Regulation of Coronary Blood Flow

Transcription

1 Regulation of Coronary Blood Flow for the Interventionalists Bernard De Bruyne Cardiovascular Center Aalst Belgium

2 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, mass, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

3 Extravascular Compressive Forces Pressure Aorta LV

4 Extravascular Compressive Forces Pressure Aorta LV LAD FLOW

5 Extravascular Compressive Forces Pressure Aorta Coronary LV LAD FLOW

6 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

7 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

8 Extravascular Compressive Forces Pressure Aorta RV LAD FLOW RCA FLOW

9 Cross-Sectional Lumenal Area (cm²) Relation between Vessel Size and Myocardial Mass 0.3 Normals CAD Regional Myocardial Mass (g) C. Seiler et al Circulation 1992

10 About Pressure, Flow, Resistance, and Vessel Size BASE APEX 100 % of value at the ostium Diameter Mass Pressure Flow Distance from the ostium

11 About Pressure, Flow, Resistance, and Vessel Size

12 About Pressure, Flow, Resistance, and Vessel Size 5 Ref Diam (mm) 4 < 4 mm² = significant stenosis? % Stenosis for an Cross Sectional Area of 4 mm² 25 0

13 Anatomy vs Physiology: the Chimeric Link IVUS OCT Waksman et al. JACC 2013 Guagliumi et al EuroInterv 2013 DS CCT Angio Sarno et al JACC 2009 FFR Toth et al EHJ 2014 Statistical (mechanistic) relation but little clinical relation

14 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

15 Two-Compartment Model of the Coronary Circulation The coronary angiogram detects only 5% of the total coronary tree

16 Two-Compartment Model of the Coronary Circulation Epicardial Artery Microvasculature FFR IMR CFR

17 Two-Compartment Model of the Coronary Circulation Conductance Arteries Resistance Arteries >500 µ <500 µ Microvasculature P a 100 MACRO MICRO

18 Pressure and Flow Velocity in Normal Coronary Arteries Adenosine FFR = 0.98 CFR = 4.15

19 Conductance Arteries Focal Stenosis >500 µ Resistance Arteries <500 µ Microvasculature P a 100 MACRO MICRO

20 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature Stent P a 100 MACRO MICRO

21 Conductance Arteries Focal Stenosis >500 µ Resistance Arteries <500 µ Microvasculature P a 100 Diffuse Atherosclerosis MACRO MICRO

22 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature Stent P a 100 Diffuse Atherosclerosis MACRO MICRO

23 Conductance Arteries >500 µ Resistance Arteries <500 µ Microvasculature P a 100 Diffuse Atherosclerosis MACRO MICRO

24 Endothelial Control of Coronary Blood Flow ACh Blood Flow Shear Stress Bradykinine Endotheline Normal Endothelium L-Arginine enos NO PGI 2 EDHF Vascular Smooth Muscle Cell Guanyl Cyclase cgmp Dilatation

25 Endothelial Control of Coronary Blood Flow ACh Blood Flow Shear Stress Bradykinine Endotheline Abnormal Endothelium L-Arginine enos NO Vascular Smooth Muscle Cell Guanyl Cyclase cgmp Constriction

26 Importance of Maximal Vasodilation Epicardial = Conductance Arteries > 550 µ Microvasculature = Resistance Arteries < 550 µ Nitrates Vasospasm Adenosine Autoregulation

27 Endothelial Control of Coronary Blood Flow Effects of Mental Stress on the Diameter of Stenosed, Irregular, and Smooth Epicardial Coronary-Artery Segments. Effect of Mental Stress on the Diameter of Coronary Arteries Yeung AC et al. N Engl J Med 1991;325:

28 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

29 % Reduction in Subendocardial Function Flow-Function Relationship % Reduction in Subendocardial Flow S. Vatner Circ Res 1980;47:201

30 Flow-Function Relationship 100 LV Wall Thickening (% of control value) Arterial saturation = 98 % Cor sinus saturation = 20 % Resting Coronary Flow (% of control value) J. Canty Circ Research 1988;63:

31 LV Wall Thickening (% of control value) Flow-Function Relationship Resting Coronary Flow (% of control value)

32 Flow-Function Relationship

33 ABC of Coronary Physiology For the Interventionalist 1. About Pressure, flow, resistance, etc, Epicardial vs microvascular compartments 3. Flow-function relationship 4. Coronary autoregulation

34 The Control of Myocardial Blood Flow Neuro-humoral factors α 1 α 2 Metabolic factors Noradrenaline Adrenaline β 1 β 2 NO PGI 2 EDHF A 2 adenosine Acethylcholine M M α 2 PO 2 Arterial Pressure Coronary pressure RAP, LVDP and P f=0 TXA 2 5-HT TXA 2 NO PGI 2 EDHF 5-HT P 2 Endothelium P 2 B H 1 2 NO PGI 2 EDHF ET B H 2 ET AT 1 ET A ET B PCO 2, H +, K + Angiotensine II H 1 Histamine Systolic compression Diastolic compression Bradykinine Physical factors Endo- and paracrine factors Adapted from D.J.G.M. Duncker

35 The Control of Myocardial Blood Flow Metabolic factors Endothelium Physical factors Neuro-humoral factors Endo- and paracrine factors Multiple, interacting, cumulative, nonlinear mechanisms Coronary Autoregulation Adapted from D.J.G.M. Duncker

36 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

37 Coronary Blood Flow (ml/min) Coronary Autoregulation Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

38 Coronary Blood Flow (ml/min) Autoregulatory Range Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

39 Coronary Blood Flow (ml/min) Autoregulatory Range Initial Pressure Coronary Perfusion Pressure (mm Hg) Rubio and Berne, Prog CV Disease 1975

40 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P R epi + R myo % Area Stenosis K. Lance Gould, 1974

41 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P R epi + R myo % Area Stenosis K. Lance Gould, 1974

42 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P R epi + R myo % Area Stenosis K. Lance Gould, 1974

43 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v F = P R epi + R myo % Area Stenosis K. Lance Gould, 1974

44 % Control Flow Flow, Pressure, and Resistance R myo P a F R epi P v P F = R epi + R myo % Area Stenosis K. Lance Gould, 1974

45 Autoregulation Proximal LAD stenosis (n = 26) Normal LV systolic function PET fow measurements ( 15 O-labeled water) at rest Distal Coronary Pressure (mm Hg) De Bruyne et al, 1996

46 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation Hyperemic Coronary Perfusion Pressure ( % of normal )

47 People who wish to treat patients with CAD without coronary physiology must settle for a suboptimal treatment

48 Fractional Flow Reserve 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 P a S Q max FFR = = N Q max P d P a P d During maximal hyperemia (i.e. during maximal transstenotic flow)

49 Fractional Flow Reserve 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 P a FFR = Q s max max Q N P d FFR =? P d P a (at hyperemia)

50 Definition Fractional Flow Reserve is the ratio of maximal myocardial flow In the stenotic territory to normal maximal myocardial flow max Q N P a 100 P d 100 P v 0 FFR = FFR = Q s max Q N (P d -P v ) / R S (P a -P v ) / R N max max max P a 100 P d 70 P v 0 Hyperemia R s =R N max Q s P v <<< P a and P d FFR = P d P a

51 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation P a 100 P d 100 P v Q N max P a 100 P d 70 P v Q s max Hyperemic Coronary Perfusion Pressure ( % of normal )

52 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation Hyperemic Coronary Perfusion Pressure ( % of normal )

53 Non-Linearity of the Pressure-Resistance Relationship? Spaan, J. A.E. et al. Circulation 2006

54 Diameter Normalized to the Passive Diameter at 100 mm Hg Non-Linearity of the Pressure-Resistance Relationship? Pressure (mm Hg) Adapted from Spaan, J. A.E. et al. Circulation 2006

55 Diameter Normalized to the Passive Diameter at 100 mm Hg Non-Linearity of the Pressure-Resistance Relationship? Pressure (mm Hg) Adapted from Spaan, J. A.E. et al. Circulation 2006

56 The relation between P d /P a and Q S /Q N is LINEAR during HYPEREMIA Pijls NHJ et al, Circulation,1993;86:1354

57 The relation between P d /P a and Q S /Q N is LINEAR during HYPEREMIA 22 Patients with an isolated proximal LAD stenosis H 2 15 O PET maximal flow in LAD vs normal territories FFR within 24 hours De Bruyne B et al, Circulation,1994;89:1013

58 FFR: Physiologic Meaning S Q max FFR = = N Q max P d P a During maximal hyperemia (i.e. during maximal transstenotic flow) FFR has a well defined physiologic meaning (in sharp contrast to other indices like the ΔP, resting P d /P a, ifr, FFR diast )

59 Hyperemic Coronary Blood Flow ( % of Normal ) Pressure-Flow Relationship During Maximal Vasodilation Hyperemic Coronary Perfusion Pressure ( % of normal )

60 People who wish to treat patients with CAD without coronary physiology must settle for a suboptimal treatment