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. 2D Echocardiography 2. Contrast echocardiography3. 3D Echocardiography4. Radionuclide ventriculography (MUGA, ERNA,

RNA)5. MRI6. Gated SPECT7. CT8. 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

Krenning 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 forCVG ( 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%), end-diastolic 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. 2D Echocardiography 2. Contrast echocardiography3. 3D Echocardiography4. Radionuclide ventriculography (MUGA, ERNA,

RNA)5. MRI6. Gated SPECT7. CT8. Contrast cineventriculography (ventriculogram

on catheterization)

References1. Naik MM. J Am Coil Cardiol 1995;25:937-422. Ping Sun J et al. J Am Soc Echocardiogr 2004;17:132-8.3. R Senior et al. European Heart Journal (1994) 15, 1235-12394. Bhatia VK, Senior R. Contrast Echocardiography: Evidence for Clinical Use. Journal of the

American Society of Echocardiography May 2008. 409-416.5. 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

6. Hundley WG, Kizilbash AM et al. Administration of an Intravenous Perfluorocarbon Contrast Agent Improves Echocardiographic Determination of Left Ventricular Volumes and Ejection Fraction: Comparison With Cine Magnetic Resonance Imaging. J Am Coll Cardiol 1998;32:1426 –32.

7. Stewart MJ. Contrast echocardiography. Heart 2003;89;342-3488. Olszewski R, Timperely J, et al. The clinical applications of contrast echocardiography. Eur J

Echocardiography (2007) 8, S13eS23.9. Jenkins C, Bricknell K, et al. Reproducibility and Accuracy of Echocardiographic

Measurements of Left Ventricular Parameters Using Real-Time Three-Dimensional Echocardiography. (J Am Coll Cardiol 2004;44:878–86).

10. Soliman O.I.I., Kirschbaum SW, et al. Accuracy and Reproducibility of Quantitation of Left Ventricular Function by Real-Time Three-Dimensional Echocardiography Versus Cardiac Magnetic Resonance. (Am J Cardiol 2008;102:778 –783)

11. McGowan JH, Cleland JGF. Reliability of reporting left ventricular systolic function by echocardiography: A systematic review of 3 methods. Am Heart J 2003;146:388–97.

12. Dewey M, Muller M, et al. Evaluation of Global and Regional Left Ventricular Function With 16-Slice Computed Tomography, Biplane Cineventriculography, and Two-Dimensional Transthoracic Echocardiography Comparison With Magnetic Resonance Imaging. J Am

Coll Cardiol 2006;48:2034–44.

10. Henneman MM, Bax JJ, et al. Global and regional left ventricular function: a comparison between gated SPECT, 2D echocardiography and multi-slice computed tomography. Eur J Nucl Med Mol Imaging (2006) 33:1452–1460.

11. Brodoefel H, Kramer U, et al. Dual-Source CT with Improved Temporal Resolution in Assessment of Left Ventricular Function: A Pilot Study. AJR:189, November 2007: 1064-1070.

12. Juergens KU, Fischbach R. Left ventricular function studied with MDCT. Eur Radiol (2006) 16: 342–357

13. Jenkins C, Bricknell K, et al. Comparison of Two- and Three-Dimensional Echocardiography

With Sequential Magnetic Resonance Imaging for Evaluating Left Ventricular Volume and Ejection Fraction Over Time in Patients With Healed Myocardial Infarction. Am J Cardiol 2007;99:300–306)

14. Soliman OII, Kirschbaum SW, et al. Accuracy and Reproducibility of Quantitation of Left Ventricular Function by Real-Time Three-Dimensional Echocardiography Versus Cardiac Magnetic Resonance. Am J Cardiol 2008;102:778 –783.

15. Khandheria BK. Noninvasive Imaging. J Am Coll Cardiol Vol. 45, No. 11 2005: 17B-9B.

16. Gula LJ, Klein GJ, et al. Ejection fraction assessment and survival: An analysis of

the Sudden Cardiac Death inHeart Failure Trial (SCD-HeFT). Am Heart J 2008;156:1196-200.

14. Stratemeier EJ, Thomspon R, et al. Ejection Fraction Determination by MR Imaging: Comparison with Left Ventricular Angiography. Radiology 1986;158:775-777.

15. Utz JA, Herfkens RJ, et al. Cine MR Determination of Left Ventricular Ejection Fraction. AJR 148:839-843, May 1987.

16. Fifer MA, Grossman W. Measurement of Ventricular Volumes, Ejection Fraction, Mass, Wall Stress, and Regional Wall Motion. SECTION V: EVALUATION OF CARDIAC FUNCTION. Baim’s Cardiac Catheterization.

17. Cury RC, Nieman K, et al. Comprehensive Assessment of Myocardial Perfusion Defects,

Regional Wall Motion, and Left Ventricular Function by Using 64-Section Multidetector CT. Radiology: Volume 248: 2: 2008;466-475.

22. Nichols K, Dorbala S, et al. Influence of Arrhythmias on Gated SPECT Myocardial Perfusion and Function QuantificationJ Nucl Med1999;40:924-934.

23. Williams KA, Taillon LA. Left Ventricular Function in Patients With Coronary Artery Disease Assessed by Gated Tomographic Myocardial Perfusion Images Comparison With Assessment by Contrast Ventriculography and First-Pass Radionuclide Angiography. J Am Col Cardiol 1996;27:173- 81.

24. Krenning BJ et al. Comparison of Contrast Agent–Enhanced Versus Non-Contrast Agent–Enhanced Real-Time Three-Dimensional Echocardiography for Analysis of Left Ventricular Systolic Function. (Am J Cardiol 2007;100:1485–1489)

25. B. Hesse et al. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging (2008) 35:851–885.

26. Germano G et al. Quantitative LVEF and Qualitative Regional Function from Gated Thallium-201 Perfusion SPECT. J NucIMed1997;3&749-754.

27. Bellenger et al. (European Heart Journal (2000) 21, 1387–1396)