of Changes in Troponin Levels in CKD Patients
hs-cTnI
Baseline 14.5 ng/L 0.60 (0.15, 0.95) 0.94 (0.89, 0.98) 10.8 (3.91, 29.8) 0.42 (0.14, 1.24) 0.3 (0.07, 0.65) 0.98 (0.94, 1)
≤30 ng/L
2.8-fold 0.60 (0.15, 0.95) 0.90 (0.84, 0.95) 6.3 (2.57, 15.43) 0.44 (0.15, 1.3) 0.2 (0.04, 0.48) 0.98 (0.94, 1)
Baseline 14.5 ng/L 0.95 (0.83, 0.99) 0.50 (0.25, 0.75) 1.9 (1.16, 3.11) 0.1 (0.02, 0.43) 0.82 (0.68, 0.92) 0.8 (0.44, 0.97)
>30 ng/L
2.8-fold 0.41 (0.26, 0.58) 0.88 (0.62, 0.98) 3.28 (0.85, 12.66) 0.67 (0.49, 0.93) 0.89 (0.65, 0.99) 0.38 (0.22, 0.55)
hs-cTnT
Baseline 36.0 ng/L 0.55 (0.32, 0.76) 0.92 (0.87, 0.96) 7.27 (3.74, 14.14) 0.49 (0.31, 0.78) 0.5 (0.29, 0.71) 0.94 (0.89, 0.97)
≤14 ng/L
2.5-fold 0.86 (0.65, 0.97) 0.84 (0.77, 0.89) 5.31 (3.6, 7.84) 0.16 (0.06, 0.47) 0.42 (0.28, 0.58) 0.98 (0.94, 1.0)
Baseline 36.0 ng/L 0.7 (0.64, 0.75) 0.89 (0.86, 0.92) 6.37 (4.82, 8.43) 0.34 (0.29, 0.4) 0.82 (0.77, 0.87) 0.8 (0.76, 0.84)
>14 ng/L
2.5-fold 0.41 (0.36, 0.47) 0.92 (0.89, 0.95) 5.37 (3.77, 7.64) 0.64 (0.58, 0.7) 0.8 (0.73, 0.86) 0.68 (0.64, 0.72)
Study data set: n=186 patients with CKD and increase in hs-cTnI; NSTE-AMI in n=44 patients. Clinical data set: n=926 patients with CKD and increase in hs-cTnT; NSTE-AMI in n=337
patients. CKD indicates chronic kidney disease; hs-cTnI, high-sensitivity troponin I; hs-cTnT, high-sensitivity troponin T; LR , negative likelihood ratio; LR+, positive likelihood ratio; NPV,
negative predictive value; NSTE-AMI, non–ST-segment elevation acute myocardial infarction; PPV, positive predictive value.
were diagnosed with NSTE-AMI is almost the same in the guideline of the European Society for Cardiology,1 but they
prospective study cohort as in the much larger retrospective lack specific recommendations for patients with CKD.
registry cohort, lending credence to the validity of the latter. Change cutoffs have previously been optimized in the
One might argue that the selection criteria for the registry study cohort for the overall patient population irrespective of
cohort—2 measurements of troponin—may include patients CKD.6 Maximum PPV was obtained with a change cutoff of
with suspected diagnoses other than acute infarction. How- 2.7-fold,6 which is comparable to the 2.8-fold derived for the
ever, it is local policy to perform 2 measurements only when CKD subgroup. It should be noted, however, that a much
AMI is suspected, and the difference of 3.2 hours between lower optimized change cutoff of 1.3-fold within 6 hours using
the 2 hs-cTnT measurements is very close to the guideline a non–high-sensitive assay has also been proposed.20
recommendations for suspected AMI that were applicable in For the hs-cTnT assay and patients free of CKD, an
the data collection period.18 optimized change cutoff of 1.17-fold within 3 hours has been
The relative change cutoffs that we derived from our data reported.21 This is considerably lower than the 2.5-fold cutoff
sets, 280% for hs-cTnI and 250% for hs-cTnT, differ greatly that we derived for the CKD patients in the registry cohort.
from the 20% proposed earlier.12 However, this recommen- The difference may be explained by the greater intraindividual
dation was not based on evidence.14,19 Change cutoffs have variability of troponin levels in patients with impaired renal
been incorporated into diagnostic algorithms in the latest function.
hs-cTnI hs-cTnT
Sensitivity 0.90* (0.79, 0.96) 1.00* (0.94, 1.00) 0.80* (0.76, 0.84) 0.98* (0.97, 0.99)
Specificity 0.87* (0.81, 0.91) 0.51* (0.43, 0.58) 0.78* (0.76, 0.81) 0.24* (0.21, 0.26)
PPV 0.68 (0.56, 0.78) 0.38 (0.31, 0.47) 0.59 (0.55, 0.63) 0.34 (0.31, 0.36)
NPV 0.96 (0.92, 0.99) 1.00 (0.96, 1.00) 0.91 (0.89, 0.93) 0.97 (0.95, 0.99)
LR+ 6.74 (4.63, 9.81) 2.02 (1.75, 2.34) 3.68 (3.26, 4.15) 1.29 (1.25, 1.34)
LR 0.12 (0.06, 0.26) 0.00 (0.00, NaN) 0.26 (0.21, 0.31) 0.07 (0.03, 0.14)
For the rule-in approach, patients in the “observe” category were counted as having a negative test result; for the rule-out approach, patients in the “observe” category were counted as
having a positive test result (cf. Figure 3). Values in parentheses indicate the 95% confidence intervals. Study data set: n=172 patients with CKD and suspected NSTE-AMI; NSTE-AMI in
n=52 patients. Clinical data set: n=880 patients with CKD and suspected NSTE-AMI; NSTE-AMI in n=364 patients. CKD indicates chronic kidney disease; hs-cTnI, high-sensitivity troponin I;
hs-cTnT, high-sensitivity troponin T; LR , negative likelihood ratio; LR+, positive likelihood ratio; NaN, not a number; NPV, negative predictive value; NSTE-AMI, non–ST-segment elevation
acute myocardial infarction; PPV, positive predictive value.
*P<0.001 by McNemar test compared with optimized static cutoff (54 ng/L for hs-cTnI, 50 ng/L for hs-cTnT); McNemar test asserts significant differences between sensitivities and
specificities only.
ORIGINAL RESEARCH
Overall, the hs-cTnI assay outperforms the hs-cTnT assay in Disclosures
patients with CKD. The poor performance of the hs-cTnT
Lackner has a modest relationship with Abbott Diagnostics
assay with impaired renal function has been noted
(honoraria recipient, member of the Advisory Board). The
previously.3,22
other authors have nothing to disclose.
In our study, initial creatinine was used to compute eGFR.
However, initial eGFR is not the same as chronic, stable eGFR.
Acute renal failure is not uncommon in acute cardiovascular References
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NSTEMI
CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention. Statistical
NSTEMI
CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention. Statistical
troponin T; LR+, positive likelihood ratio; LR-, negative likelihood ratio; PPV, positive
Values are expressed in ng/L as median and interquartile ranges. Only cases with rising troponin
levels were included in this analysis (1185 of 1494 cases in the study dataset and 1944 of 4478
cases in the clinical dataset; cf. Tables 1 and 2). AMI, acute myocardial infarction; CKD,
measurements. Because a rise or fall in troponin levels may indicate myocardial infarction,
absolute values of the differences between the second and the first measurement were averaged;
results expressed in ng/L with median and interquartile ranges. Relative changes were
computed by dividing the larger value by the smaller value and subtract 1; the results are given
CKD patients.
For this analysis, all changes between the first and second measurements were converted to
(A) hs-cTnI and (B) hs-cTnT levels upon admission in patients with acute chest pain divided
according to renal function (eGFR, estimated glomerular filtration rate) and final diagnosis.
Figure S2. Sensitivity and specificity of initial troponins for the diagnosis of NSTE-AMI
Sensitivity, specificity and sum of sensitivity and specificity of (A) hs-cTnI and (B) hs-cTnT
determined upon admission in patients with acute chest pain and CKD to identify an acute
myocardial infarction.
Figure S3. Second troponin measurements in patients with or without CKD and with or
without NSTE-AMI
(A) hs-cTnI and (B) hs-cTnT levels three hours after admission in patients with acute chest
pain according to renal function (eGFR, estimated glomerular filtration rate) and final
diagnosis.
Figure S4. Serial differences in troponin levels in patients with or without CKD and with
or without NSTE-AMI
Differences between serial (A) hs-cTnI and (B) hs-cTnT measurements. Values are expressed
in ng/L as median and interquartile ranges. Only cases with an increase in troponin levels
after 3 hours were included in this analysis (1185 of 1494 cases in the study dataset and 1944
without NSTE-AMI
Relative changes of serial (A) hs-cTnI and (B) hs-cTnT measurements. Values are expressed
in ng/L as median and interquartile ranges. Only cases with an increase in troponin levels
after 3 hours were included in this analysis (1185 of 1494 cases in the study dataset and 1944