Disclosures VASCULATURE AND Hemodynamic Core lab for Merck Research - PowerPoint PPT Presentation

6/22/2013 THE PULMONARY Disclosures VASCULATURE AND � Hemodynamic Core lab for Merck Research ASSESSMENT OF THE RIGHT Laboratories VENTRICLE � Heart Failure Core Lab for Women’s Health Initiative Heart Failure Study Ryan J. Tedford, MD � NIH sponsored research Heart Failure, Mechanical Circulatory Support, and Cardiac Transplantation Division of Cardiology, Department of Medicine Johns Hopkins School of Medicine 6 th International Neonatal and Childhood Pulmonary June 22 nd , 2013 Vasculature Disease Conference, San Francisco, CA RV Afterload Afterload on the PV loop � “Load” the RV must eject blood against 50 � Most precisely, afterload is related to wall stress ( σ ) RV Pressure (mmHg) that occurs during ejection: 40 PV closes EJ EJ PV opens 30 EJ EJ 20 � P = ventricular pressure; r = ventricular radius; h = wall thickness 10 � r is a relatively small number, h is constant so: 0 60 80 100 120 140 � Afterload RV Pressure EJ RV Volume (mL) � RV EJ pressure ~ PA EJ pressure in most cases Afterload ~ Sum of RV systolic pressure throughout ejection 1

6/22/2013 What are the components of Three Element Windkessel Model afterload? � Mean resistance (resistance to blood flow during steady state) (i.e. PVR or TPR) � Compliance of the vascular system � Blood storage capacity of the vessels � Arterial wave reflections due to pulsatile blood flow � Pulse wave velocity (timing) affected by compliance � Inertance of blood during ejection Am J Physiol Heart Circ Physiol 291: H1731–H1737, 2006. Pulmonary Artery Input Impedance Pulmonary Artery Impedance • Fourier analysis of • Comprehensive description of the RV vascular load and takes simultaneous measures of into account: • Resistance of the pulmonary bed pressure and flow • Pulse wave reflections • Forms a graph of modulus • Inertance of blood that is accelerated during ejection (amplitude of pressure • Ability of vessels to accommodate ejected blood bolus divided by amplitude of flow) and phase (delay (compliance properties) between flow and pressure) plotted against frequency (typically, multiples of heart rate). Piene H. Physiol Rev. 1986 Jul;66(3):606-52 Milnor WR et al. Circ Res. 1966 Sep;19(3):467-80. 2

6/22/2013 Pulmonary Impedance Spectra Pulmonary Impedance Spectra � Separate and study individual components of RV Z 0 (mean pressure/mean flow) = Total Pulmonary vascular load Resistance � Additionally it allows for calculation of: Characteristic Impedance (Z c ) = ratio of blood � Reflection coefficients mass inertia to proximal vessel compliance; Sum of high frequency impedance (~2-12 Hz) � Ratio of forward to reflective waves � Total hydraulic power � Integrating product of pressure and flow � Oscillatory power (total – mean) � Impedance spectrum shifts toward the right with PAH; Z o Frequency (Hz) First Z min = function of pulse wave velocity and the Z 1 = low frequency impedance; and Z 1 increase; Z min occurs at higher frequencies distance to the major site(s) Large portion of total blood flow and important fraction of wave reflection of total hydraulic load; large influence by wave reflections Chesler NC et al. Conf Proc IEEE Eng Med Biol Soc. 2009 Milnor et al. Circ Res. 1966 Sep;19(3):467-80 Kussmaul WG et al. J Appl Physiol. 1993 Jan;74(1):161-9. Afterload in the Systemic Circulation Large Vessel Compliance (~80%) Do we have to measure impedance to Aging � Stiffening of the aorta � understand afterload in pulmonary Lower Large Vessel Compliance hypertension ? Increased Pulse Wave Velocity Elevation of Left Ventricular Afterload Maybe not! Small Vessel Compliance (~20%) Enhanced Wave Reflection Vascular Resistance Lower compliance independent of resistance 3

6/22/2013 Calculating components of afterload in Pulmonary R-C relationship the pulmonary circulation � Pulmonary Vascular Resistance = (mPAP – PCWP) / Cardiac output � Compliance can best estimated a number of ways PCWP < 15 mmHg including: (stroke volume / pulse pressure) � “Lumped” parameter that also takes into account contributions of wave reflections � As wave reflections return during RV systole, RV systolic pressure increases � increasing pulse pressure and lowering “Compliance” Tedford RJ et al. Circulation. 2012;125:289-297 Pulmonary RC time vs. Systemic RC time Systemic R-C relationship PCWP < 15 mmHg Tedford RJ et al. Circulation. 2012;125:289-297 Tedford RJ et al. Circulation. 2012;125:289-297 4

6/22/2013 Peripheral compliance in the lung: Afterload in the Pulmonary Circulation Why might this occur? � Compliance is more Large Vessel � In the lungs, there are ~8-10 times more peripheral evenly distributed across Compliance (~20%) vessels than in the systemic tree the pulmonary bed and the peripheral or distal � Total # of pulmonary arterioles with a length of 2mm and vessels are responsible diameter of 8 µm is ~ 4 x 10 9 for most of the pulmonary � One such arteriole has a compliance of 0.5 x 10 -9 vascular compliance mL/mmHg � Total peripheral compliance is 2 mL/mmHg Small Vessel � Total pulmonary arterial system has a compliance < 4 Compliance (>50%) Vascular Resistance mL/mmHg Sauoti et al. 2009; 297: H2154-H2160 . Saouti N et al. Eur Respir Rev 2010; 19: 117, 197–203 Consequences of the How does PH treatment effect? pulmonary RC relationship � Main determinant of compliance is PVR, and therefore PVR a major determinant of pulsatile load n=62 � Saouti et al have suggested the oscillatory power – power required to account for pulsatile load – is constant fraction of total power (~23%) Before After High IPAH: PA mean >58mmHg (median) Mod IPAH: PA Mean <58mmHg Lankhaar JW et al. Eur Heart J. 2008 Jul;29(13):1688-95. Sauoti et al. AJRCCM 2010 Nov 15;182(10):1315-20 5

6/22/2013 Characteristic Impedance Back to our Windkessel Model (pulmonary circulation) Because Z is higher in the IPAH (distal small vessel dz) than CTEPH (proximal large vessel narrowing +/- small vessel dz), very proximal arterial narrowing does not appear have a large affect on Zc. Am J Physiol Heart Circ Physiol 291: H1731–H1737, 2006. Am J Physiol Heart Circ Physiol 291: H1731–H1737, 2006. Characteristic Impedance and RV afterload (n) NONPH (10) CTEPH (10) IPAH (9) mPAP 18 ±4 45±14 58±14 Does the pulmonary RC relationship ever change? • Higher mPAP lead to a decrease in total C and proximal C, the later of which is the main determinant of Zc. Am J Physiol Heart Circ Physiol 291: H1731–H1737, 2006. 6

6/22/2013 Does Severe Interstitial Fibrosis Aging Alters the Relationship - Slightly Alter The Relationship? All DLCO <41% Tedford RJ et al. Circulation. 2012;125:289-297 Tedford RJ et al. Circulation. 2012;125:289-297 Systemic Sclerosis – No! PCWP large affect on Compliance Tedford et al. Circulation: Heart Failure, 2013, in press Tedford et al. Circulation. 2012;123:2414-2422 7

6/22/2013 Effect of Aging vs. PCWP on Quantifying PCWP effect Compliance AGE PCWP If PCWP is used as a continuous variable: Age 18-51 Age 52-63 [Log Pulm C = 0.112 - (0.553 * log Pulm R) - (0.0122 * PCWP); R 2 = 0.70, p<0.001] Age 64-87 PVR=3 WU At a resistance of 3 Wood unit, compliance is be lowered from 3.34 to 1.65 to 0.82 mL/mmHg as PCWP increases from 0 to 25 to 50 mmHg respectively Range of 2.52 ml/mmHg or a 75% decline in compliance (Age 0.49 mL/mmHg or a 19% decline over 70 years) Tedford RJ et al. Circulation. 2012;125:289-297 Proportional To PCWP Elevation Implications for PCWP � Increasing PCWP substantially lowers pulmonary vascular compliance for a given pulmonary vascular P<0.001 resistance and lowers the RC time � Lower compliance leads to increased pulsatile afterload and therefore total RV afterload Tedford RJ et al. Circulation. 2012;125:289-297 8

6/22/2013 Does the PCWP effect translate to Even in PH, RC is clinical outcomes in heart failure? not completely constant 2.5 Pulmonary RC time (seconds) 2.0 1.5 1.0 0.5 0.0 0 20 40 60 80 100 Mean Pulmonary Artery Pressure (mmHg) • PAC was a stronger predictor of RV dysfunction and all cause mortality or transplantation than PVR Slight overall increase in RC time as mPAP rises • PAC bundles the effects of PVR and left-sided filling pressures on RV afterload Dupont M et al. Circ Heart Fail. 2012;5:778–785. Human RV Pressure Volume Analysis How can we assess RV function independent of afterload ? • Conductance based volume estimations could be made in the RV Bishop A et al. International Journal of Cardiology 58 (1997) 211–221 9