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European Journal of Heart Failure 2004 6(1):85-93; doi:10.1016/j.ejheart.2003.09.011
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© 2004 European Society of Cardiology

Effect of tissue harmonic imaging and contrast upon between observer and test–retest reproducibility of left ventricular ejection fraction measurement in patients with heart failure{star}

Gillian A. Whalleya,*, Greg D. Gamblea, Helen J. Walsha, Susan P. Wrighta, Stefan Agewallb, Norman Sharpea and Robert N. Doughtya

a Division of Medicine, Faculty of Medicine and Health Sciences University of Auckland, Private Bag 92 019, Auckland, New Zealand
b Department of Cardiology Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden

* Corresponding author. Tel.: +64-9-373-7599x89813; fax: +64-9-302-2101. E-mail address: g.whalley{at}auckland.ac.nz


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Aims
 3. Methods
 4. Results
 5. Discussion
 6. Summary
 References
 
Aims: To investigate the effects of tissue harmonic imaging (THI) and contrast chamber opacification (LVO) upon measurement variability and reproducibility of echocardiographic left ventricular (LV) volume and ejection fraction (EF) measurements in patients with heart failure (HF).

Background: Echocardiography is often used in HF patients to determine LV volumes and EF. However, current echo methods are variable and may not be applicable for repeat testing in individual patients. THI and LVO have both been shown to improve endocardial visualisation, but it remains to be determined whether this results in better measurement reproducibility.

Methods: Thirty-one HF patients and 30 control subjects underwent echocardiography on two separate days. LV volumes were measured under four different imaging conditions: fundamental, THI, LVO and LVO with ECG–triggered Power Doppler. Chamber opacification, pulmonary transit time (PTT), endocardial enhancement, reproducibility and bias were assessed.

Results: Chamber opacification was inferior and the PTT longer in the HF patients. PTT was related to LV volumes, EF, jugular venous pressure and mitral filling pattern. THI improved endocardial visualisation, and although LVO improved endocardial visualisation in the controls, it offered no benefit over THI in the HF patients. LV volumes and EF were different for each method and THI was the least variable method for repeat measurements.

Conclusions: THI improved endocardial visualisation and was the least variable of the techniques. LVO offered no further advantage in patients with HF and thus cannot be routinely advocated and since LV volumes and EF were different for each, these methods are neither comparable nor interchangeable for follow-up assessments.

Key Words: Echocardiography • Heart failure • Contrast • Harmonics • Ejection fraction • Reproducibility

Received May 26, 2003; Revised July 7, 2003; Accepted September 29, 2003


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Aims
 3. Methods
 4. Results
 5. Discussion
 6. Summary
 References
 
Echocardiography is now widely recommended and established as part of the clinical management of patients with HF [1,2]. LV end-systolic volume (LVESV) [3], ejection fraction (EF) [4–6] and change in EF [5,7,8] are important prognostic indicators in HF. Two-dimensional (2D) echo has been used successfully as an endpoint in many HF trials to detect small changes in EF in groups of patients [9–11] and is often used as a threshold for the initiation of pharmacotherapy [12,13]. However, if echocardiography is to be routinely applied to patients to assess EF, it needs to be highly accurate and reproducible in order to detect small changes.

Unfortunately, 2D echo measurements of EF are variable, lack precision and have inferior reproducibility when compared to magnetic resonance imaging (MRI) [14]. At best it is possible to detect a 10% difference in EF, but often only large differences are discernable [15]. As such, quantitative 2D echo is often regarded as time-consuming and unreliable, principally because of the manual identification and tracing of the endocardial–blood boundary, which depends upon the observer and image quality.

Modern digital ultrasound machines have improved image resolution and depth penetration, resulting in superior B-mode images, even in patients with very large hearts. Both tissue harmonic imaging and LV opacification (LVO) using new transpulmonary contrast agents improve endocardial visualisation further [16–23]. Contrast LVO enhances the accuracy of LV volume and EF measurements when compared to MRI [24], electron beam computed tomography [25] and radionuclide ventriculography [26]. Improved intra-observer and inter-observer variability with harmonic imaging [17] and contrast LVO [25] has been reported, but no studies have specifically targeted patients with HF. Furthermore, no studies have evaluated the test–retest reproducibility of these methods, which is potentially the most important parameter when considering the usefulness of a test for follow-up or monitoring of patients over time.

The enhanced endocardial visualisation observed in other patient groups may not necessarily be the same in HF patients, who often have enlarged hearts and abnormal geometry, both of which may contribute to non-uniform endocardial visualisation. If better endocardial visualisation results in more precise, unbiased and reproducible EF measurements there would be important and widespread implications for the management of HF patients.


   2. Aims
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
3. Methods
 4. Results
 5. Discussion
 6. Summary
 References
 
The aim of this study was to evaluate the role of both tissue harmonic imaging (THI) and LVO for improving endocardial visualisation in a population of HF patients and to subsequently determine whether this impacted upon the intra-observer, inter-observer, and test–retest variability and reproducibility associated with 2D echo EF measurements in HF patients and a comparative group of control subjects.


   3. Methods
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
 3. Methods
4. Results
 5. Discussion
 6. Summary
 References
 
3.1. Subjects and echocardiography
We studied 31 subjects with chronic HF (all patients had at least one prior hospitalisation requiring diuresis) and 30 healthy volunteers, who were not selected on the basis of echo quality. All subjects provided written informed consent and the study was approved by the Auckland Ethics Committee. All subjects underwent the same echo protocol on two different days (at least 1 day apart, median 7 days). Images for each subject were obtained on the same ultrasound machine (ATL HDI-3000 or HDI-5000, ATL Ultrasound, Bothell, WA). Standard diagnostic echo views were obtained in five thoracic windows and recorded onto super-VHS videotape and digitally acquired. All analyses were performed off-line (Nova Microsonics, Kodak Eastman, NJ).

3.2. Study imaging protocol
Apical four- and two-chamber views were optimised with the depth to maximise the LV chamber on the screen, eliminating most of the left atrial chamber from view, and the focus placed in the mid cavity level. Two ECG triggers were set: at end-diastole (on the R wave) and at end-systole (the smallest LV cavity volume). Six to 10 beats for each view were obtained under each condition and in the same order for each subject: (1) fundamental imaging; (2) harmonic imaging (factory tissue harmonics settings); (3) harmonic imaging with Levovist®; (4) dual ECG-triggered Power Doppler with Levovist®.

3.3. Contrast protocol
The ultrasound machine was set to the factory settings for Levovist® and further optimised for each patient. Grey scale images were obtained using contrast specific harmonics machine settings (mechanical index 1.2, frame rate medium) and recorded in real-time. Intravenous access was obtained via a cannula in the subjects’ right arm. A three-way tap was put in place and the line flushed with saline. Levovist® (Schering NZ Ltd) is an air based contrast agent composed of galactose (99.9%) and palmitic acid (0.01%). Contrast was prepared according to the manufacturer's recommendations for patients with large ventricular volumes (4 g, in solution 400 mg/ml) and given as a bolus followed by a 0.9% saline flush. Six to 10 cardiac cycles of the four- and two-chamber views were recorded onto videotape with real-time THI and then immediately repeated using dual-triggered Power Doppler (mechanical index 1.3, PRF 2000, wall filter high).

3.4. Contrast performance—degree of opacification
LV cavity opacification was graded for both the apical four- and two-chamber view at end-diastole and end-systole according to the following criteria [27]: 0= no contrast seen in the cavity; 1=partial opacification of the cavity; 2=full opacification, but not uniformly dense throughout cavity; 3=full chamber opacification with uniformly dense opacification. The time taken from initial appearance of contrast in the right ventricle (RV) until first appearance in the LV was recorded as a measure of pulmonary transit time (PTT).

3.5. Endocardial visualisation
The 12 segments seen in the apical four- and two-chamber views were graded for visualisation [27]: 0=not visible, 1=barely visible, 2=well visualised. The grading was performed by reviewing the videotapes, in random order by one observer (GW) without knowledge of the results of the other methods or any clinical details.

3.6. Left ventricular volume measurements
LV volume was calculated by the modified Simpson's biplane method using apical four- and two-chamber views. The endocardial border was manually traced at end-diastole and end-systole and the papillary muscles were included in the blood volume. One observer (G.W.) measured all volumes on both visits and repeated measurements on visit one only. A second observer (R.D.) measured all volumes on visit one only. All measurements (mean of three cardiac cycles) were made in random order, without any knowledge of previous measurements or clinical details. LV volumes were measured when a minimum of 10 segments were visualised (n=56: HF=29).

3.7. Statistics
Bias was assessed by comparing the mean values obtained by each method for each echo parameter and comparing the measurement difference in relation to the mean measurement, according to the Bland–Altman method. Reproducibility was assessed by the mean difference and confidence interval (limits of agreement) for each method and coefficient of variation, calculated as the standard deviation of the difference divided by {surd}2 expressed as a percentage of the mean for that measurement. Least squares regression was used to look at effects across all four groups and Student's t-test was used to determine significance of pairwise comparisons. Significance was maintained at P=0.05 throughout the analysis. All analysis was carried out for the whole group and separately (HF and control subjects).


   4. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
 3. Methods
 4. Results
5. Discussion
 6. Summary
 References
 
4.1. Patient characteristics
The HF patients were clinically stable (87% in NYHA class I or II), with mixed aetiology of HF (39% hypertension, 19%, revascularisation, 23% diabetes). There were more men than women (24:7) and 25% of HF patients were in atrial fibrillation. The patients were receiving standard treatment for HF including ACE-inhibitors (94%) and diuretics (97%). Compared to the control subjects, the HF patients had larger LVEDV and LV end-systolic volume (LVESV) and lower ejection fraction (EF) (Table 1). There were no differences between the groups in current smoking rates (HF 13%, controls 10%, P=0.76) or body surface area (HF 1.81, controls 1.85, P=0.63) or gender distribution (% male: HF 77.4%, controls 58.6%, P=0.12).


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  		Table 1 Baseline echocardiographic measurements and contrast performance in heart failure patients and control subjects

 
4.2. Contrast performance
Contrast performance was different between the two groups-LVO was consistently lower quality in the HF patients and pulmonary transit time (PTT) was prolonged in the HF patients (Table 1). PTT was positively correlated with LVEDV (r=0.29, P=0.03), LVESV (r=0.32, P=0.01) and negatively correlated with EF (r=–0.32, P=0.02) and opacification grade (four-chamber systole: r=–0.38, P=0.003; four-chamber diastole: r=–0.23, P=0.08; two-chamber systole: r=–0.24, P=0.07; two-chamber diastole: r=–0.32, P=0.01). PTT was not related to NYHA functional class (P=0.91) or heart rate (r=–0.25, P=0.17) but there was a trend towards correlation with the level of jugular venous pressure (JVP) (r=0.33, P=0.07).

4.3. Endocardial visualisation
Endocardial visualisation with fundamental imaging was good, but there was a consistent improvement in the number segments either visualised or well visualised with THI in both groups (Table 2). In the controls, there was an additional benefit of LVO, but no further benefit using LVO ECG-triggered Power Doppler imaging. However, in the HF patients, no further improvement in endocardial visualisation was seen with LVO, either used alone or with ECG-triggered Power Doppler.


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  		Table 2 Endocardial visualisation by wall segments

 
4.4. Left ventricular volume measurements
In both groups, measurements were similar using either THI or fundamental imaging (Table 3). However, in the control subjects real-time LVO with THI resulted in larger LVEDV but similar LVESV and higher EF. LVO with ECG-triggered Power Doppler imaging resulted in smaller (similar to the non-contrast) LVEDV but larger LVESV and hence, lower EF. In the HF patients, both the LVEDV and LVESV were smallest with LVO and ECG-triggered Power Doppler, and although the EF was closer to the non-contrast values, it was still significantly different to that measured with THI.


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  		Table 3 Left ventricular volume measurements (Simpson's biplane method) obtained with four different imaging modalities in patients with HF and control subjects

 
4.5. Intra-observer, inter-observer and test–retest variability and reproducibility
Comparing the four methods, the limits of agreement and coefficients of variation (CV) for EF were not significantly different (Table 4). Comparing the HF patients with the control subjects, the limits of agreement were generally wider and CV approximately double (Table 4). Bland–Altman plots confirmed that the variation was similar and no bias was associated with repeat measurements of EF by any method. No modality offered any major improvement in the spread of data and THI consistently had the lowest spread and smallest CV (Fig. 1).


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  		Table 4 Intra-observer, inter-observer and between days reproducibility for ejection fraction, by four different echo methods, in whole group (N=61)

 


Figure 1
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  		Fig. 1 Intra-observer, inter-observer and test–retest variability associated with ejection fraction measurements by four different echo modalities ({circ}: control subjects, bullet: HF patients).

 

   5. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
 3. Methods
 4. Results
 5. Discussion
6. Summary
 References
 
This study investigated the variability and test–retest reproducibility of LV volume and EF measurements using fundamental imaging, THI and LVO in patients with clinical HF. There are four main findings. Firstly, endocardial definition is enhanced with THI compared to fundamental imaging, but not substantially further improved with the use of contrast. Secondly, contrast performed differently in HF patients compared to control subjects. Thirdly, contrast produced different LV volume and EF measurements when compared to non-contrast imaging and thus, these methods are not interchangeable. Lastly, the intra- and inter-observer and test–retest variability was optimal with THI and improved with LVO. To our knowledge, this is the first study to target patients with HF to evaluate the potential benefits of THI and LVO for echo measurement of EF. The results of the study suggest that, with excellent equipment and optimised non-contrast imaging the benefits of LVO may be minimal.

This study supports other studies demonstrating improvement of endocardial visualisation with THI [17,28–36] and contrast LVO [21,37–41] compared to fundamental imaging. However, our findings were inconsistent between the two subject groups: LVO improved endocardial definition compared to THI in the control subjects, but not in the HF patients. In fact, endocardial definition was slightly inferior with LVO in patients with HF.

Previous studies comparing these modalities have had variable results [36,42–44]. Some did not demonstrate any improvement of LVO over THI [42,43] and of those studies demonstrating benefit, many were performed in the intensive care unit [36,44–47] and contrast contributed significantly to patient management [44–47]. Thus, in different circumstances, THI may provide maximum benefit, whilst in other situations LVO is necessary and that sub-optimal endocardial visualisation does not always necessitate the use of contrast.

The inferior chamber opacification in HF patients may be explained by multiple factors. Firstly, longer ultrasound exposure may cause excessive bubble destruction and loss of signal. Secondly, larger blood volume may result in significant signal attenuation, resulting in poor basal segment visualisation and may also weaken the concentration of contrast. Lastly, higher pulmonary pressures may slow passage through the lungs and also weaken the concentration of contrast in the LV. Patients with HF had prolonged PTT and this was related to larger LV volumes, reduced EF, diastolic function and higher JVP. Thus, those patients with worse HF, may benefit the least from using contrast for LVO.

The measurement of EF and the inferior contrast performance for LVO in HF patients has important implications for its widespread use. Data regarding the contrast use in patients with depressed systolic function are limited. In one study, using an earlier agent (Albunex) 64% of patients with systolic dysfunction had no chamber opacification [48]. In the current study, which used a newer agent (Levovist®), LVO was more successful and this is consistent with animal data [48] and data from other patient groups [21,22].

This study showed that measurements made by the different methods are not interchangeable. Importantly, the range of measurement difference of EF was large: 7.8% in the controls and 6.5% in patients with HF. This may mask or magnify real changes that may be present and may result in patient misclassification on the basis of EF.

Several studies have demonstrated that echo LV volumes are smaller than those obtained by angiography [49,50], radionuclide ventriculography [36] or biplane MRI [51]. LVO may be more accurate because it produces larger volumes [36,51] and better agreement with radionuclide EF measurements [26]. Likewise, ECG-triggered Power Doppler LVO produces larger LV volumes similar to angiographic volumes [51]. Although LVEDV with LVO was significantly larger in the current study, this was not the case for the ECG-triggered Power Doppler images. This may represent a true finding, or the Power Doppler volumes may be underestimated for one or more reasons. Firstly, the Power Doppler images were collected using the same injection of contrast as the LVO images. The time delay was minimal and no significant reduction in LVO with Power Doppler was apparent, but this cannot be reliably excluded. Secondly, loss of signal at the base of the heart due to attenuation by a large ventricular volume may have been exaggerated. Thirdly, some of the HF patients had atrial fibrillation (25%) which may have affected the ECG triggering, although this did not appear to be a problem in these patients.

The current study did not find significant improvements in the variability of EF measurement with LVO to warrant widespread use. The baseline variability was significantly lower in our study population with fundamental imaging compared to studies performed using older ultrasound equipment (in one case, it was halved) [52–55]. The benefits of THI and LVO have been demonstrated in patients with sub-optimal fundamental imaging, whilst the current study was performed in unselected patients. We chose to image ‘all-comers’ in an effort to document the benefits if applied routinely for the assessment of EF. Two other studies did not preselect their subjects [17,25]. One of these studies demonstrated reduced intra-observer variability with THI compared with fundamental imaging in patients with ischaemic heart disease [16]. However, the baseline fundamental variability and confidence intervals were very wide and thus the relative difference between the two modalities was exaggerated. A more recent study evaluated intra- and inter-observer variability of EF associated with LVO and compared it with THI in a group of patients (n=32) with LV remodelling due to mitral regurgitation and/or LV dysfunction [25]. This study compared measurers with different levels of experience and found that contrast LVO resulted in reduced variability compared to THI (intra-observer variability: THI 13%, LVO 9.8%; inter-observer: THI 18%, LVO 6%). In the current study, no difference in measurement variability was detected (intra-observer variability: THI 8.2%, LVO 9.8%; inter-observer: THI 8.9%, LVO 8.4%), but the THI variability was much lower and this may limit the potential for improvement. These two studies highlight the effect of measurer expertise upon variability.

The current study was performed in an academic research echo laboratory by two readers with considerable quantitative measurement experience and produced highly reproducible measurements of EF without contrast. LVO improves ‘non-expert’ reading and measurement of echocardiograms [25] and has been advocated on this basis. Although LVO minimises the bias associated with non-expert measurements, it is questionable whether an expensive, time-consuming technique should be used to make up for sub-optimal imaging. The increased cost must be weighed up against the cost of ultrasound equipment upgrades and continuing education and training of personnel.

Many studies report intra-observer and inter-observer variability for EF measurements [17,25], but it is rare to report test–retest variability. Whilst it is essential to establish measurement consistency within individual sonographers or readers (intra-observer reproducibility) and between different readers within a laboratory (inter-observer reproducibility), it is perhaps even more important to determine the reproducibility of measurements obtained on two completely different days (test–retest reproducibility). Test–retest reproducibility best mimics the true clinical setting—it is often months, perhaps even years between follow-up visits and measurement reliability becomes a crucial issue. The current study found no significant differences in test–retest reproducibility using contrast for LVO.

In order to maximise the diagnostic and prognostic benefits of echocardiography, physicians, sonographers and patients need to be assured that the measurements are unbiased and accurate and able to accurately detect clinically relevant changes. Many studies have validated these echo measurements and reproducibility is the sole determinant of the ability of repeat echocardiography to detect changes. It depends upon several factors including the patient, sonographer, ultrasound equipment, image acquisition, storage techniques, image analysis and interpretation. Several recent innovations have transformed ultrasound imaging: broadband transducer technology, digital beam formers, digital storage, enhanced digital processing of images and harmonic imaging. Modern echo technology is dynamic and hence it is inappropriate to compare the accuracy of echocardiography a few years ago with the imaging in modern laboratories. Many patient factors affect image quality, including age, weight, body habitus, obstructive airways disease, heart rate and rhythm. In addition, HF patients often have further difficulties: dyspneoa, atrial fibrillation, bradycardia, oedema, fluctuating fluid status and dilated and deformed ventricles.

5.1. Limitations
Although measurements were made independently, in random order and without knowledge of clinical details or prior measurements, it was not possible to blind the observers to the imaging modality. The study did not use an existing gold standard technique, such as angiography or MRI for external validation, because the focus of the current study was reproducibility and its effects upon follow-up. In this situation, the actual measurements may assume less importance in favour of the ability to detect small changes. Many other studies have demonstrated the external validity of both THI and LVO. All of the images were obtained using state-of-the-art equipment and both the sonographer and reader have considerable quantitative echocardiography experience in an academic setting. With older equipment and inexperienced operators different results may have be obtained.


   6. Summary
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
 3. Methods
 4. Results
 5. Discussion
 6. Summary
References
 
Harmonic imaging significantly improved endocardial wall visualisation in both the control subjects and HF patients and a small incremental improvement was seen with contrast. However, contrast enhancement of endocardial borders was inferior in patients with HF and this appeared to be related to the delayed passage of contrast through the lungs, which in turn was related to worse HF. Despite improvement in wall visualisation, we were unable to demonstrate any improvement in measurement variability for biplane 2D echo measurements of ejection fraction by any of the methods used (harmonics, contrast or Power Doppler contrast) and therefore could not recommend the wide-spread use of contrast for this purpose. However, in this study the variability observed with fundamental imaging was much lower than has been previously reported and in fact, was of a similar magnitude to that observed with either 3D echo or MRI. Further, this study has demonstrated that the left ventricular volumes and ejection fraction measured by fundamental, harmonic and contrast imaging are not comparable and thus not interchangeable for follow-up assessments.


   Acknowledgements
 
This study was conducted independently, with financial assistance from Schering (NZ) Ltd and ATL Ultrasound (Australia). Robert Doughty was the recipient of the National Heart Foundation of New Zealand BNZ Senior Fellowship. The Cardiovascular Ultrasound Laboratory was supported by a Welcome Trust biomedical equipment grant. Gillian Whalley is the recipient of a post-graduate scholarship from the National Heart Foundation of New Zealand. The authors wish to thank Renelle French and Graeme Orsbourne for technical assistance.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Aims
 3. Methods
 4. Results
 5. Discussion
 6. Summary
 References
 
{star} J Am Coll Cardiol. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Aims
 3. Methods
 4. Results
 5. Discussion
 6. Summary
 References
 

  1. Cheeseman M., Leech G., Chambers J., Monaghan M., Nihoyannopoulos P. Central role of echocardiography in the diagnosis and assessment of heart failure. Heart (1998) 80:S1–S5.[Free Full Text]
  2. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). American College of Cardiology Website 2001.
  3. White H.D., Norris R.M., Brown M.A., Brandt P.W.T., Whitlock R.M.L., Wild C.J. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation (1987) 76:44–51.[Abstract/Free Full Text]
  4. Cohn J.N., Rector T.S. Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol (1988) 62:25A–30A.[CrossRef][Medline]
  5. Gradman A., Deedwania P., Cody R., et al. Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril–Digoxin Study Group. J Am Coll Cardiol (1989) 14:564–570.[Abstract]
  6. Harjaj K.J., Nunez E., Turgut T., et al. The independent effects of left ventricular ejection fraction on short-term outcomes and resource utilization following hospitalization for heart failure. Clin Cardiol (1999) 22:184–190.[Web of Science][Medline]
  7. Cintron G., Johnson G., Francis G., Cobb F., Cohn J.N. For the V-HeFT VA Cooperative Studies Group. Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. Circulation (1993) 87(Suppl_VI):VI-17–VI-23.
  8. Parameshwar J., Shackell M.M., Richardson A., Poole-Wilson P.A., Sutton G.C. Prevalence of heart failure in three general practices in north west London. Br J Gen Pract (1992) 42:287–289.[Web of Science][Medline]
  9. Sharpe N., Murphy J., Smith H., Hannan S. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet (1988) 1988:255–259.
  10. Pfeffer M.A., Braunwald E., Moye L.A., et al. On behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. N Engl J Med (1992) 327:669–677.[Abstract]
  11. Doughty R.N., Whalley G.A., Gamble G., MacMahon S., Sharpe N. Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia–New Zealand Heart Failure Research Collaborative Group. J Am Coll Cardiol (1997) 29:1060–1066.[Abstract]
  12. Cohn J., Ferrari R., Sharpe N. On behalf of an International Forum on Cardiac Remodeling. Cardiac remodeling-concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol (2000) 35:569–582.[Abstract/Free Full Text]
  13. StJohn Sutton M., Sharpe N. Left ventricular remodelling after myocardial infarction. Circulation (2000) 101:2981–2988.[Free Full Text]
  14. Grothues F., Smith G.C., Moon J.C., et al. Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol (2002) 90:29–34.[CrossRef][Web of Science][Medline]
  15. McGowan J.H., Cleland J.G.F. The reliability of reporting left ventricular systolic function by echocardiography: a systematic review of three methods. Am Heart Journal (2003) 146:388–397.[CrossRef]
  16. Mulvagh S.L., DeMaria A.N., Feinstein S.B., et al. Contrast echocardiography: current and future applications. J Am Soc Echocardiogr (2000) 13:331–342.[CrossRef][Web of Science][Medline]
  17. Caidahl K., Kazzam E., Lidberg J., et al. New concept in echocardiography: harmonic imaging of tissue without use of contrast agent. Lancet (1998) 352:1264–1270.[CrossRef][Web of Science][Medline]
  18. Nixdorff U., Matschke C., Winklmaier M., et al. Native tissue harmonic imaging improves endocardial and epicardial border definition in dobutamine stress echocardiography. Eur J Echocardiogr (2001) 2:52–61.[Abstract/Free Full Text]
  19. Van Camp G., Franken R.R., Schoors D., et al. Impact of tissue harmonic imaging on the determination of the global and regional left ventricular function by 2D echocardiography: a comparison with MIBI gated SPECT. Eur J Echocardiogr (2000) 1:122–129.[Abstract/Free Full Text]
  20. Feinstein S.B., Cheirif J., Ten Cate F.J., et al. Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. J Am Coll Cardiol (1990) 16:316–324.[Abstract]
  21. Cohen J.L., Cheirif J., Segar D.S., et al. Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. J Am Coll Cardiol (1998) 32:746–752.[Abstract/Free Full Text]
  22. Grayburn P.A., Weiss J.L., Hack T.C., et al. Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms. J Am Coll Cardiol (1998) 32:230–236.[Abstract/Free Full Text]
  23. Kitzman D., Goldman D., Hack T., Gillam L., Fenster P., Segar D. Efficacy of DMP-115 contrast for left ventricular evaluation in patients with suboptimal baseline images: a multicentre, double blind, randomized, placebo controlled trial [abstract]. J Am Soc Echocardiogr (1998) 11:555.
  24. Hundley W.G., Kizilbash A.M., Afridi I., Franco F., Peshock R.M., Grayburn P.A. 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) 32:1426–1432.[Abstract/Free Full Text]
  25. Thomson H.L., Basmadjian A., Rainbird A.J., et al. Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements. J Am Coll Cardiol (2001) 38:867–875.[Abstract/Free Full Text]
  26. Nahar T., Croft L., Shapiro R., et al. Comparison of four echocardiographic techniques for measuring left ventricular ejection fraction. Am J Cardiol (2000) 86:1358–1362.[CrossRef][Web of Science][Medline]
  27. Becher H., Burns P.N. Handbook of contrast echocardiography (2000) 1st ed. Berlin: Springer.
  28. Kornbluth M., Liang D.H., Paloma A., Schnittger I. Native tissue harmonic imaging improves endocardial border definition and visualisation of cardiac structures. J Am Soc Echocardiogr (1998) 11:693–701.[CrossRef][Web of Science][Medline]
  29. Mulvagh S.L., Foley D.A., Belohlavek M., Seward J.B. Image enhancement by noncontrast harmonic echocardiography. Part 1. Qualitative assessment of endocardial visualisation. Mayo Clin Proc (1998) 73:1062–1065.[Abstract]
  30. Spencer K., Bednarz J., Rafter P., Korcarz C., Lang R. Use of harmonic imaging without echocardiographic contrast to improve two-dimensional image quality. Am J Cardiol (1998) 82:794–799.[CrossRef][Web of Science][Medline]
  31. Belohlavek M., Tanabe K., Mulvagh S.L., Foley D.A., Greenleaf J.F., Seward J.B. Image enhancement by noncontrast harmonic echocardiography. Part II. Quantitative assessment with use of contrast-to-speckle ratio. Mayo Clin Proc (1998) 73:1066–1070.[Abstract]
  32. Skolnick D.G., Sawada S.G., Feigenbaum H., Segar D.S. Enhanced endocardial visualisation with noncontrast harmonic imaging during stress echocardiography. J Am Soc Echocardiogr (1999) 12:559–563.[CrossRef][Web of Science][Medline]
  33. Senior R., Soman P., Khattar R.S., Lahiri A. Improved endocardial visualisation with tissue harmonic imaging compared with fundamental two-dimensional echocardiographic imaging. Am Heart J (1999) 138:163–168.[CrossRef][Web of Science][Medline]
  34. Rubin D.N., Yazbek N., Garcia M.J., Stewart W.J., Thomas J.D. Qualitative and quantitative effects of harmonic echocardiographic imaging on endocardial edge definition and side-lobe artifacts. J Am Soc Echocardiogr (2000) 13:1012–1018.[CrossRef][Web of Science][Medline]
  35. Franke A., Hoffman R., Kuhl H.P., et al. Non-contrast tissue harmonic imaging improves interobserver agreement and accuracy of dobutamine stress echocardiography in patients with impaired image quality. Heart (2000) 83:133–140.[Abstract/Free Full Text]
  36. Yu E.H., Sloggett C.E., Iwanochko R.M., Rakowski H., Siu S.C. 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) 13:216–224.[Web of Science][Medline]
  37. Crouse L.J., Cherif J., Hanly D.E., et al. Opacification and border delineation improvement in patients with suboptimal endocardial border definition in routine echocardiography: results of the phase III Albunex multicenter trial. J Am Coll Cardiol (1993) 22:1494–1500.[Abstract]
  38. Schröder K., Agrawal R., Völler H., Schlief R., Schröder R. Improvement of endocardial border delineation in suboptimal stress-echocardiograms using the new left heart contrast agent SH U 508 A. Int J Cardiac Imaging (1994) 10:45–51.[CrossRef][Medline]
  39. Hundley W.G., Kizilbash A.M., Afridi I., Franco F., Peshock R.M., Grayburn P.A. Effect of contrast enhancement on transthoracic echocardiographic assessment of left ventricular regional wall motion. Am J Cardiol (1999) 84:1365–1368. A8–A9.[CrossRef][Web of Science][Medline]
  40. Kitzman D.W., Goldman M.E., Gillam L.D., Cohen J.L., Aurigemma G.P., Gottdiener J.S. Efficacy and safety of the novel ultrasound contrast agent Perflutren (Definity) in patients with suboptimal baseline left ventricular echocardiographic images. Am J Cardiol (2000) 86:669–674.[CrossRef][Web of Science][Medline]
  41. Weissman N.J., Cohen M.C., Hack T.C., Gillam L.D., Cohen J.L., Kitzman D.W. Infusion versus bolus contrast echocardiography: a multicenter, open-label, crossover trial. Am Heart J (2000) 139:399–404.[CrossRef][Web of Science][Medline]
  42. Main M.L., Asher C.R., Rubin D.N., et al. Comparison of tissue harmonic imaging with contrast (sonicated albumin) echocardiography and Doppler myocardial imaging for enhancing endocardial border resolution. Am J Cardiol (1999) 83:218–222.[Web of Science][Medline]
  43. Kasprzak J.D., Paelinck B., Ten Cate F.J., et al. Comparison of native and contrast-enhanced harmonic echocardiography for visualisation of left ventricular endocardial border. Am J Cardiol (1999) 83:211–217.[Web of Science][Medline]
  44. Reilly J.P., Tunick P.A., Timmermans R.J., Stein B., Rosenzweig B.P., Kronzon I. Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients. J Am Coll Cardiol (2000) 35:485–490.[Abstract/Free Full Text]
  45. Kornbluth M., Liang D.H., Brown P., Gessford E., Schnittger I. Contrast echocardiography is superior to tissue harmonics for assessment of left ventricular function in mechanically ventilated patients. Am Heart J (2000) 140:246–291.
  46. Nguyen T.T., Dhond M.R., Sabapathy R., Bommer W.J. Contrast microbubbles improve diagnostic yield in ICU patients with poor echocardiographic windows. Chest (2001) 120:1287–1292.[CrossRef][Web of Science][Medline]
  47. Yong Y., Wu D., Fernandes V., et al. Diagnostic accuracy and cost-effectiveness of contrast echocardiography on evaluation of cardiac function in technically very difficult patients in the intensive care unit. Am J Cardiol (2002) 89:711–718.[CrossRef][Web of Science][Medline]
  48. Gandhok N.K., Block R., Ostoic T., et al. Reduced forward output states affect the left ventricular opacification of intravenously administered Albunex. J Am Soc Echocardiogr (1997) 10:25–30.[CrossRef][Web of Science][Medline]
  49. Uchimoto R., Niwa K., Tsuda N., Miyazawa T., Bräutigam M. Comparison of the efficacy of two air-based contrast agents in dogs. Eur J Ultrasound (2000) 11:127–133.[CrossRef][Medline]
  50. Sapin P.M., Schroder K.M., Gopal A.S., Smith M.D., DeMaria A.N., King D.L. Comparison of two- and three-dimensional echocardiography with cineventriculography for measurement of left ventricular volume in patients. J Am Coll Cardiol (1994) 24:1054–1063.[Abstract]
  51. Lafitte S., Dos Santos P., Kerouani A., Robhan T., Roudaut R. Improved reliability for echocardiographic measurement of left ventricular volume using harmonic power imaging mode combined with contrast agent. Am J Cardiol (2000) 85:1234–1238.[CrossRef][Web of Science][Medline]
  52. Chuang M.L., Hibberd M.G., Salton C.J., et al. Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging. J Am Coll Cardiol (2000) 35:477–484.[Abstract/Free Full Text]
  53. Himelman R.B., Cassidy M.M., Landzberg J.S., Schiller N.B. Reproducibility of quantitative two-dimensional echocardiography. Am Heart J (1988) 115:425–431.[CrossRef][Web of Science][Medline]
  54. Senior R., Sridhara B.S., Basu S., 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) 15:1235–1239.[Abstract/Free Full Text]
  55. Otterstad J.E., Froeland G., StJohn Sutton M., Holme I. Accuracy and reproducibility of biplane two-dimensional echocardiographic measurements of left ventricular dimensions and function. Eur Heart J (1997) 18:507–513.[Abstract/Free Full Text]

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G. A. Whalley, G. D. Gamble, H. J. Walsh, N. Sharpe, and R. N. Doughty
Quantitative evaluation of regional endocardial visualisation with second harmonic imaging and contrast left ventricular opacification in heart failure patients
Eur J Echocardiogr, March 1, 2005; 6(2): 134 - 143.
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