Can IVUS be Used to Assess
Intermediate Lesions?
Ron Waksman, MD, FACC,FSCAI
Professor of Medicine, Georgetown University
Director, Cardiovascular Research Advanced Education
MedStar Heart Institute, Washington DC
Ron Waksman, MD
Consulting:
Biotronik, Inc.
Abbott Laboratories
Boston Scientific Corporation
Medtronic, Inc.
Merck and Company, Inc.
Honoraria:
Abbott Laboratories,
Boston Scientific Corporation
Merck and Company, Inc.
Medtronic, Inc.
Background
• An intermediate coronary stenosis, defined as a diameter
stenosis between 40-70% on angiography, is a source of
controversy with regard to the appropriate criteria for
undertaking PCI.
• Deferring PCI of intermediate lesions on angiography with
FFR>0.80 reported safe, with excellent clinical outcome.
• To date, few data are available regarding the relationship
between the anatomical and morphological IVUS
parameters and functional FFR
Clinical outcome-FFR
DEFER
DEFER 5-Year Results
Event-Free Survival
Cardiac Death and MI
N=325
(Pijls et al. J am Coll Cardiol 2007;49:2105-11)
Clinical outcome-FFR
FAME
Flow Chart
FFR-Guided
N=509
PCI performed on
indicated lesions
only if FFR <0.80
Lesions warranting
PCI identified
Randomized
Primary Endpoint
Composite of death,
MI and repeat revasc.
(MACE) at 1 year
Key Secondary Endpoints
Individual rates of death, MI,
and repeat revasc, MACE,
and functional status at 2 years
Angio-Guided
N=496
PCI performed on
indicated lesions
FAME Study: Results
MACE-Free Survival
1006 Patients with MVD randomized to - angio-guide DES
- FFR-guided DES
FFR-guided
30 days
2.9% 90 days 180 days
3.8%
4.9%
P. Tonino et al NEJM 2009
Angio-guided
360 days
5.3%
Adverse Events at 2 Years
AngioGuided
n = 496
FFRGuided
n = 509
139
105
Death
19 (3.8)
13 (2.6)
0.25
Myocardial Infarction
48 (9.7)
31 (6.1)
0.03
CABG or repeat PCI
61 (12.3)
53 (10.4)
0.35
Death or Myocardial Infarction
63 (12.7)
43 (8.4)
0.03
Death, MI, CABG, or re-PCI
110 (22.2)
90 (17.7)
0.07
Total no. of MACE
P
Value
Individual Endpoints
Composite Endpoints
William F. Fearon et al TCT 2009
When to perform FFR?
IVUS & FFR
correlation ?
IVUS assessment of ischemia
IVUS MLA ≥
IVUS MLA
2 has
2
2 a high diagnostic
IVUS
MLA>4mm
4.0 mm
<4.0mm
CFR < 2.0
a CFR≥2
2accuracy in predicting
27
CFR ≥ 2.0
39
4
Diagnostic accuracy = 92% (Abizaid et al, AJC 1998;82:42-8)
IVUS MLA ≥
4.0 mm2
IVUS MLA
<4.0mm2
+ SPECT
4
42
-SPECT
20
1
N=86
Diagnostic accuracy = 93% (Nishioka et al, JACC 1999;33:1870-8)
IVUS MLA<4mm 2 was the most sensitive and specific for ischemia determine by CFR or SPECT
IVUS determinants of LMCA FFR <0.75
55 patients with ambiguous left main correlation FFR and IVUS
(Jasti et al. Circulation 2004;110:2831-6)
Relationship between IVUS MLA and reference lumen area
IVUS MLA (mm2)
Ben-Dor, Kang, Koo, F1RST, Gonzalo → FFR< 0.80
Takagi, Briguori, Lee → FFR < 0.75
Ø2.5mm
Ø3.0mm
Reference lumen area (mm2)
Ø3.5mm
Can IVUS be Used to Assess
Intermediate Lesions?:
THE F1RST TRIAL Results
On Behalf of the F1RST Investigators
Ron Waksman, MD, FACC, FSCAI
Professor of medicine Cardiology Georgetown University
Associate Director Division of Cardiology
Washington Hospital Center
Director Cardiovascular Research
MedStar Heart Institute, Washington, DC
Overall Population Analyses
1
0.9
1.2
0.8
FFR
1
0.8
0.7
Probability
r= 0.30
p <0.0001
0.6
MLA: 3.07 mm2
0.6
Sensitivity 0.64
Specificity 0.65
C= 0.65
0.4
0.5
0
1
2
3
4
5
MLA
6
7
8
9
10
0.2
specifity
_SENSIT_
0
0
2
4
6
MLA
8
10
12
IVUS MLA Cut-off by FFR by Vessel Size
RVD < 3.0 mm
RVD 3.0 to 3.5 mm
1.2
1.2
1
1
0.8
0.8
2.68 mm2
Sensitivity 0.67
Specificity 0.66
C= 0.64
0.6
0.4
0.2
3.16 mm2
Sensitivity 0.67
Specificity 0.76
C= 0.72
0.6
0.4
specifity
_SENSIT_
0.2
specifity
_SENSIT_
0
0
0
2
4
MLA
6
0
8
2
4
MLA
1.2
1
0.8
RVD > 3.5 mm
6
3.74 mm2
Sensitivity 0.55
Specificity 0.69
C= 0.64
0.6
0.4
0.2
specifity
_SENSIT_
0
0
2
4
6
MLA
8
10
12
8
10
VH Findings by FFR
Overall
FFR < 0.8
FFR ≥ 0.8
P value
Plaque Burden, %
68.7 ± 11.2
72.1 ± 8.7
67.4 ± 11.7
<.001
Plaque Area, mm
8.8 ± 3.8
8.8 ± 3.7
8.8 ± 3.9
0.903
Necrotic Core Tissue, %
21.7 ± 9.3
21.9 ± 7.9
21.7 ± 9.9
0.809
Necrotic Core Tissue, mm2
1.4 ± 0.6
1.4 ± 0.9
1.4 ± 1.0
0.676
Fibrofatty Tissue, %
13.1 ± 9.3
13.3 ± 8.1
13.0 ± 9.7
0.787
Fibrofatty Tissue, mm2
0.9 ± 0.9
0.9 ± 0.8
0.9 ± 0.9
0.861
52.5 ± 15.6
54.3 ± 12.6
51.8 ± 16.5
0.205
3.2 ± 2.0
3.3 ± 1.8
3.2 ± 2.0
0.723
11.1 ± 10.7
10.5 ± 8.1
11.4 ± 11.5
0.469
0.7 ± 0.7
0.7 ± 0.7
0.7 ± 0.7
0.992
Fibrous Tissue, %
Fibrous Tissue, mm2
Dense Calcium, %
Dense Calcium, mm2
VERDICT + F1RST: Pooling
F1RST
291 pts, 303 lesions
304 pts, 320 lesions
Prior MI, unless LVEF nl (n=94)
LVEF<50% without prior MI (n=xx)
Exclude:
STEMI (n=4)
TIMI 1 flow (n=1)
Left main lesion (n=1)
291 pts, 303 lesions
189 pts, 194 lesions
IVUS reviewed at CRF core lab
497 intermediate lesions assessed in 480 pts
from xx centers in xx countries
MLA vs. FFR Regression Plot
1.0
0.9
FFR
0.8
0.7
Optimal cutoff: 2.9 mm2
C-statistic:
0.66
Accuracy:
66.0%
0.6
0.5
FFR = 0.756 + 0.026*MLA
r = 0.34
0.4
0.3
1
2
3
4
5
6
7
MLA
8
9
(mm2)
10
11
12
13
14
15
Multivariable Predictors
544 intermediate lesions assessed in 516 pts from 24 centers
FFR ≤0.80 in 169/544 lesions (31.1%) and 166/516 pts (32.2%)
Logistic regression (FFR ≤0.80)
Odds ratio [95%CI]
P value
Age (per 10 year ↓)
1.43 [1.15, 1.79]
0.002
LAD (vs LCX)
7.27 [3.52, 15.04]
<0.0001
RCA (vs LCX)
2.44 [1.05, 5.66]
0.04
QCA diameter stenosis (per 10% ↑)
1.73 [1.32, 2.26]
0.0001
IVUS MLA (per 1 mm2 ↓)
2.70 [1.92, 3.85]
<0.0001
IVUS EEM (per 10% ↑)
1.09 [1.02, 1.17]
0.01
Other variables in model: Clinical - gender, diabetes, smoking, stable angina, BSA; QCA - prox
vs distal, RVD, length, calcification, bifurcation; IVUS – plaque burden
Clinical data on
outcome based on FFR
and IVUS
Outcomes of Percutaneous Coronary Intervention
in Intermediate Coronary Artery Disease
Fractional Flow Reserve–Guided Versus Intravascular Ultrasound–Guided
Nam et al.:JACC Intervention. 2010
Outcomes of Percutaneous Coronary Intervention
in Intermediate Coronary Artery Disease
Fractional Flow Reserve–Guided Versus Intravascular Ultrasound–
Guided
Both FFR- and IVUS-guided PCI for intermediate coronary artery disease were associated with favorable
outcomes. The FFR-guided PCI reduces the need for revascularization of many of these lesions.
Nam et al.:JACC Intervention. 2010
Conclusions
• FFR remains the gold standard to assess functional ischemia
• Anatomic measure of intermediate coronary lesion obtained by IVUS
show only a moderate correlation to FFR values.
• The new MLA cut off is 2.9 mm2 for patients with normal LV and 3.07
mm2 for patients with reduce LV.
• The MLA is vessel size dependent and better correlated in large
diameter vessels.
• Morphology assessment currently is not correlated to FFR or clinical
outcome.
• However, the utility of IVUS MLA as an alternative to FFR for guidance
of intervention of intermediate lesions may be limited and should be
tested clinically.