Mechanisms of heart failure with normal EF Arterial stiffness and ventricular-arterial coupling. What is the pathophysiology at presentation?

Transcription

1 Mechanisms of heart failure with normal EF Arterial stiffness and ventricular-arterial coupling What is the pathophysiology at presentation? Ventricular-arterial coupling elastance Central arterial pressure aplanation Conduit arterial stiffness; wave intensity Dyssynchrony and asymmetry of VA coupling Implications for understanding & treating HFNEF

2 DURING AFTER 38 patients 18 patients with EF >50% Gandhi SK et al, NEJM 2001; 344: 17-22

3 What is the mechanism of acute hypertensive pulmonary oedema? 51 pts, aged 69 ±11 y, echo 66 ± 39 after treatment p = 0.25 p = p = (0.14) 0.36 (0.14) (8.6) (7.8) (2.1) 6.4 (2.0) 0 LVEF % Basal LV strain % Mitral annular displacement mm Mitral annulus displacement (mm) Margulescu AD et al, ESC 2010

4 Comparisons of LV global systolic function N Acute episode Follow-up (at 3 days) p-value (t-test) Indexed cardiac output (l/min/m 2 ) +dp/dt (mmhg/s) Isovolumic acceleration (m/s 2 ) (1.0) 2.4 (0.7) (271) 978 (275) (0.9) 1.1 (0.7) 0.08 LVOT acceleration (m/s 2 ) (5.2) 15.4 (4.9) 0.94 Estimated SVR (dyne.s.cm -5 ) (1017) 1987 (599) 0.84 Margulescu AD et al, ESC 2010

5 Comparisons of LV diastolic function N Acute episode Follow-up p-value (t-test) E wave (cm/s) (30.9) 72.3 (27.3) 0.95 A wave (cm/s) (30.4) 81.7 (32.0) 0.64 E/A ratio (0.5) 1.2 (0.9) 0.21 Deceleration time (ms) (83.6) (69.0) 0.08 IVRT (ms) (36.4) (33.0) 0.57 Vp (cm/s) (9.8) 31.1 (10.9) 0.59 Mean peak E (cm/s) (1.8) 4.7 (1.5) 0.19 E/E' (6.5) 16.8 (8.2) 0.26 E/Vp (0.8) 2.4 (0.8) 0.53 Untwist rate ( /s) (32) -64 (29) 0.94 Time AVC- untwist rate (ms) (78) 127 (122) 0.60

6 Left ventricular pressure-volume loop Pressure ESP DP Isovolumic Isovolumic relaxation End-systolic pressure volume relationship contractility ESV Filling Ejection End-diastolic pressure volume relationship EDV contraction Volume

7 The traditional concept of ventricular-arterial coupling Pressure ESP Elastance = change in pressure for a given change in volume DP ESV EDV Volume

8 Elastance Change in pressure for a unit change in volume (mmhg/ml) Arterial elastance E A = ESP / SV (SV stroke volume) Higher elastance = greater sensitivity to volume change, more variable pressure Ventricular elastance E LV = ESP / ESV (ESV LV end-systolic volume) Net arterial load exerted on the ventricle

9 Coupling ratio VAC = E A / E LV with volumes indexed for body surface area Greatest efficiency when elastances are matched Optimal transfer of blood from LV to aorta BP, LV pressure, and CO are maintained in a physiological range Normal ratio ~ 1.0 ± 0.36 (VAC = (1/EF) 1) Normal E A 2.2 ± 0.8 mmhg/ml Normal E LV 2.3 ± 1.0 mmhg/ml Chantler, 2008

10 Circulation 2003; 107:

11 Functional reserve with low-level exercise (20W) 10 controls 19 hypertensives 21 HFPEF Peak power index Preload recruitable stroke work End-systolic elastance Arterial elastance SVR index VA coupling Borlaug B et al, JACC 2010; 56:

12 Central arterial pressure changes with age Central pressure augmentation Peripheral pressure amplification McDonald s Blood Flow in Arteries

13 AUGMENTATION Stiff conduit arteries cause increased central aortic pressure, isolated systolic hypertension, and increased arterial pulse pressure Applanation tonometry

14 Impact of arterial load (AI) on LV function (n=303) Fukuta H et al, Circ J 2010; 74:

15 BETA INDEX - Pressure-independent Young s modulus of stiffness - Adjusted for BP - No units log n (Ps / Pd) EPSILON Arterial Stiffness Parameters b = (Ds - Dd / Dd) - Peterson s pressure-strain elastic modulus - Measured in kpa (Ps - Pd) Dd Ep = (Ds - Dd) Anterior wall Posterior wall Diameter

16 Aloka SSD MHz linear array transducer Pressure Velocity Anterior wall Wave Intensity dp/dt.du/dt Compression wave Posterior wall Expansion wave Reflections Parker K & Jones C, J Biomechanical Engineering 1990; 112: 323

17 Derivation of local wave speed Pressure kpa Velocity m/s Rakebrandt F et al, Ultrasound Med Biol 2009; 35:

18 Separated pressure and velocity components Rakebrandt F et al, Ultrasound Med Biol 2009; 35:

19 There are 4 types of arterial waves Velocity Pressure Forward compression wave Forward expansion wave Backward compression wave Backward expansion wave The integral of wave intensity is energy

20 The major determinant of reflected wave energy is left ventricular systolic function n 106, 57 M, aged 46 ± 12 (22-71) years Log n BCW integral 6,5 5,5 6 r = 0.81, p< from wave intensity studies 5 4,5 4 3,5 MALE FEMALE 3 4,5 5 5,5 6 6,5 7 7,5 Log n FCW integral Rakebrandt F et al, Ultrasound Med Biol 2009; 35:

21 Ventricular-arterial coupling Conduit arterial stiffness impairs long-axis function Beta index Pressurestrain elastic modulus Longitudinal S -0.45** -0.37** -0.37** Longitudinal E -0.53** -0.47** -0.50** Radial S Radial E -0.28* -0.25* Ejection fraction E/Ea 0.48** 0.50** 0.34** Integral of midsystolic wave reflections Vinereanu D et al, Heart 2003; 89: 449

22 Wave intensity in the ascending aorta W/m 2 Velocity of shortening m/s FCW Radial 28 ± 21 ms BCW Longaxis FEW Time ms Heterogeneity of ventricular-arterial coupling 0. Aortic valve opening 1. Peak aortic flow Onset of reflections V max of radial function 2. V max long-axis function 3. Peak aortic pressure 4. Aortic valve closure Page C et al, Int J Cardiol 2010;142: Fraser AG et al, Heart (under review)

23 Non-invasive measurement of arterial waves Correlation with left ventricular function Compression wave amplitude Expansion wave amplitude Ohte N et al, Heart Vessels 2003

24 Myocardial perfusion in left ventricular hypertrophy First-pass gadolinium magnetic resonance imaging Rest Adenosine stress Courtesy of Dr Ali Yilmaz

25 What is the mechanism of coronary arterial flow? The conventional view = driven by Ao LV diastolic pressure gradient The actual view = generated by the LV itself, through relaxation expansion & diastolic wave suction A backwards-travelling Davies J et al, Circulation 2006; 113:

26 Ageing of conduit arterial function 928 European men in the ETIC Study b index Pulse wave velocity, m/s Age 80 Uejima T et al, Euroecho 2010

27 Aortic function in hypertension & diabetes Eren et al, Heart 2004; 90; 37-43

28 LV long-axis diastolic function is inversely related to arterial stiffness Arterial stiffness correlates strongly with VO 2 max Distensibility VO 2 max (ml/min) Mottram, Heart 2005;91:1551 Hundley, JACC 2001;38:796

29 Mechanisms of heart failure with normal EF Arterial stiffness and ventricular-arterial coupling Mechanism(s) of acute decompensation unclear Impaired ventricular-arterial coupling Impact especially on longitudinal function Correlates with reduced functional reserve Surrogate targets for treatment New tools for clinical research