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Troponin T and Quantitative ST-segmentTroponin T and Quantitative ST-segment
Depression Offer ComplementaryDepression Offer Complementary
Prognostic Information in the RiskPrognostic Information in the Risk
Stratification of Acute CoronaryStratification of Acute Coronary
Syndrome PatientsSyndrome Patients
Padma Kaul; L. Kristin Newby; Yuling Fu; VicPadma Kaul; L. Kristin Newby; Yuling Fu; Vic
Hasselblad; Ken W. Mahaffey; Robert H.Hasselblad; Ken W. Mahaffey; Robert H.
Christenson; Robert A. Harrington; E. MagnusChristenson; Robert A. Harrington; E. Magnus
Ohman; Eric J. Topol; Robert M. Califf; Frans Van deOhman; Eric J. Topol; Robert M. Califf; Frans Van de
Werf; Paul W. Armstrong; for the PARAGON-BWerf; Paul W. Armstrong; for the PARAGON-B
InvestigatorsInvestigators
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
ObjectivesObjectives
 Assess incremental value of cTnT and ECG forAssess incremental value of cTnT and ECG for
risk-stratification of non-ST-segment elevationrisk-stratification of non-ST-segment elevation
ACS patientsACS patients
 Examine whether ST-segment depressionExamine whether ST-segment depression
provided additional insight into therapeuticprovided additional insight into therapeutic
efficacy of GPIIb/IIIa therapyefficacy of GPIIb/IIIa therapy
Unstable Angina/NQWMI
(n=5225)
Lamifiban 500 µg Bolus
1.0 - 2.0 µg/min x 3 days or d/c +
weight-adjusted IV heparin
Placebo Bolus/Infusion
+ weight-adjusted IV heparin
All patients receive aspirin 150 - 325 QD
Lamifiban infusion rate based on renal function
Endpoint:
Composite of 30-day death, MI,
recurrent ischemia with urgent intervention
Trial Design
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Patient PopulationPatient Population
T -
2 6 2 ( 6 8 % )
T +
1 2 5 ( 3 2 % )
N o S T - d e p
3 8 7 ( 4 0 % )
T -
2 5 9 ( 6 0 % )
T +
1 7 4 ( 4 0 % )
1 m m S T - d e p
4 3 3 ( 4 5 % )
T -
5 7 ( 4 1 % )
T +
8 2 ( 5 9 % )
+ 2 m m S T - d e p
1 3 9 ( 1 5 % )
9 5 9 p a t i e n t s w i t h
n o E C G c o n f o u n d e r s
1 1 4 0 w i t h b a s e l i n e E C G d a t a
1 1 6 0 T n T s u b - s t u d y p a t i e n t s
P A R A G O N - B S t u d y
5 2 2 5 p a t i e n t s
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
MethodsMethods
 cTnT assays performed at acTnT assays performed at a core laboratorycore laboratory
 TnT positive: TnT levels greater than 0.1TnT positive: TnT levels greater than 0.1
ng/mlng/ml
 ECGECG evaluated centrallyevaluated centrally..
 ST-segment depression (STST-segment depression (ST↓↓) :) :
 1) no ST1) no ST↓↓
 2) 1mm ST2) 1mm ST↓↓ in two contiguous leadsin two contiguous leads
 3) ST3) ST↓↓ ≥≥ 2 mm in two contiguous leads2 mm in two contiguous leads
 Patients with ECG confounders werePatients with ECG confounders were
excludedexcluded
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Selected Baseline CharacteristicsSelected Baseline Characteristics
Variable No ST-dep 1mm ST-dep 2mm ST-dep
N 387 433 139
Age 61 (51, 68) 65 (55, 73) 69 (61, 74)*
Female 35.1 42.0 28.8*
Diabetes 17.6 20.8 23.0
Previous MI 26.4 27.5 41.7*
Troponin+ 32.3 40.2 59.0*
*p<0.05*p<0.05
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Relationship between ST-segmentRelationship between ST-segment
depression and outcomesdepression and outcomes
0
5
10
15
20
25
No ST-dep 1mm ST-dep 2mm ST-dep
Death/MIRate
6-Month Dth 6-Month Dth/ MIχχ2 dth=17.1; p<0.012 dth=17.1; p<0.01
χχ2 dth/MI=13.8;2 dth/MI=13.8;
N=387N=387
N=433N=433
N=139N=139
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Relationship between cTnT quartilesRelationship between cTnT quartiles
and 6M death/(re)-MIand 6M death/(re)-MI
0
5
10
15
20
25
0.0 ng/ dL 0.01 - 0.047 0.048 - 0.277 0.278 +
Death/MIRate
6-Month Dth 6-Month Dth/ MI
N=365N=365
N=113N=113
N=241N=241
N=240N=240
χχ2 dth=18.5; p<0.012 dth=18.5; p<0.01
χχ2 dth/MI=30.6;2 dth/MI=30.6;
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
6M Survival by ST6M Survival by ST ↓↓ and cTnTand cTnT
categoriescategories
Follow-up in days
1801501209060300
1.00
.95
.90
.85
.80
.75
.70
Troponin negative
Troponin positive
p=0.03
Follow-up in days
1801501209060300
1.00
.95
.90
.85
.80
.75
.70
No ST-dep
1mm ST-dep
2mm ST-dep
p=0.04
p=0.03 p<0.01
p<0.01
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
6M Death/(re)-MI rates by cTnT and ST6M Death/(re)-MI rates by cTnT and ST ↓↓
0
5
10
15
20
25
30
35
No ST-dep (N=387) 1mm ST-dep (N=433) 2mm ST-dep(N=139)
T- T+
p=0.20p=0.20
p=0.13p=0.13
p=0.15p=0.15
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Multivariable Predictors of 6M Death/Multivariable Predictors of 6M Death/
(re)-MI(re)-MI
Worse outcomeWorse outcomeBetter outcomeBetter outcome
Age (10 year)
Prior PTCA
PVD
1mm ST-dep
2mm ST-dep
T+ (0.01 - 0.047)
T+ (0.048 0 0.277)
T+ (0.278 - 8.37)
876543210
Model c-index = 0.70Model c-index = 0.70
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
Treatment Effect - 6month Death/(re)-MITreatment Effect - 6month Death/(re)-MI
0
5
10
15
20
25
T- T+
Rx Placebo
0
5
10
15
20
25
No ST-dep 1mm 2mm
Rx Placebo
387387 433433 139139578578 381381
p=0.18p=0.18
p=0.69p=0.69
p=0.13p=0.13
p=0.68p=0.68
p=1.0p=1.0
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
ConclusionsConclusions
 Quantitative STQuantitative ST↓↓ and +TnT status areand +TnT status are
complementary in assessing risk among ACScomplementary in assessing risk among ACS
patientspatients
 Levels of TnT lower than 0.10 ng/ml containLevels of TnT lower than 0.10 ng/ml contain
important prognostic information and shouldimportant prognostic information and should
be incorporated into risk-assessment analysisbe incorporated into risk-assessment analysis
cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes:
ConclusionsConclusions
 While both ST-segment depression and cTnT
positivity are effective markers of risk, cTnT
appears superior to ST-depression in assisting
treatment decisions.

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503 troponin t and quantitative st segment depression

  • 1. Troponin T and Quantitative ST-segmentTroponin T and Quantitative ST-segment Depression Offer ComplementaryDepression Offer Complementary Prognostic Information in the RiskPrognostic Information in the Risk Stratification of Acute CoronaryStratification of Acute Coronary Syndrome PatientsSyndrome Patients Padma Kaul; L. Kristin Newby; Yuling Fu; VicPadma Kaul; L. Kristin Newby; Yuling Fu; Vic Hasselblad; Ken W. Mahaffey; Robert H.Hasselblad; Ken W. Mahaffey; Robert H. Christenson; Robert A. Harrington; E. MagnusChristenson; Robert A. Harrington; E. Magnus Ohman; Eric J. Topol; Robert M. Califf; Frans Van deOhman; Eric J. Topol; Robert M. Califf; Frans Van de Werf; Paul W. Armstrong; for the PARAGON-BWerf; Paul W. Armstrong; for the PARAGON-B InvestigatorsInvestigators
  • 2. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: ObjectivesObjectives  Assess incremental value of cTnT and ECG forAssess incremental value of cTnT and ECG for risk-stratification of non-ST-segment elevationrisk-stratification of non-ST-segment elevation ACS patientsACS patients  Examine whether ST-segment depressionExamine whether ST-segment depression provided additional insight into therapeuticprovided additional insight into therapeutic efficacy of GPIIb/IIIa therapyefficacy of GPIIb/IIIa therapy
  • 3. Unstable Angina/NQWMI (n=5225) Lamifiban 500 µg Bolus 1.0 - 2.0 µg/min x 3 days or d/c + weight-adjusted IV heparin Placebo Bolus/Infusion + weight-adjusted IV heparin All patients receive aspirin 150 - 325 QD Lamifiban infusion rate based on renal function Endpoint: Composite of 30-day death, MI, recurrent ischemia with urgent intervention Trial Design
  • 4. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Patient PopulationPatient Population T - 2 6 2 ( 6 8 % ) T + 1 2 5 ( 3 2 % ) N o S T - d e p 3 8 7 ( 4 0 % ) T - 2 5 9 ( 6 0 % ) T + 1 7 4 ( 4 0 % ) 1 m m S T - d e p 4 3 3 ( 4 5 % ) T - 5 7 ( 4 1 % ) T + 8 2 ( 5 9 % ) + 2 m m S T - d e p 1 3 9 ( 1 5 % ) 9 5 9 p a t i e n t s w i t h n o E C G c o n f o u n d e r s 1 1 4 0 w i t h b a s e l i n e E C G d a t a 1 1 6 0 T n T s u b - s t u d y p a t i e n t s P A R A G O N - B S t u d y 5 2 2 5 p a t i e n t s
  • 5. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: MethodsMethods  cTnT assays performed at acTnT assays performed at a core laboratorycore laboratory  TnT positive: TnT levels greater than 0.1TnT positive: TnT levels greater than 0.1 ng/mlng/ml  ECGECG evaluated centrallyevaluated centrally..  ST-segment depression (STST-segment depression (ST↓↓) :) :  1) no ST1) no ST↓↓  2) 1mm ST2) 1mm ST↓↓ in two contiguous leadsin two contiguous leads  3) ST3) ST↓↓ ≥≥ 2 mm in two contiguous leads2 mm in two contiguous leads  Patients with ECG confounders werePatients with ECG confounders were excludedexcluded
  • 6. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Selected Baseline CharacteristicsSelected Baseline Characteristics Variable No ST-dep 1mm ST-dep 2mm ST-dep N 387 433 139 Age 61 (51, 68) 65 (55, 73) 69 (61, 74)* Female 35.1 42.0 28.8* Diabetes 17.6 20.8 23.0 Previous MI 26.4 27.5 41.7* Troponin+ 32.3 40.2 59.0* *p<0.05*p<0.05
  • 7. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Relationship between ST-segmentRelationship between ST-segment depression and outcomesdepression and outcomes 0 5 10 15 20 25 No ST-dep 1mm ST-dep 2mm ST-dep Death/MIRate 6-Month Dth 6-Month Dth/ MIχχ2 dth=17.1; p<0.012 dth=17.1; p<0.01 χχ2 dth/MI=13.8;2 dth/MI=13.8; N=387N=387 N=433N=433 N=139N=139
  • 8. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Relationship between cTnT quartilesRelationship between cTnT quartiles and 6M death/(re)-MIand 6M death/(re)-MI 0 5 10 15 20 25 0.0 ng/ dL 0.01 - 0.047 0.048 - 0.277 0.278 + Death/MIRate 6-Month Dth 6-Month Dth/ MI N=365N=365 N=113N=113 N=241N=241 N=240N=240 χχ2 dth=18.5; p<0.012 dth=18.5; p<0.01 χχ2 dth/MI=30.6;2 dth/MI=30.6;
  • 9. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: 6M Survival by ST6M Survival by ST ↓↓ and cTnTand cTnT categoriescategories Follow-up in days 1801501209060300 1.00 .95 .90 .85 .80 .75 .70 Troponin negative Troponin positive p=0.03 Follow-up in days 1801501209060300 1.00 .95 .90 .85 .80 .75 .70 No ST-dep 1mm ST-dep 2mm ST-dep p=0.04 p=0.03 p<0.01 p<0.01
  • 10. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: 6M Death/(re)-MI rates by cTnT and ST6M Death/(re)-MI rates by cTnT and ST ↓↓ 0 5 10 15 20 25 30 35 No ST-dep (N=387) 1mm ST-dep (N=433) 2mm ST-dep(N=139) T- T+ p=0.20p=0.20 p=0.13p=0.13 p=0.15p=0.15
  • 11. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Multivariable Predictors of 6M Death/Multivariable Predictors of 6M Death/ (re)-MI(re)-MI Worse outcomeWorse outcomeBetter outcomeBetter outcome Age (10 year) Prior PTCA PVD 1mm ST-dep 2mm ST-dep T+ (0.01 - 0.047) T+ (0.048 0 0.277) T+ (0.278 - 8.37) 876543210 Model c-index = 0.70Model c-index = 0.70
  • 12. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: Treatment Effect - 6month Death/(re)-MITreatment Effect - 6month Death/(re)-MI 0 5 10 15 20 25 T- T+ Rx Placebo 0 5 10 15 20 25 No ST-dep 1mm 2mm Rx Placebo 387387 433433 139139578578 381381 p=0.18p=0.18 p=0.69p=0.69 p=0.13p=0.13 p=0.68p=0.68 p=1.0p=1.0
  • 13. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: ConclusionsConclusions  Quantitative STQuantitative ST↓↓ and +TnT status areand +TnT status are complementary in assessing risk among ACScomplementary in assessing risk among ACS patientspatients  Levels of TnT lower than 0.10 ng/ml containLevels of TnT lower than 0.10 ng/ml contain important prognostic information and shouldimportant prognostic information and should be incorporated into risk-assessment analysisbe incorporated into risk-assessment analysis
  • 14. cTnT and STcTnT and ST↓↓ in Predicting Outcomes:in Predicting Outcomes: ConclusionsConclusions  While both ST-segment depression and cTnT positivity are effective markers of risk, cTnT appears superior to ST-depression in assisting treatment decisions.