Presentation on theme: "Assessment of Left Ventricular Systolic Function"— Presentation transcript:
1 Assessment of Left Ventricular Systolic Function Riya S. Chacko, MDMarch 4, 2009
2 Clinical Significance Clinical decisions based on systolic function -> MADIT II, SCDHeFT trials for ICD implantation for those with depressed EF with or without coronary diseaseHeart failure management including cardiac resynchronization therapyCoronary disease -> prognosis, evaluationUse of cardiotoxic medications such as some chemotherapeutic agentsSCDHeFT did not mandate imaging modality (echo 58, RNA 24%, and RVG 17% with no stat sign difference in survival despite sign. Differences in EF)Herceptin (Trastuzumab) should not be commenced in patients with EF <55%. Nor should it be continued in those with >10% drop in EF or to <50%
3 Definition of Ejection Fraction (EDV – ESV)/EDVOr stroke volume/EDV
4 Clinical Relevance of EF Variability Mean EF as measured by RNA was 25.1% ± 6.9%; byechocardiography, 23.8 ± 6.9%; and by angiography, 21.9 ± 6.9%. These measures were significantly different (P b .001),and each pairwise comparison differed significantly (P b .001 for each). Multivariable analysis showed no significantdifference in survival between patients enrolled based on RNA versus echocardiography (HR 1.06, 95% CI ), RNAversus angiography (HR 1.25, 95% CI ), or echocardiography versus angiography (HR 1.18, 95% CI ).Gula L. et al. Am Heart J 2008;156:
5 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)
6 CorrelationThe broader the range of values studied (ie EF) the higher the r value or correlation even though agreement may not differ (McGowan)Bland JM, Altman DG. (1986). Statistical methods for assessing agreement between two methods of clinical measurement. Lancet, i,
7 AgreementBland JM, Altman DG. (1986). Statistical methods for assessing agreement between two methods of clinical measurement. Lancet, i,
8 (1) Naik MM. J Am Coil Cardiol 1995;25:937-42) Note Starling had intermediate correlation at 0.81 but broad range of agreement from 26 to 20.8 and Folland although had narrower agreement had lower correlation coefficient(1) Naik MM. J Am Coil Cardiol 1995;25:937-42)
9 Imaging Modalities Used to Assess LV Systolic Function 2D EchocardiographyContrast echocardiography3D EchocardiographyRadionuclide ventriculography (MUGA, ERNA, RNA)MRIGated SPECTCTContrast cineventriculography (ventriculogram on catheterization)Myocardial Strain, Simpson’s Rule, Displacement
10 2 Dimensional EchoDepends on identification of endocardial border and image qualityMany methods of assessing LV systolic function both qualitative and quantitativeVisual 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 agentsWMI scores each segment : 1 normal motion or hyperkinesia, 2 hypokinesia,3 akinesis, 4 dyskinesia, 5 aneurysmal.Regional wall motion is scored in all standard 2 views. 9-segment model, LVEF = 30WMIVisual assessment and WMI may be as good if not better (McGowan) at assessing EF in those with RWMA or poor echo pictures but less accurate in afib.
11 Simpson’s Rule http://depts.washington.edu/cvrtc/simplvgm.html Known as the “disc summation method” allows volume estimates based on 2D pictures. Trace the endocardial border in 2 orthogonal planes (apical 4 and 2 chamber) or 1 view. It is the recommended echo way to assess EF.Assumes symmetric geometry and studies that proved its accuracy were mostly performed in people with preserved EFs (>40%).Interestingly, in post-MI studies, visual estimation of EF (based on regional WMA) had better correlation and agreement than Simpson’s Rule. Therefore, less useful in poor EF, RWMA (post-MI) or dilated CM.
12 Concepts of LV StrainDefined as (L-Lo)/Lo where L is the length at the end of systole and Lo is the original lengthMeasure tissue deformationMay be obtained through M-mode, tissue doppler or speckle trackingAs 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 strainStrain rate, more a measure of contractility than regional EF (strain), is less dependent on loading conditions.
13 Ping Sun J et al. (J Am Soc Echocardiogr 2004;17:132-8.) Regression calculation gives strain rate curveIntegrate C to get D (strain)Ping Sun J et al. (J Am Soc Echocardiogr 2004;17:132-8.)
14 LV Strain Rate Defined as Va-Vb/L Velocity at point (a) Velocity at point (b)L is the distance between both points
15 Normal Values of Systolic Myocardial Strain Normal longitudinal systolic strain in most segments varies from 15% to 25%, with normal radial strains ranging from50% to 70%, and standard deviations of 5% to 7% (22). Normal resting values for longitudinalSR vary between 1.0/s and 1.4/s, with the standarddeviation in most locations ranging from 0.5/s to 0.6/s.Ping Sun J et al. (J Am Soc Echocardiogr 2004;17:132-8.)
16 Limitations of LV Strain Limited by noise measurementsAngle of the doppler must be parallel to the myocardium and thus, useful only in the long axisAngles changes during cardiac cycle and respiration
17 Speckle Tracking Based on B-mode harmonics Tracks characteristic speckle patterns based on interference from ultrasound waves and myocardiumAngle-independent
19 Speckle vs. MRI Amundsen BH et al. (J Am Coll Cardiol 2006;47:789 –93) Amundsen et al showed in a study of 9 mongrel dogs, that speckle and MRI tagging had good correlationAmundsen BH et al. (J Am Coll Cardiol 2006;47:789 –93)
20 Advantages of 2D Echo No radiation exposure Portable Accurate assessment of regional wall motion abnormalitiesImage acquisition not limited by presence of arrhythmiasAssessment of other cardiac structures (ie valves, etc)Although not limited by arrhythmias, EF is influenced by, for example, presence of afib. Among studies of subjective visualassessment, 95% CIs were 19% to 24% versus16% to 18% in groups with and withoutatrial fibrillation subjects, respectively.Methodological differences. (McGowan)
21 2D Echo Limitations Poor test-retest reliability Geometric assumptions Dependence on variable loading conditionsImage quality – operator dependent and poor endocardial borders in 5-10% (12)Although effective for single assessment, less producible with serial assessmentsDependent on image quality, loading conditions, off-axis cuts, and geometricExample of systolic function dependent on loading conditions: inaccurately high EF with mitral regurgitation or low EF with severe aortic stenosisImprovements include harmonic imaging and contrast (enocardial border)
22 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,
23 Contrast Echocardiography Utilizing microbubbles or fluorcarbon gas to stabilize bubbles such as Optison or SonovueMajor clinical use at this time is to assess LV function by enhancing endocardial bordersEspecially 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)Michael Stewart. Contrast echocardiography.
24 A = end diastole, B = end=systole in a patient with a recent MI where lateral wall not visualized. C and D with contrast showing lateral wall thickening.Hoffman et al found that the mean difference btwn echo and MRI differed by less than 5% and that correlation increased from 0.60 to 0.77 with addition of contrast
25 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)
26 Hoffmann R et al. (J Am Coll Cardiol 2006;47:121– 8) Comparison of all 4 modalities showed an inferior/inferolateral WMA that was not detected on 2D echo without contrast due to poor visualization.In this study, contrast echo showed an improved agreement with MRI as compared to NCE. Hoffman also demonstrated an increase in interobserver agreement with CE vs. NCE. MORE DETAILS OF TRIAL !!!Hoffmann R et al. (J Am Coll Cardiol 2006;47:121– 8)
27 Hundley et al. J Am Coll Cardiol 1998;32:1426 –32. In this study by Hundley et al from UTSW and UNC, a total of 35 patients underwent both MRI and echocardiography and they found correlation coefficients of >0.92.However, with the addition of contrast, the limits of agreement narrowed. Moreover, they found that CE was most helpful in increasing the accuracy for LVEF quanitification in patients with intermediate EFs btwn 25 and 50%.Hundley et al. J Am Coll Cardiol 1998;32:1426 –32.
28 Table from Dr. Vinay Bhatia in his review of contrast echocardiography demonstrating trials that have shown consistent increased agreement between CE and MRI (often gold standard)Bhatia et al Journal of the American Society of Echocardiography May.
29 3D EchocardiographyAttempts to use 3D echo rely on less geometric assumptions as compared to 3D echo3D analysis minimizes variation in EF assessment
30 Limitations of 3D Echo Large hearts (increased LV volume) Image quality - Inability to differentiate endocardial borders
31 Intra and Inter-observer variability In this study, 50 patients underwent 2D and 3D echo + MRI. Retest variation was observed within 1 hour by complete repeat of exam by a different ultrasonographer. LV volume was statistically underestimated by 2D (less so by 3D) but ejection fraction by all 3 methods was similar.Jenkins et al.
32 3D versus 2D as compared to MRI Both 2D and 3D underestimate LV mass but 3D less so.Jenkins et al.
33 CMR versus 3D Echo Soliman O et al. Am J Cardiol 2008;102:778 –783 Linear regression from a sample of 24 patients (both ischemic, idiopathic and healthy) showing correlation by CMR and 3D echo for LVEF.Inter-observer variability was 7.6% for LV ejection fraction, and intra-observer variability was 6.0%.Soliman O et al. Am J Cardiol 2008;102:778 –783
34 Contrast 3D Echocardiography 39 patients with 3D echo with and without contrast as well as MRI within the same day, After contrast agentenhancement, mean image quality index improved from to (p <0.001).Contrast agent–enhanced RT3DE measurements showed better correlation with MRI (LVend-diastolic volume, r vs 0.86; LV end-systolic volume, r vs 0.94; LV ejectionfraction, r vs 0.81). The limits of agreement (Bland-Altman analysis) showed asimilar bias for RT3DE images with and without contrast agent but with smaller limits ofagreement for contrast agent–enhanced RT3DE. Also, inter- and intraobserver variabilitiesdecreased. In a subgroup, patients with poor to moderate image quality showed animprovement in agreement after administration of contrast agent (24.4% to 12.7%) tothe same level as patients with moderate to good image quality without contrast agent(10.4%).Krenning et al.
35 Radionuclide Angiography Introduced in the 1970s as a “gold standard” against invasive ventriculography for accurate assessment of LV functionTechnetium-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).
36 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 dysplasiaAortic regurgitationCardiac resynchronization therapyLung transplantation candidates : RV assessmentTechnetium 99m-pertechnenate is then injected 30 min. later, diffuses across RBC and binds to Hgb. Stannous agent serves as chelator. If pertechnenate is reduced out RBC, cannot diffuse across and instead has high background activity.RBC labelling may be affected by certain drugsB. Hesse et al. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging (2008) 35:851–885
37 RVGNormal 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 EFEF can also be assessed during exerciseNo assumptions made about geometryUsually bike exercises
43 Best correlation of EF by CVG and RNA is EF less than 55% Best correlation of EF by CVG and RNA is EF less than 55%. Correlation coefficient of 0.86 and Folland reported CC of serial exams was 0.92Folland et al.
44 Bellenger et al. compared RVG vs 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 (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%.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%.
45 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 measurementShows a high level of reproducibilityAdvantages include: lack of radiation exposure,avoidance of contrast media injection, and excellent temporal and acceptable spatial resolutionWays to overcome inaccuracies of MRI and volume are increasing the number of disks and thus decreasing the thickness of each one.
46 Limitations of Cardiac MRI ExpenseAvailabilityLimited use in cardiac patients with defibrillators/pacemakers and heart failure
47 Cardiac CTIn 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 %; p ) and Echo ( 11.0% vs %; p ).For the end-diastolic and end-systolic volumes, the limits of agreement with CVG (p ) and Echo (p and p 0.02, respectively) were also significantly larger than with MSCT.Radiation varies from 1-2 mSv2Sievert
48 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 and p ), whereas MSCT and Echo were not significantly different in identifying patients with abnormal regional function.
49 In a study of 88 patients, MSCT, CVG and echo within 48 hours. Dewey et al.
50 Short axis views when endocardial and epicardial borders are identified and used to identify thickness, ESV and EDV,MDCT may underestimate EF 1-7% compared to CMR (Juergens).The inter-observer variability was from 2% to11% for LV-EDV and from 6% to 9% for LV-ESV (Fig. 12);corresponding values for CMR are 2–6%
51 Intraobserver Variability On second analysis, 90% of patients were assigned to the same category with statistically “good agreement”.For the 29 randomly selectedpatients who had intraobserver variability of MSCT analyzedafter an interval of at least 6 months, the limits ofagreement for ejection fraction, end-diastolic volume, endsystolicvolume, and myocardial mass were 4.8%, 15.6ml, 8.0 ml, and g, respectively, demonstrating alow variability for MSCT.As compared to MRI, the sensitivity to detect regional wall motion dysfunction was 75% for MSCT versus 38% for VgramAccuracy of MSCT was 94.9% and specificity was 96.8%Dewey et al also found that while echo and MSCT had no statistical differences in detecting regional abnormalities, there was a stat difference in the agreement of LVEF and was superior in MSCT.Noncontrast echo versus MRI shows limits of agreement of 21% and with contrast, reduced to 17%. Dewey et al showed agreement of 10% with MSCT.Dewey et al.
52 Limitations of Cardiac CT Poor temporal resolution and radiation exposure have limited use of MDCT to assess LV functionDecremental decrease in image quality in systole
53 Brodofoel used a dual-source CT to improve temporal resolution in 20 patients A and B are from dual source CT and C and D from MRI. Measurements shown in end diastole and end systole.
54 Statistical Correlation of EF by MRI and CT Very good agreement of 96.7% myocardial segments for regional wall motion abnormalities.Brodofoel et al.
55 Agreement between Regional Wall Motion Dysfunction A study from MGH showed Bland-Altman analysisrevealed a trend of multidetector CTslightly underestimating LV EF comparedwith TTE (mean difference, 2% 12)(Fig 2). The interobserver reliability forassessment of global LV EF with multidetectorCT was excellent (r 0.83).The interobserver reliability for assessmentof global LV EF with echocardiographywas good (r 0.68) (Fig 3). Bland-Altman analysiswas good (r 0.68) (Fig 3). Cury et al. Although the temporal resolution ofmultidetector CT (82–165 msec) is stillinferior to that of TTE, we found thatabnormal systolic function in terms ofRWM could be discerned in almost allcases of MI. Further, multidetector CTwas not limited by poor acoustic echocardiographicwindows. It is also importantto point out that the detection ofacute MI in patients by using multidetectorCT was not inferior to that of TTE(similar accuracy of 96%) and that theinterobserver reliability for EF quantificationwas better with multidetector CT(r 0.83), as compared with TTE (r0.68).Brodofoel et al.
56 Gated SPECTUtilizes 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
58 Correlation between Thallium and MIBI Germano G et al.
59 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 < )J Nucl Med 2000; 41:
60 Analyzed 3 computer models from SPECT to assess EF versus echo. Reproducibility of SPECT image inversionejection fractions was excellent (intraobserver r = 0.99, interobserverr = 0.93). Williams et al.
61 Gated SPECT Disadvantages Limited by arrhythmias by ECG-gating (22)Attenuation, fixed perfusion defects may incorrectly underestimate wall thickening and thus underestimate LVEFRadiation exposure equals that of an RVG
62 CVGBiplane 30 degrees RAO and 60 degrees LAO or single view
63 Left ventricle assumed to be an ellipsoid 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 mLLeft ventricle assumed to be an ellipsoidGrossman and colleagues in 1978 proved that the volume calculcated by CVG correlated well with post-mortem casts made of the LV.Fifer MA and Grossman W.
64 Initial comparisons to MRI Stratemeier et al compared 22 patients undergoing Vgram and cine MRI within 3 days. See correlation between EFs.Stratetmeier et al.
65 Confirmed by Utz et al.Difference between EF by MRI and CVG by Hoffman et al was 5.8%. Hoffman R et al found a large inter-observer variability with CVG bringing into question role of EF assessment (European Heart Journal (2005) 26, 607–616)Difference between EF by MRI and CVG by Hoffman et al was 5.8%. MRI and CVG had only moderate agreement. CVG overestimated EDV and ESV.
66 Limitations of CVG Radiation exposure Invasive risk of procedure Geometric assumptions on biplane viewContrast medium risk
67 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.
68 Imaging Modalities Used to Assess LV Systolic Function 2D EchocardiographyContrast echocardiography3D EchocardiographyRadionuclide ventriculography (MUGA, ERNA, RNA)MRIGated SPECTCTContrast cineventriculography (ventriculogram on catheterization)Myocardial Strain, Simpson’s Rule, Displacement
70 Soliman O. I. I. , Kirschbaum SW, et al 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)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.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 AmColl Cardiol 2006;48:2034–44.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.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:Juergens KU, Fischbach R. Left ventricular function studied with MDCT. Eur Radiol (2006) 16: 342–357Jenkins C, Bricknell K, et al. Comparison of Two- and Three-Dimensional EchocardiographyWith 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)
71 Soliman OII, Kirschbaum SW, et al 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.Khandheria BK. Noninvasive Imaging. J Am Coll Cardiol Vol. 45, No : 17B-9B.Gula LJ, Klein GJ, et al. Ejection fraction assessment and survival: An analysis ofthe Sudden Cardiac Death inHeart Failure Trial (SCD-HeFT). Am Heart J 2008;156:Stratemeier EJ, Thomspon R, et al. Ejection Fraction Determination by MR Imaging: Comparison with Left Ventricular Angiography. Radiology 1986;158:Utz JA, Herfkens RJ, et al. Cine MR Determination of Left Ventricular Ejection Fraction. AJR 148: , May 1987.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.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;Nichols K, Dorbala S, et al. Influence of Arrhythmias on Gated SPECT Myocardial Perfusion and Function QuantificationJ Nucl Med1999;40: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:
72 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)B. Hesse et al. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging (2008) 35:851–885.Germano G et al. Quantitative LVEF and Qualitative Regional Function from Gated Thallium-201 Perfusion SPECT. J NucIMed1997;3&Bellenger et al. (European Heart Journal (2000) 21, 1387–1396)