How to achieve maximal coronary vasodilatation? - Zsolt Piroth

1. How to achieve maximal
coronary vasodilatation?
Zsolt Piróth MD FESC
Hungarian Institute of Cardiology
Conflict of interest: nothing to disclose
Budapest, Sep. 21, 2016
AimRADIAL 2016 FFR WorkshopAimRADIAL 2016 FFR Workshop

2. Why bother to achieve maximal
coronary vasodilatation?
AimRADIAL 2016 FFR WorkshopAimRADIAL 2016 FFR Workshop

3. FFR is really a flow metric
Its measurement mandates
elimination of autoregulation
The full diagnostic power of FFR
can only be achieved during
maximal coronary vasodilatation
Fractional Flow Reserve

4. Importance of maximal hyperemia
K. G. Oldroyd, TCT 2009
Insufficient hyperemia
Underestimation of gradient
Overestimation of FFR
Underestimation of lesion severity

5. Hyperemia puts the stenosis in a windtunnel

6. 100% = gold standard
50% = coin flip
Nico HJ Pijls, 2014 ETP Course
Pyramid of diagnostic accuracy

7. Coronary angiography ≈ 65% accuracy
Gábor Tóth, Eur H J 2014; 35: 2831-8

8. 100% = gold standard
50% = coin flip
65% ≈ angiogram alone
Sones, 1958
Pyramid of diagnostic accuracy

9. RESOLVE = Jeremias A, JACC. 2014 Apr 8;63(13):1253-61
ADVISE 2 = Escaned J, JACC Cardiovasc Interv. 2015 May;8(6):824-33 and 834-6
VERIFY 2 = Watkins S, late-breaking clinical trial at SCAI in Las Vegas, May 30, 2014
50% 0.5
60%
70%
80%
90%
100% = FFR with adenosine
RESOLVE ADVISE 2 VERIFY 2 RESOLVE ADVISE 2 VERIFY 2
0.6
0.7
0.8
0.9
1.0 = FFR with adenosine
Pd/Pa
iFR
Resting indices ≈ 80% accuracy
Courtesy of Nils P Johnson

10. “The resting gradient is far from enough
but unfortunately it’s all I have now”.

11. 100% = gold standard
50% = coin flip
65% ≈ angiogram alone
80% ≈ rest physiology
(Pd/Pa or iFR)Grüntzig, 1979
Sones, 1958
Pyramid of diagnostic accuracy

12. 100% = gold standard
50% = coin flip
65% ≈ angiogram alone
80% ≈ rest physiology
(Pd/Pa or iFR)
95+% ≈ FFR
hyperemia
Grüntzig, 1979
Sones, 1958
Pyramid of diagnostic accuracy

13. More hyperemia,
more accuracy

14. contrast medium (1974, Gould KL, Am J Cardiology)
dipyridamole (1978, Gould KL, Am J Cardiology)
coronary occlusion (1984, Marcus ML, NEJM)
papaverine (1986, Wilson RF, Circulation)
adenosine (1990, Wilson RF, Circulation)
ATP (2003, De Bruyne B, Circulation)
nitroprusside (2004, Kern MJ, Circulation)
nicorandil (2006, Kang JC, Int J Cardiology)
regadenoson (2011, Nair PK, JACC Interventions)
Vasodilatators in human
physiology
Courtesy of Nils P Johnson

15. Papaverine i.c.
Cheap
Easy to admininster
Peak hyperemia after 30-45 sec, lasting for 30-60 sec,
allowing pull-back recording, CFR, IMR measurement
Causes T-wave abdormalities, seldom TDP VT
Especially in hypokalemia
Avoid use with QT-prolonging drugs
No more than 3 doses
Dosage:
10-15 mg in RCA
12-20 mg in LCA

16. Adenosine receptors
J Nucl Cardiol 2012; 19: 126-41

17. Adenosine (ATP) i.v.
Expensive in some countries
Somewhat cumbersome to admininster: central venous
access recommended, infusion pump and line required
Peak hyperemia after 30-60 sec, then steady state
hyperemia as long as infusion lasts, effect wearing off
30-60 sec after infusion is stopped
Well established dose: 140 μg/kg/min
Gold standard of FFR measurement
AV block much less than with i.c. adenosine
GC with side holes allowed
Most technical caveats can be prevented

18. Adenosine (ATP) i.v.
Bronchoconstriction may be caused: CAVE: asthma
bronchiale, theophylline should be available (coffee...)
May be associated with significant fall in systemic blood
pressure
Angina-like sensation often felt
Warn and reassure the pt: pain is harmless
Nothing to do with myocardial ischemia
Caused by stimulation of free nerve fibres
Good feed-back for operator: substance has been delivered
Large cubital vein may be used, but arm must be
extended
The patient should breathe normally

19. Intravenous adenosine administration

20. Adenosine i.v. – do we need fem puncture?
JACC CV Intv 2015; 8: 527-35

21. Adenosine i.v. in the transradial era
JACC CV Intv 2015; 8: 527-35
 Single center observational study of 20-gauge hand iv vs 5/6 G fem iv adenosine
 84 vessels paired
 Very good correlation, 0 crossed gray zone
 Stability unchanged
 With hand, be patient!

22. Adenosine i.v. - fluctuations
Nils P Johnson, JACC CV Intv 2015; 8: 1018-27
 „Smart minimum”: lowest average of 5 consecutive cardiac cycles of sufficient
quality within a run of 9 consecutive quality beats

23. Adenosine i.v. - fluctuations
Nils P Johnson, JACC CV Intv 2015; 8: 1018-27

24. Adenosine (ATP) i.c.
Cheap
Easy to admininster
Peak hyperemia < 10 sec, lasting < 20 sec
Generally precludes pull-back recording, CFR, IMR
measurement, may miss peak hyperemia
Main side effect: transient AV block (esp. RCA)
No GC with side holes!
Doses:
RCA: at least 40-60 μg
LCA: at least 50-80 μg
Incremental dose escalation !
0,6
0,7
0,8
0,9
p=0.4p<0.01
p<0.01
0,790,780,83
IV
140ug/kg/min
IC high dose
60-80 ug
IC low dose
18-20 ug
FFR

25. Optimal i. c. adenosine dose
JACC CV Intv 2015; 8: 1422-30

26. Optimal i. c. adenosine dose
JACC CV Intv 2015; 8: 1422-30

27. Optimal i. c. adenosine dose
JACC CV Intv 2015; 8: 1422-30
LCA: 200 µg RCA: 100 µg

28. Selective A2A receptor agonists
J Nucl Cardiol 2012; 19: 126-41

29. Regadenoson i. c.
Selective A2A receptor agonist
New hyperemic stimulus: 400 μg (5 cm3
)
given as a bolus either in a central or a peripherial vein
Maximal hyperemia: within 1 minute, lasting 1-7
minutes (variable) ≈ i. v. adenosine
Sufficiently long lasting hyperemia allowing pullback
recording

30. Agreement with iv adenosine
JACC CV Intv 2011; 4: 1085-92

31. van Nunen LX, EuroIntervention 2014 Aug. 20 [Epub ahead of print]
Agreement with iv adenosine

32. min = 10 seconds
max = >10 minutes
mean = 163 seconds
90% at least 19 sec
75% at least 58 sec
van Nunen LX, EuroIntervention 2014 Aug. 20 [Epub ahead of print]
Length of hyperemia

33. An important note...
No matter what hyperemic
stimulus you use, never
forget i. c. Ngl to prevent
epicardial coronary
vasospasm.

34. Conclusions
I.V. adenosine infusion is a safe, reliable and well
tolerated method for induction of maximal
coronary hyperemia (gold standard), but little
cumbersome.
 I.C. adenosine is a good alternative, but does not
produce steady state maximal hyperemia. Ensure
the interruption in recorded Pa is as short as
possible. LCA: 200 µg, RCA: 100 µg.
 I.V. regadenosone gives perfect FFR, but has
unpredictable duration, costly
I.C. papaverine only as last resort.

35. Settle for compromises…
For the sake of accuracy, full diagnostic
potential

36. Thank you