Coronary Artery Disease

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ifr ifr Pressure (mmhg) Pressure (mmhg) ECG Coronary Artery Disease Functional assessment of disease severity (invasive) Fractional Flow Reserve (FFR) 140 130 120 110 100 90 80 70 1.05 1 0.95 0.9 0.85 Pressure drop across a stenosis (P distal / P aorta) 0.5 1 1.5 2 2.5 3 3.5 4 Flow limiting stenosis = 0.8 Seconds 14 13 12 11 10 9 8 7 1.0 0.9 0. 0.8

Decision making Which coronary stenosis deserves a stent? Symptoms + Anatomical lesion + Evidence of limitation of flow A B??

Decision making Which coronary stenosis deserves a stent? Symptoms + Anatomical lesion + Evidence of limitation of flow

Decision making: which coronary stenosis deserves a stent? ifr Pressure (mmhg) ECG ifr ifr Pressure Pressure (mmhg) (mmhg) ECG ECG Similar anatomical significance 140 140 140 130 130 130 Different 120 haemodynamic 110 consequences 120 120 110 110 100 100 100 90 90 90 80 80 80 70 70 70 1.05 1.05 1.05 11 1 0.95 0.95 Antomical-functional 0.95 0.9 0.9 discrepancy FFR = 0.87 FFR = 0.78 0.9 0.85 0.85

Coronary pressure drop (mmhg) Stable distal coronary resistance Simplified model of flow limitation caused by a coronary stenosis Coronary stenosis What can influence P (FFR)? 1. Characteristics of stenosis (K1 and K2) 2. Trans-coronary velocity Distal resistance P = K 1 v + K 2 v 2 P = A v + B v 2 B A C Diabetes HTN Lipids Miocardial suction Location of stenosis Response to adenosine Coronary flow (cm/s)

Pressure (mmhg) Pressure Pressure (mmhg) (mmhg) ECG ECG ECG Exact same stenosis will never be interrogated under the same physiological circumstances in clinical studies Similar anatomical significance 140 140 140 130 130 130 Different 120 haemodynamic 110 consequences 100 100 100 90 90 90 80 80 80 FFR = 0.87 70 70 70 1.05 1.05 FFR = 0.78 1.05 11 120 120 110 110

Clinical applications of cardiac modelling Using Computational Fluid Dynamics (CFD) to understand the clinical phenomenon of anatomical-functional discrepancy of coronary artery disease Unique benefits of CFD modelling A 1 Isolations of parameters 2 3 B Free manipulation of parameters 6 4 5 7 No unknown confounders Coronary perfusion pressure High Low No measurement error

Anatomical parameters of coronary disease severity: a (too) simple model inherited from a limited modality? Coronary angiography Anatomical parameters of severity: Stenosis length Percentage stenosis (area / diameter) Minimal Lumen Area (MLA)

Anatomical parameters of coronary disease severity: a model (too) simple inherited from a limited modality? Intravascular ultrasound Optical Coherence Tomography Anatomical parameters of severity: Stenosis length Percentage stenosis (area / diameter) Minimal Lumen Area (MLA)

FFR Anatomical-functional discrepancy 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0 1 2 3 4 5 6 7 8 9 MLA (mm 2 ) Intravascular Ultrasound

Anatomical-functional discrepancy Is there a true discrepancy between anatomy and physiology or we are looking at the wrong parameters? Is our anatomical model too simplified? Are stenosis length, MLA and percentage stenosis the main cause of flow limitation?

Anatomical-functional discrepancy The foundation of the current model is that luminal reduction is the only responsible for flow limitation Bernoulli s experiment

Morphological characteristics of lesions is neglected in the current model How can CFD help? Methodology A 1 2 1. Create models based on individual parameters (A) or patient-specific anatomy (B) B 3 2. Set a specific coronary velocity (inlet or outlet) and distal resistance 4 Coronary perfusion pressure 5 6 7 3. Set fluid characteristics and boundary conditions similar to blood flow 4. Steady-state or pulsatile models High Low

Patient specific CFD simulations

Shear stress Flow disturbances Flow velocity = 0.7 m/s FFR = 0.6 STENT NO STENT High Low

Area stenosis Anatomical-functional discrepancy How the lumen is reduced is as important (or perhaps more) than the magnitude of reduction 80% FFR= 0.88 FFR=0.47 FFR<0.1 70% FFR=0.91 FFR=0.75 FFR=0.47 60% FFR= 0.93 FFR=0.88 FFR=0.66 A Smooth Mildly rough Very rough Luminal roughness

Patient specific CFD simulations Insights into mechanisms of flow limitation B A C

Lessons from CFD in coronary disease Insights into mechanisms of flow limitation (schematic figure) A 1 Stenosis morphology: Inlet and outlet transitions 2 Areas of flow disturbances B 3 6 Overall macroscopic roughness 4 5 7 Coronary perfusion pressure High Low

Anatomical-functional discrepancy Is there a true discrepancy between anatomy and physiology? NO, we are looking at the wrong parameters Is the current anatomical model too simplified? YES Are stenosis length, MLA and percentage stenosis the main cause of flow limitation? NO

Clinical usefulness of CFD modelling Directly applicable clinically? Not yet... A B

Pressure (mmhg) Pressure Pressure (mmhg) (mmhg) ECG ECG ECG Clinical usefulness of CFD modelling Immediately applicable clinically useful messages: Education, education, education Similar anatomical significance Very different 140 140 140 130 130 130 Different 120 haemodynamic 110 consequences 100 100 100 90 90 90 Obviously!! 80 80 80 70 70 FFR = 0.87 70 FFR = 0.78 1.05 1.05 120 120 110 110

THANK YOU!! Ricardo Petraco BHF Clinical Research Fellow Specialist Registrar in Cardiology Justin Davies, Darrel Francis, Jamil Mayet, Alun Hughes, Philip Kilner Sayan Sen, Sukhjinder Nijjer Chrysa Kousera International Centre for Circulatory Health National Heart and Lung Institute Imperial College London