Introduction to Instantaneous Wave-Free Ratio€¦ · DEFINE FLAIR Clinical Endpoints Study...
Transcript of Introduction to Instantaneous Wave-Free Ratio€¦ · DEFINE FLAIR Clinical Endpoints Study...
Alejandro Aquino MD
Interventional Cardiology Fellow
Washington University in St. Louis
Barnes-Jewish Hospital
Instantaneous
Wave-Free Ratio
Alejandro Aquino MD
Disclosure
No disclosures
Instantaneous Wave-Free Ratio
Outline
• iFR Basics
• iFR Data
• Future Directions
• Wash U Experience
• Cases - Caveats
Physiologic Assessment of CAD
• Basis of FFR modality linear relationship between
pressure and flow under constant and minimized
coronary resistance1
• Under these conditions, changes in pressure across
a stenosis can be a surrogate for blood flow to
myocardium
P = Q x R Pressure = Flow x Resistance
1) Spaan JA. Physiologic basis of clinically used coronary hemodynamic indices. Circulation 2006.
or ∆P = ∆Q x R Change in Pressure = Change in Flow
x Constant Resistance
Intracoronary Resistance
• Intracoronary resistance fluctuates in a phasic pattern
• Reflects interaction between myocardium and
microvasculature
High Intracoronary resistance
Microvasculature compression
Low Intracoronary resistance
Microvasculature
decompression
Systole Diastole
P =Q x R Pressure = Flow x Resistance
FFR
HYPEREMIA
• Minimizing IC resistance during measurement of FFR • Calculated during hyperemia (adenosine)
• Average over several cycles
P =Q x R Pressure = Flow x Resistance
Do we need adenosine?
• Contraindicated or disliked by patients
• Adds to procedural time
• Adds to procedural costs
Davies J. Primary Results of ADVISE. TCT 2011.
Can a time of naturally occurring stable
resistance be identified?
iFR
• Instantaneous pressure ratio across a stenosis during
the wave-free period, when resistance is naturally
constant and minimized in the cardiac cycle
Davies J. Primary Results of ADVISE. TCT 2011.
Wave Free Period
Pd/Pa
P =Q x R Pressure = Flow x Resistance
Development of iFR
• Development and Validation of a New Adenosine-Independent
Index of Stenosis Severity From Coronary Wave–Intensity Analysis:
Results of the ADVISE (ADenosine Vasodilator Independent Stenosis
Evaluation) Study
J Am Coll Cardiol. 2012;59(15):1392-1402.
Tested
hypothesis by
comparing iFR
with FFR
measurements
Identify diastolic
interval in which
IC resistance is
equal to time-
averaged
resistance during
FFR
PROOF OF CONCEPT
Resistance During the Wave Free Period
Within a defined diastolic wave-free period, resting coronary
resistance was similar to that seen during adenosine-mediated FFR
Correlation between iFR and FFR
iFR correlates closely with FFR in all coronary arteries
AUC = 93%
Diagnostic accuracy of iFR as compared to
FFR cutoff value of 0.8
VERIFY
• Prospective, multicenter study of 206 consecutive pts
referred for PCI and 500 archived pressure recordings
• Excluded h/o CABG, extreme tortuosity, severe calcification,
MI w/in 5 days
• Diagnostic Performance of iFR 0.83 vs FFR 0.80
VERIFY
• iFR did change during hyperemia
• 0.82 ± 0.16 0.64 ± 0.18
• ROC
• iFR similar to resting Pd/Pa and
trans-stenotic pressure gradient
iFR vs FFR
ADVISE Registry
• Evaluated the relationship between iFR and FFR in pts
with intermediate lesions
• Lesions where functional assessment is clinically relevant and in
agreement with guidelines
• 312 pts with 339 coronary stenoses
• AUC 0.86
• Identified optimal
iFR cutoff value of
0.89 to match
FFR value of 0.8
ADVISE Registry Agreement between
Repeated Measurement of
FFR
Agreement between iFR
and FFR
Overall
classification
agreement of 85%
Overall
classification
agreement of 8o%
Taking into account the FFR repeatability (85%), iFR/FFR
agreement was 94% for classifying lesions as
significant/insignificant
Hybrid iFR-FFR Approach • Hybrid iFR-FFR decision-making strategy: implications for
enhancing universal adoption of physiology-guided coronary
revascularisation (Euro Intervention, Dec 2012)
ADVISE II
• Prospective, observational, nonrandomized, double blind, global, multi-center
registry
• iFR value to characterize coronary stenosis as determined by FFR
• n=797 patients evaluated
1) 94.0% match to FFR
2) 65.1% of patients may be free from hyperemic agents
DEFINE FLAIR Clinical Endpoints
Study Objectives:
• Determine safety and efficacy of PCI-
guided iFR vs. FFR
• Determine if iFR is non-inferior to FFR
to guide PCI
Primary Endpoints:
• Major adverse cardiac events (MACE)
rate in the iFR and FFR groups at 1
year
• MACE (combined endpoint of death,
non-fatal MI, or unplanned
revascularization)
Largest Physiology Study to
Date
• n=2500
• 51 Sites, 17 countries
Summary Slide
• ADVISE
• Proof of Concept
• ADVISE Registry
• Intermediate Lesions
• Overall good agreement
• Less so around cutoff points
• Hybrid iFR-FFR
• Introduced concept
• ADVISE II
• Hybrid approach tested prospectively
• DEFINE FLAIR
• Ongoing
• Testing clinical endpoints
• VERIFY
Wash U Experience • Prospective, observational study
• 46 consecutive lesions at BJH Cathlab
• 44 lesions with both FFR and iFR performed
• Mean age 65 ± 8 years
• 26% with diabetes
• All vessels, ostial, proximal, mid and distal lesions
0
.25
.5.7
5
1
Sen
sitiv
ity
0 .25 .5 .75 11 - Specificity
Area under curve = 0.9157, 95%CI 0.83 to 0.99
Diagnostic Accuracy of iFR
Best Cut-point iFR =
0.91
Sensitivity = 86%
Specificity = 86%
Conclusions – Part 1 • iFR has good correlation with FFR
• High correlation coefficient
• High area under the ROC curve
• Correctly classifies 86% of lesions
• It thus appears to be reasonably reliable in assessing
the functional significance of intermediate lesions
• Recognize the gray zone between 0.86 – 0.93
• May be used in routine clinical practice, saving time
and money
Cases
26
1 2
FIO2 & Hct (or Hb) Arterial
Lilly, L. Pathophysiology of Heart Disease. Lippincott, 2007. 4th ed..
Coronary Reserve
History of Present Illness
63yo gentleman with a history of CAD with prior
PCI and ischemic cardiomyopathy.
Presents with 2-3 weeks of worsening chest
tightness and dyspnea with exertion.
Given rapid progression of symptoms over the last week he is referred for L heart catheterization.
Past Medical History
• CAD:
• Promus Element 3.5 x 20mm and 2.5 x 16mm stents placed in
LAD/2nd diagonal bifurcation in 2012
• Promus Element 2.5x28 and 2.5x20 placed in mid LCx in 2012
• Ischemic cardiomyopathy
• EF 25-30% since 2012
• Status post ICD for primary prevention
• HTN
• HLD
• Former tobacco use
Patent Stents
RCA
IFR/FFR Analysis of RCA Lesion
• 6 French JR4 guide
catheter
• Volcano Verrata™
pressure wire
• Runthrough™ wire to
anchor guide
IFR Assessment of the mid-RCA
FFR with IV Adenosine
Stent Deployment
• 4.0x15mm Resolute DES
Results
Why the discordance?
• Intact microvasculature needed to achieve minimal
resistance?
Case 2
• 50yo with ESRD, HTN, HepB
• Prior PCI to RCA with BMS in 2004 (known occlusion of the stent in 2007)
• Prior PCI to LAD with Xience DES in 9/2013
• Presented with unstable angina
• Echo 3/2014: EF 56%, mild concentric LVH
CFX
Functional
Assessment
Case 3
• 81yo with prior CAD admitted with USA and CHF.
• Known EF 30%.
• PCI to LCx and LAD in 2006
• Recent history of GI bleeding resulting in
discontinuation of Plavix.
LAD
LAD Assessment – iFR markedly +
RCA
Hemodynamic Assessment
of the RCA lesion
Conclusions – Part 2
• iFR (basal late diastolic) may be more accurate in
patients with tachycardia, LVH , anemia and elevated
LVEDP, ESRD – due to increased basal flow and
max’d out vasodilatory reserve +/- paradoxical
response to adenosine
• FFR is more accurate in patients with damaged or
diseased resistance vessels (ischemic
cardiomyopathy, prior infarct in terrritory and myopathic
supplied muscle) - need intact resistance vessels to
achieve minimal resistance
• Most other subsets have excellent correlation