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Regulation of Coronary Blood Flow
… for the Interventionalists
Bernard De Bruyne
Cardiovascular Center Aalst
Belgium
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1. About Pressure, flow, mass, resistance, etc, ...
2. Epicardial vs microvascular compartments
3. Flow-function relationship
4. Coronary autoregulation
ABC of Coronary Physiology For the Interventionalist
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Extravascular Compressive Forces
Pressure
Aorta
LV
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Extravascular Compressive Forces
Pressure
LAD FLOW
Aorta
LV
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Extravascular Compressive Forces
Pressure
LAD FLOW
Aorta
LV
Coronary
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Pressure
LAD FLOW
RCA FLOW
Extravascular Compressive Forces
Aorta
RV
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Pressure
LAD FLOW
RCA FLOW
Extravascular Compressive Forces
Aorta
RV
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Pressure
LAD FLOW
RCA FLOW
Extravascular Compressive Forces
Aorta
RV
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0 100 200 300 400 500 0
0.05
0.1
0.15
0.2
0.25
0.3
Regional Myocardial Mass (g)
Cro
ss-S
ect
ion
al L
um
en
al A
rea
(cm
²)
C. Seiler et al Circulation 1992
Relation between Vessel Size and Myocardial Mass
CAD
Normals
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Flow
Mass
Pressure
Distance from the ostium
% of value at the ostium
100
Diameter
APEX BASE
About Pressure, Flow, Resistance, and Vessel Size
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About Pressure, Flow, Resistance, and Vessel Size
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Ref Diam (mm)
% Stenosis for an
Cross Sectional Area of 4 mm²
< 4 mm² = significant stenosis ?
0 25 50 2
3
4
5
About Pressure, Flow, Resistance, and Vessel Size
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Anatomy vs Physiology: the Chimeric Link
Waksman et al. JACC 2013
Sarno et al JACC 2009
Guagliumi et al EuroInterv 2013
IVUS OCT
CCT
Statistical (mechanistic) relation but little clinical relation
FFR
Angio
DS
Toth et al EHJ 2014
ETP April 24-26, 2014
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1. About Pressure, flow, resistance, etc, ...
2. Epicardial vs microvascular compartments
3. Flow-function relationship
4. Coronary autoregulation
ABC of Coronary Physiology For the Interventionalist
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Two-Compartment Model of the Coronary Circulation
The coronary angiogram detects only 5% of the total coronary tree
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Epicardial Artery Microvasculature
FFR IMR
CFR
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Two-Compartment Model of the Coronary Circulation
Conductance Arteries
<500 µ
Pa
100
MICRO
>500 µ
Resistance Arteries
MACRO
Microvasculature
Two-Compartment Model of the Coronary Circulation
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Pressure and Flow Velocity in Normal Coronary Arteries
CFR = 4.15
FFR = 0.98
Adenosine
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Conductance Arteries
<500 µ
Pa
100
>500 µ
Resistance Arteries
Microvasculature
Focal Stenosis
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MICRO MACRO
Conductance Arteries
<500 µ >500 µ
Resistance Arteries
Microvasculature
Stent
Pa
100
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MICRO MACRO
Conductance Arteries
<500 µ
Pa
100
>500 µ
Resistance Arteries
Microvasculature
Focal Stenosis
Diffuse Atherosclerosis
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MICRO MACRO
Conductance Arteries
<500 µ
Pa
100
>500 µ
Resistance Arteries
Microvasculature
Diffuse Atherosclerosis
Stent
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MICRO MACRO
Conductance Arteries
<500 µ
Pa
100
>500 µ
Resistance Arteries
Microvasculature
Diffuse Atherosclerosis
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MICRO MACRO
Endothelial Control of Coronary Blood Flow
Normal Endothelium
Vascular Smooth Muscle Cell
NO
Guanyl Cyclase
eNOS
L-Arginine
cGMP Dilatation
ACh
Blood Flow
Bradykinine
Endotheline
Shear Stress
PGI2 EDHF
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Vascular Smooth Muscle Cell
NO
Guanyl Cyclase
eNOS
L-Arginine
cGMP Constriction
ACh
Bradykinine
Endotheline
Blood Flow
Shear Stress
Abnormal Endothelium
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Endothelial Control of Coronary Blood Flow
Importance of Maximal Vasodilation
Nitrates Adenosine
Vasospasm Autoregulation
Epicardial = Conductance Arteries > 550 µ
Microvasculature = Resistance
Arteries < 550 µ
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Effects of Mental Stress on the Diameter of Stenosed, Irregular, and Smooth Epicardial Coronary-Artery Segments.
Yeung AC et al. N Engl J Med 1991;325:1551-1556.
Endothelial Control of Coronary Blood Flow
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Effect of Mental Stress on
the Diameter of Coronary Arteries
1. About Pressure, flow, resistance, etc, ...
2. Epicardial vs microvascular compartments
3. Flow-function relationship
4. Coronary autoregulation
ABC of Coronary Physiology For the Interventionalist
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% R
ed
ucti
on
in
Su
ben
do
card
ial F
un
cti
on
S. Vatner Circ Res 1980;47:201
-100 - 80 -60 -40 - 20 0
0
-20
-40
- 60
- 80
-100
-120
-140
-160
-180
-200
% Reduction in Subendocardial Flow
Flow-Function Relationship
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J. Canty Circ Research 1988;63:821-836
LV Wall
Thickening
(% of control
value)
Resting Coronary Flow
(% of control value)
100
100
0 0
Arterial saturation = 98 %
Cor sinus saturation = 20 %
Flow-Function Relationship
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LV
Wall T
hic
ken
ing
(%
of
co
ntr
ol
valu
e)
Resting Coronary Flow
(% of control value)
100
100
0 0
Flow-Function Relationship
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Flow-Function Relationship
ETP April 24-26, 2014
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1. About Pressure, flow, resistance, etc, ...
2. Epicardial vs microvascular compartments
3. Flow-function relationship
4. Coronary autoregulation
ABC of Coronary Physiology For the Interventionalist
ETP April 24-26, 2014
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Adapted from D.J.G.M. Duncker
Physical factors
Endo- and paracrine
factors
Noradrenaline Adrenaline
Acethylcholine
adenosine
PO2
Histamine
Bradykinine
Systolic compression Diastolic compression
Arterial Pressure Coronary pressure RAP, LVDP and Pf=0
PCO2, H+, K+
Angiotensine II
Physical
factors
α1 α2
β1 β 2
H1
A2
M
H2
AT1
ETB
ET
ETA
ETB 5-HT
TXA2
NO
PGI2
EDHF
M
α2
NO PGI2 EDHF
NO PGI2 EDHF
B2
P2
H1
P2
Endothelium TXA2
5-HT
M
P2
Neuro-humoral
factors
Metabolic
factors
The Control of Myocardial Blood Flow
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Neuro-humoral factors
Metabolic factors
Endo- and paracrine factors
Physical factors
Endothelium
Multiple, interacting, cumulative, nonlinear mechanisms
Coronary Autoregulation
The Control of Myocardial Blood Flow
Adapted from D.J.G.M. Duncker ETP April 24-26, 2014
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Autoregulation
The ability of the heart of maintaining flow constant in case of change of perfusion pressure
without the intervention of any other external mechanism
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25
50
75
100
125
150
175
200
0 25 50 75 100 125 150 175 200
Coronary Perfusion Pressure (mm Hg)
Co
ron
ary
Blo
od
Flo
w (
mL
/min
)
Rubio and Berne, Prog CV Disease 1975
Coronary Autoregulation
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25
50
75
100
125
150
175
200
0 25 50 75 100 125 150 175 200
Coronary Perfusion Pressure (mm Hg)
Co
ron
ary
Blo
od
Flo
w (
mL/
min
)
Rubio and Berne, Prog CV Disease 1975
Autoregulatory Range
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25
50
75
100
125
150
175
200
0 25 50 75 100 125 150 175 200
Coronary Perfusion Pressure (mm Hg)
Initial Pressure
Autoregulatory Range
Co
ron
ary
Blo
od
Flo
w (
mL
/min
)
Rubio and Berne, Prog CV Disease 1975 ETP April 24-26, 2014
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F = P
Repi + Rmyo
Rmyo
Pa
F
Repi
Pv
K. Lance Gould, 1974
0 25 50 75 100 % Area Stenosis
25
50
75
100
% C
ontr
ol F
low
Flow, Pressure, and Resistance
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F = P
Repi + Rmyo
Rmyo
Pa
F
Repi
Pv
K. Lance Gould, 1974
0 25 50 75 100 % Area Stenosis
25
50
75
100
% C
ontr
ol F
low
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Flow, Pressure, and Resistance
F = P
Repi + Rmyo
Rmyo
Pa
F
Repi
Pv
K. Lance Gould, 1974
0 25 50 75 100 % Area Stenosis
25
50
75
100
% C
ontr
ol F
low
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Flow, Pressure, and Resistance
F = P
Repi + Rmyo
Rmyo
Pa
F
Repi
Pv
K. Lance Gould, 1974
0 25 50 75 100 % Area Stenosis
25
50
75
100
% C
ontr
ol F
low
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Flow, Pressure, and Resistance
F = P
Repi + Rmyo
Rmyo
Pa
F
Repi
Pv
K. Lance Gould, 1974
0 25 50 75 100 % Area Stenosis
25
50
75
100
% C
ontr
ol F
low
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Flow, Pressure, and Resistance
Distal Coronary Pressure (mm Hg)
De Bruyne et al, 1996
• Proximal LAD stenosis (n = 26)
• Normal LV systolic function
• PET fow measurements (15O-labeled water) at rest
Autoregulation
0
1
2
3
4
5
30 40 50 60 70 80 90 100 110 120 130
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Pressure-Flow Relationship
During Maximal Vasodilation
Hyperemic Coronary Perfusion Pressure
( % of normal )
Hyp
ere
mic
Co
ron
ary
Blo
od
Flo
w
( %
of
No
rmal
)
40
50
70
80
90
100
0
10
20
30
60
40 50 70 80 90 100 0 10 20 30 60
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People who wish to treat patients with CAD without coronary physiology must settle for
a suboptimal treatment
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FFR = ratio of hypermic flow in the stenotic vessel to hyperemic flow in the same vessel but in the absence of the stenosis
FFR = = Qmax
S
Qmax N
Pd
Pa
Pd
Pa
During maximal hyperemia (i.e. during maximal transstenotic flow)
FFR = extent to which (%) maximal myocardial flow is limited by the epicardial stenosis
Fractional Flow Reserve
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Pd
Pa
FFR = Qs
QN
max
max
FFR = Pd
Pa
? (at hyperemia)
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FFR = ratio of hypermic flow in the stenotic vessel to hyperemic flow in the same vessel but in the absence of the stenosis
FFR = extent to which (%) maximal myocardial flow is limited by the epicardial stenosis
Fractional Flow Reserve
Fractional Flow Reserve is the ratio of maximal myocardial flow
In the stenotic territory to normal maximal myocardial flow
Definition
FFR =
Qs
QN
max
max
FFR =
(Pd-Pv) / R S
(Pa-Pv) / R N
max
max
FFR = Pd
Pa
• HyperemiaRs=RN
• Pv <<< Pa and Pd
Pa
100
Pd
100
Pv
0
Pa
100
Pd
70
Pv
0
QN
max
Qs
max
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Hyperemic Coronary Perfusion Pressure ( % of normal )
Hyp
erem
ic C
oro
na
ry B
loo
d F
low
( %
of
No
rma
l )
40
50
70
80
90
100
0
10
20
30
60
40 50 70 80 90 100 0 10 20 30 60
Pressure-Flow Relationship During Maximal Vasodilation
Pa
100
Pd
100
Pv
0
Pa
100
Pd
70
Pv
0
QN
max
Qs
max
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Pressure-Flow Relationship During Maximal Vasodilation
Hyperemic Coronary Perfusion Pressure ( % of normal )
Hyp
erem
ic C
oro
na
ry B
loo
d F
low
( %
of
No
rma
l )
40
50
70
80
90
100
0
10
20
30
60
40 50 70 80 90 100 0 10 20 30 60
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Non-Linearity of the Pressure-Resistance Relationship ?
Spaan, J. A.E. et al. Circulation 2006 ETP April 24-26, 2014
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Dia
me
ter
No
rmal
ize
d t
o t
he
P
assi
ve D
iam
ete
r at
10
0 m
m H
g
Pressure (mm Hg)
0.7
0.75
0.8
0.85
0.9
0.95
1
1.05
1.1
30 50 70 90 110
Adapted from Spaan, J. A.E. et al. Circulation 2006 ETP April 24-26, 2014
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Non-Linearity of the Pressure-Resistance Relationship ?
Pressure (mm Hg)
0
0.2
0.4
0.6
0.8
1
1.2
30 50 70 90 110
Dia
me
ter
No
rmal
ize
d t
o t
he
P
assi
ve D
iam
ete
r at
10
0 m
m H
g
Adapted from Spaan, J. A.E. et al. Circulation 2006 ETP April 24-26, 2014
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Non-Linearity of the Pressure-Resistance Relationship ?
Pijls NHJ et al, Circulation,1993;86:1354
The relation between Pd/Pa and QS/QN is
LINEAR during HYPEREMIA
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De Bruyne B et al, Circulation,1994;89:1013
• 22 Patients with an isolated proximal LAD stenosis
• H215O PET maximal flow in LAD vs normal territories
• FFR within 24 hours
The relation between Pd/Pa and QS/QN is
LINEAR during HYPEREMIA
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FFR = = Qmax
S
Qmax N
Pd
Pa
During maximal hyperemia (i.e. during maximal transstenotic flow)
FFR: Physiologic Meaning
FFR has a well defined physiologic meaning (in sharp contrast to other indices like the ΔP, resting Pd/Pa, iFR, FFRdiast)
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Pressure-Flow Relationship During Maximal Vasodilation
Hyperemic Coronary Perfusion Pressure ( % of normal )
Hyp
erem
ic C
oro
na
ry B
loo
d F
low
( %
of
No
rma
l )
40
50
70
80
90
100
0
10
20
30
60
40 50 70 80 90 100 0 10 20 30 60
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People who wish to treat patients with CAD without coronary physiology must settle for
a suboptimal treatment
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![Predictive Study of Velocimetry in the Coronary …coronary flow rate of 250 mL/min , equivalent to a mean blood flow velocity [7] of 0.59 m/s. Therefore the relative deviation with](https://img.dokumen.tips/doc/110x75/5e991775f0ffd70cd809427d/predictive-study-of-velocimetry-in-the-coronary-coronary-flow-rate-of-250-mlmin.jpg)
