Download Nils P. Johnson. J Am Coll Cardiol Intv

Methods for Hyperemic
Assessment of FFR
Jeff Chambers, MD FSACI, FACC
Director Cardiac Cath Lab
Metropolitan Heart and Vascular Institute
Mercy Hospital , Minneapolis, MN
Jeff Chambers, MD
Disclosures
Consulting
CSI
Boston Scientific
ACIST Medical
Method To Assess Myocardial Ischemia in
the Cath Lab
• Angiography
• Resting Indices
– iFR
– Pd/Pa
• Contrast FFR
• Hyperemic FFR
– Adenosine
• Intravenous - IV
• Intracoronary -IC
Why Does the Angiogram Fail to Predict Physiology?
Pancake and Starfish Lesions
From: Current Concepts of Integrated Coronary Physiology in the Catheterization Laboratory
Why Does the Angiogram Fail to Predict Physiology?
The angiogram is a 2-dimensional image of 3-dimensional structures. Most intermediate lesions are oval shaped with 2 diameters, 1
narrow and 1 wide dimension. The angiogram of an eccentric lesion cannot reliably indicate flow adequacy. Other lesions (lower
right) may appear hazy but widely patent, only to be responsible for angina due to plaque rupture, as demonstrated by intravascular
ultrasound cross-section (far right corner). Figure illustration by Rob Flewell.
Morton J. Kern, MD?;J Am Coll Cardiol. 2010;55(3):173-185. doi:10.1016/j.jacc.2009.06.062
Date of download: 4/30/2016
FAME study: Event-free Survival
FFR guide therapy is superior to angio -guided
absolute difference in MACE-free survival
FFR-guided
30 days
2.9%
90 days
3.8%
180 days
4.9%
Angio-guided
360 days
5.3%
p=0.02
N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.
Angiography-guided percutaneous coronary intervention (PCI) versus fractional
flow reserve-guided PCI major adverse cardiac events/major adverse cardiac
and cerebrovascular events.
Dongfeng Zhang et al. Heart doi:10.1136/heartjnl-2014-306578
How to best access FFR
RESTING INDICES
iFR
Instantaneous pressure ratio (iFR) is measured across a stenosis during the wavefree period when resistance is naturally constant and minimized in the cardiac cycle
Resting Indices - RESOLVE study
No adeno ,PCI
FFR
No adeno , No PCI
iFR 0.86 - 0.93
Jeremias et al; JACC 2013
Multicenter Core Laboratory Comparison of the Instantaneous
Wave-Free Ratio and Resting Pd/Pa With Fractional Flow
Reserve: The RESOLVE Study
Association Between Use of Adenosine and Diagnostic Accuracy of iFR and Pd/Pa
An inverse relationship between use of adenosine and diagnostic accuracy is shown, such that with
increasing accuracy the adenosine-free zone decreases in width for both iFR and Pd/Pa. The blue line
displays this association for iFR and the red line for Pd/Pa.
J Am Coll Cardiol. 2014;63(13):1253-1261. doi:10.1016/j.jacc.2013.09.060
Accuracy
Accuracy = (True Positive +True Negative)
(True Positive+ False Positive + True Negative + False Negative)
Resolve Study - Accuracy
iFR
Study/
Participating Site
Pd/Pa
No. of
Lesions
Cutoff Point
AUC From
ROC(C
statistic)
Overall
Accuracy (%)
Correlation
(R2)
Cutoff Point
AUC From
ROC(C
statistic)
Overall
Accuracy (%)
Correlation
(R2)
1,593
0.90
0.81
80.4
0.66
0.92
0.82
81.5
0.69
ADVISE∗
432
0.91
0.82
81.9
0.71
0.92
0.82
81.9
0.75
VERIFY†
654
0.89
0.80
79.4
0.60
0.92
0.81
79.8
0.65
Seoul National
University
179
0.92
0.83
82.7
0.68
0.93
0.82
82.1
0.70
Stony Brook
University
149
0.93
0.81
79.2
0.54
0.93
0.83
83.2
0.61
Columbia
University
95
0.91
0.84
82.1
0.62
0.92
0.87
89.5
0.70
AMC/VUMC/KCL
84
0.90
0.78
78.6
0.72
0.93
0.72
72.6
0.70
Total
J Am Coll Cardiol. 2014;63(13):1253-1261.
∗Includes data from the ADVISE study and ADVISE registry.
†Includes data from the prospective and retrospective VERIFY cohorts.
AMC = Academic Medical Center, University of Amsterdam KCL = King's College London
; VUMC = VU University Medical Center, Amsterdam.
Contrast FFR
CONTRAST Study:
• Comparison of FFR with IV or IC adenosine to:
cFFR, Resting Pd/Pa and iFR
• Multicenter, international trial including ≈750
patients (1 lesion/patient)
• Blinded, independent core lab
Nils P. Johnson. J Am Coll Cardiol Intv. April 25, 2016,9(8):757-767
Continuum of Vasodilator Stress From Rest to Contrast Medium
to Adenosine Hyperemia for Fractional Flow Reserve
Assessment
Example of Protocol
Complete example from the study that demonstrates essentially no gradient at rest (high Pd/Pa and iFR) with a clearly
positive result by cFFR then confirmed by both intracoronary and intravenous adenosine FFR. No significant drift was
observed, and each metric was measured twice (#1 and #2). Aortic pressure (Pa) in red, distal coronary (Pd) in blue, and their
ratio Pd/Pa in black. cFFR = contrast-based fractional flow reserve; IC = intracoronary; iFFR = instantaneous wave-free ratio;
Pd/Pa = resting ratio of distal coronary pressure to aortic pressure
J Am Coll Cardiol Intv. 2016;9(8):757-767. doi:10.1016/j.jcin.2015.12.273
Resting Indices
Diagnostic Accuracy:
True positives (%)
100%
80%
60%
Pd/Pa = 80% accuracy
iFR = 79% accuracy
 same accuracy (p=0.89)
iFR = 0.879*
Pd/Pa = 0.874
40%
20%
* = same AUC (p=0.28)
0%
0%
20%
40%
60%
80%
100%
False positives (%)
Nils P. Johnson. J Am Coll Cardiol Intv. April 25, 2016,9(8):757-767
Diagnostic Accuracy:
cFFR = 86% accuracy
Pd/Pa = 80% accuracy
iFR = 79% accuracy
 superior accuracy (p<0.001)
Optimal binary cutoff for cFFR ≤ 0.83
Nils P. Johnson. J Am Coll Cardiol Intv. April 25, 2016,9(8):757-767

cFFR is:



Easy, inexpensive, and safe
Reproducible
Available immediately does not depend on specific
software platform or ECG
Optimal binary cutoff for cFFR ≤ 0.83
Nils P. Johnson. J Am Coll Cardiol Intv. April 25, 2016,9(8):757-767
Hyperemic FFR
What Vasodilator to use?
Dose Response Curves
Adenosine Bolus Dose Response curve
Adenosine Infusion Dose Response curve
Wilson R et al. Circulation 1990;82:1595-1606
Comparative Hyperemia
J Am Coll Cardiol Intv. 2015;8(11):1422-1430.
When to measure FFR
Take the lowest value
Automated software records the
lowest Pd/Pa as the FFR.
Take the Pd/Pa ratio at the lowest Pd
Wait for stable hyperemia
Vranckx, Cutlip, McFadden, Kern, Mehran, Muller.
Circ CV Interv 2012. 5:312-317
Pijls, van Son, Kirkeeide, DeBruyne, Gould.
Circulation 1993. 86:1354-1367
FFR Patterns with IV Adenosine
Fearon, W. CircCardiovascularInterv. 2015;j8:doi:10.1161
Comparison of IC Versus IV Adenosine for FFR
80 μg adenosine (left coronary artery) or
40 μg adenosine (right coronary artery)
140 μg/kg per minute
Christian Schlundt et al. Circ Cardiovasc Interv. 2015;8:e001781
Intracoronary Adenosine: Dose–Response
Relationship With Hyperemia
J Am Coll Cardiol Intv. 2015;8(11):1422-1430.
Intracoronary Adenosine: Dose–Response
Relationship With Hyperemia
This dose-response study with flow measurements indicates that IC bolus injections
of adenosine of 100 μg in the RCA and 200 μg in the LCA induce maximum
hyperemia without affecting systemic hemodynamics and with minimal side effects.
J Am Coll Cardiol Intv. 2015;8(11):1422-1430.
Medications and Doses to Produce Maximal
Hyperemia
Fearon, W. CircCardiovascularInterv. 2015;j8:doi:10.1161
Major Reasons for inaccurate FFR
• Maximal hyperemia not achieved
– Epicardial Artery spasm – 200 IC nitro
– IV adenosine
• Adenosine T ½ < 10 sec
• Small distal IV – Adenosine metabolized before it reaches
the coronaries
– IC adenosine
• Side hole guide
•
•
•
•
Guide cath damping
Drift
Serial lesions
AMI territory
Diagnosing Ischemia in the Cath Lab
FFR
95%
Contrast FFR
86%
Resting Measures
(iFR, Pd/Pa)
80%
Coronary Angiography
70%
Nils P. Johnson. J Am Coll Cardiol Intv. April 25, 2016,9(8):757-767
Conclusions
• FFR guided therapy improves outcomes and should be
used more often.
• Resting indices are less accurate than Contrast FFR.
• Contrast FFR may eliminate the need for adenosine is
some cases.
• IV and IC adenosine are both effective in inducing
maximal hyperemia.
• Attention to detail is required to avoid technical
induced inaccuracies when performing FFR.