Heart-type fatty acid-binding protein in early diagnosis of acute myocardial infarction in comparison to sensitive troponin I

Size: px

Start display at page:

Download "Heart-type fatty acid-binding protein in early diagnosis of acute myocardial infarction in comparison to sensitive troponin I"

Juniper Conley
6 years ago
Views:

1 Heart-type fatty acid-binding protein in early diagnosis of acute myocardial infarction in comparison to sensitive troponin I E. Czyz 1, S. Tzikas 1, A. Schulz 1, T. Zeller 1,3, S. Baldus 3, C. Bickel 2, T. Keller 1,3, C. Sinning 1,3, P.S. Wild 1, F. Post 1, S. Genth-Zotz 1, A. Warnholtz 1, K. Lackner 1, T. Münzel 1, S. Blankenberg 1,3 1 University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany 2 Central Hospital of the Federal Armed Forces in Koblenz, Koblenz, Germany 3 Heart Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

2 Disclosure No conflicts of interest to declare 2

release (within 30 minutes) after myocardial injury due to unbound cytoplasmic location Plasma peak 6h to 8h and

3 Heart-type fatty acid-binding protein - an early biomarker of myocardial injury Schematic presentation of the transport pathways of fatty acids from the capillary to the mitochondria Stable protein of low molecular mass (14-15kDa) Early release (within 30 minutes) after myocardial injury due to unbound cytoplasmic location Plasma peak 6h to 8h and normalisation of concentration within 20h after cell injury More specific than myoglobin Limited cardiospecificity Kiens B Physiol Rev Jan

4 Sensitive troponin vs. htfabp Diagnostic accuracy of single biomarker testing for acute myocardial infarction (n=1818) TnThs, h-fabp and myoglobin at admission for prediction of non STelevation myocardial infarction (n=94) Keller et al N Engl J Med 2009 Kurz et al Clin Res Cardiol

5 Objective To assess the impact of htfabp in comparison to sensitive troponin I in diagnosis of acute myocardial infarction 5

Study design University Hospital Hamburg-Eppendorf University Medical Center Mainz Federal Armed Forces Hospital Koblenz N=1818 Inclusion criteria Exclusion criteria Age between 18 and 85 years,

6 Study design University Hospital Hamburg-Eppendorf University Medical Center Mainz Federal Armed Forces Hospital Koblenz N=1818 Inclusion criteria Exclusion criteria Age between 18 and 85 years, suspected ACS, chest discomfort 24h before admission Major trauma 4 wks, pregnancy, anemia (Hb< 10 mg/dl), iv. drug abuse At 0h, 3h, 6h: clinical assessment, 12 lead ecg, blood work up Final diagnosis based on conventional troponin assays: Troponin T Roche (Mainz, Hamburg), Troponin I Siemens Dimension RxL (Koblenz) Non coronary chest pain Unstable angina pectoris Acute myocardial infarction 6

7 Investigational biomarkers Heart-type fatty acid-binding protein (htfabp), Evidence Assay Biochip by Randox (UK) Cut-off for women 5,3 ng/ml, for men 5,8 ng/ml (inter-assay CV 5% at 5,8 ng/ml) (1) Troponin I Ultra ADVIA Centaur, XP System by Siemens Healthcare Diagnostics (USA) Cut-off 0,04 ng/ml (10% CV at 0,03 ng/ml) (1) Serum 99 th centile values for two heart-type fatty acid binding protein assays. Bathia D P et al Ann Clin Biochem 2009;46:

8 Baseline characteristics Non coronary chest pain Acute myocardial infarction No. of patients (%) 1165 (64,1) 413 (22,3) - p-value Male sex (%) 804 (64,1) 729 (62,6) <0,001 Age (y) 59,7±14,3 64,0±11,8 <0,001 BMI (kg/m ) 26,9 (24,6/30,3) 27,2 (24,7/30,4) 0,46 LDL/HDL Ratio 2,30 (1,65/3,00) 2,82 (2,08/3,62) <0,001 Diabetes mellitus (%) 172 (15,0) 88 (21,7) 0,002 Smoking (%) 254 (22,0) 143 (35,2) <0,001 Hypertension (%) 822 (70,6) 313 (75,8) 0,05 Dyslipidemia (%) 824 (70,7) 311 (75,3) 0,09 Family history of CAD (%) 379 (33,4) 118 (29,9) 0,24 Prevalence of CAD (%) 361 (31,8) 136 (33,7) 0,52 8

9 Baseline characteristics Admission according to time after symptom onset (%) Non coronary chest pain Acute myocardial infarction p-value 3h 451 (38,7) 166 (40,2) 0,64 6h 694 (59,6) 237 (57,4) 0,47 Laboratory parameters on admission Non coronary chest pain Acute myocardial infarction p-value htfabp (ng/ml) 2,06 (1,47/3,00) 8,29 (4,14/20,97) <0,001 Troponin I (ng/ml) 0,01 (0,00/0,02) 0,58 (0,13/3,55) <0,001 egfr (ml/min) 107,49±38,32 98,49±37,57 <0,001 Creatinine (mg/dl) 0,94 (0,82/1,08) 0,99 (0,88/1,16) <0,001 9

10 Time course of biomarker concentrations in AMI subgroup htfabp (ng/ml) 0h 3h 6h 8,29 (4,14/20,97) 11,18 (4,33/39,99) Troponin I (ng/ml) 10,39 (4,27/33,08) 0h 3h 6h 0,58 (0,13/3,55) 2,79 (0,66/17,46) 7,06 (1,58/41,71) 10

11 Diagnostic value of biomarkers in study sample 0h 3h 6h htfabp Troponin I htfabp+troponin I 0h 0,892 0,959 0,967 3h 0,906 0,983 0,985 6h 0,899 0,991 0,991 11

12 Diagnostic value of biomarkers in patients presenting 3 h after symptom onset 0h 3h 6h htfabp Troponin I htfabp+troponin I 0h 0,905 0,943 0,957 3h 0,921 0,972 0,975 6h 0,909 0,989 0,989 12

0h Troponin I (+) 2,1% AMI 35/1184 20,6%

htfabp (-) 0h htfabp (+) 1,7% AMI 29/1136

13 htfabp- a rule-out marker of AMI Study sample 22,7% AMI 384/1694 0h Troponin I (-) 0h Troponin I (+) 2,1% AMI 35/ ,6% AMI 349/510 0h htfabp (-) 0h htfabp (+) 0h htfabp (-) 0h htfabp (+) 1,7% AMI 29/1136 0,4% AMI 6/48 6,9% AMI 117/243 13,7% AMI 232/267 13

(-) 0h Troponin I (+) 3,6% AMI 23/469 20,5% AMI 132/176 0h htfabp (-) 0h htfabp (+)

14 htfabp- a rule-out marker of AMI in patients htfabp as a rule-out marker of AMI presenting 3h after symptom onset Early presenters 24,0% AMI 155/645 0h Troponin I (-) 0h Troponin I (+) 3,6% AMI 23/469 20,5% AMI 132/176 0h htfabp (-) 0h htfabp (+) 0h htfabp (-) 0h htfabp (+) 3,1% AMI 20/453 0,5% AMI 3/16 5,7% AMI 37/73 14,7% AMI 95/103 14

15 Rule-out of AMI in the study Negative sensitive Troponin I Cut-off 0,04 ng/ml Negative htfabp Cut-off 5,3/5,8 ng/ml (female/male) Normal ECG No ST elevation/depression, no T inversion, no LBBB/RBBB 15

16 Rule-out of AMI in the study Negative predictive value Sensitive Troponin I Cut-off 0,04 ng/ml On admission 97,0% After 3 hours 99,5% Added htfabp Cut-off 5,3/5,8 ng/ml (female/male) 98,0% 99,6% Added ECG No ST elevation/depression, no T inversion, no LBBB/RBBB 98,9% 99,9% 16

17 Limitations Data obtained in a German population Enrollment in Chest Pain Units leads to high pretest probability Frozen samples (-80 C) 17

18 Conclusions Single htfabp assessment provides inferior diagnostic information compared to sensitive troponin I alone htfabp might improve early rule-out for acute myocardial infarction, when combined with sensitive troponin I 18

19 Thank you 19

Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction JAMA. 2011;306(24):

ORIGINAL CONTRIBUTION Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction Till Keller, MD Tanja Zeller, PhD Francisco Ojeda, PhD Stergios Tzikas, MD Lars Lillpopp