1. NEW INSIGHTS INTO RISK ASSESSMENT & PREVENTION IN STEMI PATIENTS
Peter Sinnaeve
Department of Cardiovascular Medicine
University Hospitals Leuven
University of Leuven
Belgium

2. Disclaimer
Please note some of the data presented herein may contain off- label dosages and use. Please always refer to the current prescribing information as approved in your country.

3. Disclosures
Peter Sinnaeve is a Clinical Investigator for the Fund for Scientific Research – Flanders
Institutional grants from AstraZeneca, Bayer, Daiichi-Sankyo
Advisory, consultancy, RCT, CEC and speaker’s fees (all institutional) from AstraZeneca, Sanofi, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, BMS, Pfizer, Abbott, Amgen, MSD, Itreas, GSK, Medtronic, Celgene, Idorsia

4. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

5. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

6. Initial STEMI - ECG: a sophisticated yet still universal tool
Baseline ΣSTD
Relative risk (95% CI)*
P Value
Quartiles:
Event rate:
0-9 mm (reference)
43/479 (9.0) 1
0.024 mm
63/467 (13.5)
1.42 ( ) mm
66/448 (14.7)
1.66 ( )
>19.5 mm
69/456 (15.1)
1.52 ( )
Continuous:
every 5 mm increase
1.09 ( )
0.008
The sum of ST-segment deviation (or elevation) correlates with 30-day death/shock/ CHF/reMI
No impact on the response to different reperfusion strategies
Bainey KR et al. for the STREAM Investigators. Heart 2016;102:
CHF, congestive heart failure; ΣSTD, sum of ST-segment deviation

7. But just make sure you get your ECG right
Reasons for false-negative ECG interpretations (N=47)
Reasons for false-positive ECG interpretations (N=585)
False-positive ECG 
“Other” includes (in order of decreasing frequency): J point marked early in wide QRS, J point marked late, atrial flutter elevated J point, left bundle branch block, cardiac arrest, ventricular rhythm, wrong QRS type averaged, QRS onset marked late in Q wave, intra-ventricular conduction delay, paced rhythm with premature ventricular complexes used, Brugada pattern, QRS onset marked early in negative P wave, ventricular pacing not detected, left ventricular aneurysm, Wolf-Parkinson-White pattern, and hyperkalemia.
Bosson N et al. J Prehosp Em Care 2017;21(3):
*STEMI statement suppressed

8. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

9. Mortality in STEMI: the shock index (HR/SBP)
(Simple) Risk scores in the acute phase of a STEMI? The Shock Index (SI)
Mortality in STEMI: the shock index (HR/SBP)
Bilkova D et al. Can J Cardiol 2011;27(6):
~ Killip class, btw

10. (Simple) Risk scores in the acute phase of a STEMI? TIMI Risk Index
NS TEMI
STEMI-RT
STEMI-No RT
Heart Rate x (age/10)2
Systolic Pressure
Seems to reflect (pre-)shock, right?
Wiviott SD et al. J Am Coll Cardiol 2006;47(8):

11. Risk scores in the acute phase of a STEMI? Outside the box…
CHA2DS2-VASc & failed lysis
CHA2DS2-VASc-(HS) is predictive for successful or failed reperfusion after fibrinolytic therapy
CHA2DS2-VASc-HS & failed lysis
100 80 60 40 20
Sensitivity
100-Specificity ≥2
CHA2DS2-VASc ≥ 2
(AUC 0.660; 95% CI: ; p<0.001)
CHA2DS2-VASc-HS ≥ 3
(AUC 0.764; 95% CI: ; p<0.001) ≥3
Not really necessary to calculate, but shows that comorbidities predict efficacy of lytic Rx
Kilic S et al. Cardiol J 2019;26(2):

12. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

13. Time is a modifiable risk factor in STEMI My favourite STEMI risk tool is my (stop)watch…

14. How we perform in real life…
How do we perform …?
Poorly!
“More than one third of STEMI patients referred to a PCI-centre for primary PCI fail to achieve a time delay of less than 120 minutes, despite estimated transfer times of <60 minutes”
Ibanez B et al. Eur Heart J 2018;39(2):
Dauerman HL et al. Circ Cardiovasc Interv 2015;8(5):e

15. Improved “quality”, yet higher mortality!
2012 Guidelines
90 minutes
60 minutes if early presenter (<2h)
2017 Guidelines
120 minutes
2012
2017
% patients Rx within guideline window
5.7%
85.8%
% mortality
1.6% (95% CI: )
3.3% (95% CI: )
Lapostolle F et al. Eur J Emerg Med 2019 Jan 14. doi: /MEJ [Epub ahead of print].

16. Perception… time delays in PPCI really do kill patients too
6 RCTs of Primary PCI
by Zwolle Group – 2001 (n=1,791)
p <0.0001
RR=1.08 [1.01 – 1.16] for each 30-min delay (p=0.04)
De Luca G et al. Circulation 2004;109(10):

17. ESC ACCA Pre-hospital Management Position paper
MINDSET “Possible”? Shouldn’t that rather be “(almost) guaranteed”??
Primary PCI possible within
120 minutes after FMC
Beygui F et al. Eur Heart J Acute Cardiovasc Care; 2015:1-23.

18. Beyond mortality: preventing cardiogenic shock in STEMI
Meta-analysis: pharmacoinvasive strategy vs PPCI on the incidence of cardiogenic shock
Pharmacoinvasive
PPCI
Vanhaverbeke M et al. Circulation 2019;139(1):
Please note some of the data presented herein may contain off-label dosages and use.
Please always refer to the current prescribing information as approved in your country.

19. Beyond mortality: preventing cardiogenic shock in STEMI
Infarct Size
Pharmacoinvasive
PPCI
Relative Risk* (95%CI)
Vanhaverbeke M et al. Circulation 2019;139(1):

20. Beyond mortality: preventing cardiogenic shock in STEMI
Meta-analysis of PPCI vs pharmacoinvasive Rx – 17 studies (incl. 6 RCTs), n=13,037
Study or Subgroup
1. All-cause short-term mortality
2. Likelihood of achieving TIMI-3 flow
3. Total stroke
4. Haemorrhagic Stroke
5. Ischaemic stroke
6. Cardiogenic shock
7. Major bleeding
8. Reinfarction
9. All-cause long-term mortality
Odds Ratio IV, Random, 95% Cl
0.99 [0.73, 1.34]
1.06 [0.70, 1.59]
0.41 [0.18, 0.93]
0.23 [0.06, 0.81]
0.49 [0.15, 1.56]
1.53 [1.08, 2.18]
0.97 [0.37, 2.54]
0.55 [0.31, 0.99]
0.83 [0,59, 1.17]
Odds Ratio IV, Random, 95% Cl
Endpoints are 30-day/in-hospital
PPCI
Pharmacoinvasive
Siddiqi TJ et al. Am J Cardiol 2018;122:

21. Predicting/preventing pre-hospital sudden death in STEMI
Mortality x 10
Predictors:
Age
Congestive Heart Failure
Mortality 4.0%
Mortality 37.7%
Extensive MI
Karam N et al. Circ Vasc Int 2019;12(1):e doi: /CIRCINTERVENTIONS

22. As important as risk for ischaemic events: avoiding bleedings
Half-dose bolus TNK in elderly STEMI patients
… and a radial angio
STREAM Amendment
Before
After
<75y
≥75y
TNK
Bolus
½ Bolus‡
Clopidogrel
600 mg loading
75 mg/d
No loading
Enoxaparin
30 mg bolus
1 mg/kg bid
No bolus
0.75 mg/kg bid n
156 42
653 93
Primary EP (%)
12.9
31.0
9.2
24.7
All-cause death
30-day (%)
5.2
19.1
2.5
11.8
1-year (%)
7.8
21.4
4.3
15.1
ICH(%)
1.3
7.1
1.2
0.0 = = ↓
Sinnaeve PR et al. Drugs Aging 2016;33(2):
‡ Please note some of the data presented herein may contain off-label dosages and use.
Please always refer to the current prescribing information as approved in your country.

23. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

24. Reperfusion before PCI ➟ lower NT-proBNP ~ mortality
Survival
Regardless of reperfusion strategy
p=0.024
Pint=0.523
P=0.004
Pint=0.138 n=
Months since randomisation
PCI
Sinnaeve PR et al. Eur Heart J 2009;30(18):

25. Reperfusion before & after PCI ➟ role of thrombus
TIMI Thrombus Grade & 90d death
T-TIME: no benefit of low-dose lytic after PCI
Death at 90 days
p=0.003
p=0.001
p=0.407
p=0.235
TTG after PCI
Plus: thrombectomy doesn’t work as well
Zalewski J et al. J Am Coll Cardiol 2011;57(19):
McCartney PJ et al. JAMA 2019;321(1):56-68.

26. Poor endogenous fibrinolysis
Does endogenous fibrinolysis play a role? New opportunities for interventions….
Point-of-care Global Thrombosis Test in STEMI pts
LT = Lysis Time
Poor endogenous fibrinolysis
Farag M et al. Eur Heart J 2019;40(3):
Sinnaeve PR & Van de Werf F. Eur Heart J 2019;40(3):

27. Risk assessment & prevention opportunities in STEMI
Pre-hospital
ECG ST-segment ↑
Clinical presentation
Catheterisation Lab
TIMI flow pre/post
Haemodynamics/FFR
Coronary Care Unit
ECG ↓ ST resolution
Biomarkers
Discharge
Cardiac US / MRI
Risk scores
After Ahmed N et al. J Comp Eff Res 2016;5(6):

28. TIMI risk score in secondary prevention (TRS-2P)
Risk indicators
CHF
HTN
Age≥75 DM
Prior Stroke
Prior CABG
PAD
eGFR<60
Current Smoking
#Risk Indicators
Populations (N)
1506
3940
3108
2101
1231
829
Populations (%) 12 31 24
16.5 10 7
Total events (n) 27
100
177
294
311
288
Puymirat E et al. Clin Cardiol 2019;42:

29. Take home messages
Risk scores can be useful in STEMI – reflect comorbidities & risk of developing shock
In STEMI, TIME is definitely a modifiable risk factor (and should be part of every risk assessment)
Reducing time delays in reperfusion for STEMI saves cardiac muscle & lives, and may prevent shock
Paradoxically, more relaxed guidelines seem to be associated with increased mortality through longer delays
In STEMI patients unable to undergo expedited PPCI, (half-dose‡) lytic therapy and transport to a PCI- capable centre is the preferred strategy
‡ Please note some of the data presented herein may contain off-label dosages and use.
Please always refer to the current prescribing information as approved in your country.

30. NEW INSIGHTS INTO RISK ASSESSMENT & PREVENTION IN STEMI PATIENTS
Peter Sinnaeve
Department of Cardiovascular Medicine
University Hospitals Leuven
University of Leuven
Belgium