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