Echo Doppler Assessment of PVR The Children s Hospital Denver, CO Robin Shandas Professor of Pediatrics, Cardiology Professor of Mechanical Engineering Director, Center for Bioengineering University of Colorado IS PVR THE RIGHT METRIC FOR RV AFTERLOAD? Affiliated with University of Colorado Health Sciences Center No disclosures Components of load on the RV pump Hypothesis Ventricle v Upstream Arteries (Capacitance) Resistance (Arterioles and microcirculation) Veins (Exit) Upstream vascular compliance is an important component of RV afterload. Coupling between ventricle and proximal vasculature is important in efficiently transporting blood. Assumption: Proximal vessels are NOT simply conduits. 1
Decreased Hemodynamic Efficiency Importance in the adult systemic circulation Normotensive Hypertensive Growing body of evidence documenting the importance of arterial stiffness as an independent factor in predicting morbidity and mortality. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, and London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 99: 2434-2439, 1999. Cheng LT, Chen HM, Tang LJ, Huang HY, Gu Y, Wang T: The study of aortic stiffness in different hypertension subtypes in dialysis patients. Hypertension Res 2008;31(4):593-599. Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekam MA, Asmar R, Reneman RS, Hoeks AP, Breteler MM, Witteman JC: Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study, Circulation 2006;113(5)657-663. Many, many others. Methods for Measuring Stiffness Issues to Consider Most conventional methods fall into those that measure or estimate pressure, flow, compliance (stiffness). Pulse pressure (stress) Distensibility / pulsatility (strain) Arterial wave velocity (indirect estimate of compliance) Flow or pressure augmentation (indirect estimate of compliance and effect of wave reflection) Newer methods Correlates of endothelial function Flow mediated dilation Pulse wave speed measurement techniques: Biological variability Ex: Arterial wave velocities range from 2-10 m/sec. Assumptions of pulse wave speed methods: Constant wave speed over length of vessel. No complicating influences (ex: derivation of the wave speed equation) No blood viscosity Only small deformations of vessel wall Simple relationship between pressure and vessel area» Usually linear Measurement uncertainty Typical sampling rate is 200 Hz - gives a inherent measurement uncertainty of +/- 2.5 msec. In 5 msec, a wave traveling at 10 m/sec will travel 5 cm. 2 m/sec wave will travel 1 cm. Length of vessel thus becomes critical. 2
RV failure due to elevated afterload is the proximate cause of death in patients with PAH Two basic loads on the right heart: 1. Vascular resistance MPAP PCWP PV Resistance = CO Reproduced from Ghio S et al. JACC Vol. 37, No 1, 2001. Jan 2001:183-8 Two basic loads on the right heart: 2. Vascular distension/stiffness Impedance quantifies both vascular resistance and stiffness MPAP PCWP PV Impedance = PV Resistance = CO PV Impedance = 3
Impedance Measure of static (PVR) + dynamic (PVS) resistance imposed by vasculature on cardiac pump. First described by Milnor ( 66, 69) Separated total right heart work into mean + oscillatory Showed significance of oscillatory component Performed first impedance study in the human Showed right and upward shift in impedance curves for PAH indicative of vascular stiffening. Difficult to obtain clinically since instantaneous pressure and flow are required. Noninvasive measurement of systemic impedance Combination of Doppler (aortic flow) and carotid applanation tonometery Attempted in 95 healthy subjects (successfully obtained data in 71). Only correlate found was minimum frequency of the impedance spectrum. QuickTime and a decompressor are needed to see this picture. Mazzaro L, et al: Aortic input impedance increases with age in healthy men and women, Hypertension 2005;45:1-6 Impedance Typical Impedance Curves Beam Line Input impedance found from corresponding harmonics of pressure and flow Z(w) = P(w) / Q(w) Flow Q(t) found from midline velocity in MPA V echo (t), mean flow Q cath, and the expressions A corr = V echo / Q cath Q(t) = A corr V echo (t) Significant differences between groups in both zero harmonic (Z 0 ) and first two higher harmonics (Z 1, Z 2 ) 4
Impedance and Proximal Stiffness PVR vs Zero Harmonic of Impedance (Z 0 ) Effect of PA Stiffness on Input Impedance Impedance Modulus (mm Hg / L / min) 25 20 15 10 5 PVR p<0.001 * Normal Compliance Stiff PA PVS p<0.001 * Z 0 shows exceptional correlation (R 2 = 0.974) to hemodynamically measured PVR Reduces need for wedge pressure measurements. 0 0 1 2 Harmonic Z 1 + Z 2 -vs- PVS - Impedance demonstrates proportionally greater afterload from vascular stiffening in patients with PAH Z1+Z2=Stiffness Z0=Resistance Z 1 +Z 2 correlates well to global measure of vascular stiffness, PP/SV 5
Impedance provides increased sensitivity to outcomes than PVR Impedance Does pulmonary vascular stiffness (PVS) increase in PAH? Reactive in Resistance? Reactive in Stiffness? Free of Complications at 1 year? Patient 1 Yes Yes Yes Patient 2 Yes Yes Yes Patient 3 Yes Yes Yes PVR Patient 4 Yes Yes Yes Patient 5 Yes Yes Yes Patient 6 Yes Yes Yes Patient 7 Yes No No Patient 8 Yes No No Patient 9 No No No Patient 10 No No No How do pulmonary arteries stiffen? Strain stiffening. Remodeling. SMC activation. How do pulmonary arteries stiffen? Strain stiffening. Remodeling. SMC activation. Stress-Strain, RPA Normoxic Calf Pressure-Diameter, RPA PAH patient challenged with 100% O 2. 6
Role of Elastin How do pulmonary arteries stiffen? Strain Stiffening Remodeling. SMC activation. Pressure (kpa) 1592 HLMB 20 L C 15 10 5 L 2101 NLMB C 0 1 1.2 1.4 1.6 1.8? λ 2-Photon 3D image reconstruction Media Elastin Area Fraction MPA H-1 41% H-2 36% N 29% Elastin in the MPA stiffens and its fractional area decreases in PAH Role of Elastin in Arterial Stiffening 7
How do pulmonary arteries stiffen? Strain Stiffening. Remodeling. SMC Activation. Young's Modulus (kpa) 30 25 20 15 10 5 0 SMC Effect Control Nifedipine Fasudil 10 15 20 25 % Strain RPA - Normoxic Rat Pulmonary vascular stiffness is a critical yet overlooked component in the evaluation of PAH. Impedance - Hypoxic Rat Proximal Artery Pressure-Diameter Loops Clinical Acquisition and Analysis of P-D and Impedance Simultaneous acquisition of arterial diameter and pressure -vs- time. Information on local artery stiffness. May be useful in evaluating proximal vascular remodeling. Suprasternal short-axis. Combination of conventional and tissue-doppler M-mode to obtain diameter. Pressure signal digitized simultaneously into ultrasound system. 8
Non-invasive measurement of PA stiffness Clinical measurement of pulmonary vascular stiffness (PVS) B-Mode Image Upper & Lower RPA Walls + Computed Trace = RPA Diameter Pressure (yellow) and ECG (blue) traces Growing body of evidence regarding its importance. Vascular mechanics easier to understand than myocardial mechanics. Cardiac catheterization laboratory is well-suited to making routine vascular function measurements. Measurements are relatively simple to implement clinically. Do not need significant additional equipment Need pressure to maintain robustness in mechanical calculations. Awareness of measurement uncertainty. Validation is important. Acknowledgements Supported by: NIH (HL 067393, HL 072738, MO1 RR00069, SCCOR HL084923, K24 HL 081506) Children s Hospital Heart Institute, Denver, CO 9