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European Journal of Echocardiography 2008 9(2):250-254; doi:10.1016/j.euje.2007.03.025
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Assessment of left ventricular ejection fraction after myocardial infarction using contrast echocardiography

Tjebbe W. Galema*, Marcel L. Geleijnse, Sing-Chien Yap, Ron T. van Domburg, Elena Biagini, Wim B. Vletter and Folkert J. Ten Cate

Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands

Received 30 November 2006; accepted after revision 16 March 2007; online publish-ahead-of-print 10 May 2007.

* Corresponding author: Department of Cardiology, Thoraxcenter, Room Ba 350, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel: +31 10 463 5356; fax: +31 10 463 5513. E-mail address: t.w.galema{at}erasmusmc.nl


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Aims: Despite its relatively high intra- and inter-observer variability for left ventricular ejection fraction (LV-EF) echocardiography is clinically still the most used modality to assess LV-EF. We studied whether adding a second-generation microbubble contrast agent could decrease this variability.

Methods and results: Forty-eight patients underwent transthoracic echocardiography in second-harmonic mode (SHI) with and without contrast within 5 days after an acute myocardial infarction. LV-EF was determined using the Simpson's biplane method. With contrast intra-observer variability decreased from 12.5 ± 11.5% to 7.0 ± 7.0% (P < 0.001) and inter-observer variability decreased from 16.9 ± 9.9% to 7.0 ± 6.2% (P < 0.001). Bland–Altman analysis confirmed these findings by demonstrating smaller 95% limits of agreement for both the intra- and inter-observer variability when contrast was used. This improvement in intra- and inter-observer variability was seen to a comparable extent in patients with moderate-to-poor and good quality SHI echocardiograms.

Conclusion: Echo contrast significantly improves intra- and inter-observer variability for LV-EF, both in patients with moderate-to-poor and good quality SHI echocardiograms.

Keywords: Echocardiography; Contrast; Ejection fraction; Myocardial infarction


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Left ventricular ejection fraction (LV-EF) after acute myocardial infarction (AMI) is an important marker for mortality.1,2 LV-EF may be assessed by nuclear imaging,3 magnetic resonance imaging4 and echocardiography.5 Nuclear imaging and magnetic resonance imaging provide relatively reliable information and with acceptable intra- and inter-observer variability.6,7 However, the use of these imaging modalities is limited by radiation exposure during nuclear imaging, high costs and non-availability in the coronary care unit and catheterization laboratory. Echocardiography is currently the most frequently used imaging modality for the assessment of LV-EF. However, echocardiographic images are sometimes of poor quality and in a recent review article high intra- and inter-observer variabilities were reported for echocardiographic LVEF assessment.5

Left ventricular opacification (LVO) with echo contrast has been shown to improve image quality and in particular endocardial border delineation8,9 and this may improve intra- and inter-observer variability. Therefore, we conducted a post-AMI trial in which LV-EF was assessed with second-harmonic imaging (SHI) and LVO.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Both SHI and LVO echocardiography were performed in 48 consecutive (regardless of image quality) patients within 5 days after primary angioplasty for AMI by one single experienced sonographer (W.B.V.). Imaging was performed using the Sonos 5500 system (Philips, Best, The Netherlands). SHI images were acquired with a transmitted frequency of 1.6 MHz and a received frequency of 3.2 MHz, mechanical index was 1.6 and frame rate 50 Hz. For LVO imaging mechanical index was 0.3 and frame rate 25 Hz. Contrast agent SonoVue (Bracco, Milan, Italy) was used. This contrast agent consists of stabilized sulfur hexafluoride micro bubbles surrounded by a phospholipid shell with a mean size of 2.5 µm.10 The contrast agent was given as a bolus of 0.5 ml with additional boluses of 0.25 ml when needed. Care was taken to record the images at a phase when contrast flow was relatively stable with absent or minimal swirling of contrast in the apex.

Non-foreshortened apical two- and four-chamber views were used for assessment of LV-EF (Figure 1). Manual tracing of LV end-systolic and end-diastolic frames was performed offline according to Simpson's method, recommended by the American Society of Echocardiography,11 using commercially available Enconcert software (Philips, Best, The Netherlands) by two experienced cardiologists (T.W.G. and E.B.). Papillary muscles were considered as part of the LV cavity, and thus included in LV volume.


Figure 1
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Figure 1 Four- and two-chamber image SHI (upper panel) and LVO (lower panel). In the SHI image the endocardium is only partially visible (arrow).

 
To determine the inter-observer variability for both SHI and LVO images, all measurements were repeated by a second observer (E.B.) blinded to the values obtained by the first observer (T.W.G.). To assess intra-observer variability, all measurements were repeated one month later by an observer (T.W.G.) blinded to the results of the previous measurements.

Endocardial border visualization was scored for 12 segments derived from the two- and four-chamber apical views in SHI mode to investigate if intra- and inter-observer variability was influenced by quality of SHI. Endocardial border visualization was scored according to a 3-level scoring system where 0 = border invisible, 1 = border visualized only partially throughout the cardiac cycle and/or incomplete segment length, and 2 = complete visualization of the border.9 An endocardial visualization score was calculated by adding the score of all 12 segments in every patient. On basis of the quality score two image quality groups were defined: good (score 19–24), and moderate-to-poor (score <19) quality echo.

The local ethics committee approved the study protocol and all patients gave written informed consent.

Statistical analysis
Continuous variables are expressed as mean ± standard deviation (SD). Intra- and inter-observer variabilities were calculated as the absolute difference between two measurements in percent of their mean. To test differences in intra- and inter-observer variability between techniques a paired t-test was used. A two-tailed P-value < 0.05 was considered statistically significant. In addition, Bland–Altman analysis was used to determine the 95% limits of agreement (1.96 SD) between measurements.12


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Patients
Baseline characteristics of all patients are summarized in Table 1. Mean age of the patients was 52 ± 13 years. The AMI-related coronary artery was the LAD in 54%, the RCA in 31% and the LCX in 15%. Multivessel disease was present in 48% of patients. Two of the 48 patients (4%) experienced mild hypotension, sinus tachycardia and skin flushing most likely caused by an allergic reaction of SonoVue. Both patients were successfully treated with intravenous clemastine and hydrocortisone.


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Table 1 Baseline clinical characteristics

 
Ejection fraction
Mean LV-EF for observer 1 was 47.1 ± 9.1% with SHI and 47.5 ± 8.3% with LVO. Intra-observer variability (expressed as absolute difference in percent of their mean) decreased from 12.5 ± 11.5% to 7.0 ± 7.0% (P < 0.001) with LVO. Inter-observer variability decreased from 16.9 ± 9.9% to 7.0 ± 6.2% (P < 0.001) with LVO (Table 2).


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Table 2 Intra- and inter-observer variabilities for ejection fraction measurements without and with contrast for the total population and as a function of image quality

 
In addition, Bland–Altman analysis confirmed these results by demonstrating smaller limits of agreement for LV-EF with LVO for both intra- and inter-observer variability (Figures 2 and 3).


Figure 2
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Figure 2 Intra-observer variability by Bland–Altman analysis for LV-EF. Left panel: SHI, right panel: LVO.

 


Figure 3
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Figure 3 Inter-observer variability by Bland–Altman analysis for LV-EF. Left panel: SHI, right panel: LVO.

 
Good and moderate-to-poor image qualities were present in 15 (31%) and 33 (69%) patients, respectively. As seen in Table 2 significant improvements in intra- and inter-observer variability were found for both image quality groups. Again this was confirmed by Bland–Altman analysis showing smaller limits of agreements with LVO regardless of image quality (figures not shown).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
LV-EF after AMI is an important marker for mortality and is becoming increasingly important because the selection of patients who benefit from an internal cardiac defibrillator is based on LVEF.1,2,13 Currently, echocardiography is the imaging modality most often used to assess LV-EF. However, echocardiography is limited by high intra- and inter-observer variability.5 Reliable contour detection of the LV is only possible if the endocardial border is visible during end-systole and end-diastole. Although SHI improves endocardial border detection compared to fundamental imaging,9 even in good quality echocardiograms it is sometimes difficult to delineate the endocardium in the still frames whereas with LVO this may be more reliable. So, in our study, SonoVue echo contrast further improved endocardial border detection in post-AMI patients resulting in a significant decrease in intra- and inter-observer variability for LV-EF. Our findings confirm the results published recently by others.14,15 In Figure 4, the intra- and inter-observer variabilities for LV-EF reported in studies using SHI and LVO imaging are summarized.14,16,17 Due to the consecutive character of patient inclusion in our study (no patient was excluded because of image quality) our SHI result seems worse than those reported by others. Although some authors showed an improvement in LV endocardial border detection with SHI compared to FI,9 optimal intra- and inter-observer variability in LV-EF can only be achieved when contrast is added to SHI imaging. In a study by Hoffmann et al., inter-observer variability between three readers from different institutions was best (even compared to MRI images and cineventriculography) with contrast-enhanced echocardiography and worst with unenhanced echocardiography.18


Figure 4
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Figure 4 Intra- and inter-observer variabilities for LV-EF reported in studies using SHI and LVO imaging.

 
In patients with moderate-to-poor image quality higher intra- and inter-observer variabilities were found for SHI imaging. However, the improvement with LVO imaging in intra- and inter-observer variabilities were almost similar in patients with moderate-to-poor and good image quality. These findings are in agreement with studies published by Malm et al.14 and Nayyar et al.,19 although Hundley et al.20 noticed improvement in LV-EF variability particularly in subjects with two or more adjacent endocardial segments not seen at baseline.

Unfortunately, we did not compare SHI and LVO LV-EF with a gold standard technique. However, several studies have shown an excellent correlation between LVO and magnetic resonance imaging.15,20,21 Furthermore, observers could not be blinded to the use of contrast or not.


    Conclusion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Assessment of LV-EF is more reliable with LVO imaging, evidenced by better intra- and inter-observer variability. Our study supports the concept that when LV-EF may influence clinical decision-making, LVO imaging should not be limited to patients with moderate-to-poor echocardiographic windows. This is in disagreement with the ASE Task Force Guidelines which recommend to use LVO only when at least 2 of 6 contiguous segments in a standard apical view are not visualized.22


    Acknowledgements
 
None of the authors has any conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med (1992) 327:669–77.[Abstract]
  2. Volpi A, De Vita C, Franzosi MG, Geraci E, Maggioni AP, Mauri F, et al. Determinants of 6-month mortality in survivors of myocardial infarction after thrombolysis. Results of the GISSI-2 database. The ad hoc working group of the gruppo italiano per lo studio della sopravvivenza nell'Infarto miocardico (GISSI)-2 data base. Circulation (1993) 88:416–29.[Abstract/Free Full Text]
  3. Senior R, Sridhara BS, Basu S, Henley M, Handler CE, Raftery EB, et al. Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction. Eur Heart J (1994) 15:1235–9.[Abstract/Free Full Text]
  4. Ioannidis JP, Trikalinos TA, Danias PG. Electrocardiogramgated single-photon emission computed tomography versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction: a meta-analysis. J Am Coll Cardiol (2002) 39:2059–68.[Abstract/Free Full Text]
  5. McGowan JH, Cleland JG. Reliability of reporting left ventricular systolic function by echocardiography: a systematic review of 3 methods. Am Heart J (2003) 146:388–97.[CrossRef][Web of Science][Medline]
  6. Benjelloun H, Cranney GB, Kirk KA, Blackwell GG, Lotan CS, Pohost GM. Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function. Am J Cardiol (1991) 67:1413–20.[CrossRef][Web of Science][Medline]
  7. Hyun IY, Kwan J, Park KS, Lee WH. Reproducibility of Tl-201 and Tc-99 m sestamibi gated myocardial perfusion SPECT measurement of myocardial function. J Nucl Cardiol (2001) 8:182–7.[CrossRef][Web of Science][Medline]
  8. Senior R, Andersson O, Caidahl K, Carlens P, Herregods MC, Jenni R, et al. Enhanced left ventricular endocardial border delineation with an intravenous injection of SonoVue, a new echocardiographic contrast agent: a European multicenter study. Echocardiography (2000) 17:705–11.[Web of Science][Medline]
  9. Kasprzak JD, Paelinck B, ten Cate FJ, Vletter WB, de Jong N, Poldermans D, et al. Comparison of native and contrast-enhanced harmonic echocardiography for visualization of left ventricular endocardial border. Am J Cardiol (1999) 83:211–17.[Web of Science][Medline]
  10. Schneider M. SonoVue, a new ultrasound contrast agent. Eur Radiol (1999) 9(Suppl. 3):S347–8.[CrossRef][Web of Science][Medline]
  11. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr (1989) 2:358–67.[Medline]
  12. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet (1986) 1:307–10.[CrossRef][Web of Science][Medline]
  13. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter automatic defibrillator implantation trial investigators. N Engl J Med (1996) 335:1933–40.[Abstract/Free Full Text]
  14. Malm S, Frigstad S, Sagberg E, Larsson H, Skjaerpe T. Accurate and reproducible measurement of left ventricular volume and ejection fraction by contrast echocardiography: a comparison with magnetic resonance imaging. J Am Coll Cardiol (2004) 44:1030–5.[Abstract/Free Full Text]
  15. Thomson HL, Basmadjian AJ, Rainbird AJ, Razavi M, Avierinos JF, Pellikka PA, et al. Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements: a prospective, randomly assigned, blinded study. J Am Coll Cardiol (2001) 38:867–75.[Abstract/Free Full Text]
  16. Hirooka K, Yasumura Y, Tsujita Y, Hanatani A, Nakatani S, Miyatake K, et al. An enhanced method for left ventricular volume and ejection fraction by triggered harmonic contrast echocardiography. Int J Card Imaging (2001) 17:253–61.[CrossRef][Web of Science]
  17. Yu EH, Sloggett CE, Iwanochko RM, Rakowski H, Siu SC. Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients. J Am Soc Echocardiogr (2000) 13:216–24.[Web of Science][Medline]
  18. Hoffmann R, von Bardeleben S, ten Cate FJ, Borges AC, Kasprzak J, Firschke C, et al. Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography. Eur Heart J (2005) 26:607–16.[Abstract/Free Full Text]
  19. Nayyar S, Magalski A, Khumri TM, Idupulapati M, Stoner CN, Kusnetzky LL, et al. Contrast administration reduces inter-observer variability in determination of left ventricular ejection fraction in patients with left ventricular dysfunction and good baseline endocardial border delineation. Am J Cardiol (2006) 98:1110–14.[CrossRef][Web of Science][Medline]
  20. Hundley WG, Kizilbash AM, Afridi I, Franco F, Peshock RM, Grayburn PA. 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.[Abstract/Free Full Text]
  21. Lim TK, Burden L, Janardhanan R, Ping C, Moon J, Pennell D, et al. Improved accuracy of low-power contrast echocardiography for the assessment of left ventricular remodeling compared with unenhanced harmonic echocardiography after acute myocardial infarction: comparison with cardiovascular magnetic resonance imaging. J Am Soc Echocardiogr (2005) 18:1203–7.[CrossRef][Web of Science][Medline]
  22. Mulvagh SL, DeMaria AN, Feinstein SB, Burns PN, Kaul S, Miller JG, et al. Contrast echocardiography: current and future applications. J Am Soc Echocardiogr (2000) 13:331–42.[CrossRef][Web of Science][Medline]

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