This document discusses various techniques for assessing the physiological significance of coronary artery lesions seen on angiography. It describes: 1. Borderline or intermediate lesions that appear between 40-70% blocked on angiography but their physiological significance is unclear. 2. Various pressure-based indices that can be measured invasively using a wire, such as FFR, iFR, and others, to determine if a lesion is hemodynamically significant. 3. Additional modalities like IVUS and OCT that provide anatomical data to complement the functional assessment of lesions.

1. BORDERLINE LESIONS
VLJP

2. Borderline Lesions
• Intermediate lesions
• On angiography as a luminal narrowing with
a diameter stenosis more than 40% but less
than 70%

3. Coronary Physiology
• Limitation of Angiogram
– Esp Physiology not assessed
– 40 – 70% lesions (borderline)
• NOCAD (Non Obstructive CAD)
– Poor prognosis
– MI in 40-70% lesions
• Some angiographically severe lesions are not ischemic
• Some angiographically mild lesions are hemodynamically
significant
• Some angiographically mild lesions heavily burdened by
plaque
• Assesment of Physiology important

6. FAME

7. DEFER

8. Assessment
• Invasive
– Physiology
– Anatomy
• Non-Invasive

9. INVASIVE (physio)

10. Indices for Physiology Assessment
1. Hyperemic Indices
2. Nonhyperemic pressure ratio
3. Angiography-based indices
4. Epicardial resistance and conductance indices
5. Measures of microvascular resistance
6. Measurement of Coronary Blood Flow
7. Indices of endothelial function
8. Novel fluid dynamics based FFR modalities

11. Hyperemic Indices
• Needs creation of hyperemia
• FFR (Fractional Flow Reserve)
– Mean Pd/Pa ratio during maximum hyperemia
– Gold standard still
– Cut off 0.8
• cFFR (Contrast Fractional Flow Reserve)
– Mean Pd/Pa ratio during hyperemia induced by conventional
nonionic radiographic contrast
– 85% accuracy
– Cut off 0.83
• FFRMC (Micro Catheter based FFR)
– May overestimate stenosis severity owing to its larger profile
– Cut off 0.78

12. Nonhyperemic pressure ratio
• Pd/Pa
– Resting whole-cycle Pd/Pa
– Average Pd/Pa during the entire cardiac cycle
– Cut off 0.91
• iFR
– Instantaneous wave-free ratio
– Average Pd/Pa during wave-free period with no compression
or expansile waves
– From 25% into diastole to 5sec before end of diastole
– Cut off 0.89
– Requires a good quality stable ECG
– Quiet respiration
– No contrast or saline flushes

13. Nonhyperemic pressure ratio (contd)
• DPR (Diastolic pressure ratio )
– Average Pd/Pa during the entire diastole
– Cut off 0.89
• dPR (Diastolic pressure ratio)
– Pd/Pa during the flat period of the dP/dt signal
– Cut off 0.89
• RFR (Resting full-cycle ratio )
– Lowest mean Pd/Pa ratio during the entire cardiac cycle
– No ECG required
– Cut off 0.89
– 4 consecutive cardiac cycles
• DFR (Diastolic hyperemia-free ratio)
– Average Pd/Pa during downsloping Pa
– No ECG needed
– Cut off 0.89

14. Angiography-based indices
• QFR (Quantitative flow ratio)
– Computational fluid dynamics using 3-
dimensional angio
– Cut off 0.80

15. Epicardial resistance and conductance
indices
• HSR (Hyperemic stenosis resistance index)
– Ratio of hyperemic stenosis pressure gradient to
hyperemic average peak velocity
– Cut off 0.8
• BSR (Basal stenosis resistance)
– (Pa - Pd)/average peak velocity without
hyperemia

16. Measures of microvascular resistance
• HMR (Hyperemic microvascular resistance)
– Pd/ APV
– APV is the average peak velocity
– >2mmHg x s/cm
• IMR (Index of microcirculatory resistance)
– IMR = Pd x Tmn. Tmn = mean transit time
– >25 mmHg x s

17. Measurement of Coronary Blood Flow
• CFR (Coronary Flow Reserve)
– Ratio between coronary blood flow at maximal
hyperemia and at baseline condition
– < 2 indicates microvascular dysfunction

18. Measures of endothelial function
• NTG
• Acetyl Choline
• > 20% reduction in diameter

19. INVASIVE (Anatomy)

20. • IVUS
• OCT

21. Non Invasive

22. • TTDE
• MPI
• Novel fluid dynamics based FFR modalities
• High Resolution CMR perfusion (3 Tesla)

25. MPI
• MPI: stress and rest Tc99m sestaMIBI
myocardial perfusion SPECT
• Significant concordance, as well as high
sensitivity, specificity, PPV, and NPV when
compared with invasive IFR

27. Novel fluid dynamics based FFR
modalities
• Computational fluid dynamics calculated from
CAG
• CASS-vFFR
– Cardiovascular Angiographic Analysis Systems for
vessel FFR
• FFR angio
– FFR derived from angio
• PET FFR
• FFRCT
• OCT FFR

28. CMR

29. VALIDATED
• INVASIVE
– FFR
– iFR
– QFR (quantitative flow ratio)
– IVUS
– OCT
• NON INVASIVE
– MPI Tc99m sestaMIBI myocardial perfusion

30. FFR

33. FAME

34. DEFER

35. Introduction
• CAG – anatomy of stenosis
• Physiologic assessment of stenosis severity is a
critical component
• Coronary autoregulation
– flow remains constant as stenosis severity increases
• Imaging resting perfusion cannot identify
hemodynamically significant stenoses
• Maximally vasodilated pressure-flow relation is
much more sensitive

36. CORONARY FLOW RESERVE
• Ratio of the maximal or hyperemic flow down a
coronary vessel to the resting flow
• Maximal flow / Resting flow
• CFR is a measure of the entire coronary circulation
• Interrogates the epicardial vessel as well as the
coronary microvasculature
• Doppler wire
• Difficult to measure with a Doppler wire because of
the challenge in obtaining a suitable Doppler signal
• Identifies coronary microvascular dysfunction
• Normal CFR is considered to be greater than 2.0
• < 2 indicates microvascular dysfunction

37. CFR

38. FRACTIONAL FLOW RESERVE
• Method for assessing the functional significance
of epicardial CAD
• FFR is defined as the maximum myocardial
blood flow in the presence of an epicardial
stenosis compared with the maximum flow in
the hypothetical absence of the stenosis
• Coronary pressure wire to measure mean distal
pressure during maximal hyperemia and
dividing that by the mean proximal coronary or
aortic pressure measured simultaneously

39. FFR
FFR =
Pd
Pa

40. Unique Attributes of Fractional Flow
Reserve
1. Normal value of 1.0 in every patient and
every vessel
2. Well-defined ischemic cut-off value
3. Independent of hemodynamic perturbations
4. Extremely reproducible
5. Relatively easy to measure
6. Specific for the epicardial vessel
7. Independent of the microvasculature

41. Hyperemia
• Adenosine (either IV or intracoronary)
• Papaverine (10 mg)
• Nitroprusside (50 to 100 μg)
• Adenosine triphosphate (ATP, 50 to 100 μg)
• Regadenosone 400 ugm bolus
– Immediate effect
– No Bradycardia

42. Indications
• Intermediate coronary lesions (40%-70%)
– useful for guiding revascularization
– FFR ≥0.75 – defer
• FFR-guided PCI in patients with multivessel
disease
• Left Main Stenosis
• Ostial and Side Branch Lesions
• Saphenous Vein Graft Lesions
– FFR greater than 0.80 – no graft

46. IV vs IC
IV IC
Dose 140 μg/kg/min continuous infusion or
Incremental dose until 160-180 μg/kg/min
Bolus injection of 20 - 30 μg/kg
for RCA and 60-100 μg/kg for
LCA
Effect peak ≤2 minutes after administration via central
vein
<10 seconds
Effect duration <2 minutes <20 seconds
Side effect Bradycardia , AV block (rare)
Bronchospasm (especially in patients with
asthma)
Decrease in blood pressure
Increase in heart rate
Angina-like symptoms and chest sensations
AV block, especially when
administered in RCA
Benefit/limitati
on
In 8% of patients, only suboptimal
hyperemia
In 10%-15% of patients, only
suboptimal maximal
hyperemia
Underestimation of values after caffeine or
theophylline intake.
Underestimation of values
after caffeine or theophylline
intake.

47. Procedure steps

55. • Keep in aortic root
• Equalize

63. Problems
• STEMI & NSTEMI
– Microvascular dysfunction
– Underestimation
– Not useful
– Useful in non-culprit lesion

64. • Diffuse disease
• Serial lesions
• LM lesions
• Coronary Artery Bypass Grafts
• Aorto-ostial Stenoses

65. Diffuse disease

66. Tandem lesions

67. LM

68. LM

69. LM OSTIAL

70. False-Negative FFR
• Insufficient hyperemia
• Small perfusion territory
• Myocardial infarction scar
• Small vessel
• Abundant collaterals
• Guiding catheter too large, resulting in ostial
occlusion
• Severe left ventricular hypertrophy
• Spasm

71. Newer developments
• Wireless connections
• Complete Integration of FFR with IVUS/ OCT
• Regadenoson
– IV: 0.4 mg over ~10 seconds, followed
immediately by a 5 mL saline flush
• Non-invasive FFR
– CTffr

72. Instantaneous Wave-Free Ratio(iFR)
• Based on a specific period in diastole called
the wave-free period
• During which resistance at rest is stable
• Beginning 25% into diastole ending 5
milliseconds before the end of diastole
• Does not require vasodilators
• iFR cutoff is 0.89

75. iFR
• CLARIFY
• DEFINE-FLAIR
• SWEDE-HEART

76. Study design
DEFINE FLAIR. https://clinicaltrials.gov/ct2/show/NCT02053038.
FFR >0.8
Defer PCI
FFR ≤0.8
Perform PCI
FFR-guided
revascularization
iFR ≤0.89
Perform PCI
iFR >0.89
Defer PCI
Coronary stenosis in which physiological
severity was in question
1:1 Randomization
iFR-guided
revascularization
30 day, 1-, 2- and 5-year follow-up
Primary endpoint to be reported at 1-year
MACE composite endpoint of:
• Death
• Non-fatal myocardial
infarction
• Unplanned
revascularization
Non-inferiority margin for risk
difference: 3.4%

77. Procedural characteristics
iFR (N=1242) FFR (N=1250) p-value
Radial access, N (%) 896 (72.1) 888 (71.0) 0.54
Vessels evaluated, N (%)
All 1575 1608 0.58
LAD 844 (53.6) 845 (52.5) 0.56
LCx 323 (20.5) 333 (20.7) 0.89
RCA 374 (23.7) 393 (24.4) 0.65
Other 33 (2.1) 31 (1.9) 0.74
Unknown 1 (0.1) 6 (0.4) 0.06
Hyperemic agents, N (%)
IC adenosine - 455 (28.3)
IV adenosine - 950 (59.1)
Other agents - 203 (12.6)
Multi-vessel disease, N (%) 505 (40.7) 519 (41.5) 0.66
Vessels evaluated or treated, N 1879 1940 0.42
Functionally significant lesions, N 451 557 0.004
Treated or evaluated vessels/patient; mean (sd) 1.51 (0.76) 1.55 (0.80) 0.42

78. Primary end point
0 1 2 3 4
<3.4%
Margin
iFR Non-Inferior to FFR
iFR not non-Inferior
to FFR
95% CI
95% CI
Risk Difference (%)
Hypothesis confirmed
Hypothesis rejected
✓
✘

79. FFR or iFR
• Complementary
• FFR requires adenosine
• iFR – no adenosine
– Less cost
– Less side effects
• iFR measurements greater than 0.93 -> defer
• Less than 0.86 – treat
• 0.86 and 0.93 - “grey” zone  do FFR

80. IVUS/OCT

81. • MLA
– varied depending on the vessel size, with
increasing correlations in larger vessel
• PAV

82. CSA

83. MLA
• Area bounded by the luminal border
• In LM , MLA < 6.0 mm2 – intervene
• Asians < 4.8 mm2
• In non-LM MLA < 4.0 mm2
• MLA <2.4 mm2 (RVD) <3.0 mm
• MLA <2.7 mm2 RVD of 3.0 to 3.5 mm
• MLA <3.6 mm2 RVD 3.5 mm

84. Atheroma Burden

86. Thank You