FFR and Clinical Outcome
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FFR, Ischemia and Clinical Outcome
Bernard De Bruyne, MD, PhD Cardiovascular Center Aalst OLV-Clinic Aalst, Belgium ETP, Sofia Antipolis, April 2013
FFR and Clinical Outcome
Is it important to detect ischemia ?
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Log hazard ratio for revascularization (Revasc) vs medical therapy (Medical Rx) as a function of % myocardium ischemic based on final Cox proportional hazards model
Above 10% ischemic myocardium, the survival benefit from revascularisation increases with the extent of ischemia ETP, Sofia Antipolis, April 2013
Hachamovitch, R. et al. Circulation 2003
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FFR and Clinical Outcome
ETP, Sofia Antipolis, April 2013
FFR and Clinical Outcome
Factors that Contribute to Abrupt Coronary Occlusion (Biochemistery/Cytology)
2. Histopathology of the wall (Histology) 3. Hemodynamic factors (Physics) • • • • • • ETP, Sofia Antipolis, April 2013
Plaque stress Venturi effect Vasa vasorum Shear stress Cholesterol crystal Exercise...
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1. Blood/Platelets/…
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
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• Plaque stress
ETP, Sofia Antipolis, April 2013
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
Pressure wave Slicing forces
Plaque fatigue ETP, Sofia Antipolis, April 2013
P1
P2
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40.000.000 / year
FFR and Clinical Outcome
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Computational Flow Dynamics Plaque Stress and Strain Distribution
ETP, Sofia Antipolis, April 2013
Li Y.Z. et al Stroke 2006
FFR and Clinical Outcome
• Plaque stress • Venturi Effect
ETP, Sofia Antipolis, April 2013
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Mechanical constraints on coronary stenoses
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
P1
ETP, Sofia Antipolis, April 2013
Low lateral pressure
P2
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Decreased lateral pressure (Venturi Effect)
FFR and Clinical Outcome
• Plaque stress • Venturi Effect • Vasa Vasorum
ETP, Sofia Antipolis, April 2013
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Mechanical constraints on coronary stenoses
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
P1
P2 P1
ETP, Sofia Antipolis, April 2013
Paterson JC , J Occupational Medicine 1961
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Importance of Vasa Vasorum And Vasa Plaquorum
FFR and Clinical Outcome
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Recent intraplaque hemorrhage in a thin-cap fibroatheroma
ETP, Sofia Antipolis, April 2013
Virmani, R. et al. Arterioscler Thromb Vasc Biol 2005
FFR and Clinical Outcome
• Plaque stress • Venturi Effect • Vasa Vasora • Shear stress
ETP, Sofia Antipolis, April 2013
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Mechanical constraints on coronary stenoses
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
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Turbulences = unfavorable rheologic conditions
ETP, Sofia Antipolis, April 2013
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
P1
ETP, Sofia Antipolis, April 2013
P2
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Turbulences = unfavorable rheologic conditions
FFR and Clinical Outcome
Cross-talks between rheology and biology Influence of Endothelial Shear Stress on Plaque Progression
Normal
Stenosis Low Endothelial Shear Stress • Vasoconstriction • ↑ platelet aggregation • matrix degradation • inflammation • SMC proliferation ETP, Sofia Antipolis, April 2013
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High Endothelial Shear Stress •Vasodilation •↓ platelet aggregation
Chatzizisis et al JACC 2007;49:2379
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
P1
P2
- Low endothelial shear stress Pro-atherogenic - High blood shear stress Pro-thrombogenic ETP, Sofia Antipolis, April 2013
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Acceleration/deceleration/turbulences = unfavorable rheologic conditions
FFR and Clinical Outcome
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Cross-talks between rheology and biology
ETP, Sofia Antipolis, April 2013
Koskinas KC et al Circulation May 2010
FFR and Clinical Outcome
Low Coronary Wall Shear Stress is Associated with Plaque Progression and High Wall Shear Stress with Plaque Transformation in Patients with CAD
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N= 20 pts, with CAD with baseline and 6 month follow up evaluation
ETP, Sofia Antipolis, April 2013
Samady H et al Circulation 2011
FFR and Clinical Outcome
Cross-talks between rheology and biology
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Influence of Shear Stress on Platelet Activations
ETP, Sofia Antipolis, April 2013
Sheriff J et al Ann Biomed Eng. 2010;38(4):1442-50
FFR and Clinical Outcome
• Plaque stress • Venturi Effect • Vasa Vasora • Shear stress • Cholesterol Crystals ETP, Sofia Antipolis, April 2013
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Mechanical constraints on coronary stenoses
FFR and Clinical Outcome
Physical Factors Trigger Crystallization and Volume Expansion of Intraplaque Cholesterol
Temperature pH Hydration Pressure
ETP, Sofia Antipolis, April 2013
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Crystallization and Volume increase with
(“very likely”)
Abela GS et al Am J Cardiol 2011;107:1710
FFR and Clinical Outcome
• Plaque stress • Venturi Effect • Vasa Vasora • Shear stress • Cholesterol Crystals • Physical exercise ETP, Sofia Antipolis, April 2013
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Mechanical constraints on coronary stenoses
FFR and Clinical Outcome
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Mechanical constraints on coronary stenoses Effect of Physical Exercise
Rest ETP, Sofia Antipolis, April 2013
Exercise
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses Effect of WATCHING Football Matches Germany vs Italy
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Germany vs Argentina
Rest ETP, Sofia Antipolis, April 2013
Exercise Wilbert-Lampen U, N Engl J Med 2008
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
• Slicing forces plaque fatigue • High flow velocities Venturi Effect • Turbulences low shear stress • Vasa Vasorum gradient in/out
Plaque Rupture (Especially when Thin Cap Fibro Atheroma) ETP, Sofia Antipolis, April 2013
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Pressure gradient
FFR and Clinical Outcome
Mechanical constraints on coronary stenoses
P1 Physical forces >> (hemodynamics) ETP, Sofia Antipolis, April 2013
P2
Material strength (histopathology)
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Plaque Rupture Importance of Plaque Composition
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FFR and Clinical Outcome
ETP, Sofia Antipolis, April 2013
FFR and Clinical Outcome
What is the Fate of Mild Stenoses ?
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Proximal LAD Stenoses
564 Patients with a prox LAD stenosis FFR > 0.80
ETP, Sofia Antipolis, April 2013
Muller O. et al. JACC Interv 2011
FFR and Clinical Outcome
Proximal LAD Stenoses
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Log Rank P=0.74
564 Patients with a prox LAD stenosis FFR > 0.80 1868 age- and gender-matched controls
ETP, Sofia Antipolis, April 2013
Muller O. et al. JACC Interv 2011
FFR and Clinical Outcome
FAME 2 Trial Primary Outcomes MT vs. Registry: HR 4.32 (1.75-10.7); p0.80)
5
0 0
1
2
3
4
5
6
7
8
9
10
11
12
127 155 52
100 117 41
70 92 25
37 53 13
Months after randomization No. at risk MT PCI+MT Registry
441 447 166
ETP, Sofia Antipolis, April 2013
414 414 156
370 388 145
322 351 133
283 308 117
253 277 106
220 243 93
192 212 74
162 175 64
De Bruyne B, Pijls NHJ , Kalesan B et al. New Engl J Med 2012;367:991
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Cumulative incidence (%)
30
FFR and Clinical Outcome
Conclusive Remarks 1. The physical forces are a major player of the “vulnerability” of stenosis („Conditio sine qua non‟ for plaque rupture)
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2. Ischemia is a marker of abnormal physical forces that take place at the level of the epicardial vessels
ETP, Sofia Antipolis, April 2013
Conclusive Remarks 1. The physical forces are a major player of the “vulnerability” of stenosis. (‘Conditio sine qua non’ for plaque rupture) 2. Ischemia is a marker (an annoying epiphenomenon) of abnormal physical forces that take place at the level of the epicardial vessels 3. Pressure gradients (and FFR) are “all-in” metrics of these physical forces and are, therefore, specific biomarkers of CAD
FFR and Clinical Outcome
Conclusive Remarks Ischemia is a marker of the abnormal physical forces that take place at the level of the epicardial vessels
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Stenosis Hemodynamics
Thrombotic Occlusion Blood/ Platelets
Histopathology
Virchow‟s Triad Revisited ETP, Sofia Antipolis, April 2013
