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The changing paradigm

Noninvasive Cardiac Imaging

Clyde R. Meckel, MD

Nothing to disclose

Anatomica l

Testing

Anatomical and

Functional

Noninvasive Imaging in Coronary

Artery Disease

Coronary CTangiography FFRCT

Functiona l

Testing

Treadmill ECG Stress Echo

Stress MRI SPECT

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Stress testing leads to overutilization of invasive procedures

CONFIDENTIAL - FOR CLASS USE ONLY 4

• Patel et al, NEJM 2010.

• Patel et al, AHJ 2014.Data includes nearly 400,000 patients at over 650 US

hospitals

Findings During

Invasive Coronary Angiograms

Over half of patientswho undergo invasive angiograms

have no clinically relevant disease

Because standard non-invasive stress

testing is low yield

and could have avoided Invasive

Coronary Angiographyif better non-invasive screening

were available

Non-obstructive

CAD

Obstructive

CAD 55%

Coronary Computed Tomography Angiography

and the Future Risk of Myocardial Infarction

5-Year Follow-up of the SCOT-HEART Trial

on behalf of the SCOT-HEART Investigators

The SCOT-HEART

TrialStudy

ProtocolPrimary Care Physician Referral

Clinic Consultation

History, Examination, 12-lead ECG

Exercise ECG if appropriate

Diagnosis, Investigations and Treatment Plan

Approached for Study Inclusion

Angina Questionnaire

Randomised 1:1 to

CTCA + Standard Care or

Standard Care alone

Result to Attending Clinician

TreatmentRecommendations

Cardiovascular Risk

Assessment:

ASSIGN Score

6-Week Attending Clinician Review

Diagnosis, Investigations and Treatment Plan

6-Week Patient Review

Angina Questionnaire

Clinical Outcome

NHS Health Records

Computed Tomography

Coronary Angiogram

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Newby et al. Trials. 2012;13:184

Randomisation 1:1 to

Standard Care Alone or CTCA + Standard Care

• 4,080 of 4,146 (98.4%)

patients remained

registered in Scotland.

• No patient withdrew

consent

• Complete data over a

median of 4.8 years

comprising 20,254

patient-years of follow-up

The SCOT-HEART Trial

Primary Clinical EndPoint

Standard Care Alone CTCA + Standard Care

Co

ron

ary

He

art

Dis

ea

se D

ea

tho

r

No

n-f

ata

l M

yo

card

ial

Infa

rcti

on

Follow up (years)

Hazard Ratio 0.59

(95% CI, 0.41 to 0.84)

P=0.004

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The SCOT-HEART Trial

Non-fatal Myocardial Infarction

Hazard Ratio 0.60

(95% CI, 0.41 to 0.87)

P=0.007

Standard Care Alone CTCA + Standard Care

No

n-f

ata

l M

yo

card

ial

Infa

rcti

on

Follow up (years)

Hazard ratio 1.00

(95% CI, 0.88 to 1.13)

P=0.993

Hazard Ratio 1.07

(95% CI, 0.91 to 1.27)

P=0.409

The SCOT-HEART Trial

Invasive Coronary Angiography

and Coronary Revascularization

Standard Care Alone CTCA + Standard Care

Inva

siv

eC

oro

na

ry

An

gio

gra

ph

y

Co

ron

ary

Re

vasc

ula

riza

tio

n

Follow up (years)Follow up (years)

The SCOT-HEART Trial

Invasive Coronary Angiography

and Coronary Revascularization Beyond One-Year (Post-hoc

Analysis)

Hazard ratio 0.70

(95% CI, 0.52 to 0.95)

P=0.022

Hazard Ratio 0.59

(95% CI, 0.38 to 0.90)

P=0.015

Standard Care Alone CTCA + Standard Care

Inva

siv

eC

oro

na

ry

An

gio

gra

ph

y

Follow up (years)

Co

ron

ary

Re

vasc

ula

risa

tio

n

Follow up (years)

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Statin Therapy Use over 5 Years

The Right Patient Gets the Right

Treatment

Standard Care Alone

CTCA + Standard Care

Fre

qu

en

cy(%

)

100

75

50

25

0

0 1 4 5

Fre

qu

en

cy(%

)

100

75

50

25

0

10-Year Cardiovascular Risk (ASSIGN SCORE)

5 10 20 30

* * * * *

2 3

Follow up (years)

*P<0.0001

Coronary CT Angiography and the Future

Risk of Myocardial InfarctionThe Right Patient Gets the Right Treatment

• Coronary CT angiography leads to a reduction in

5-year coronary heart disease death or non-fatal

myocardial infarction

• Early increases in invasive coronary

angiography and coronary revascularization

are offset by lower rates beyond 1 year

• Benefits appear to be attributable to better targeted

preventative therapies that persist out to 5 years

• Should coronary CT angiography be the non-

invasive test of choice?

The NEW E NGL AND

J O U R N AL of M.ED I CI N E

Coronary CT Angiography and 5-Year Risk

of Myocardial Infarction

David E. Newby, M.D., Phil D. Adamson, M.D., Colin Ber ry, M.D.,

Nicholas A. Boon, M.D., Marc R. Dweck, M.D., Marcus Flather, M.D.,

John Forbes, Ph.D., Amanda Hunter, M.D., Stephanie Lewis, Ph.D.,

Scott Maclean, M.Sc., Nicholas L. Mills, M.D., Jo hn Norrie, M.Sc.,

Giles Roditi, M.D., Anoop S.V. Shah, M.D., Adam D. Timmis, M.D.,

Edwinj.R. van Beek, M.D., and Michelle C. Williams, M.D., for the SCOT-HEART

Investigators*

jESC Congress

Munich 2018 • •

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Case Study: A Common Clinical Occurrence

• 79 yo, female

• History: shortness of breath, DM, previous silent MI

• SPECT positive

Case Study: CTA shows moderate-severe mid

LAD (70-80%) disease

abnormal

FFRinvasive 0.86

Risks: Radiation, heart attack, stroke, arterial injury, death

Patient: Discomfort, absenteeism, anxiety

CMS allowed charges: ~$10,000 immediate, $20,000 1 yr

Courtesy of Dr. Daniel Simon

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HeartFlow FFRCT Process

HeartFlow Analysts use proprietary software to

create a personalized, digital 3D model of the coronary arteries.

Powerful computer algorithms solve millions of

complex equations to assess the impact that blockages have on blood flow.

Physicians interrogate the model and interpret

the FFRCT results to assess, vessel-by-vessel, if sufficient blood is reaching the heart.

A standard cardiac CT scan is performed and the

data is uploaded to HeartFlow.

ANATOMY

Identify obstructive CAD

FUNCTION

Identify lesion-specific

ischemia that may benefit from PCI

Invasive

Noninvasive

Diagnosing Anatomic and Functionally Significant CAD

25-50%

of patient’s management

strategy changes

with FFR

Nagaraja et al, Cardiovasc Revasc Med 2017

• 70 year old Male

• 1-2 months exertional chest pain

• Normal Stress Echo

• Assessment: High pre-test probability for CAD.

Recommend cCTA and FFRCT to assess extent of CAD and ischemia.

Case Study

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Case Study - CT Findings

LAD CT

Case Study – FFRct Findings

Case Study – Invasive Findings

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HeartFlow FFRCT Results

Refer to product Instructions For Use for patient populations in which FFRCT has been

clinically evaluated, relevant clinical data, and product warnings.

25

HeartFlow FFRCT Results

Refer to product Instructions For Use for patient populations in which FFRCT has been

clinically evaluated, relevant clinical data, and product warnings.

26

Performance of Coronary Diagnostic Test Compared to

Reference Standard - Invasive FFR

27Nørgaard, et al., Eur Radiol 2015.

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DISCOVER-FLOW

• Completed 2011

• N=103 patients

High Accuracy of FFRCT Compared to Gold Standard

DeFACTO

• Completed 2012

• N=252 patients NXT

• Completed 2013

• N=254 patients

NXT Per-Vessel

Performance

• Specificity: 86%

• Sensitivity: 84%

• Accuracy: 86%

Data supported 2014

FDA Clearance

Koo et al., JACC 2011.

Min et al., JAMA 2012.

Norgaard et al., JACC 2014.

The PACIFIC Trial May 22, 2018

PACIFIC trial

• Prospective head-to-head comparison of non-invasive imaging

• 208 Patients with suspected stable coronary artery disease

• All patients underwent coronary CTA, SPECT, PET, and routine 3 vessel invasive

FFR within 2 weeks

• Blinded and dedicated core labs analysed each imaging modality1

PACIFIC FFRCT sub study

• Blinded core lab performed CT quality check and FFRCT analysis (HeartFlow,

software v2.8)

• Per-vessel diagnostic performance of FFRCT compared with CT stenosis, SPECT,

and PET, referenced by invasive FFR

1 Danad et al, JAMA Cardiology 2017

Highest discrimination of ischemia causing lesions for FFR-CT compared to other modalities:

• CT stenosis: Δ AUC 0.11, p < 0.001

• SPECT: Δ AUC 0.24, p < 0.001

• PET: Δ AUC 0.07, p < 0.001

The PACIFIC trial May 22, 2018

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Health

Costs

Experience

Prospective clinical utility trial

comparing two distinct patient management strategies.

PLATFORM Shows FFRCT Delivers on the Triple Aim

vs.

FFRCT-Guided

Strategy

Usual Care

Douglas, et al. EHJ 2015.

Hlatky, et al. JACC 2015.

Douglas, et al. JACC 2016.

Usual Care FFRCT-Guided

27%

Non-obstructive CADObstructive CAD

27%

73% 12%

61%

ICA

Canceled

83% reduction

Dramatic Reduction in Invasive Catheterization (ICA) with No

Obstructive Disease

Douglas, et al. EHJ 2015.

Health

Costs

Experience

Cost Savings Increase Over TimeCosts Over 1 Year –

Patients with Planned ICA

*p<0.0001

26%

Savings*

Douglas, et al. JACC 2016.

$ p

er-

pa

tie

nt

T H E P L A T F O R M T R I A L

Cost savings increase:

23% ($2,481) at 90 days 26% ($3,109) at 12 months

after accounting for $1,500 cost of the HeartFlow Analysis.

Hlatky, et al. JACC 2015

Utilization over 1 year

In patients referred for ICA

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HeartFlow Can Improve the Patient

Experience Through the Entire

Clinical Journey

1Bilbey, et al. Clinical Imaging 2016 (in press)2Hlatky, et al. JACC 2015.

Diagnostic

Testing

Review of

Diagnosis

Treatment

• Decrease in medical radiation exposure compared to the standard pathway1

• Significantly greater improvement in Quality of Life than evaluation with usual non-invasive testing2

• Increase patient satisfaction by shortening time to diagnosis and accelerating discharges

• Drive patient engagement, participation, and communication via interactive and patient

friendly reporting

35

FFRCT Improves Efficiency in the Cath Lab

n= 745 patients

Average 34%

Average 69%

Usual Care Cohort CTA/FFRCT Cohort

PLATFORM1,2 Aarhus3 UZ Brussels4 Loyola University8 PROMISE FFRCT7

Technology Advances and Guidelines had not Improved Rates ofNegative Angiography

US

Circa 2004-20081

MPI CTA

ECHO ETT

Canada

Circa 2012-20133

HeartFlow4,5,6

1. Patel et al, NEJM 20102. Lu et al, JACC-CVI, 20173. Roifman et al, JAHA, 20174. Hlatky et al, JACC 20165. Norgaard et al, JAHA 20176. Lu et al, JACC-CVI 2017

US

Circa 2010-20132

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Real-world clinical utility and impact on clinical

decision making of FFRCT

Lessons from the ADVANCERegistry

Dr Tim Fairbairn on behalf of theADVANCE investigators

Nieman K, Akasaka T , Norgaard BL, Berman DS, Raff G , Hurwitz-Koweek LM, Pontone G, Kawasaki T, Sand NP, Jensen J, Amano T, Poon M, Ovrehus K, Sonck J, Rabbat M,

Mullen S, De Bruyne B, Rogers C, Matsuo H, Bax JJ, Leipsic J, Patel MR

ADVANCERegistry

• 5083 subjects undergoing CCTA with clinically stable symptoms were

prospectively enrolled at 38 sites in Europe, North American and Japan

between July 2015 – October 2017

• Primary Endpoint:

– Reclassification rate between CCTA-based versus FFRCT-based management

plans as determined by blinded core laboratory adjudication

• Secondary endpoints:

– Reclassification rate between CCTA-based and FFRCT-based management by site

adjudication

– Incidence of ICA demonstrating no obstructive coronary stenosis >50%

– 90-day survival free from all cause or major adverse cardiovascular events

(MACE) inclusive of MI, all-cause mortality or unplanned hospitalization for ACS

leading to revascularization*

* Event adjudication performed by independent Clinical Events Committee

Planned and Actual Management

Management Plan

Separate site and blinded core lab interpretation and recommendations

• Primary management plan based on CCTAalone

• Second ‘revised’ management plan based on CCTA +FFRCT

• Actual Management at 90-days

Treatment Strategies

1. Medical Treatment

2. PCI

3. CABG

4. Further testing

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Disease Burden

>50% stenosis: 72.1%

>50% stenosis (multivessel): 36.9%

Ischaemia (FFRCT≤0.80): 66.4%

Median FFRCT0.87LAD Median FFRCT0.79 RCALCX Median FFRCT0.88

Reclassification by Core Lab

Post CCTA

Management Strategy

(n=4715)β

β 22 post CCTA treatment recommendations were not made

* 924 (19.8%) had ICA and no revascularization66.9% reclassification

ActualManagement*

(n=4737)

Post FFRCT

Management Strategy

(n=4715)β

Reclassification by Site

Post CCTA

Management Strategy

(n=4119)β

β 618 post CCTA treatment recommendations were not made

* 924 (19.8%) had ICA and no revascularization

Post FFRCT

Management Strategy

(n=4119) β

63.5% reclassification

ActualManagement*

(n=4737)

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FFRCTStratum

90 day Clinical Outcomes

Rate of ICA, Non-Obstructive CAD , and Revascularization

ICA 40%

Non-obstructive CAD 14.4%*ICA 19%

Non-obstructive CAD 43.8%*

* No coronary stenosis ≥50% by site interpretation ofICA

90 day Clinical Outcomes

MACE (MI, Death, Hospital Admission for ACS and Unplanned Revascularization)

Days

Days

AllMACE

FFRCT ≤ 0.80

FFRCT > 0.80

Death orMI

FFRCT ≤ 0.80

FFRCT > 0.80

Days

P=0.0019

HR: 19.75 (1.19-326)

P=0.0077

HR: 14.68 (0.88-246)n=3145

n=1592

n=3145

n=1592

Summary

In an international multicenter real-world population of

over 5000 patients, the addition of FFRCTto CCTA:

• Changed management plans in over 60% of subjects

• Was associated with low rates of invasive angiography, and

good safety when FFRCT>0.80 (no MACE)

• Significantly lowered the rate of anatomical (<50% DS) non-

obstructive disease at ICA (14 vs 44%) with abnormal FFRCT

• An inverse relationship exists between FFRCTvalue and

likelihood of downstream ICA, revascularization, and MACE

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Case 3: MVD planning

• 68yo male with history of atrial tachycardia s/p ablation

1/2015, prior tobacco abuse, HTN, HLD, DM

• Episodes of nausea, left shoulder discomfort, shortness of breath and diaphoresis

4747

LAD

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RCA: no PCI indicated

RCA

FFR = 0.88

LAD: Pre-procedure planning of approach, ostial and

branch angulation, vessel sizing

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Coordinated Guidelines and Payment Programs to a Enable CTA-first Chest Pain Pathway

Based on NICE guidance for chest pain of recent onset (CG95) and medical technology consultation

document “HeartFlow FFRCT for estimating fractional flow reserve from coronary CT angiography”.

Results of coronary CTA may indicate coronary artery disease (CAD) of uncertain functional significance or be otherwise indeterminate

Coronary CTA as a frontline test* for patients with:• typical or atypical chest pain, or• abnormal 12-lead resting EKG

The HeartFlow FFRCT Analysis:• provides clinicians with proven functional information to aid in

diagnosing, vessel by vessel, the existence of ischemia• has better diagnostic performance than CCTA alone, or other

non-invasive or invasive tests

• is cost saving compared with all functional imaging tests

NICE Clinical

Guideline [CG95]November 2016

NICE Medical

Technologies Guidance [MTG32]

February 2017

?

NHS Innovation

Technology Payment

[ITP]April 2018

The ITP program is a new NHS program to fund emerging technologies• HeartFlow was 1 of 4 technologies selected from > 270 applications• Funding provides for full adoption for 1 year across 25 leading NHS sites

J Thorac Imaging 2017

Denial of CCTA

pre-auth shuts

down pathway

Enabling the Clinical

Pathway

AIM

50%

eviCore

30%

NIA

17%

HealthHelp

3%

RBM MARKETSHARE

80% covered lives

now authorize CCTA

as frontline test

Former RBM policies required stress test prior to

coronary CTA. Updated policies now enable

CCTA as first test for diagnosing CAD.

Effective 1/1/18

Effective 5/1/18

BCBS CA has eliminated the PA process so that

physicians can order the test w/o authorization.

Recent clinical guidelines/recommendations

54

“FFRct may avoid the need for

invasive coronary angiography

…and lead to cost savings”

“FFRct may avoid the need for

invasive coronary angiography

…and lead to cost savings”

“…FFRct is a combination technique

that is noninvasive

like CT but provides FFR, which has

traditionally only been

an invasive test”

“…FFRct is a combination technique

that is noninvasive

like CT but provides FFR, which has

traditionally only been

an invasive test”

FEBRUARY 2017

Recommended CT and FFRCT as pathway for patients with onset of chest pain

FEBRUARY 2017

Recommended CT and FFRCT as pathway for patients with onset of chest pain

MARCH 2017

Appropriate Use Criteria: HeartFlow FFRCT is utilized to determine appropriate revascularization in clinical scenarios

MARCH 2017

Appropriate Use Criteria: HeartFlow FFRCT is utilized to determine appropriate revascularization in clinical scenarios

“FFRct strategy would likely lead to

changes in management that would

be expected to improve health

outcomes”

“FFRct strategy would likely lead to

changes in management that would

be expected to improve health

outcomes”

JUNE 2017

Issued a positive healthcare evidence review. Recommends CT and FFRCT as pathway for patients with onset of chest pain.

JUNE 2017

Issued a positive healthcare evidence review. Recommends CT and FFRCT as pathway for patients with onset of chest pain.

Evidence

Street®

Issuer Action Cited Benefits

Positive HTA assessments are now required for broad adoption

CONFIDENTIAL - FOR CLASS USE ONLY

8/29/2018

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CMS OPPS New Tech APC

CMS final rule assigned CPT 0503T to a New Tech APC for payment of

$1450.50 effective January 1, 2018

• Increasingly used as primary diagnostic strategy for assessment ofchest pain with suspected CAD

• High sensitivity but modest specificity

–Not all calcified bulky plaque is flow limiting

• Improves patient outcomes compared to functional testing

–Decreased risk of death/MI at 5 years

• High rates of invasive coronary angiography showing non-obstructivecoronary disease similar to stress testing

• Cannot guide revascularization alone owing to the lack of functional

information

Summary – Coronary CTA

• Improves discrimination of ischemia

• Frequently results in change in initial post CCTA management strategy

• Decreases rates of nonobstructive CAD at cath

• Cost-effective

• Improves patient experience

• Gaining third party acceptance

Summary - FFRct