1. The seminar discussed coronary blood flow and myocardial oxygen consumption. Key determinants include heart rate, systolic pressure, and left ventricular contractility. 2. Myocardial oxygen extraction is near maximal at rest, so increases in demand are met by proportional increases in coronary flow and oxygen delivery. 3. Fractional flow reserve measures the ratio of distal coronary pressure to aortic pressure during maximal hyperemia. An FFR below 0.75 is associated with ischemia while above 0.80 is usually not.

1. CORONARY BLOOD FLOW
SEMINAR ON 4/12/2017
DR SACHIN SONDHI
IGMC SHIMLA

2. • The resting coronary blood flow is 0.7-1 ml/min/gm
• Myocardial oxygen consumption --- balance between
supply and demand
• According to Fick’s principle, oxygen consumption in an
organ is equal to the product of regional blood flow
and oxygen extraction capacity.
• The heart is unique in having a maximal resting O2
extraction (~70-80%)
• So, MVO2 = CBF * CaO2

3. Phasic coronary inflow and venous outflow

4. • MYOCARDIAL OXYGEN CONSUMPTION
• In contrast to most other vascular beds, myocardial oxygen
extraction is near-maximal at rest, averaging approximately
75% of arterial oxygen content.
• Increases in myocardial oxygen consumption are primarily
met by proportional
increases in coronary flow and
oxygen delivery.
• In addition to coronary flow, oxygen delivery is
directly determined by arterial oxygen content (Cao2)
(depends on HB, spO2 and PaO2)

5. The major determinants of myocardial oxygen
consumption are
• heart rate,
• systolic pressure (or myocardial wall stress),
and
• left ventricular (LV) contractility.
• A twofold increase in any of these individual
determinants of oxygen consumption requires
an approximately 50% increase in coronary
flow.

6. • Myocardial oxygen consumption is 6-
8ml/min/100gm
• 60% is used in force generation, 15% in
myocardial relaxation, 3-5% for electrical
activation and 20% for basal cellular
metabolism

7. Auto regulation
• Regional coronary blood flow remains constant
as coronary artery pressure is reduced below
aortic pressure over a wide range when the
determinants of myocardial oxygen
consumption are kept constant. This
phenomenon is termed autoregulation
• When pressure falls to the lower limit of
autoregulation, coronary resistance arteries are
maximally vasodilated to intrinsic stimuli, and
flow becomes pressure-dependent, resulting in
the onset of subendocardial ischemia

9. • Flow in the maximally vasodilated heart is dependent on
coronary arterial pressure.
• Maximum perfusion and coronary reserve are reduced
- when the diastolic time available for subendocardial
perfusion is decreased (tachycardia) or
- the compressive determinants of diastolic perfusion
(preload) are increased.
- anything that increases resting flow, including increases
in the hemodynamic determinants of oxygen consumption
(systolic pressure, heart rate, contractility) and reductions
in arterial oxygen supply (anemia, hypoxia).
• Thus, circumstances can develop that precipitate
subendocardial ischemia in the presence of normal
coronary arteries

10. • Subendocardial flow primarily
occurs in diastole and begins
to decrease below a mean
coronary pressure of 40 mm
Hg.
• In contrast, subepicardial flow
occurs throughout the cardiac
cycle and is maintained until
coronary pressure falls below
25 mm Hg.
• This difference arises from
increased oxygen
consumption in the
subendocardium, requiring a
higher resting flow level, as
well as the more pronounced
effects of systolic contraction
on subendocardial vasodilator
reserve.

11. Endothelium-Dependent Modulation
of Coronary Tone
• Epicardial arteries do not normally contribute
significantly to coronary vascular resistance.
arterial diameter is modulated by a wide
variety of paracrine factors that can be
released from platelets, as well as circulating
neurohormonal agonists, neural tone, and
local control through vascular shear stress.

13. DETERMINANTS OF CORONARY
RESISTANCE
Flow is determined by
the segmental
resistance and
therefore
an understanding of
the resistance beds is
necessary:
3 resistance beds
R1
R2
R3

14. • Epicardial arteries R1 (>400 μm in diameter) serve a
conduit artery function, with diameter primarily regulated
by shear stress, and contribute little pressure drop (<5%)
over a wide range of coronary flow.
• Coronary resistance vessels R2 can be divided into
• resistance arteries (100 to 400 μm), which regulate their
tone in response to local shear stress and luminal pressure
changes (myogenic response), and
• arterioles (<100 μm), which are sensitive to changes in
local tissue metabolism and directly control perfusion of
the low resistance coronary capillary bed.
• Capillary density R3 of the myocardium averages
3500/mm2,
resulting in an average intercapillary distance of 17 μ m,
and is greater in the subendocardium than the
subepicardium. Fixed resistance only 20%.Increased in HF

15. R1 – Conduit artery
resistance , insignificant
normally
R2 – Precapillary
arterioles and small
arteries (under metabolic
and autoregulatory
adustment)
R3 – Time varying
compressive resistance
more in subendocardial
area
In absence of stenosis –
R2>R3>R1
In presence of stenosis
or pharmacological
vasodilatation –
R1>R3>R2

16. Intraluminal Physical Forces Regulating Coronary Resistance.
Myogenic control
ability of vascular smooth
muscle to oppose changes
in coronary arterial
diameter.3 Thus vessels
relax when distending
pressure is decreased and
constrict when distending
pressure is elevated
L type calcium channels
Occurs in arterioles
<100um
Flow mediated
shear stress
related
Coronary small arteries
and arterioles also
regulate their diameter
in response to changes
in local shear stress.
Flow-induced dilation
in isolated coronary
arterioles is
endothelium-
dependent and
mediated by NO,
Metabolic
control
By ATP senstive
pottasium
channels
BY Adenosine, PH,
Hypoxia

17. Small distal
arterioles
immediately before
the capillaries are
sensitive to tissue
metabolites.
Upstream intermediate
arterioles are pressure-
sensitive, with
myogenic mechanisms
predominating.
Small resistance
arteries are removed
from the metabolic
milieu and primarily
adjust local tone in
response to shear
stress and flow..

19. PHYSIOLOGICAL ASSESSMENT OF
CORONARY ARTERY STENOSES
• STENOSES PRESSURE FLOW RELATIONSHIP
• The relationship between pressure drop across a
stenosis and coronary flow for stenoses between
30% and 90% diameter reduction can be described
using the Bernoulli principle.
• The total pressure drop across a stenosis is governed
by three hydrodynamic factors—
• viscous losses,
• separation losses, and
• turbulence

20. - The single most important
determinant of stenosis resistance
for any given level of flow is the
minimum lesional cross-sectional
area within the stenosis.
- Resistance is inversely
proportional to the square of the
cross-sectional area.
- Separation losses determine the curvilinearity
or steepness of the stenosis pressure-flow
relationship.
- Stenosis length and changes in cross sectional
area distal to the stenosis are relatively minor
determinants.

21. Very little increase in
epicardial conduit artery
resistance (R1) develops
until stenosis severity
reaches a 50% diameter
reduction.
As a result, there is no
significant pressure drop
across a stenosis or
stenosis-related alteration
in maximal myocardial
perfusion until stenosis
severity exceeds a 50%
diameter reduction.

22. • As stenosis severity increases further, the curvilinear
coronary pressure-flow relationship steepens and increases
in stenosis resistance are accompanied by concomitant
increases in the pressure drop (ΔP) across the stenosis.
• This reduces distal coronary pressure, the major
determinant of perfusion to the microcirculation, and
maximum vasodilated flow decreases.
• A critical stenosis, one in which subendocardial flow
reserve is completely exhausted at rest, usually develops
when stenosis severity exceeds 90%.

23. Measuring CBF in cath lab
• Angiography – TIMI Flow, CTFC, Myocardial
Blush
• Coronary venous sinus efflux measurements
• Intracoronary sensor wire pressure and flow
velocity measurements

24. • TFC – is number of cine frames from
introduction of contrast in coronary artery to
predetermined distal landmark at
30frames/sec.
• Distal landmarks – For LAD, distal bifurcation
of LAD, For LCX is distal bifurcation of branch
segment with longest total distance, For RCA it
is first branch of poster lateral artery

26. • TFC can be corrected to CTFC by normalizing for
length of LAD in comparison to two other major
arteries. Thus CTFC accounts for the distance
contrast has to travel in LAD relative to other
arteries. (average length LAD 14.7cm, lcx 9.3cm
and RCA 9.8cm)
• CTFC for LAD – TFC/1.7
• For LAD TFC 36+/-3, CTFC 21+/- 1.5
• FOR LCX TFC 22+/-4, FOR RCA TFC is 20+/-3
• Prolonged TFC – Microvascular dysfunction
Gibson CM et al TIMI FRAME COUNT
CIRCULATION 1996

27. • TIMI BLUSH score – sucessful reperfusion in ACS
is defined as TIMI 3 flow, However TIMI 3 flow
does not allways result in effective myocardial
reperfusion.
• MBG – measure of reperfusion at capillary level.
• MBG grade 3 indicates normal blush or contrast
density comparable with angiography of
contralateral or ipsilateral non infarct related
coronary arteries.
• Length of angiography run needs to be extended
• For LAD – left lateral view and for RCA RAO view

28. LIMITATIONS OF CORONARY ANGIOGRAPHY
• Interpretation is highly subjective
• CAG provides a 2–dimentional view of a 3-dimensional lumen.
• Severity of a stenotic lesion is reported in comparison to a normal
reference segment . This is particularly fallacious in case of diffuse
disease.
• CAG is a lumenography & does not provide information regarding
vessel wall & extent of positive or negative remodeling.
• An ecentric stenosis has varying appearance of severity in different
views. The length, size and severity of a lesion & its relationship
with the vessel wall can affect the coronary flow.
• Several artifacts contribute to the disparity in interpretation like
vessel foreshortening, overlapping vessels, calcification & contrast
streaming.

29. Concept of Maximal Perfusion and
Coronary Reserve
• GOULD originally proposed the concept of
coronary reserve.
• There are currently three major indices used
to quantify coronary flow reserve—
• absolute,
• relative, and
• fractional

30. Measurements of intracoronary pressure and flow
velocity using sensor tipped guide wire

32. CORONARY HYPEREMIA FOR STENOSIS ASSESMENT
• At maximal hyperemia, auto regulation is abolished and
microvascular resistance remains fixed and minimal.
• At this point CBF is closely dependent on coronary arterial
pressure.
• Reactive hyperemia by transient occlusion, IC papaverine, IC
dipyridamole, ATP, Nitroprusside, Adenosine is DOC
• Jermias et al compared IC (15-20ug for RCA/18-24ug for LAD) with
IV adenosine (140ug/kg/min) found linear relationship
• Sustained Hyperemia, weight based dosing and lack of operator
interaction Makes IV route preferable than IC
GROSSMAN and BAIMS

34. ABSOLUTE FLOW RESERVE
It is expressed as the ratio of maximally vasodilated flow to the
corresponding resting flow value in a specific region of the heart and
quantifies the ability of flow to increase above the resting value
Normal AFR ~ 4-5
- Clinically significant impairment if <2
- AFR incorporates functional importance of a stenosis + microcirculatory
dysfunction
Absolute flow reserve is altered not only by factors that affect maximal
coronary flow but also by the corresponding resting flow value.
Resting flow can vary with hemoglobin content, baseline hemodynamics, and
the resting oxygen extraction.
As a result, reductions in absolute flow reserve can arise from inappropriate
elevations in resting coronary flow and from reductions in maximal
perfusion.

35. Absolute flow reserve can be quantified using
intracoronary Doppler velocity or
thermodilution flow measurements, as well as by
quantitative approaches to image absolute tissue
perfusion based on PET
In the absence of diffuse atherosclerosis or LV
hypertrophy, absolute flow reserve in conscious
humans is similar to measurements in animals,
with vasodilated flow increasing four to five times
the value at rest.
In patients of hypercholesterolemia, diffuse
atherosclerosis, even in absence of obstructive
CAD, CFR is less
A significant limitation of absolute flow reserve
measurements is that the importance of an
epicardial stenosis cannot be dissociated from
changes caused by functional abnormalities in the
microcirculation that are common in patients
(e.g., hypertrophy, impaired endothelium-dependent
vasodilation).

36. ABNORMAL CBF WITH NORMAL
CORONARY ARTERIES
• MICROCIRCULATORY IMPAIRMENT
• As discussed earlier the CFR decreases with
• 1)Tachycardia (decreased diastolic time),
• 2) Increased preload ( compressive determinants)
• 3) Increased afterload
• 4) Increased contractility
• 5) Decreased Oxygen supply ( anaemia, hypoxia)
• 6) Abnormal endothelium (DM, HTN, DLP, CTDs)

37. Relative Flow Reserve
• Measured using nuclear
perfusion imaging .
• In this approach, relative
differences in regional
perfusion are assessed
during maximal
pharmacologic vasodilation
or exercise stress and
expressed as a fraction of
flow to normal regions of the
heart.

38. Limitations:
• First, conventional SPECT imaging requires a
normal reference segment within the left
ventricle for comparison.
• Because of this, relative flow reserve
measurements cannot accurately quantify
stenosis severity when diffuse abnormalities in
flow reserve related to balanced multivessel CAD
or impaired microcirculatory vasodilation are
present.

39. Fractional Flow Reserve
This technique, pioneered by PIJLS, is based on the
principle that
the distal coronary pressure measured during
vasodilation is directly proportional to maximum
vasodilated perfusion

40. Fractional flow reserve (FFR) is an indirect index determined by
measuring the driving pressure for microcirculatory flow distal to the
stenosis (distal coronary pressure minus coronary venous pressure)
relative to the coronary driving pressure available in the absence of a
stenosis (mean aortic pressure minus coronary venous pressure).
FFR model assumes that under maximum arterial vasodilation,
the resistance of the myocardium is minimal and constant across
different myocardial vascular beds, and thus blood flow to the
myocardium is proportional to the driving pressure
(myocardial perfusion pressure).
FFR can be derived separately for the myocardium, for the epicardial coronary artery,
and for the collateral supply.
An FFR of 0.9 = Only 90% of maximal CBF is able to cross the lesion
An FFR of 0.71 = 71% of maximal CBF crosses lesion

41. The FFR is simplified to Pd/Pa given the
assumption that Pv is negligible relative to Pa

42. FFR MEASUREMENT

44. • FFR is required in
• Moderate coronary stenosis (e.g. 50–70% angiographic severity) when
functional information is lacking.
• Serial coronary stenoses
• Intermediate left main stem disease
• Post-PCI / stent optimisation
• Side branch lesion severity
• Saphenous vein graft disease severity
• Non-culprit lesions in acute coronary syndromes
• Non-coronary indication: assessment of aortic valve stenosis severity

45. UNIQUE FEATURES OF FFR
• Normal value of 1 irrespective of the patient , artery or vascular bed. It is
independent of gender & other factors like DM & HTN
• Well defined cut-off values :
– FFR values ≤ 0.75 is invariably associated with inducible ischemia
(sensitivity 88%, specificity 100%, positive predictive value 100% &
overall accuracy 93%)
– FFR ≥0.80 is usually not associated with inducible ischemia.
– The gray zone of 0.75 to 0.80 spans over a small range of FFR values.
• Systemic haemodynamics like heart rate , blood pressure & LV
contractility do not affect the value of FFR since the value of Pd & Pa are
taken simultaneously.
• Reproducibility : FFR is reproducible since the microvasculature has the
capacity to vasodilate the same extent repeatedly.

46. Advantages of FFR
• - Independent of HR, SBP & driving
pressure.
• - A lesion specific index and
independent of status of
microcirculation
• - Independent of contribution by
collateral flow
• - Highly reproducible when compared
to AFR
• - Superior to quantitative CAG and
IVUS in physiological assessment
Limitations of FFR assessment
• Maximum hyperemia is
mandatory for assessment
• Assumptions : 1) Coronary venous
pressure is 0, 2) P-Q relationship is
linear
• FFR cut-off of 0.75 is derived from
a stable population with SVD and
• normal LV function – not
universally applicable to all
scenarios.
• “Pitfalls” of pressure
measurement need to be avoided
• Wedging of the guide catheter
(0.16mm2 ) may alter absolute
pressure measurements in critical
stenosis
• Limited data for acute MI

47. IMPACT OF MICROCIRCULATORY ABNORMALITIES ON
PHYSIOLOGIC MEASURE OF STENOSIS SEVERITY
• In absence of microvascular dysfunction – AFR,RFR and
FFR are closely reated
• Microvascular dysfunction in presence of normal
coronaries (0% stenosis) attenuates coronary flow
reserve.
• Conversely for any given stenosis, FFR measured in
presence of microvascular dysfunction will be higher
than when vasodilator response is normal
• Thus when maximum vasodilatation not achieved, FFR
will underestimate physiologic severity of stenosis.

48. • So combined measurement of FFR and CFR by
single wire are helpful in which mixed
abnormality is there.

49. APPLICATIONS OF FFR IN SPECIFIC
SUBSETS
• Intermediate lesions
• • Intermediate lesions with a FFR of ≥ 0.80 can be safely
defered.
• The DEFER study has shown that patients with single
vessel stenosis and FFR >0.75 who did not undergo PCI
had excellent outcomes.
• The risk of cardiac death or MI related to the stenosis was
< 1% per year and was not reduced with PCI.
• In contrast, patients with single-vessel stenosis and FFR
<0.75 are 5× more likely to experience cardiac death or MI
within 5 years, despite undergoing revascularization

51. Conclusions :
Five-year outcome after deferral of PCI of an intermediate coronary stenosis based on
FFR 0.75 is excellent.
The risk of cardiac death or myocardial infarction related to this stenosis is <1% per year
and not decreased bystenting

52. Multivessel Coronary Artery Disease

56. CONCLUSIONS:
Routine measurement of FFR in patients with multivessel disease (MVD) who are
undergoing PCI with drug-eluting stents (DES) significantly improves outcomes at 1
year by reducing MACE (composite rate of death, nonfatal myocardial infarction, and
repeat revascularization

63. If 2 lesions in same territory then
Measure summed FFR by passing
wire distal to last lesion, if FFR >0.8,
defer stenting
If FFR <0.8, get pullback, lesion with
maximum pressure gradient should
be stented
If after stenting FFR>0.75 – no further
action
If after stenting FFR<0.75, stenting of
second lesion is also required.
Post stenting
• Nico H.J. Pijls at al showed that FFR
measured after stenting should be
>0.90 & is an independent predictor of
6 month mortality.