Transcript Fractional Flow Reserve and Intravascular Ultrasound RelationShip THE F1RST TRIAL Ron Waksman, MD on Behalf of the F1RST Investigators.

Fractional Flow Reserve and
Intravascular Ultrasound
RelationShip
THE F1RST TRIAL
Ron Waksman, MD on Behalf of the
F1RST Investigators
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
• Grant/Research Support
•
Consulting Fees/Honoraria
Company
• Volcano
• Medtronic Vascular
• Abbott Vascular
• Boston Scientific
• Biotronik
• Medtronic
• Abbott Vascular
• Boston Scientific
• Lilly Daiichi
• Astra Zeneca
Background I
• An intermediate coronary stenosis, defined as a
luminal narrowing with a diameter stenosis
between 40-70% on angiography, is a source of
controversy with regard to the appropriate
criteria for undertaking revascularization.
• It has been previously reported that postponing
revascularization of intermediate severity lesions
on angiography with FFR>0.80 is safe and results
in an excellent clinical outcome.
Background II
• The PROSPECT trial followed 700 patients with
acute coronary syndrome for 3 years, reported
that the MACE was low with one of the correlated
of non-culprit lesion related events was an MLA
<4 mm2 by IVUS
• To date, few data are available regarding the
relationship between the anatomical and
morphological IVUS parameters and the
functional FFR results.
Purpose and Aims
• To evaluate the relationship between IVUS VH ®
anatomical parameters and FFR value in patients
with intermediate coronary stenoses.
• To determine the IVUS VH ® anatomical criteria
and cutoff value associated with significantly
functional criteria of FFR< 0.8.
Endpoints
• Primary
Correlation between MLA and FFR and to
identity a cut-off value for MLA corresponding to
and FFR of 0.8
• Secondary

Correlation between FFR and plaque burden
and to identify a cut-off value for plaque
burden corresponding to and FFR of 0.8

Assess the relationship between FFR (<0.80)
and determined cut-off values of MLA with

Presence of:
• Thin cup fibroatheroma (TCFA)
defined as Necrotic Core (NC) >10%, confluent over 3 consecutive frames with a
plaque burden of > 40% and NC against the lumen surface > 30 degrees
• Plaque burden ≥ 70%
Hypothesis
We hypothesize that IVUS VH morphological
criteria, such as minimal lumen area, plaque
burden and plaque type by VH, can predict
can predict physiological ischemia by FFR.
Study participating Sites
Site Name
City, State Country
Principal
Investigators
# Enrolled
Washington Hospital Center
Washington, DC USA
Ron Waksman, MD
91
University Hospital Krakow
Krakow, Poland
Jacek Legutko, MD
59
Barnes Jewish Hospital
St. Louis, MO USA
Jasvindar Singh, MD
49
Hamot Medical Center
Erie, PA USA
Quentin Orlando, MD
33
St. Luke’s Health Center
Kansas City, MO USA
Steven Marso, MD
27
Patients First
Washington, MO USA
Timothy Schloss, MD
26
Ohio Heart Research
Columbus, OH USA
John Tugaoen, MD
7
Dartmouth Medical Center
Lebanon, NH USA
James DeVries, MD
6
Liverpool Heart and Chest
Liverpool, United Kingdom
Nicholas Palmer, MD
5
Städtische Kliniken Neuss
Neuss, Germany
Michael Haude, MD
1
Study Management
Key Members
Sponsor
Volcano Corp
Study Principal Investigator
Ron Waksman, MD
Data Analysis
Cardiovascular Research Institute
Rebecca Torguson
Stacy Swymelar
Zhenyi Xue
QCA Core Laboratory
Cardiovascular Research Institute
Cathy Gurgol
David Hellinga
Rebecca Torguson
IVUS Core Laboratory
Krakow Cardio-Vascular Research
Institute
Clinical Monitoring
IMARC Research Inc & Krakow
Cardio-Vascular Research Institute
Inclusion/Exclusion Criteria
Inclusions
•
•
•
Exclusions
Clinical indication for coronary
angiography for stable or unstable
angina
•
•
STEMI within the past 24 hours
Intermediate coronary lesion with
stenosis 40-80% in one or more
native, major epicardial coronary
artery
•
Left ventricular hypertrophy >1.5 cm by
echo
•
•
History of bronchospasm or asthma
•
•
Unprotected left main or ostial lesions
•
•
•
Lesions in arterial or saphenous vein grafts
•
More than one lesion in an epicardial vessel
Lesions suitable for FFR and
IVUS/VH
Decompensated HF or hypotension
requiring intubation, inotropes, intravenous
diuretics or IABP
ECG evidence of conduction defect (2º or 3º
AVB)
Severe calcification or tortuosity of the
target vessel
Thrombus
Lesion in a vessel with <2.5 mm reference
diameter
Methods
• We have enrolled 304 patients and 320 lesions at 10 sites in
the United States and Europe, who were undergoing a
clinically indicated coronary angiogram and who have
intermediate coronary lesions.

Where, clinical indication for coronary angiography was stable or
unstable angina.

Patients required to have an intermediate coronary lesion (stenosis
40-80% by visual estimate) in one or more native, major epicardial
coronary artery (defined as LAD and subsequent branches, LCX and
subsequent branches, and RCA and subsequent branches) with
reference diameter ≥2.5mm (visual estimate)
• IVUS VH and FFR were performed to explore the
relationship between those different imaging modalities.
• Data lock for this presentation was made on 24/OCT/2011
Clinical Trial.gov ID NCT01153555
Methods
•
Intermediate lesion was identified by the operator
•
FFR measured by pressure wire using either the
RADITM or the Volcano Wires hyperemia induced by
i.v. adenosine 140 µg/kg/min in periheral vein
•
IVUS VH was performed in the target vessel to
assess lesion severity
•
The operator was free to decide whether to
intervene or defer
•
Independent IVUS and QCA core labs assessed
blindly the Angio and the IVUS studies respectively
Results
Baseline Demographics
F1RST population (N=304)
Age (years)
61.5 ± 9.9
Male
223 (73.4%)
Hypertension
261 (86.1%)
Hyperlipidemia
265 (88.0%)
Current Smoker
58 (27.5%)
History of Pulmonary Disease
21 (6.9%)
History of CAD
22 (7.3%)
Family history of CAD
134 (47.9%)
Diabetes
92 (30.3%)
IDDM
40 (13.1%)
Renal Dysfunction
19 (6.3%)
Prior PCI
Prior CABG
144 (47.4%)
6 (2.0%)
Prior myocardial infarction
94 (31.8%)
Ejection fraction (%)
55.2 ± 10.7
Results
Clinical Presentation
Stable Angina
159 (52.3%)
Unstable Angina
117 (38.5%)
NSTEMI
16 (5.3%)
STEMI
4 (1.3%)
Positive Functional Test
95 (31.3%)
Other
17 (5.6%)
Medications Upon Presentation
Aspirin
255 (83.9%)
Clopidogrel
139 (46.0%)
Ticlid
Prasugrel
0 (0%)
6 (2.0%)
Beta Blocker
214 (70.6%)
ACE Inhibitor
254 (83.6%)
Statin
244 (80.5%)
Results
Intraprocedural Anticoagulation
Unfractionalted Heparin
179 (58.9%)
Bivalirudin
152 (50.0%)
LMWH
8 (2.7%)
GP IIb/IIIA Inhibitor
9 (3.0%)
Post-Procedure Anticoagulation
Unfractionalted Heparin
2 (0.7%)
Bivalirudin
1 (0.7%)
LMWH
2 (0.7%)
GP IIb/IIIa Inhibitor
4 (1.6%)
Results
Lesion Characteristics
(N=320)
Left Main Coronary Artery
2 (0.6%)
Left Anterior Descending Artery
185 (58.2%)
Circumflex Artery
52 (16.4%)
Right Coronary Artery
78 (24.6%)
Proximal
103 (32.5%)
Mid
182 (57.4%)
Distal
23 (7.3%)
TIMI Flow 0
0
TIMI Flow I
1 (0.3%)
TIMI Flow II
4 (1.3%)
TIMI Flow III
312 (98.4%)
AHA/ACC Type B1/B2 Lesion
201 (63.4%)
AHA/ACC Type C Lesion
4 (4.4%)
PCI
121 (37.8%)
Angiographic Success post PCI
121 (100%)
Diagnostic Imaging Characteristics
Fractional Flow Reserve
Mean FFR
0.84 ± 0.09
FFR <0.8
89 (27.8%)
FFR <0.75
49 (15.3%)
Intravascular Ultrasound
Minimal Luminal AreaIVUS (mm2)
3.5 ± 1.3
QCA Analysis
Lesion LengthQCA (mm)
15.0 ± 7.7
Reference Vessel Diameter QCA (mm)
2.9 ± 0.6
Minimal Luminal DiameterQCA (mm)
1.6 ± 0.4
Diameter StenosisQCA (%)
45.3 ± 8.4
VH in MLA Plaque Distribution
PIT
22 (11.0%)
FC
35 (17.4%)
FA
34 (16.9%)
CaFA
20 (10.0%)
TCFA
20 (10.0%)
CaTCFA
65 (32.3%)
IVUS MLA cut-off for ischemic FFR
Cut off for FFR = 0.75
Cut off for FFR = 0.80
1.2
1.2
1
1
0.8
0.8
0.6
2.99 mm2
Sensitivity 65.3%
Specificity 65.6%
C= 0.66
0.4
0.2
0.4
0.2
0
0
2
4
Sensitivity
6
8
Specificity
3.16 mm2
Sensitivity 73.8%
Specificity 54.8%
C= 0.64
0.6
10
0
0
2
4
6
MLA
Sensitivity
Specificity
8
10
WHC IVUS FFR CUTOFF BY VESSEL
SIZE (200 LESIONS)
Correlations
FFR to MLA
FFR to MLD
10
3.5
r = 0.287
P < 0.0001
3
r = 0.320
P < 0.0001
9
8
2.5
7
6
MLD
2
1.5
MLA
5
1
3
4
2
0.5
1
0
0.5
0.6
0.7
0.8
FFR
0.9
1
0
0.5
0.6
0.7
0.8
FFR
0.9
1
Correlations
FFR to % Plaque BurdenVH
FFR to % Diameter StenosisQCA
100
80
90
70
80
60
Plaque Burden
Diameter Stenosis
70
50
60
50
40
40
30
30
20
20
r = -0.201
p = 0.0003
10
r = -0.184
p = 0.0082
10
0
0
0.5
0.6
0.7
FFR
0.8
0.9
1
0.5
0.6
0.7
0.8
FFR
0.9
1
Correlations of FFR to MLA by RVD
RVD < 3.0 mm
RVD 3.0 to 3.5 mm
8
12
r = 0.234
p = 0.0036
7
6
8
MLA
5
6
MLA
4
r = 0.352
p = 0.0024
10
3
4
2
2
1
0
0
0.6
0.7
0.8
FFR
0.9
1
0.5
0.6
0.7
RVD > 3.5 mm
10
9
8
r = 0.339
p = 0.0261
7
6
MLA
0.5
5
4
3
2
1
0
0.5
0.6
0.7
0.8
FFR
0.9
1
0.8
FFR
0.9
1
Correlations of FFR to MLA by TCFA
Lesions without CaTCFA or TCFA
Lesions with CaTCFA or TCFA
10
12
r = 0.279
p = 0.011
9
r = 0.338
p < 0.0001
10
8
7
8
6
5
MLA
MLA
6
4
4
3
2
2
1
0
0
0.5
0.6
0.7
0.8
FFR
0.9
1
0.5
0.6
0.7
0.8
FFR
0.9
1
FFR Correlation with VH
Mean ± SD
r value
p value
Plaque Burden, %
68.7 ± 11.2
-0.184
0.0082
Plaque Area, mm
8.5 ± 3.6
0.044
0.5319
Necrotic Core Tissue, %
22.0 ± 9.1
-0.011
0.8758
Necrotic Core Tissue, mm2
1.3 ± 0.9
0.033
0.6337
Fibrofatty Tissue, %
12.4 ± 8.4
-0.019
0.786
Fibrofatty Tissue, mm2
0.8 ± 0.8
-0.032
0.6458
52.6 ± 15.7
-0.059
0.4009
3.1 ± 1.9
0.011
0.8809
11.1 ± 10.8
0.024
0.7371
0.6 ± 0.7
0.065
0.3581
n (%)
kappa
p value
Plaque Burden % < 70%
30 (9.4%)
-0.038
0.1971
TCFA
1 (0.5%)
-0.100
0.1595
VH Variable
Fibrous Tissue, %
Fibrous Tissue, mm2
Dense Calcium, %
Dense Calcium, mm2
With FFR < 0.75
VH Findings by FFR
VH Variable
FFR < 0.8
FFR ≥ 0.8
P value
Plaque Burden, %
72.1 ± 8.7
67.2 ± 11.9
0.001
Plaque Area, mm
8.7 ± 3.8
8.5 ± 3.6
0.676
Necrotic Core Tissue, %
21.8 ± 7.8
22.1 ± 9.6
0.872
Necrotic Core Tissue, mm2
1.4 ± 0.9
1.4 ± 0.9
0.859
Fibrofatty Tissue, %
13.7 ± 8.9
11.9 ± 8.1
0.154
Fibrofatty Tissue, mm2
0.9 ± 0.9
0.8 ± 0.7
0.216
54.5 ± 12.3
51.8 ± 16.9
0.207
Fibrous Tissue, mm2
3.3 ± 1.9
3.1 ± 1.9
0.550
Dense Calcium, %
10.0 ± 7.8
11.5 ± 11.8
0.271
Dense Calcium, mm2
0.6 ± 0.5
0.7 ± 0.7
0.657
Fibrous Tissue, %
Conclusions
• The FIRST Study demonstrates modest correlation
of IVUS anatomical to FFR physiological
measurements in intermediate lesions
• The new IVUS cutoff for FFR of 0.80 is 2.99 mm2
• The new IVUS cutoff for FFR of 0.75 is 3.16 mm2
• Lesions without CaTCFA or TCFA had better
correlation to FFR when compared to lesions with
CaTCFA or TCFA
• FFR was correlated with plaque burden but was not
correlated with plaque morphology
• The utility of IVUS as a tool to determine whether to
intervene on borderline should be studied in a
prospective study
Limitations
• This trial does not assess long term
outcome with respect to the IVUS/FFR
findings.
• Once this IVUS/FFR correlation has been
established it would require to conduct an
IVUS guided lesion assessment study to
determine the need for intervention and
the impact of this strategy on long term
clinical outcome.