Jonathon Leipsic MD FRCPC FSCCT Vice Chairman of Radiology University of British Columbia Canada Research Chair - Advanced Cardiac Imaging Associate Professor Radiology and Cardiology President Society of Cardiovascular CT
Lesion Specific Ischemia with FFRCT- Current Data
Disclosures
Speaker’s bureau: GE Healthcare and Edwards LifeSciences
Grant Support- CIHR, NIH, GE Healthcare, Heartflow
Advisory Board- GE Healthcare,
Edwards LifeSciences, Neovasc, Circle CVI, Philips, Samsung
CT Corelab- Edwards Lifesciences, Neovasc, Tendyne
Most patients with suspected CAD undergoing ICA do not have obstructive disease at the time of ICA
Source: Patel et al, NEJM 2010.
Nearly 2/3rd of patients without known CAD who went to elective diagnostic
angiogram were found to have no obstructive disease
Data from an analysis of ~400,000 patients at > 650 US hospitals
62%
Non-obstructive CAD Obstructive CAD
Coronary CTA- Anatomical test correlates better with invasive anatomical assessment
94% 99%
95%
85% 83%
64%
91% 90%
48%
85%
71%
91%
99% 97% 99%
83%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
ACCURACY Europe MEDIC CorE64
Sensitivity
Specificity
PPV
NPV
Diagnostic Performance of CCTA is well established
N=230
CAD in 13%
N=360
CAD in 68%
N=415
Pretest LK 20-80%
N=291
CAD in 56%
Left anterior descending artery
Left circumflex artery Right coronary artery
“Should I be Revascularized”
2,368 diabetic patients assigned to
revascularization or medical tx and
followed for 5 years
2,287 individuals with angiographically
obstructive CAD and ischemia assigned to
PCI or medical tx and followed for 4.6 years
COURAGE Trial
(D/MI/CVA)
BARI 2D Trial
(D/MI/CVA)
Source: Boden et al. NEJM 2007; BARI 2D Study Group, NEJM 2009
Decisions of coronary revascularization should not be based upon anatomic stenosis alone
Lesion specific ischemia exhibits an unreliable relationship with angiographic stenosis
21% of 30-50% (<50%) angiographic stenosis has +FFR
19% of 90-95% stenoses have -FFR Source: Layland et al EHJ 2014
1. From typical CCTA
2. No radiation
3. No Δ image protocols
4. No medications
3D FFRCT map computed
FFRCT = 0.72 (can select any point on model)
FFR can now be derived from CT
FFR Can Now Be Derived from CCTA
1. Image-Based Modeling – Segmentation of patient-specific arterial geometry
2. Heart-Vessel Interactions – Allometric scaling laws relate caliber to pressure and flow
3. Microcirculatory resistance – Mophometry laws relate coronary dimension to resistance
4. Left Ventricular Mass – Lumped-parameter model couples pulsatile coronary flow to time-
varying myocardial pressure
5. Physiologic Conditions – Blood as Newtonian fluid adjusted to patient-specific viscosity
6. Induction of Hyperemia – Compute maximal coronary vasodilation
7. Fluid Dynamics – Navier-Stokes equations applied for coronary pressure
(1) (2) (3) (4) (5) (6)
140 mcg/kg/min
Source: Taylor et al. J Am Coll Cardiol 2013; Leipsic et al AJR 2015
FFR 0.65 = Lesion-specific ischemia
FFRCT 0.62 = Lesion-specific ischemia LAD stenosis
FFRCT 0.87 = No ischemia RCA stenosis
FFR 0.86 = No ischemia
Determining Lesion-Specific Ischemia C
ase
1 C
ase
2
CT ICA and FFR FFRCT
CT FFRCT ICA and FFR
FFRCT: Three (3) Prospective Multicenter Trials
DISCOVER-FLOW DeFACTO NXT
Primary end point Per pt. diag accuracy Per pt. diag accuracy; lower limit 95% CI 0.7
Per pt. AUC
Study sites/ countries 4 / 3 17 / 5 10 / 8
Site expertise qualification FFR CT or FFR CT plus FFR
CT training of site Yes No Yes
FFR training of site No No Yes
CT quality check No No Yes
CT results reading Core lab Core lab Site
FFR results report Site Site Site with core lab
overview
Vessel size for inclusion ≥ 2.0 mm ≥ 1.5 mm ≥ 2.0 mm
Use of NTG with CT ? 75% 99.6%
Software version* V 1.0 manual V 1.2 partial automation
approx 6 hours (this is
specified in manuscript)
V 1.4 increased
automation
<4 hours
Per-Patient Diagnostic Performance
Source: Norgaard et al. JACC 2014
Per-Patient Diagnostic Performance
Source: Norgaard et al. JACC 2014
1- Comparable diagnostic performance in Men and Women
0.0
00
.25
0.5
00
.75
1.0
0
Se
nsitiv
ity
0.00 0.25 0.50 0.75 1.001-Specificity
Women ROC area: 90% Men ROC area: 93%
Source: Leipsic et al RSNA 2013, Thompson et al JCCT 2014
2- What about intermediate stenoses?
Stenosis
Severity
0-24%
25-49%
50-69%
>70%
100% Source :Cheng et al. JACC CV Imaging 2008
FFRCT significantly enhances the evaluation of intermediate stenosis
Source: Nakazato et al. Circ Cardiovasc Imaging 2013
Significant improvement in the diagnostic performance over CTA for intermediate stenoses
FFRCT NPV in intermediate lesions. Nakazato R Circulation CI 2013.
CT ≥50% FFRCT ≤0.80
4-FFRCT is robust across varying degrees of CACS
Source: Norgaard JACC Imaging 2015
Diagnostic performance of FFRCT stratified by CACS
81 79 86
75 69
88
53
34
94
44
23
94
0
10
20
30
40
50
60
70
80
90
100
Accuracy Specificity Sensitivity
%
CT (all) FFRCT (all) FFRCT (CACS>400) CT (CACS>400)
The PLATFORM Study
25 PI: P Douglas
Trial Design
Planned Invasive
Catheterization (ICA)
Usual Care
Cohort n=187
CTA/FFRCT
Cohort n=193
Time Period 1 Time Period 2
• Prospective LongitudinAl Trial of FFRCT: Outcome and Resource IMpacts
– Prospective, controlled, pragmatic comparative effectiveness trial utilizing a comparative cohort design
– Comparing the effectiveness of two distinct clinical strategies – 584 patients with suspected CAD (pre-test likelihood of 20-80%) were enrolled
at 11 centers in 6 EU countries
• Primary Endpoint: Patients with a
planned ICA – Are patients evaluated using a CTA/FFRCT
guided strategy less likely to undergo
ICAs that show no obstructive CAD?
Usual Care CTA/FFRCT Guided
27%
Non-obstructive CAD (QCA) Obstructive CAD (QCA)
27%
73% 12%
61%
No ICA
83% reduction
• FFRCT prevented >80% of negative invasive angiograms • No adverse clinical events in patients in whom ICA was cancelled
CCTA and FFRCT help reduce the burden of non-obstructive disease in the cath lab
Douglas, P. S. 2015
PLATFORM: Patients without Obstructive Disease at ICA (site read)
NCDR
2004-08
NCDR
2009-11
US VA
2007-10 PROMISE
Functional
2010-13
PLATFORM
Usual Care
2013-14
PLATFORM
FFRCT Guided
2013-14
Source: Douglas, P. S. 2015
Cost effectiveness analysis of FFRCT in Platform
Costs Over 90 Days – Patients with Planned ICA
$10,734
$7,343
$10,734
$8,619
$0
$2,000
$4,000
$6,000
$8,000
$10,000
$12,000
FFRCT
Guided
Usual
Care
FFRCT
Guided
Usual
Care
*p<0.0001
32% Savings* 20% Savings*
No Medicare Reimbursement
FFRCT = $0
Author Assumption
FFRCT = $2107
Source: Hlatky, M. A. 2015
Conclusions
• FFRCT has been shown to be an accurate tool for the identification of and exclusion from lesion specific ischemia
• Good correlation with measured FFR • Higher diagnostic performance than other
non-invasive tests • Ability to guide clinic decision making is
fodder for ongoing investigation