- Coronary physiology guided interventions like fractional flow reserve (FFR) have the potential to provide benefit by reducing myocardial infarction and death compared to angiogram-guided revascularization alone. - Tests like FFR measure the pressure difference across a stenosis to determine the functional significance and guide whether intervention is needed. Studies show FFR can identify patients unlikely to benefit from intervention who can avoid unnecessary procedures. - Coronary flow reserve (CFR) measured by positron emission tomography (PET) provides a continuous measure of coronary physiology severity associated with risk of future adverse events like death or MI. Patients with severely reduced CFR may benefit from revascularization while mild/moderate reductions can be managed medically.

2. Coronary Physiology To Guide Interventions
K. Lance Gould, M.D.
Martin Bucksbaum Distinguished University Chair,
Professor of Cardiovascular Medicine and
Executive Director, Weatherhead P.E.T. Center for
Preventing and Reversing Atherosclerosis
University of Texas Medical School – Houston
No Conflict of Interest.

3. COURAGE Trial. Sedlis et al
NEJM 2015;373:1937
STICH Trial with SPECT ischemia
Velasquez EJ et al NEJM 2011;364:1607
STICH Trial with SPECT ischemia
Panza JA et al JACC 2013;61:1860
SPECT “ischemia” did not identify patients with improved mortality by CABG
In Acute Coronary Syndromes PCI reduces
death and MI. Hoedemaker et al
JACC2017;69:1883.
PercentdeathorMI
Routine Early PCI
Selective PCI
Angiogram Driven Revascularization

4. All Tests & Elective Revascularization Trials Have Failed To
Reduce MI or Coronary Death In Stable CAD
Coronary Angiogram
COURAGE - N Engl J Med 2007;356:1503-1516.︎
STICH - N Engl J Med 2011;364:1607-1616.
MASS - Circulation 1999;100:II-107-II-113
Meta analysis - Arch Intern Med 2012;172:312-319. JAMA Intern Med
2014;174:232-240. Circ Cardiovas Interv 2012;5:476-490
CTA - N Engl J Med 2015;372:1291-300.
SPECT and other non-invasive tests
DIAD - JAMA.2009;301(15):1547-1555
STICH SPECT sub analysis - J Am Coll Cardiol. 2013;61:1860-1870.
Emergency Department – JAMA Intern Med 2013;173:1128-1133.
SPARC - J Am Coll Cardiol 2012;59:462-474
Meta analysis - Am Heart J 2014;167:846-852.e2 and Circ
Cardiovasc Imaging. 2015;8:e002666. DOI: 10.1161
But Coronary Physiology guided stents ➔ potential benefit
FFR - N Engl J Med 2009;360:213 & N Engl J Med. 2014;371:1208-17
CFR and stress perfusion by PET - Circulation. 2015;131:19-27 & Circ
Cardiovascular Imaging. 2015;8:e003099. DOI: 10.1161

5. FAME 5 yr follow-up: Kaplan–Meier Curves for Death from Any Cause, Myocardial Infarction
and Urgent Revascularization. Xaplanteris et al. N Engl J Med 2018;379:250-259.
Composite: death, MI, urgent revascularization
Urgent
revasc

6. De Bruyne B et al. N Engl J Med 2012;367 991-1001
PCI Risk at PCI Benefit at
0 to 7 days 8 da to 2 yrs
Hazard Ratio 9.0 Hazard Ratio 0.56
FAME 2
Hazard Ratio
Landmark analysis =⬇︎acute PCI
Intention to treat = No benefit
Physiologic Severity is
the Signal for⬇ MI, death
FFR: No⬇ MI & death by intension to treat

7. Johnson et al. JACC 2014;64:1641. Gould et al. Circ CV Imag 2015;8:e003099.
Physiologic Severity is
the Signal for⬇ MI, death
No Harm
Benefit
⬇ MI & death
Fractional Flow Reserve (FFR) – The
Continuum Of Risk vs Benefit For CAD,

8. LogHazardRatioforDeathorMyocardialInfaction FFR Threshold For Death & Myocardial Infarction – Korean Registry
Ahn JM et al.
Circ 2017;135:2241.
Median follow-up 1.9 yrs
Deferral 6468 stenosis
PCI or CABG 2165 stenosis
PhysiologicSeverity is
the Signal for⬇ MI, death
⬇ MI & death No Harm
Benefit

9. LowMIandDeathHigh
•
Natural Course of CAD
With PCI or CABG
0.5 0.65 0.8 0.9
Fractional Flow Reserve (FFR)
Imprecision of ± 0.04
FFR 0.76 to 0.84
Imprecision of
FFRCT 0.62 to 0.98
N = 1555
Johnson et al. JACC 2014;64:1641 and Ahn JM et al. Circulation 2017;135:2241
For FFRct N = 1555 (Koo JACC. 2011;58:1989-97. Min JAMA. 2012;308:1237-45.
Norgaard JACC. 2014;63:1145-55. Driessen (Pacific Trial)
Benefit Neutral
Harm
Fractional Flow Reserve (FFR) – The Continuum Of Risk vs
Benefit For CAD, N = 14,612, P = 0.01 is defined by the
critical severity threshold & test imprecison

10. Rest flow, F
Rest flow, F
aortic, Pao, & coronary pressures
aortic pressure, Pao
Coronary pressure, Pcor
Fractional Flow Reserve
FFR = Pcor / Pao =
max Fno stenosis
max Fstenosis
max Fsten / max Fno sten
= relative CFR
Not = absolute CFR
Am Heart J 1975;89:60
Pijls to Gould Circ 1993;86:1354
As flow increases, coronary pressure falls
No stenosis
CFR = max/rest flow
relative CFR =
Max Fsten/Max Fno steno
Gould 1974
Stenosis

11. FFR was
Validated by
PET Relative
CFR
1199 lesions
489 subjects.
Johnson and
Gould. Circ CV
Imag 2016;
9:e005435 DOI
10.1161/
116.005435.)
DeBruyne et al.
Circ 1994
Lee et al.
Circ CV Img 2016
Stuijzander et al.
Circ CV Img 2015
Marques et al.
J Nucl Med 2007

12. LowMIandDeathHigh
Severe 50% 0 to 3% Normal
CFC % of LV severely reduced
•
Natural Course of CAD
MACE 60%, death
or MI 30%
With PCI or CABG
Coronary Flow Capacity (CFC) – Continuum Of Risk vs Benefit For CAD
N = 3774, P = 0.037 for reduced MI or death at severe CFC
Imprecision of
CFC ± 10%
Gould KL, et al. JNM published on line August 16, 2018 as doi:10.2967/jnumed.118.211953
Kitkungvan D et al. J Am Coll Cardiology CV Imaging 2017 2017;10:565-77.
54%⬇ MI
& death Neutral
Harm

13. F = M/(1-e-(0.45+0.16F/F))(A) Units for F = (M in µCi/cc)(0.95cc/gm) ÷ A
In units of (µCi/cc)(minute) = cc/min-g = cc/min/g Yoshida et al JNM 1996;37:1701

14. Gould KL, Johnson NP
JACC 2018;72(21):2642-62

15. CFR 2.0
Stress flow 1.5
Str flo 1.5
CFR 2.0
22% Young volunteers
14% Minimally reduced
16% Mildly reduced
11% Moderately reduced
36% Severely reduced
(24% myocardial steal)
Septal Anterior Lateral Inferior
Coronary Flow Capacity
CFRcc/min/g
Gould KL, Johnson NP
JACC 2018;72(21):2642-62

16. Gould KL, Johnson NP
JACC 2018;72(21):2642-62

17. Gould KL, Johnson NP. JACC 2018;72(21):2642-62

18. K. L. Gould

19. ProbabilityofMACE
Follows Up In Years
n
mace
n
mace
MACE for Mild to moderately reduced Coronary
Flow Capacity - PETs with no CFC blue
MACE for Severely Reduced Coronary Flow
Capacity PETs with any CFC blue (CFR ≤ 1.3
And stress flow ≤ 0.8 cc/min/g)
N = 3774 Log rank P< 0.0001
mace = death, MI, stroke, PCI, CABG
Gould KL et al. . J Nucl Med 2018 (in press August 16, 2018 as doi:10.2967/jnumed.118.211953. jnm.snmjournals.org).

20. Death and MI for Severely Reduced Coronary Flow
Capacity - PETs with any CFC blue (CFR ≤ 1.3 and
stress flow ≤ 0.8 cc/min/g)
Probabilityofdeath,MIorstroke(dms)
Follows Up In Years
N = 3758 Log rank P < 0.0001
Death and MI for Mild to moderately reduced Coronary
Flow Capacity - PETs with no CFC blue
n
dms
n
dms
Gould KL et al. . J Nucl Med 2018 (in press August 16, 2018
as doi:10.2967/jnumed.118.211953. jnm.snmjournals.org).

21. Years follow-up
CumulativeHazardofDeath,MIandStroke(d/m/s)
associatedwithrevascularizationbyPCIorCABG
Severely Reduced Coronary Flow Capacity
Indicates pci/cabg as clinically appropriate
Moderately Reduced Coronary Flow Capacity
Indicates medical treatment as valid or optimal
pci/cabg associates with reduced d/m/s
versus no pci/cabg
P = 0.0396
hazard ratio 0.55
95% HR CI 0.31-0.97
N = 3774
Insignificant trend for pci/cabg associated
with increased d/m/s versus no pci/cabg
P=0.45
hazard ratio = 1.5
95% HR CI = 0.52-4.3
N = 3774
For PETs with
any CFC blue
For PETs with
no CFC blue
CFCblue
is 13%
of 3774
CFCgreen
For >15%
LV is 68%
of 3774
. L. Gould

22. Characteristic All pci/cabg* No pci/cabg Test statistic P-value
Count 3624 123 3501
age 62±12 66±10 61±12 t-test 5.5905 1.19E-7
BMI 28.0±4.4 28.5±4.4 27.9±4.4 t-test 1.3276 0.186613
male 74% 86% 74% chi-square 9.5065 0.002047
Hx of PCI 27% 54% 26% chi-square 44.1293 < .00001
Hx of CABG 11% 18% 11% chi-square 5.2547 0.021887
Hx of MI_recent 1% 5% 1% chi-square 12.3016 0.000453
Hx of MI_distant 15% 18% 15% chi-square 0.895 0.344144
Hx of hypertension 65% 77% 65% chi-square 8.2266 0.004128
Hx of dyslipidemia 88% 95% 88% chi-square 6.2612 0.012341
Hx of diabetes 21% 26% 21% chi-square 2.1715 0.140591
Hx of smoking 67% 53% 68% chi-square 11.8349 0.000581
CFC severe % of LV 2%±9% 18%±21% 2%±7% t-test 8.651732 2.32E-14
Stress ejection fraction 70%±10% 61%±12% 71%±9% t-test -8.33012 2.94E-13
CFR worst 25% of LV 2.4±0.7 1.4±0.6 2.4±0.7 t-test -17.9177 2.18E-37
Strs Flo worst 25% of LV 1.8±0.7 1.0±0.5 1.9±0.7 t-test -20.1952 3.55E-43
visually abnormal stress 36% 95% 34% chi-square 195.2912 < .00001
Mild CFC ≥ 15% of LV 42% 87% 40% chi-square 107.0116 < .00001
Mod CFC ≥ 15% of LV 6% 29% 5% chi-square 114.0139 < .00001
Severe CFC > 0% of LV 18% 80% 16% chi-square 326.101 < .00001
CFR<2.0 for ≥ 25% of LV 29% 80% 27% chi-square 163.1159 < .00001
cor calcium >120 74% 98% 73% chi-square 39.5474 < .00001
risk factors NoCAD 58% 26% 59% chi-square 54.1821 < .00001
documented CAD 39% 74% 38% chi-square 63.6446 < .00001
* percutaneous coronary intervention or coronary artery bypass surgery (pci/cabg) within 90 days after PET
Characteristics of cases with and without pci/cabg* within 90 days after PET

23. Before
LAD stent
After
LAD stent
Stenosis prox
to 1st Septal
Stent caged
1st SeptalRecurrent angina after stent

24. 67 yo man with CABG in
2003 with LIMA to LAD,
SVG to OM and RCA.
Asymptomatic until mild
progressive angina with
walking over past year.
Protocol PET in 2014
showed a small basal
inferior scar 4% LV small
border zones of reduced
subendocardial perfusion
during stress without
angina.
Current PET: rest 4% of LV
Inferior scar. Stress caused
angina, 2.8mm ST∆ and rest
PET EF 51% and 40% stress,
relieved with aminophylline,
metoprolol iv and SL NTG.

25. 63% diameter stenosis
in vivo with hyperemia
steel ball 3.18mm
size reference
epicardium endocardium endocardium epicardium
Experimental stress perfusion
tomograms (post mortem)
0 2.5 5.1 7.6 10.2 12.7 15.2 17.8
millimeters
Gould Am J Cardiol 1978;42;761

26. 0 20 40 60 80 100 Normal Minimum Mild
% of maximum
CFC before PCI After PCI rel strs CFCsubendo FFRpet
anterior
subendocardial
ischemia
rest
relativeactivity
stress
relativeactivity
78 year old man with PET leading to successful LAD stent, post PCI angina and
ST∆ > 1mm Due to caged small D1 with mild subendo ischemia for 10% of LV

27. Rest flow, F
Rest flow, F
aortic, Pao, & coronary pressures
aortic pressure, Pao
cor pressure, Pcor
Fractional Flow Reserve
FFR = Pcor / Pao =
max Fno stenosis
max Fstenosis
max Fsten / max Fno sten
= relative CFR
Not = absolute CFR
Am Heart J 1975;89:60
Pijls to Gould Circ 1993;86:1354
As flow increases, coronary pressure falls
No stenosis
CFR = max/rest flow
relative CFR =
Max Fsten/Max Fno steno
Gould 1974
Stenosis
EPIC-SEC
Lipscomb, Gould Am Heart J 1975;89:60

28. Hoffman et al
J Am Heart Assoc 2014;3:e000285

29. 79 year old active man with one month of mild angina with hard exercise
LAD
RCA
LCx
LAD LCx
RCA
Fractional Flow Reserve (FFRpet) ➔ % of LV and FFR gradient
EPIC-SEC

30. LCx CFR < 1 subtotal RCA FFRPET≈0.75LAD FFRPET<0.6
FFR = 0.54
FFR = 0.75
Stress perfusion in cc/min/g converted to a relative scale = FFRpet reflects
FFRpressure, regional severity and size of subendocardial perfusion
Fractional Flow Reserve (FFRpet) ≈ PET subendocardial perfusion
EPIC-SEC Nils P. Johnson presented at the Nordic Cardiac CT Conference 2017

31. After coronary
bypass surgery
Complex CAD
71 yr old man
With PVCs and mild
atypical non-exertional
chest discomfort.
PET showed occluded
collateralized LCx,
moderate stenosis of
mid LAD and PDA
LAD LCx RCA
K. L. Gould

32. 0 20 40 60 80 100
% of maximum
Nor Min Mild Mod Sev
Rest activity Stress activity CFC FFRpet
Rest
Stress
septal lateral
subendocardial
ischemia
greyscalegreyscale
EPIC-SEC K. L. Gould

33. 75 yo man with LAD stent
15 yrs previously, 9 mo
before PET had STEMI
with PCI osteal LCx and
mid LAD. PET for follow
up status. At dipyridamole
Stress, had 1.2 mmST∆
with no angina

34. 0%
10%
20%
30%
40%
50%
60%
70%
0 >0 <5% >5 <10% >10 <15% >15 <20% >20 <25% >25%
MACE%ofSizeRange
Size % of LV
MACE for Size – Severity Ranges of CFC
over 9 years, median 3.2 years follow up
CFC severe
K. L. Gould
*JACC2014;64:1641
Circ 2017;136:2241
Transmural perfusion
severely reduced
Subendocardial
severely reduced
Subendocardum
mildly reduced
CFC minimally
reduced
CFCsevere associates with
greatest reduced MI or death
after PCI or CABG
N= 3773

35. Van de Hoef et al
JACC Interv 2015;8:1670
Invasive Coronary Flow Capacity predicts greater risk than FFR
Kaplan–Meier curves according to concordance
with normal FFR) and coronary flow velocity
reserve (CFVR), and the discordance groups
according to an FFR cut-off value of 0.80.
van de Hoef et al.
Circ Cardiovasc Interv. 2014;7:301-311

36. Diagnostic Performance Of Cardic Imaging Methods For CAD with FFR ≤ 0.8
Analyzd by Intention to Diagnose that includes 17% rejected FFRct data
Danad I et al. Pacific Trial. JAMA cardiology 2017;21:1100-1107
PET

37. Non-invasive tests for significant coronary artery stenosis in stable angina: a meta-analysis.
Knuuti et al. Eur Heart J. 2018;39(35):3322-3330.

38. normal mild diffuse CAD moderate stenosis severe stenosis
HeartSee quantitative PET software, FDA approved K171303,
being adapted by GE Healthcare and Bracco Diagnostics, Inc
No conflict of interest - No royalties or payments to Gould
PCI / CABG for Sx with
no reduced MI or death
Healthy living & Medical Rx
In 7000 routine clinical PET cases, Coronary Flow
Capacity is the Standard of Severity To Guide
PCI and CABG that reduces MI or death by >50%

39. Only 11% of heart
attacks have single
plaque rupture.
89% of heart attacks
have small multiple
prior plaque ruptures,
finally occluding prior
severe stenosis, avg
72% DS in ACS
For Severe PET
PCI/CAB ⬇MI, death
Virmani JIMG 2011;4:656
Tian et al. JACC 2014;63:2209
PET sees
early CAD

40. No PET angina or ECG∆.
Inferior avg transmural
strs flow = 1.81 cc/mi/g
& CFR = 1.84 (yellow).
PET stress EF = 66%.
Normal stress ECHO.
Risk ≤ 0.6% per year for
PETs with no severe CFC
(no blue = str flo ≤ 0.8
And CFR ≤ 1.2).
59 yo man with coronary
calcium, asymptomatic
with hard workouts, has
Hypercholesterolemia,
BMI 31, suboptimal statin
Rx, normal stress ECHO.
Severity
53% Normal
27% Minimal
20% Mild
0% Moderate
0% Severe inferior strs 1.81 cc/min/g

41. Gould KL, Johnson NP. State-of-the-art-review. JACC 2018;72(21):2642-62
59 yo man with coronary calcium, asymptomatic with hard workouts,
hypercholesterolemia, BMI 31, suboptimal statin Rx, EF 66% and normal
stress ECHO
CFC severity
avg transmural
53% Normal
27% Minimal
20% Mild
0% Moderate
0% Severe
CFC severity
subendocardial
53% Normal
27% Minimal
0% Mild transmural
4% Miin subendocardial
16% Mild subendocard
0% Moderate
0% Severe
rest
stress
Risk ≤ 0.6% per year for PETs
with no severe CFC (no blue)

42. Gould KL, Johnson NP. State-of-the-art-review. JACC 2018;72(21):2642-62
59 yo man with coronary calcium, asymptomatic with hard workouts,
hypercholesterolemia, BMI 31, suboptimal statin Rx, EF 66%, normal strs
ECHO
CFC severity
avg transmural
53% Normal
27% Minimal
20% Mild
0% Moderate
0% Severe
CFC severity
subendocardial
53% Normal
27% Minimal
0% Mild transmural
4%Miin subendocardial
16%Mild subbendocard
0% Moderate
0% Severe
rest
stressrest
Risk ≤ 0.6% per year for no severe CFC (no blue)
High stress flow causes low FFR without ischemia

45. 1978 Validation of Quantitative
Coronary Arteriography with
resolution 10 line pairs/mm
on diastolic gated
cut film. Gould
Circ Res 1978;43;242
Y = 1.12X + 1.6
R = 0.902
95% CI = ± 0.13
or 15% of the
0.8 threshold
RelativeCoronaryFlowReserveflowmeter
95% CI = ± 0.12 or 15% of 0.8 threshold
95% CI = ± 0.23 or 29% of 0.8 threshold
FFRct
Koo et alJACC 2011;58:1989
QFR (FFRangiogram)
Tu et al. JIMG 2014;7:768
Relative CFR by quantitative
coronary angiogram 1990
A
C
D
B
Gould et al.
JACC 1990;15:459

46. Fractional Flow Reserve Measured vs FFR predicted by CT Model
Koo et al. J Am Coll Cardiol. 2011;58:1989 and Nakazato et al. Circ CV Imaging 2013;6:881
and adapted from Johnson et al. Circ CV Imaging 2013;6:817
For true FFR = 0.8 by pressure wire, the CT FFR may be 1.0 to 0.6 for 95%
certainty. Therefore, CT predicted FFR is not accurate for severity
Bland-Altman Plot of FFR and FFRCT
on a Per-Vessel Basis
1.0
0.6

47. LowMIandDeathHigh
•
Natural Course of CAD
With PCI or CABG
0.5 0.65 0.8 0.9
Fractional Flow Reserve (FFR)
Imprecision of
FFR 0.76 to 0.84
Imprecision of
FFRCT 0.62 to 0.98
N = 1555
Johnson et al. JACC 2014;64:1641 and Ahn JM et al. Circulation 2017;135:2241
For FFRct N = 1555 (Koo JACC. 2011;58:1989-97. Min JAMA. 2012;308:1237-45.
Norgaard JACC. 2014;63:1145-55. Driessen (Pacific Trial)
Benefit Neutral
Harm
Fractional Flow Reserve (FFR) – The Continuum Of Risk vs
Benefit For CAD, N = 14,612, P = 0.01 is defined by the
critical severity threshold & test imprecison

48. CFR 2.0
Strs flow 1.5 Strs flow 1.4
Relative stress
cc/min/g
CFC
CFR 1.3
Relative stress
cc/min/g
CFCsubendocardiumandrelativestress(cc/min/g)
CFCsubendocardiumandsmallvesseldisease

49. Conclusion: Maximum MBF adds no predictive value
to CFR for CV mortality hence Coronary Flow Capacity
• Global CFR < 2.0 + Global Max MBF ≥ or ≤ 1.8 does Not = Coronary Flow Capacity (CFC).
• Global measurements average out regional perfusion defects ≠ patient diagnostic value.
• Regional pixel (CFR + stress flow) = Regional integrated Coronary Flow Capacity
• CFC guided PCI/CABG associates with significantly reduced MI or death
Gupta et al. Circulation 2017
Fig 4 on-line 10.1161/
CIRCULATIONAHA.117.029992
Years

50. CFR 2.0
Strs flow 1.5
Strs flow 1.8
Pixel values Coronary Flow Capacity Global values
Rest relative
Stress relative
CFCpixel
subendo
CFCwith
pixels
CFC with avg
whole LV values
CFR 2.7
CFR 2.7

52. Rest
Dipyriamole stress caused
angina
at very
high
epicard
flow and
endocard
ischemia
CFC Severity & stress flow
92% Excellent 2.9cc/min/g
6% Minimal
2% Mild
Relative tomograms
subepicardium
subendocardial
ischemia
relativepeak⬇
Inferior & lateral
inferior
& lateral
diffuse PDA & post
LV extension branch
diffuse LCx
& LAD

54. Cumulative Hazard of MACE by clinical group with covariates
CumulativeHazardofMACE
Follow up time in years
P < 0.0001
Hazard ratio = 0.57
95% HR CI = 0.51-0.64
(2)

55. 0%
10%
20%
30%
40%
50%
60%
70%
80%
0 >0 - <5% >5 - <10%
>10 - <15% >15 - <20% >20 - <25%
>25%
PercentofSeverityGroupWithMACE
Percent of the Left Ventricle
0 >0 - 5% >5% - 10% >10% - 15% >15% - 20% >20% - 25% >25%
CFCsevere associates with
greatest reduced MI or death
after PCI or CABG
CFC severe
CFR 1.0 to 1.5
CFR 1.5 to 2.0
stress flow
≤ 1.0 cc/min/g
relative ≤ 60%
For PET guided angiograms
Coronary Flow Capacity vs Other PET Metrics For Predicting MACE
K. L. Gould

56. From: The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in
patients with stable angina: a meta-analysis focused on post-test disease probability
Knuuti et al. Eur Heart J. 2018;39(35):3322-3330. doi:10.1093/eurheartj/ehy267
Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For
permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford
University Press, Standard Journals Publication Model

57. 4
6
8
10
A at 0-mo A at 24-mo B at 0-mo B at 24-mo
TotalModifiableRiskScore
LowriskHighrisk
Much Better
P = 0.0001
Minimally Better
P = 0.02
Standard Care at
baseline and 24 mo
Comprehensive Care at
baseline and 24 mo
P= 0.001 for the difference in the changes of each group
Century Health Project At Two Year Interim Follow Up
Total Modifiable Risk Score For Vascular Disease

58. Century Health Project At Two Year Interim Follow Up

59. Good Heart Worse Bad Heart Better
Baseline
Heart Blood Flow
Two years later
Heart Blood Flow
With Poor Medical
Rx and Lifestyle
With Good Medical
Rx and Lifestyle

60. Impact of Medication Adherence On Long term CV Outcomes
Sameer Bansilal et al. JACC 2016;68:789-801
Percent of days covered < 40% 40-79% > 80%
CumulativeIncidenceofMACE
(death,MI,stroke,PCI,CABG)
N = 16,991
27% non-adherent
37% partially adherent
36% fully adherent

61. From: Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic
Cardiovascular Disease. JAMA Cardiol. 2017;2(1):47-54. doi:10.1001/jamacardio.2016.4052
Adjusted Mortality Curves for Different Intensities of Statin Therapy Curves are adjusted for the propensity to receive a high-intensity
statin. Differences are significant (P < .001).

62. Statins in 24,674 Subjects 73±2.9yo Without CV Disease: A Meta-Analysis
39% reduction in myocardial infarction and 24% reduction in stroke
No difference in total or CV mortality
Relative Risk MI
Relative Risk Stroke
RR (95%) Weight
Gray squares represent relative risks (RRs) in trials. The 95% confidence intervals (CIs) for individual trials are denoted by lines
and those for the pooled RRs by open diamonds. J Am Coll Cardiol. 2013;62(22):2090-2099. doi:10.1016/j.jacc.2013.07.069

63. Bayesian Forest plot for CAD mortality reduced by 30%
Afilalo et al. Statins for secondary prevention in elderly patient.
JACC 2008;51:37
Statins for secondary prevention in elderly patient. Meta-analysis 9 randomized
trials involving 19,569 patients aged 65 to 82. Same reduction in all cause
mortality, non-fatal MI, revascularizations and stroke

64. Lancet Online May 17, 2012 DOI:10.1016/S0140-6736(12)60367-5
The effects of lowering LDL cholesterol with statin therapy
for low & high risk of vascular disease: meta-analysis of
individual data from 27 randomized trials (N = 134,537)
Low risk patients benefitted comparably to high risk patients.
Reduced major coronary events, strokes, vascular events and
coronary revascularization, per 1.0 mmol/L LDL reduction was
independent of baseline risk, LDL, age, gender or prior CAD as
basis of new guidelines. RR=rate ratio. CI=confidence interval.
Baseline 5 yr risk of Events % per yr
major vascular event Statin Control RR (CI) per 1.0mmol/L LDL reduction

65. Statin Therapy for Primary Prevention of Cardiovascular Disease
N = 56,934 in Primary Care
Relative Risks and Numbers Needed to Treat for 5 Years for Outcomes in Primary
Prevention Trials of Statins. CVD = cardiovascular disease; CHD = coronary heart disease.
NO increased adverse events of cancer, myalgia, rhabdomyolysis, arthritis, increased LFT
JAMA. 2013;310(22):2451-2452. doi:10.1001/jama.2013.281348
Pravastatin was most commonly used. Three trials accounting for 47% of the total recruited
population were stopped prematurely due to significant reduction in primary outcome.

66. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease, Heart
Outcomes Prevention Evaluation (HOPE-3) Trial – CV events, Rx rosuvastatin 10mg.
Yusuf S et al.
N Engl J Med 2016;
374:2021-2031.
12.705 subjects
21 countries
Randomized trial
One ≥ risk factors
1º endpoint
CV death, MI, CVA
2º endpoint
revasc, CHF,
resusitated SD
Age 65 yo
TC 202
LDL128
HDL 45
TG 129
Glucose 95
BP 138

67. Kaplan–Meier curves of future risk of CHD stratified by years of hyperlipidemia experienced by 55 years of age
(age range, 53–57) among adults not recommended for statin therapy at 55 years of age, N = 1478. Log-rank P
value <0.0001. *Excludes those recommended for statins: ASCVD risk ≥7.5%, LDL-C ≥190, diabetes mellitus and
LDL-C ≥100. Navar-Boggan A M et al. Circulation. 2015;131:451-458. (Framingham Offspring Cohort)
11 - 20 years
1 – 10 years
0 years
N = 1478
Log rank P < 0.0001
(%)
Time to diagnosis of CHD by number of years of
hyperlipidemia at baseline among adults not
recommended for statin therapy at baseline
at 55 years of age

68. Agatson Score
Mahabadi et al. JACC Img 2017;10:143-53
CAC score
& statin risk
assessment

69. Coronary Flow Capacity To Guide Interventions
K. Lance Gould, M.D.
Martin Bucksbaum Distinguished University Chair,
Professor of Cardiovascular Medicine and
Executive Director, Weatherhead P.E.T. Center for
Preventing and Reversing Atherosclerosis
University of Texas Medical School – Houston
No Conflict of Interest.
OM1
mid LAD
Subtotal

71. 79 yo man with one
month of mild angina
with hard exercise.
PET showed occ LCx,
mod LAD & RCA
stenosis with diffuse
CAD parallel FFRpet.
Confirmed by angiogm
FFRpet
LADRCALCx
LADRCA

72. LAD FFR 0.54 with jump
over proximal lesion during
pullback with IV adenosine
LCx with subtotal lesion
(no FFR due to severity
and +PET defect)
RCA FFR 0.75 after
mid segment

73. Joo Myung Lee et al. JCIN 2018;11:1423-1433
Vessel related composite cardiac death, MI and revascularization during 5 year
follow up of 519 patients and 737 stenosis with FFR and thermodilution CFR

74. Joo Myung Lee et al. JCIN 2018;11:1423-1433
Vessel related composite cardiac death, MI and revascularization during 5 year
follow up of 519 patients and 737 stenosis with FFR and thermodilution CFR

75. The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients
with stable angina: a meta-analysis focused on post-test disease probability
Knuuti et al. Eur Heart J. 2018;39(35):3322-3330. doi:10.1093/eurheartj/ehy267

76. D1 caged by
stent w FFRpet
0.7 for 10% of LV
78 yo asymptomatic man
with HTN, DM, dyslipidemia,
3mm ST∆ on routine ETT
with no angina.
PET shows LAD occlusion or
subtotal occlusion with
myocardial steal associated
with collaterals. Had LAD PCI
Recurrent angina led to repeat
PET after PCI of LAD
FFRpet after PCI of LAD
Showing caged D1 with
FFRpet ≤ 0.70 for 10% of LV
Post PCI, PET dipyridamole
stress caused angina and ST∆
Subendocardial ischemia ≤ 10%
of LV causes angina and ST∆
but is low risk for MI or death
rest stress

78. Severity of CAD In PET Cohort (n = 3758)
Risk factors or suspected CAD 59%
Documented CAD – MI, angiogram, PCI/CABG 41%
Coronary calcium > 120 Hounsfield units 86%
Visually abnormal PET – misses diffuse CAD 34%
Coronary Flow Reserve < 2.0 for ≥ 20% of LV 31%
Abnormal quantitative PET – mild, moderate or
severely abnormal CFC for ≥ 10% of LV 51%
Every PET consultation report integrates quantitative PET
with clinical data to recommend PCI/CABG or med Rx alone