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Transcript
Assessment of Left Ventricular
Systolic Function
Riya S. Chacko, MD
March 4, 2009
Clinical Significance
• Clinical decisions based on systolic
function -> MADIT II, SCDHeFT trials for
ICD implantation for those with depressed
EF with or without coronary disease
• Heart failure management including
cardiac resynchronization therapy
• Coronary disease -> prognosis, evaluation
• Use of cardiotoxic medications such as
some chemotherapeutic agents
Definition of Ejection Fraction
• (EDV – ESV)/EDV
• Or stroke volume/EDV
Clinical Relevance of EF Variability
Gula L. et al. Am Heart J 2008;156:1196-200.
Correlation vs. Agreement
• Correlation coefficient describes the linear
relationship between 2 variables. Closer to 1 or 1 means stronger correlation.
• Difference between correlation coefficient and
agreement. Correlation coefficient (CC) may be
high with poor or moderate agreement (ie, EF
differs by 20%)
• One study shows high correlation between 2D
echo, RVG, and contrast left ventriculography
but only moderate agreement (1)
Correlation
Bland JM, Altman DG. (1986). Statistical methods for assessing agreement between
two methods of clinical measurement. Lancet, i, 307-310.
Agreement
Bland JM, Altman DG. (1986). Statistical methods for assessing agreement between
two methods of clinical measurement. Lancet, i, 307-310.
(1) Naik MM. J Am Coil Cardiol 1995;25:937-42)
Imaging Modalities Used to Assess
LV Systolic Function
1.
2.
3.
4.
5.
6.
7.
8.
2D Echocardiography
Contrast echocardiography
3D Echocardiography
Radionuclide ventriculography (MUGA, ERNA,
RNA)
MRI
Gated SPECT
CT
Contrast cineventriculography (ventriculogram
on catheterization)
2 Dimensional Echo
• Depends on identification of endocardial
border and image quality
• Many methods of assessing LV systolic
function both qualitative and quantitative
• Visual estimation using the 17 segment
model or wall motion index (WMI)
• Quantitative assessment using M-mode,
strain, displacement, speckle tracking,
Simpson’s Rule, use of contrast agents
Simpson’s Rule
http://depts.washington.edu/cvrtc/simplvgm.html
Concepts of LV Strain
• Defined as (L-Lo)/Lo where L is the length at the end of
systole and Lo is the original length
• Measure tissue deformation
• May be obtained through M-mode, tissue doppler or
speckle tracking
• As muscle contracts, it shortens in the longitudinal and
circumferential axis (negative strain) and lengthens in
the radial axis (positive strain). Taken from apex,
negative during systole and positive during diastole.
• Associated with loading conditions. Increased pre-load
increases strain, increased afterload decreases strain
Ping Sun J et al. (J Am Soc Echocardiogr 2004;17:132-8.)
LV Strain Rate
•
•
•
•
Defined as Va-Vb/L
Velocity at point (a)
Velocity at point (b)
L is the distance between both points
Normal Values of Systolic
Myocardial Strain
Ping Sun J et al. (J Am Soc Echocardiogr 2004;17:132-8.)
Limitations of LV Strain
• Limited by noise measurements
• Angle of the doppler must be parallel to
the myocardium and thus, useful only in
the long axis
• Angles changes during cardiac cycle and
respiration
Speckle Tracking
• Based on B-mode harmonics
• Tracks characteristic speckle patterns
based on interference from ultrasound
waves and myocardium
• Angle-independent
Speckle vs. MRI
Amundsen BH et al. (J Am Coll Cardiol 2006;47:789 –93)
Advantages of 2D Echo
• No radiation exposure
• Portable
• Accurate assessment of regional wall
motion abnormalities
• Image acquisition not limited by presence
of arrhythmias
• Assessment of other cardiac structures (ie
valves, etc)
2D Echo Limitations
• Poor test-retest reliability
• Geometric assumptions
• Dependence on variable loading
conditions
• Image quality – operator dependent and
poor endocardial borders in 5-10% (12)
Comparing RVG to Echo
• Echocardiography detected 14 out of 15 patients
• with LVEF <40%, as estimated by radionuclide
ventriculography (sensitivity=93%), and 32 out of
34 patients with LVEF >40%, as estimated by
radionuclide ventriculography (specificity=94%).
The overall accuracy of echocardiography in
identifying patients with a low ejection fraction
was 94%.
• But test-retest correlation much lower for 2D
echo than other modalities such as 3D echo (22)
R Senior et al. European Heart Journal
(1994) 15, 1235-1239
Contrast Echocardiography
• Utilizing microbubbles or fluorcarbon gas to stabilize
bubbles such as Optison or Sonovue
• Major clinical use at this time is to assess LV function by
enhancing endocardial borders
• Especially in those with less than 80% of endocardial
border identified or those in ICU setting (mechanical
ventilation)
• It is believed that 37% more diagnostic information may
be obtained with contrast and even up to 50-90%
improvement if poor echo windows in non-contrast
studies (4)
Assessment of Regional Wall
Motion
• 8 European Centers enrolled 100 patients to each have
CVG, contrast echo and MRI within 72 hours of each
other for LV assessment.
• Interobserver agreement expressed as kappa coefficient
was 0.41 (range 0.37 to 0.44) for unenhanced
echocardiography, 0.43 (range 0.29 to 0.79) for cMRT,
0.56 (range 0.44 to 0.70) for cineventriculography, and
0.77 (range 0.71 to 0.88) for contrast echocardiography.
• Accuracy to detect EPD-defined RWMA was highest for
contrast echocardiography, followed by cMRI,
unenhanced echocardiography, and
cineventriculography.
Hoffmann R et al. (J Am Coll Cardiol 2006;47:121– 8)
Hoffmann R et al. (J Am Coll Cardiol 2006;47:121– 8)
Hundley et al. J Am Coll Cardiol 1998;32:1426 –32.
Bhatia et al Journal of the American Society of Echocardiography May 2008. 409-416.
3D Echocardiography
• Attempts to use 3D echo rely on less
geometric assumptions as compared to
3D echo
• 3D analysis minimizes variation in EF
assessment
Limitations of 3D Echo
• Large hearts (increased LV volume)
• Image quality - Inability to differentiate
endocardial borders
Intra and Inter-observer variability
Jenkins et al.
3D versus 2D as compared to MRI
Jenkins et al.
CMR versus 3D Echo
Soliman O et al. Am J Cardiol 2008;102:778 –783
Contrast 3D Echocardiography
Krenn
ing et
al.
Radionuclide Angiography
• Introduced in the 1970s as a “gold standard”
against invasive ventriculography for accurate
assessment of LV function
• Technetium-labeled erythrocytes or albumin
• “Pre-tinned” with a stannous agent (Sn+2) which
crosses easily across the RBC membrane and
binds to cellular components. Serves as
chelating agent for technetium- 99m
pertechninate (binds to hemoglobin)
• Certain drugs interfere with RBC labeling such
as: doxorubicin and epirubicine. No interactions
with human serum albumin (HSA).
RVG
• Two types: first pass and equilibrium gated RNA
or MUGA
• Radionuclide ventriculography is used for
assessment of dilated cardiomyopathies in
presence of cardiotoxic drugs (chemotherapy)
• Right ventricular dysplasia
• Aortic regurgitation
• Cardiac resynchronization therapy
• Lung transplantation candidates : RV
assessment
B. Hesse et al. EANM/ESC guidelines for radionuclide
imaging of cardiac function. Eur J Nucl Med Mol Imaging
(2008) 35:851–885
RVG
• Normal values are center-dependent (ie, could
range from 35-75% as normal)
• EF assessed by creating ROI (region of interest)
around LV at end-diastole and then background
ROI at end-systole.
• A time activity estimated stroke volume using
EDV and ESV is used to calculate EF.
• Highly reproducible quantification of EF
• EF can also be assessed during exercise
• No assumptions made about geometry
http://www.stocktonmri.com/Images/smallmuga06.gif
RVG
Folland EG et al. JNuclMed 18: 1159-1166, 1977
First Pass RVG Technique
Limitations of RVG
• Radiation dose 4.9-5.6 mSv.
• Relative contraindication in pregnancy and
lactating women.
• In MUGA, there is an overlap of cardiac
chambers (vs. first pass)
Folland et al.
• Bellenger et al. compared RVG vs. 2D echo
(Simpson and M-mode) and cardiac MRI to
assess LVEF and found a statistical difference
between all except Simpson 2D and MRI.
• Naik et al reported variation of echo EF of 40%
with EF of 20-60% by RNA despite an excellent
correlation coefficient of 0.86. (1)
• In Naik’s study, echo had an intra-observer
variability of 4.4% and inter-observer variability
of 6.1%. RNA had 2.5% and 6.8%.
Cardiac MRI
• Assesses volume by a disk summation method.
• This may inaccurately include basal structures
such as the aortic root or left atrium at the level
of the mitral valve.
• Considered the “gold standard” for EF
measurement
• Shows a high level of reproducibility
• Advantages include: lack of radiation exposure,
• avoidance of contrast media injection, and
excellent temporal and acceptable spatial
resolution
Limitations of Cardiac MRI
• Expense
• Availability
• Limited use in cardiac patients with
defibrillators/pacemakers and heart failure
Cardiac CT
• In a study by Dewey et al, 88 patients underwent MSCT,
CVG and MRI. Echo was retrospectively analyzed in a
subset.
• Agreement was significantly superior for MSCT than for
CVG ( 10.2% vs. 16.8%; p 0.001) and Echo ( 11.0% vs.
21.2%; p 0.001).
• For the end-diastolic and end-systolic volumes, the limits
of agreement with CVG (p 0.001) and Echo (p 0.001
and p 0.02, respectively) were also significantly larger
than with MSCT.
• Radiation varies from 1-2 mSv2
• Intra-observer analysis of MSCT yielded limits of
agreement for ejection fraction ( 4.8%), enddiastolic volume ( 15.6 ml) and end-systolic
volume ( 8.0 ml), and myocardial mass ( 18.2 g).
• The accuracy in identifying patients and
myocardial segments with abnormal regional
function was significantly higher with MSCT
(84% and 95%) than with CVG (63% and 90%; p
0.002 and p 0.001), whereas MSCT and Echo
were not significantly different in identifying
patients with abnormal regional function.
Dewey et al.
Intraobserver Variability
Dewey et al.
Limitations of Cardiac CT
• Poor temporal resolution and radiation
exposure have limited use of MDCT to
assess LV function
• Decremental decrease in image quality in
systole
• Brodofoel used a
dual-source CT to
improve temporal
resolution in 20
patients
Statistical Correlation of EF by MRI
and CT
Brodofoel et al.
Agreement between Regional Wall
Motion Dysfunction
Brodofoel et al.
Gated SPECT
• Utilizes either thallium or technetium 99m tracers
such as tetrofosmin or sestamibi.
• Utilizes the concept of partial volume effect or
recovery coefficient which means the brightness
of the tracer varies with the thickness of the wall
(despite same level of tracer). Thus, in systole,
walls are brighter.
• Automated evaluation of EF using endo and
epicardial borders to create a 3D display
http://us.myoview.com/tech/images/gated_spect.jpg
Correlation between Thallium and
MIBI
Germano G et al.
SPECT vs. Echo
• Nichols et al compared SPECT to 2D echo
• By ANOVA, there were no significant
differences among ejection fractions
(EFs), but there were for volumes.
• Linear regression analysis comparing
gated SPECT and echocardiographic
volumes showed a nearly identical strong
correlation (r = 0.92; P < 0.000001 )
J Nucl Med 2000; 41:1308-1314
Gated SPECT Disadvantages
• Limited by arrhythmias by ECG-gating (22)
• Attenuation, fixed perfusion defects may
incorrectly underestimate wall thickening
and thus underestimate LVEF
• Radiation exposure equals that of an RVG
CVG
• Biplane 30 degrees RAO and 60 degrees
LAO or single view
• 15 to 60 frames per second (fps), and
radiographic contrast material is usually
injected into the left ventricle at rates of 7 to 15
mL/ sec for a total volume of 30 to 50 mL
• Left ventricle assumed to be an ellipsoid
Fifer MA and Grossman W.
Initial comparisons to MRI
Stratetmeier et al.
Limitations of CVG
•
•
•
•
Radiation exposure
Invasive risk of procedure
Geometric assumptions on biplane view
Contrast medium risk
In Summary…
• Many different imaging modalities used to
assess EF.
• However, EF interpretation is not
interchangeable among the studies
despite good correlation.
• Choice of modality should reflect
understanding of intra and inter-observer
variability.
• Exposure to radiation also a consideration.
Imaging Modalities Used to Assess
LV Systolic Function
1.
2.
3.
4.
5.
6.
7.
8.
2D Echocardiography
Contrast echocardiography
3D Echocardiography
Radionuclide ventriculography (MUGA, ERNA,
RNA)
MRI
Gated SPECT
CT
Contrast cineventriculography (ventriculogram
on catheterization)
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
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Ping Sun J et al. J Am Soc Echocardiogr 2004;17:132-8.
R Senior et al. European Heart Journal (1994) 15, 1235-1239
Bhatia VK, Senior R. Contrast Echocardiography: Evidence for Clinical Use. Journal of the
American Society of Echocardiography May 2008. 409-416.
Hoffmann R et al. Analysis of Regional Left Ventricular Function by Cineventriculography,
Cardiac Magnetic Resonance Imaging, and Unenhanced and Contrast-Enhanced
Echocardiography: A Multicenter Comparison of MethodsJ Am Coll Cardiol 2006;47:121– 8) ©
2006
Hundley WG, Kizilbash AM et al. Administration of an Intravenous Perfluorocarbon Contrast
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