Assessment of Arterials Functions: Is Pulse Wave Velocity ready forprime Time Gérard M. LONDON INSERM U970 Hopital Georges Pompidou Paris, France
The causes of Cardiovascular Diseases in CKD Systolic BP; Diastolic BP Arteriosclerosis Atherosclerosis (Decreased coronary perfusion) Adaptive LVH (Decreased coronary reserve) CORONARY ARTERY DISEASE Volume* Overload *Hgb; AVF; Na+ Maladaptive LVH Systolic/diastolic dysfunction HEART FAILURE SUDDEN DEATH CEREBROVASCULAR PERIPHERAL ARTERY DISEASE
Atherosclerosis Arteriosclerosis
Flow Flow Pressure Pressure Arterial system as a «conduit» Blood transfer Arterial system as «hydraulic filter» Cyclic high and pulsatile pressure Continuous low pressure Aorta Microcirculation capillaries Cyclic highly pulsatile flow Continuous flow and perfusion
Large arteries mechanics Artery as a conduit Artery as a «hydtraulic filter» Diameter Stiffness Wall viscosity Conduction Transduction Transmission Kinetic Energy expenditure Potential Energy storage Potential Energy dissipation Energetic balance of heart-vessel coupling
Threshold Decades Years-Months Months-Days healthy subclinical symptomatic Thrombus Intima Media Lumen Plaque
Prevalence of discrete plaques on common carotid artery in control subjects and ESRD patients Controls ESRD Age (years) 48.5 ± 16 51 ± 16 NS Plaques (%) 17.8% 56.3% < 0.01 Type of plaques Calcified 23.1% 91.5% <0.01 Soft/mixed 77% 9% <0.01 London et al Sem Dial 1999
Carotid artery calcifications: (longitudinal incidence) Calcified plaque Common carotid artery
Carotid artery calcifications: (tranversal incidence) Calcified plaque Common carotid artery
Kono K et al. Composition of plaque patter of coronary culprit lesion in CKD KI 2012;82:344-51 Green-fibrous Yellow-fatty Red-necrotic White-calcified
NC/DC necrotic core/dense calcium AMI-acute myoc.inf; UAP-unstable ang.pect. SAP-stable ang.pect Kono K et al. KI 2012;82:344-51
Ankle-Arm Index as a Predictor of Cardiovascular Disease and Mortality in the Cardiovascular Health Study Newman AB et al for the Cardiovascular Health Study Collaborative Research Group Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:538-545. Kaplan-Meier survival for 1446 CHS participants with prevalent CVD, by categories of AAI level
Ankle systolic blood pressure (mmhg) 250 200 R=0.95 P<0.00001 150 R=0.61 P<0.01 100 50 100 120 140 160 180 200 Brachial systolic blood pressure (mmhg) - Ankle-Arm index >0.9 - Ankle-Arm index <0.9 G.M London personal data
Vintage (months) PTH (pg/ml) 1200 1200 900 900 600 600 300 300 0 ABix >0.9<1.31 Normal ABix <0.9 0 ABix >0.9<1.31 Normal ABix >1.8 Uncompressible 250 250 187 187 125 125 62 62 0 ABix >0.9<1.31 Normal ABix <0.9 0 ABix >0.9<1.31 Normal ABix >1.8 Uncompressible
Flow Flow Pressure Pressure Cushioning function of arterial system: Arterial system as «hydraulic filter» Cyclic high and pulsatile pressure Continuous low pressure Aorta Microcirculation capillaries Cyclic highly pulsatile flow Continuous flow and perfusion
Pressure Diagrammatic representation of pressure-volume relationships Einc=2 Einc=1 dp/dv Volume
Blood pressure Blood pressure ARTERIAL FUNCTION AND Pure Conduit Function BP Conduit and Cushioning Function Mean pressure Mean pressure Systole Diastole Systole Diastole
Oxygen Limitation Model Blood Velocity (NOT capillary recuitment) Capillary Transit Time Normally 2-3 seconds O 2 Extraction Smaller Fraction of O 2 Available for Metabolism
Time to shoulder (TSh ms) Relationship between the time of appearance of reflected wave on the pressure wave in central artery (time to shoulder - TSh) and aortic pulse wave velocity (PWV) 225 190 155 R=-0.671 p<0.0001 120 85 50 500 825 1150 1475 1800 aortic PWV (cm/s) London et al Hypertension 1992
Pressure wave analysis measured pressure wave forward/incident pressure wave reflected pressure wave pulse wave velocity
Role of increased central aortic and pulse pressures in the increase of cardiovascular events Increase in the central pulse pressure that drives cerebral blood flow increased stroke risk Increase chronic kidney disease. PP Increase in left ventricular load (LV load) accelerates increase in LV mass increased risk of LV hypertrophy Decreased Coronary Artery Perfusion Pressure in Diastole increased risk of MI
Aortic PWV (ms) Correlation between aortic calcification score and aortic PWV in ESRD patients 20.0 17.5 15.0 12.5 10.0 7.5 5.0 0 4 8 12 16 20 24 Abdominal aortic calcification score r = 0.754 P < 0.0001 Pannier et al. Artery 2007
Ca (mmol/kg) Correlation between age and arterial calcium (Ca) concentration in the aorta and internal iliac artery in nonuremic control subjects 400 * Aorta (r=0.84) 200 0 * * * * * * * * * * * * * * * * **** * * * * 20 40 60 80 Internal Iliac (r=0.75) AGE (years) Ibels et al. Am J Med 1979
Briet M et al. KI 2012
3D plot showing the interaction of PWV and age in relation to the global composite cognitive score for the extended regression model Elias, M. F. et al. Hypertension 2009;53:668-673
Aortic PWV (m/s) Correlation Between CCr (C-G formula) and Aortic PWV 30 25 r = 0.30 P<0.0001 20 15 10 5 0 50 100 150 200 Creatinine clearance (ml/min/m²) Bortolotto et al KI 2001
Time to shoulder (TSh ms) Relationship between the time of appearance of reflected wave on the pressure wave in central artery (time to shoulder - TSh) and aortic pulse wave velocity (PWV) 225 190 155 R=-0.671 p<0.0001 120 85 50 500 825 1150 1475 1800 aortic PWV (cm/s) London et al Hypertension 1992
CV Survival CV Survival CV Survival 1.00 Aortic PWV 1.00 Brachial PWV 0.75 <9.7m/s 0.75 0.50 >9.7 m/s 0.50 0.25 ²=72.8 P<0.00001 >12 m/s 0.00 0.0 50 100 150 200 250 Follow-up (months) 1.00 0.25 0.00 Femoral PWV ²=1.78 P=0.411 0.0 50 100 150 200 250 Follow-up (months) 0.75 0.50 1st tertile 2nd tertile 3rd tertile 0.25 0.00 ²=2.34 P=0.310 0.0 50 100 150 200 250 Follow-up (months) Pannier et al Hypertension 2005
Carotid tonometry Application of the probe with light pressure on the best palpated pulse. Probe orthogonal to the long axis of the CCA Calibration on MBP and DBP of the RA measure
GOOD Applied pressure Holding the probe like a pen, do not smash the gel pad, apply as little Pressure as possible
volume Common carotid artery IMT, diameter and stiffness : Walltrack system 150 Pressure (mmhg) 125 100 D V 7.3 diameter (mm) D P 7.2 7.1 0 1 Time pressure < 1 µm IMT 2 D TM RF Signal Spatial resolution 200-400 µm 20-40 µm
Recent developments in echotracking techniques (Pie- Medical Art.Lab ) Bidimensional RF based IMT measurements
Recent developments in echotracking techniques (Pie- Medical Art.Lab ) Distension Diameter IMT Bidimensional RF based Distention profiles 302 23
X128 RF IMT ± 17 µm Diam ± 35 µm Artlab system : real time, 128 lines RF 4 cm
Walltrack system : measurement of flow profiles Velocity (cm/s) 800 700 600 500 400 300 200 100 0-100 0 Diam
Mechanical stresses in the blood R sq vessel flow Q h circumferential wall stress sq = P x R h fluid shear stress t = 4 µ Q p R 3
Arterial remodeling associated with CKD progression Briet M. et al. JASN 2011;22:967 R Circumf. wall stress = Pressure x Radius Thickness
Sensitivity ROC Curve of CV mortality 1.00 0.75 0.50 Criterions Age; AUC 72±5% Pulse Pressure; AUC 72±5% Carotid IMT;AUC 68±6% LVmassix; AUC 72±5% 0.25 Calcification score; AUC 82±4% Aortic PWV; AUC 82±4% 0.00 0.00 0.25 0.50 0.75 1.00 1-Specificity Calcification score: cut-off 390;sensitivity 83%;specificity69%; PPV41%;NPV94% Aortic PWV: cut-off 10.75 m/s;sensitivity 84%;specificity 73%;PPV72%; NPV93%