Diastolic LV function and diastolic heart failure

1. Dr.DeepakRaju Diastolic LV function and diastolic heart failure

2. Heart failure with normal ejection fraction-definition(2007 Eur Heart J) • Symptoms and signs of heart failure • Normal or mildly abnormal LV systolic function • LVEF >50% in a non dilated LV(LVEDV <97ml/m2) • Evidence of increased LV filling pressure • Tissue Doppler imaging(E/e’>15 or E/e’ 8-15 with other evidences of diastolic dysfunction) or • Invasive measurements(LVEDP>16 mmHg or mean PCWP>12 mmHg) or • Combination of natriuretic peptides or echo indices of LV diastolic dysfunction

3. Treshold value to define normal Vs reduced EF is arbitrary;consensus is for using 50% as cut off

4. Prevalence • Prevalence 50-55% of HF population • (Owan T ,NEJM 2006,Bhatia RS NEJM 2006) • Prevalence of HF nl EF among patients admitted for HF has increased over time • (Owen T ,NEJM 2006)

7. Mortality • All cause mortality is similar in HF nl EF as compared to HF with reduced EF • Compared with patients with reduced EF ,pts with HF nl EF had more deaths from non CV causes(DIG study)

8. Owan T nejm 2006

9. Survival for HF with reduced EF have improved over time ,but not for HF nl EF

11. Diastolic function • LV relaxation is an active energy dependent process • Begins during ejection phase of systole and continues through IVR and rapid filling phase • Calcium ion fluxes regulate contraction and relaxation phases • Depolarisation releases large amount of Ca into cytosol to initiate contraction • Decrease in cytosolic Ca initiates relaxation • Calmodulin mediated closure of L type Ca channels • SR reuptake of Ca by SERCA

12. Calcium uptake by SERCA • Energy dependent process • Phosphorylation of phospholamban enhances uptake • Phospholamban respond to B adrenergic stimulation ,mediator is PKA • Impaired beta adrenergic signalling and inadequate ATP levels impair ventricular relaxation

13. Major factors influencing relaxation • Cytosolic Ca level must fall- requires ATP & phosphorylation of phospholamban • Inherent viscoelastic properties of myocard – (hypertrophied heart -↑fibrosis, relaxation –slower) • ↑phosphorylation of troponin I • Influenced by systolic load- ↑the systolic load, the faster the rate of relaxation

14. Phases of diastole • Isovolumic relaxation • Early rapid filling phase • 70 to 80 % of LV filling • Driven by LA LV pressure gradient • Dependent on • Myocardioal relaxation • LV elastic recoil • LA pressures • Mitral orifice area

15. Diastasis • LA LV pressures almost equal • 5% of LV filling • Atrial systole • 15 to 25 % of LV filling • Depends on atrialpreload,afterload and inotropic state

18. Pressure volume relationship

19. Upward shift in diastolic pressure volume relation –increased LV diastolic stiffness-higher diastolic pressure required for filling • Downward shift-decreased stiffness

21. HF nl EF • Upward and leftward shifted end-diastolic pressure–volume relationship • End-systolic pressure–volume relationship- unaltered or even steeper • Very small changes in LVEDV→ Marked ↑ in LVEDP & pulm venous P→ dyspnea during exercise, even pulm edema • Impaired LV filling and inability to use Frank-Starling mech→ Failure to ↑CO during exercise→ Exercise intolerance

23. Indices of LV diastolic relaxation • Isovolumic pressure decay • Max rate of LV pressure decline after aortic valve closure in IVR phase measured(peak negdP/dt) • Affected by loading conditions • Time constant of relaxation • Load independent measure • Rate of LV pressure decay during isovolumic relaxation

24. High fidelity manometer tipped LV catheters • Pressure and time data during period from end systole to LA-LV pressure crossover used • Weiss equation • P=P0*e-t/τ • τ=-(1/slope of Ln LVP Vs time) • Normal <40 ms • Relaxation is complete by 3.5 tau • Larger value of tau-more impaired relaxation

25. Echocardiography • LV size –normal • LVH-Less than 50% • LA enlargement • Pulmonary HTN • Rule out valvular diseases causing symptoms of HF,pericardial d/s,congenital heart d/s

26. Doppler echocardiography • Mitral inflow doppler velocities • TDI septal and lateral mitral annulus • Pulmonary vein Doppler • Color M mode of mitral inflow • Valsalva maneuver used to decrease venous return by increasing intrathoracic pressure

27. Mitral inflow (left) and pulmonary venous flow (right)

31. Normal diastolic filling pattern • Most LV filling occur in early diastole • Longitudinal mitral annular velocity mirrors normal mitral inflow • Normal E/e’ in rest and exercise • Parameters • E/A 0.9-1.5 • DT 160-240 ms • IVRT 70-90 ms • septal e’>10 cm/s • E/e’<8 • Vp>50 cm/s • LAVI-16 to 28 ml/m2

32. Doppler parameters in different age groups

33. Grade 1 diastolic dysfunction(mild) • LV relaxation impaired- • Slower LV pressure decay • Pressure crossover b/w LA and LV occurs late • IVRT,DT prolonged • Early transmitral gradient is reduced-reduced E vel • Adequate diastolic filling period is critical to maintain LV filling without increase in LA pressures

35. Reduced LA emptying in early diastole increases atrial preload-A velocity increases • Pulmonary vein diastolic flow velocity parallels mitral E velocity-decreased.Compensatory increase in systolic velocity • Pul vein atrial flow reversal usually normal,can increase if atrial compliance decreases or LVEDP higher • Septal e’ < 7 cm/s • Vp< 50 cm /s • Grade 1a diastolic dysfunction • Filling pressure is increased (E/e’> 15) with grade 1 mitral inflow pattern

36. Grade 2 –moderate diastolic dysfunction • LA pressures are elevated • LA-LV pressure gradient restored • Pseudonormalised mitral inflow pattern • E/A returns to normal,DT normal • Differentiation from true normal • Septal e’<7 cm/s • Valsalva decreases E/A by more than 0.5 • Pulmonary vein atrial flow reversal exceeds mitral A duration • Vp<45 cm/s

37. Grade 3&4 LV diastolic dysfunction(severe) • Restrictive filling • Valsalva may reverse restrictive pattern to grade 1 or 2-reversible restrictive (grade 3) • Even if no change with valsalva reversibility cannot be excluded-filling pressure may be too high to be altered by valsalva • Grade 4 dysfunction not used in ASE rec.

38. Early rapid diastolic filling into a less compliant LV cause a rapid increase in early diastolic LV pressure • Rapid equalisation produces a shortened DT • A velocity and duration shortened as atrial contraction produces rapid rise in LV pressure • Systolic forward flow in pulmonary vein reduced due to increased LA pressure • E/e’ > 15

45. E/e’ ratio in rest and exercise • E/e’ ratio > 15 correspond to PCWP> 20 mmHg at rest and exercise • Normal-increase in E and e’ velocity with exercise to maintain ratio • In a subset of patients with diasolic dysfunction –increase in PCWP with exercise occur–increase in E not accompanied by increase in e’ to elevate the ratio • PCWP normal if E/e’< 8

46. BNP and NT-pro BNP • BNP & NT-proBNP- • Elevated in HF nl EF but lower than levels in HF with reduced EF(wall stress is lower) • Less sensitive and specific

47. BNP level 200 pg/ml or an NT-proBNP level 220 pg/ml to confirm the diagnosis of HFNEF in patients with symptoms of HF,LVEF 50%, and an ambiguous E/E value between 8 and 15 • Less reliable in elderly and in women • Exclusion of HF nl EF, with limits for exclusion of 100 and 120 pg/ml, respectively

49. Demographic features • Aging • Diastolic function deteriorates with aging • Structural cardiac changes • Blunted beta adrenergic responsiveness • altered Ca handling proteins • Female gender • Higher ventricular systolic and diastolic stiffness • HF nl EF increases more sharply with age in women

50. HTN • LVH which increases diastolic stiffness • Ischemia produces exaggerated increase in filling pressure • CAD • a/c ischemia causes diastolic dysfunction • Role of CAD in c/c diastolic dysfunction uncertain • Guidelines recommend revascularisation in pts in whom ischemia is felt to contribute to LV diastolic dysfunction • Reduced coronary microvascular density-impaired coronary flow reserve-diastolic dysfunction in stress