is normal ejection fraction equivalent to normal systolic...
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European Society of Cardiology copyright -All right reserved EAE course, Bucharest
Is normal ejection fraction equivalent
to normal systolic function?
D. Vinereanu
University of Medicine, Bucharest, Romania
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No
2nd criterion (out of 3) for the diagnosis of HFNEF:
“Normal or mildly abnormal systolic LV function”
Paulus et al. Eur Heart J 2007.
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Topics
How?
Why?
Implications?
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LV structure and function
PLAX A4C A2C
Radial Longitudinal Torsion
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Decreased longitudinal at rest
Systolic velocity (cm/s)
Yip et al. Heart 2002.
0
2
4
6
8
10
12
Systolic velocity (cm/s)
Vinereanu et al. Eur J Heart Fail 2005.
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Controls
Diabetics
Systolic velocity cm/s
0123456789
10
p < 0.01
Fang et al. Clin Sci 2004.Vinereanu et al. Clin Sci 2003.
Longitudinal Longitudinal
Increased radial at rest
Systolic velocity cm/s
Radial
p < 0.05
Radial
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Preserving EF
Vinereanu et al. JACC 2009 (abstr).
N = 246
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Why longitudinal but not radial?
1. LV longitudinal, but neither radial function or EF,
is related to arterial stiffness
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
Long S Long E PW S PW E EF*
*R
*p < 0.01
Vinereanu et al.
Heart 2003.
Beta
Epsilon
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2. Peak velocity
of radial
shortening of
the left ventricle
coincides with
arrival of
reflected waves
3. Generation of
longitudinal
shortening
persists against
reflections
Page et al.
Int J Cardiol 2009.
0 1 2 3 4
-5
0
5
10
15
20
FCW
BCW
FEW
50 70 90 110 130 150 170 190 310
-0.015
-0.01
-0.005
0
0.005
0.01
0.015
Radial
Long-
axis
Wave
intensity
in the
ascending
aorta
W/m2
Velocity of
shortening
m/s
Time ms
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Longitudinal/radial at stress
Vinereanu et al. JACC 2009 (abstr).
Longitudinal
systolic velocity
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Torsion at rest/stress
Tan et al. JACC 2009.
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But biphasic pattern Young Older Early HFNEF
Phan et al.
EJE 2009.
Park et al.
JASE 2008.
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Why increased in early stages?
1. Reduction of rotational deformation delay, because apical
rotation occurs later in systole, close to the peak basal rotation
(due probably to fibrosis of the conduction system);
2. Compensatory increase of the mid-wall and epicardial torque,
unopposed by the affected subendocardial longitudinal fibers.
Tan et al. JACC 2009.
Phan et al. EJE 2009.
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Summary
Systolic function in HFNEF Rest Stress
Longitudinal function
Radial function N/
Torsion (early stages)
(advanced stages)
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Mechanisms of HFNEF?
myocardial
(subendocardial) energetics
Myocardial
fibrosis
Neurohormonal
activation
Endothelial
dysfunction
Injury
Myocardial
ischaemia
Longitudinal systolic function
Radial & torsion (compensatory) Exercise/
stress All systolic parameters with recoil
Early/late diastolic filling
End-diastolic pressure (E/E’)
Breathlessness & BNP
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Myocardial energetics
Control HFNEF Phan et al.
JACC 2009.
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Implications?
Definition of HFNEF
Diagnosis
Prognosis
Treatment
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Definition of HFNEFSystolic velocity of long-axis function
Diastolic velocity of long-axis function
18161412108642
14
12
10
8
6
4
2
NormalDiastolic
heart
failure?
HFNEF
Systolic
heart
failure
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LV ejection fraction
Longitudinal
function
Radial
function
“Natural” history
LV velocities & deformation
Preserved ejection fraction = regional (long-axis) systolic dysfunction
Measuring only global function or radial Fr Sh is misleading
CHF
HF = continuous spectrum
HFNEF
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Diagnosis
“Assessment of longitudinal (subendocardial) systolic function
=
probably the most sensitive measure of ventricular function.”
Yip et al. Heart 2009.
Criteria to rule out heart failure
• LVEF > 50%• LVEDI < 76 ml/m2
• LAVI < 29 ml/m2• No atrial fibrillation• No LVH• No valvular/pericardial disease• E/E’ < 8
• Longitudinal S > 6.5 cm/s
Paulus et al. Eur Heart J 2007.
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Longitudinal S versus elevated BNPS
en
sit
ivit
y
1 - Specificity
1.00.75.50.250.00
1.00
.75
.50
.25
0.00
Longitudinal velocity
Radial velocity
Ejection fraction
Longitudinal
systolic velocity 0.94
Radial systolic
velocity 0.85
Global ejection
fraction 0.74
Receiver operating
characteristics AUC
Vinereanu et al. Eur J Heart Failure 2005.
Longitudinal S = best accuracy for the diagnosis of HF
(increased BNP)
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Prognosis (1)
Best predictor of mortality in the general population =
combined systolic & diastolic index Eas = E’/(A’+S’); HR = 1.71
Kaplan-Meier survival curves by tertiles of the eas index
Mogelvang et al. Circulation 2009.
N = 1036
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Prognosis (2)
Best predictor of mortality in HFNEF =
stress-corrected midwall fractional shortening (sc-mFS)
Borlaug et al. JACC 2009.
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Treatment
New targets: longitudinal function instead of EF
New assessment of “conventional” therapies:
• SRAA antagonists: ACEI, ARB
• Vasodilatatory BB: Nebivolol
Carvedilol
New strategies:
• Aldosterone antagonists: Spironolactone
Eplerenone
• Renin inhibitors: Aliskiren
• Endothelin receptor A antag.: Sitaxsentan
• AGE-products breakers: Alagebrium
• Metabolic agents: Ranolazine
Perhexiline
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Longitudinal strain & spironolactone
Mottram et al. Circulation 2004.
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Conclusions
1. Resting LV systolic function is impaired in patients with HFNEF:
• decrease of longitudinal function
• compensatory increase of radial function
• biphasic pattern of torsion
2. Functional reserve (longitudinal, radial, and torsion) is impaired
3. Mechanisms are related to inefficient ventriculo-arterial coupling
Diagnosis of HF as a continuum
• Assessment of long-axis
function most sensitive
• Exercise/stress might be
necessary
Treatment
• New targets
• New assessment of
conventional therapies
• New strategies
Prognosis
• Systolic function most
powerful