Evalua&on)of)Le-)Ventricular)Diastolic)Dysfunc&on)by)Echocardiography:)

Role)of)Ejec&on)Frac&on)

N.Koutsogiannis)Department)of)Cardiology)

University)Hospital)of)Patras)

!!

I have no conflicts of interest to declare

For)normal)cardiac)performance)the)Le-)Ventricle)must)be)able)

to):))■ Eject)an)adequate)stroke)volume)at)arterial)pressure)(systolic)func&on))■ Fill)without)requiring)an)elevated)le-)atrial)pressure)(diastolic)func&on))

)These))func&ons)must)be)adequate)to)meet)the)needs)of)the)body)both)at)rest)and)during)stress)

Mechanisms)of)Diastolic)Dysfunc&on))

•  Impaired)relaxa&on)(early!diastole)!!!!!!energy!dependent!mechanism!of!ac5ve!filling!and!first!func5on!to!slow!down!

•  Reduced)compliance)(mid:!to!late!diastole)!passive!LV!proper5es!(myocardial!s5ffness,!chamber!geometry,!wall!thickness)!

•  Pericardial!restraint,!ventricular!interac5on!

Resistance to filling by :

The!main!physiologic!consequence!of!!diastolic!dysfunc5on!is!elevated!LV!filling!pressures,!which!represent!the!common!

feature!for!heart!failure!regardless!underlying!ae5ology!

Mean LA pressure (PCWP) >12 mmHg

LVEDP > 16mmHg

Assessment of LV filling pressures provides important information for: • Diagnosis • Prognosis • Monitoring therapy

Determinants)of)diastolic)func&on)Active elements ■ Actin-myosine crossbrige inactivation

Passive elements ■ Elasticity (diastolic recoil)

■ Lengthening load (Filling pressures ,geometry)

■ Pressure-volume relation intrinsic factors: myocardial stiffness, wall thikness and chamber geometry extrinsic factors : pericardial restraint, ventriular interaction

Early diastole

Relaxation

Restoring forces

Filling load

Mid-late diastole

Compliance

Early!diastole!Diastolic recoil

(Restoring forces) Residual crossbridge interaction

(impaired relaxation)

Lengthening load (filling pressures and geometry)

(+)

(+)

(-)

The relative importance of these forces depends on the remodeling process

and systolic function

Laplace law T = P x r / 2h

Concentric remodeling (small LV cavity size and thick LV walls)

Eccentrc remodeling (large LV cavity size and thin LV walls)

Lengthening load is low Lenghening load is high

Early!diastole!–!Concrentric!Remodeling!Diastolic recoil

(Restoring forces) Residual crossbridge interaction

(impaired relaxation)

Lengthening load (filling pressures and geometry)

(+)

(+)

(-)

Doppler findings of early diastole are mainly determined from relaxation kinetics

Early!diastole!–!Eccentric!Remodeling!Diastolic recoil

(Restoring forces) Residual crossbridge interaction (impaired relaxation)

Lengthening load (filling pressures and geometry)

(+)

(+)

(-)

Doppler findings of early diastole are mainly determined from filling pressures

Pressure

Volume

a

b c Compliance is load depended

Myocardial stiffness

Diuretics

Hypertension HypertrophyDiadetes Obesity Fibrosis

Late diastole

Reduced compliance

Systolic!func5on!

EF = SV /EDV

Simple evidence based prognostic

How!to!assess!Diastolic!func5on!by!echo!!Step!by!step!Approach!

•  Are!there!morphologic!and!func5onal!correlates!for!diastolic!dysfunc5on!?!

•  Does!mitral!inflow!velocity!paNern!indicates!diastolic!dysfunc5on!/elevated!filling!pressures!?!

•  How!abnormal!is!myocardial!relaxa5on!(especially!when!EF!is!preserved)!?!

•  Is!filling!pressures!elevated!at!rest!and/or!with!exer5on!?!

2-D findings and diastolic dysfunction

LVEF <50% slowed relaxation interpretation of Doppler findings

LV Hypertrophy slowed relaxation

LA volume Cumulative effects of diastolic dysfunction and filling pressures over time (especially when EF>50%) LA volume > 34ml/m2 (diagnostic and prognostic implications) Exclude : Atrial fibrillation Mitral valve disease Volume overload Athletes heart

Pulmonary artery pressures and diastolic dysfunction

PA systolic pressure 4 (V)² peak TR + RA pressure

PA diastolic pressure 4 (V)² end diast PR + RA pressure

Significant correlation between PAS and LV filling pressures in the absence of

pulmonary disease

Correlates well with invasively measured PCWP in patients without mean PA

pressure > 40mmHg

Mitral inflow and Hemodynamics

E LA pressure LV impaired relaxation

A LV stiffness (LVEDP)

LA contractility

DT LV stiffness (LVDP)

LV impaired relaxation

Age Heart rate and rhythm P-R interval Cardiac output Mitral annular size LA function

E / A ratio

Disease severity

Relaxation

Compliance

Filling pressure

Impaired relaxation

pseudonormal

restrictive

normal

EF < 50% (dilated cardiomyopathies, after MI)

Mitral inflow pattern correlate with filling pressures, functional class

and prognosis better than EF.

As E/A ratio increases and DT shortens filling pressures increases,

functional class is worse and prognosis is poor

EF > 50% and morfologic correlates of diastolic

dysfunction (LA enlargment, severe hypertrorhy,

HCM,amyolidosis) Restrictive pattern indicates elevated filling pressures and poor prognosis

EF > 50%

Gray zone

Therapeutic goal

Biphasic)response)of)tradi&onal)indices)to)diastolic)dysfunc&on)

Diastolic normal mild severe Parameter function dysfunction dysfunction

IVTR ↓ ↑ ↓

E/A ratio ↑ ↓ ↑

DT ↓ ↑ ↓

S/D pulm veins ↓ ↑ ↓

+ age dependence

Systolic dysfuction

EF < 50%

Ma=100 ms PVa=165 ms

0.5

0.5

Mitral flow velocity LV pressure

Pulmonary vein

25 mm Hg

Pulmonary venous flow pattern and filling pressures

EF <50%

S/D <1 Systolic fraction < 40%

Increased PCWP

Any EF

Ar duration > 30msec from A duration

Increased LVEDP

Asymptomatic NYHA III Recurrent Hospitalizations

NYHA II

?

The Valsalva Maneuver

Baseline Strain

A decrease of >50% in the E/A ratio is highly specfic for increased fillinig pressures

A decrease of 20cm/sec in mitral peak E velocity is considered an

adequate effort

Pseudonormalization impaired relaxation

Normal normal

How abnormal is myocardial relaxation?

Color M-mode flow propagation velocity Tissue Doppler

Annular velocities

Global longitudinal SR IVRT Time interval between

E and e’

Tissue Doppler longitudinal Annular Velocities and Hemodynamics

Recoil (systolic force)

Residual crossbridge interaction

(Impaired Relaxation)

Lengthening load (filling pressures and geometry) (+)

(-) (+)

LVEDP (-)

LA contraction(+)

When relaxation is impaired especially with

normal EF

e’ is reduced and delayed

14

12

10

8

6

4

2

0 0 2 4 6 8 10

Tau <50

Tau >50

e’ vs Maximal Instantaneous Transmitral Pressure Gradient Divided According to Tau

Maximal transmitral pressure gradient (mmHg)

e’ cm/sec

Nagueh et al: JACC 37(1): 226-85, 2001

Mitral flow

Mitral annulus velocity

Clinical Application in patients with cardiac disease

e’ as a surrogate of LV relaxation

Most patients with e’ (lateral) < 10cm/sec or

e’ (septal) < 8cm/sec have impaired myocardial relaxation

E/e’ ratio as predictor of LV filling pressures

Transmitral E velocity depends on LA pressure, relaxation kinetics and age Mitral annular e’ velocity depends on relaxation kinetics and age. The E/e’ ratio eliminates the effect of relaxation and age

E/e’ ratio for the prediction of LV filling pressures

E/e’ < 8 associated with normal filling pressures E/e’ > 15 associated with increased filling pressures E/e’ between 8 – 15 other echo indices should be used

When using lateral or average values lower cutoff (12 for lateral and 13 for average) should de used for

increased filling pressures

Omen et al Circ 2000

? E/e’= 7 E/e’ = 20 E/e’= 16

E/e�!and!diastolic!func5on!

E/e� E/e� is unreliable in Normal health people (e� preload dependent)

MItral stenosis/regurg/calcification/prosthetic valves

Hypertrophic cardiomyopathy

Severe LV systolic dysfunction ( e� load dependent)

Constictive pericarditis (annulus paradoxus)

E/e’ works were we need it most, in patients with Heart Failure and normal EF

E /e’ and prognosis

After Acute MI Hillis JACC 2004

Cardiomyopathies (Ishaemic , Dilated) Troughton AJC 2005, Yamamoto JASE 2003

Wang JACC 2005, Dokainish JACC 2005

Secondary MR Bruch AJC 2007

Hypertensive heart disease Wang J Hypertens 2005

Sharp AS Eur Heart J 2010

Atrial fibrillation Okura Heart 2006

End stage Renal disease Sharma JASE 2006

Color M-Mode flow propagation Velocity (Vp)

Slope of the first aliasing velocity during early filling Normaly Vp > 50cm/sec

Index of relaxation (inverse relation to τ) and load

independent but only in patients with depressed EF

Patients with normal LV

volumes and EF but elevated filling pressures can have misleadingly normal Vp (dependency of load,

geometry ,contractile function)

E / Vp ≥ 2,5 Predicts elevated filling pressures in patients with depressed EF when other

indices appear inconclusive

Time interval between onset of the E and onset of the e’

When myocardial relaxation in normal both E and e’ coincided with the crossover of the LA-LV pressure.

When relaxation is abnormal the e’ is reduced and delayed and occurs after LA-LV pressure crossover (asymmetrical longitudinal LV expansion) T E-e’ is an index of impaired relaxation (directly related to τ)

IVRT / T E-e’ ratio < 2

Predicts increased filling pressures Useful when: - E/e’ is inconclusive -  In mitral valve diseases

Rivas-Gotz JACC 2003

Global longitudinal SR IVRT by 2D speckle tracking

Index strongly dependent on LV relaxation

E/ SR IVRT > 236

Predicts increased filling pressures Useful when : -E/e’ is inconclusive, -EF is normal -In patients with regional dysfunction

Wang J Circulation 2007

Heart failure symptoms with normal EF restrictive filling pattern, IVC dilatation

1.Increased thickness yes no 2.Septal fluttening yes no 3.Mitral inflow respiratory yes no variation 4.Hepatic vein expiratory yes no diastolic flow reversal

1.Ventricular septal Strain normal reduced 2. Septal annular e� > 7cm/sec yes no 3. E/E�� normal Increased

Abnormal Pericardium

Normal Myocardium

Constrictive Restrictive

Special populations

Conclusions)

•  Tradi5onal!doppler!indices!are!usually!adequate!for!the!evalua5on!of!filling!pressures!in!pa5ents!with!low!EF.!

•  A!relaxa5on!index!(usually!e’)!mast!be!added!in!pa5ents!with!normal!EF!

•  Diastolic!func5on!assessment!should!always!consider!all!available!echo!parameters!and!clinical!informa5on.!