Transcript Diastolic LV function and diastolic heart failure

DIASTOLIC LV FUNCTION AND
DIASTOLIC HEART FAILURE
Dr.Deepak Raju
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
• Treshold value to define normal Vs reduced EF
is arbitrary;consensus is for using 50% as cut
off
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)
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)
Owan T
nejm 2006
• Survival for HF with reduced EF have
improved over time ,but not for HF nl EF
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
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
• 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
Phases of diastole
– Isovolumic relaxation
– Early rapid filling phase
• 70 to 80 % of LV filling
• Driven by LA LV pressure gradient
• Dependent on
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Myocardioal relaxation
LV elastic recoil
LA pressures
Mitral orifice area
– Diastasis
• LA LV pressures almost equal
• 5% of LV filling
– Atrial systole
• 15 to 25 % of LV filling
• Depends on atrial preload,afterload and inotropic state
Pressure volume relationship
• Upward shift in diastolic pressure volume
relation –increased LV diastolic stiffnesshigher diastolic pressure required for filling
• Downward shift-decreased stiffness
• 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
Indices of LV diastolic relaxation
• Isovolumic pressure decay
– Max rate of LV pressure decline after aortic valve
closure in IVR phase measured(peak neg dP/dt)
– Affected by loading conditions
• Time constant of relaxation
– Load independent measure
– Rate of LV pressure decay during isovolumic
relaxation
• 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
Echocardiography
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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
Doppler echocardiography
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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
Mitral inflow (left) and pulmonary venous flow (right)
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
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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
Doppler parameters in different age
groups
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
• 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
Grade 2 –moderate diastolic
dysfunction
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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
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.
• 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
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
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
• 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
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
• 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
• AF
– AF in 20-40 % of pts with diastolic dysfn
– AF may cause decompensation in pts with HF nl EF
• Obesity
– 30-50% of pts
– Risk for HTN,DM,CAD,AF-contribute to diastolic
dysfn
• Diabetes
– Prevalence similar in both forms of HF
– Structural changes
• Myocyte hypertrophy
• Increased extracellular matrix
• Intramyocardial microangiopathy
• Renal dysfn
– No diff in both forms of HF
– b/l RAS with rapid onset pul edema is a cause of HF nl
EF
• Rare causes
– Hypertrophic cardiomyupathy
– Infiltrative cardiomyopathies
– Ideopathic restrictive cardiomyopathy
– Radiation heart disease
• Pulmonary HTN
– Prevalence is 86%
– a/w decreased survival
– Cause is resting or exertional pul venous HTN
Factors causing a/c decompensation
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Uncontrolled HTN
Arrhythmias
ischemia
Infection,anemia
Dietary changes
Treatment
• DIG trial(Ahmed A,circulation 2006 )
– Digoxin did not alter primary endpoint of HF
hospitalisation+CV mortality
– Reduced HF hospitalisation
– Increased total CV hospitalisation due to increase
in UA
• CHARM –preserved trial(Yusuf S,Lancet 2003)
– HF with EF>40%
– Candesartan reduced prim end pt-CV death or HF
hospitalisation
• I-PRESERVE(Massie BM ,NEJM 2008)
– 4128 pts,EF>45%,NYHA ii-iv
– No effect on any outcome(all cause mortality+CV
hospitalisation,death from HF or hospitalisation
for HF)
• PEP-CHF(eur heart journal 2006)
– Perindopril Vs placebo,age >70,HF nl EF
– All cause mortality+HF hospitalisation
– No benefit inprimary end pt
– Trend towards reduced HF hospitalisation
• Hong Kong diastolic heart failure study
– Diuretics,diuretic +irbesartan,diuretic +ramipril
– Hospitalisations,6 min walk ,QOL similar
• TOPCAT-spiranolactone
• RELAX-sildenafil
• RESET-atrial pacing
Guidelines
• Class I
– Control HTN
– Control ventrcular rate in AF
– Diuretics for pulmonary congestion
• Class II a
– Revascularisation in whom ischemia is judged to
have an adverse effect on cardiac function
• Thank you