PCI & AimRadial 2018 | Use of physiology in ACS - Colin Berry

1. Use of physiology
in ACS
Prof. Colin Berry
University of Glasgow
Golden Jubilee National Hospital
AIMRADIAL 2018, Sarasota Memorial Hospital
28 November 2018

2. Anterior STEMI Angiogram
Multivessel coronary
disease in STEMI
PCI to culprit only
or
PCI to all lesions?
Colin Berry, 28.11.2018

3. Incidence, stenosis ≥ 75% = 31%
Stenosis ≥ 50% ≈ 50%
Multivessel PCI only in 10%
2014
Multivessel disease STEMI
Contemporary UK practice
Colin Berry, 28.11.2018

4. • Timing: immediate or index stay.
Yes - randomised trials 
Guideline statement 
ESC 2018 practice guideline
recommendations
Colin Berry, 28.11.2018

5. NEJM September 1st, 2013
Hypothesis: In STEMI patients with multivessel
CAD, immediate preventative PCI would improve
outcomes compared to medical therapy
PRAMI trial

6. PRAMI – primary outcome
Cardiac death, recurrent MI,
refractory ischaemia
Cardiac death,
non-fatal MI, refractory angina
n = 465

7. Primary outcome Cardiac death
Refractory anginaNon-fatal MI
PRAMI - components of primary outcome
directionally consistent treatment effect
Wald et al
NEJM 2013

8. CULPRIT Trial
MV-PCI  risk of cardiac events
64% immediate PCI
n = 150
n = 146
Gershlick et al
JACC 2015
Colin Berry, 28.11.2018

9. 101 ACS patients (n = 75 STEMI, n = 26 NSTEMI);
n = 112 non-culprit lesions
PCI in culprit lesion then FFR measured in non-culprit lesion
FUP – repeat 1 month later
JACC Intervention 2010

10. In only 2
patients with
FFR >0.80
was observed
to <0.75 at
FUp
Colin Berry, 28.11.2018

11. Smits et al NEJM 2017Colin Berry, 28.11.2018

12. COMPARE-ACUTE
885 patients, STEMI + MVD
• FFR, immediate, all
Control = FFR blind
FFR = guide PCI
• FFR achieved = 99%
FFR ≤ 0.80 = 54%
PCI index = 83%
+ 6 min, 1.6 stents
Smits et al NEJM 2017
1 : 2
Colin Berry, 28.11.2018

13. Primary end point, MACCE at 12 months
Death, non-fatal MI, revascularization (>45 days), stroke/TIA
MACCE
23 (7.8) vs. 121 (20.5); p<0.001
MI
7 (2.4) vs. 28 (4.7); p=0.10
Death or MI
11 (3.7) vs. 38 (6.4); p=0.10
COMPARE-ACUTE
Results
Smits et al NEJM 2017Colin Berry, 28.11.2018

14. DANAMI-3 PRIMULTI
FFR-guided revascularisation vs. culprit only in STEMI with
MVD
n = 627
All-cause mortality,
recurrent MI,
non-culprit PCI
Engstrøm T et al. Lancet 2015
40% revascularisations were urgent
Interaction of primary endpoint in 3-vessel disease
No differences in secondary endpoints or angina

15. Primary PCI for STEMI or high-risk NSTEMI
Exclude:
Previous CABG
Left main disease
Shock
One or more non-culprit lesions (non-
culprit vessels at least 2.5mm) on
angiography (50-99%)
Index admission
FFR-guided PCI
to non-culprit lesions*
Eligible but not
randomised
Registry follow-up
Randomization
Initial conservative
management of non-
culprit lesions
Visual assessment
Trial follow-up for all-cause mortality and non fatal MI at
30d and at least 1 year
Residual non-culprit disease
Non-CTO
n = 4400

16.  Completed trials
PRAMI, CULPRIT, COMPARE-ACUTE
 Default strategy (selected approach)
 On-going clinical trials:
FULL-REVASC – all-cause death / MI
COMPLETE – staged, post discharge
Complete MV-PCI – index or
in-patient staged in STEMI ?
Colin Berry, 28.11.2018

17. STEMI
COMPARE-ACUTE International 885 patients,
COMPLETE International 4000
staged PCI
DANAMI-PRIMULTI International 627
FLOWER-AMI France 1170
FULL REVASC Sweden 4400
NSTEMI
FAMOUS-NSTEMI-2 UK trial
PRESSUREWire International registry
Clinical trials of FFR-guided treatment in ACS
Colin Berry, 28.11.2018

18. Practice variation in NSTEMI increases
30-day mortality
Revascularisation rate, %
Hospitals Median (IQR)
%
30-day Mortality, %
Revascularisation
Half in UK (19.2%) vs Sweden (34.8%) with twice the variation (21.9%
vs. 10.2%)
Practice variation directly associated with 30-day mortality
Incomplete revascularisation – 50% of NSTEMI cases in the UK
%
Chung et al BMJ 2015Colin Berry, 28.11.2018

19. MACE during 2 years follow-up
Sels et al JACC Intervention 2011
FAME - NSTEMI
Colin Berry, 28.11.2018

20. Screened
Consent
Oct. 2011
May 2013
n = 174n = 176
350
Randomise
ESC Hotline 1 Sep 2014
Registry
n = 503
Screened
n = 1297
Exclusions, n=444

21. FFR-disclosure
Impact on initial treatment
Initial
treatment
Change
post-FFR
Final
decision
FFR treatment change ~ 22% of patients

22. FFR-guided management increased
medical therapy without PCI / CABG
0
5
10
15
20
25
Post-Randomisation 1-year
FFR-guided Angiography-guided
%
p = 0.022 p = 0.054
Costs and quality of life were similarESC Hotline 1 Sep 2014

23. Myocardial infarction type
FFR-guided vs. Angio-
guidedType 4 MI
Procedure-related
Angiography - guided
FFR - guided
FFR - guided
Angiography - guided
p = 0.12 p = 0.56
ESC Hotline 1 Sep 2014
Types 1-3 MI
Spontaneous

24. NSTEMI / STEMI
– Non-culprit 
– Culprit X
Similar conclusions for NHPR
Is FFR valid in ACS ?
Colin Berry, 28.11.2018

25. METHODS: Direct measurement of coronary
microvascular function in acute MI patients
Aorta
3 cm
Saline, 18 º C
Intra-coronary injection
3 ml Dual sensor
Pressure Temperature
0.014”
Coronary flow reserve, CFR
= Tmn rest / Tmn hyperaemia
Index of microvascular resistance, IMR
= Distal coronary pressure x mean transit time during hyperaemia
Colin Berry, 28.11.2018

26. Non-culprit Angina NSTEMI STEMI
IMR is similar patients with
angina vs. NSTEMI; not STEMI
IMR
n=140
50 angina
50 NSTEMI
40 STEMI
Layland, Oldroyd, Berry et al
Circ Cardiovasc Int 2013
Colin Berry, 28.11.2018

27. • 3 primary PCI centres
(Stanford, Glasgow, Singapore), n=253 patients
• Primary endpoint = death or HF hospitalisation
• Mean Fup = 2.8 years, 13.8% PEP, 4.3% died
• Prognostic value of IMR compared to CFR, TMP,
clinical variables.
Colin Berry, 28.11.2018

28. IMR hazard ratio, p-value
Death or HF hospitalisation 2.1, p=0.034
Death, HR 3.95, p=0.028
Fearon et al
Circulation 2013
IMR > 40 predicts death post-STEMI

29. IMR 13
IMR 50
Validation of prognostic value of IMR.
n=300 STEMI: IMR at end of PCI is independently predicts:
• IMR 27 - Adverse remodelling – HR 1.01(1.00,1.03)
• IMR 40 - All-cause death / HF – HR 4.4 (2.1, 9.1)
Carrick, Berry, Circ 2016

30. CFVR predicts cardiac death
CFVR (hyperaemic velocity / resting velocity) correlates inversely
with ST-resolution at end of P-PCI. Laskey et al. CCI 2008;
CFVR ≥ 2.1 predicts reduced risk at 10 yrs, n = 100 STEMI patients
Van de Hoef et al. Circ Cardiovasc Interven 2013

31. Conclusions
Physiology in ACS
Colin Berry, 28.11.2018
1. Incomplete revascularisation and practice
variations are common and prognostically
important.
2. FFR / NHPR are safe, valid in non-culprit vessel
disease, and diagnostically useful.
3. Phase 3 trials of FFR in STEMI are on-going.
4. The clinical utility of physiology-guided decisions
in ACS will be defined within the next 5 years.
5. IMR holds promise for risk stratify therapy

32. Conclusions
FFR in ACS
1. Incomplete revascularisation and practice
variations are common and prognostically
important.
2. FFR is safe, valid in non-culprit vessel disease,
and diagnostically useful.
3. Phase 3 trials of FFR in NSTEMI and STEMI are
on-going.
4. The clinical utility of FFR in ACS will be defined
within the next 5 years.
Colin Berry, 28.11.2018

33. Thank you for
your attention

34.  465 STEMI patients with multivessel CAD
amenable to PCI & successful culprit PCI
 Strategy: Complete revascularization
acutely of all stenoses ≥50% amenable to
PCI vs. OMT and ischaemia-driven revasc.
 Procedure duration = + 20 min
 n, arteries / patient = 1.36
 n, stents / artery = 1.29
PRAMI – key points
Wald et al NEJM 2013Colin Berry, 28.11.2018