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