Unenhanced Echocardiography Research Articles

Experimental study of right ventricular structure and function by contrast-enhanced transthoracic echocardiography

Objective To investigate the accuracy and repeatability of contrast-enhanced transthoracic echocardiography for measurements of right ventricular structure and function. Methods The apical four-chamber views and the three-dimensional full-volume images of the right heart were collected from 12 beagles with unenhanced and contrast-enhanced transthoracic echocardiography. The intimal display rate of the right ventricular segments, right ventricular end diastolic longitudinal dimension (RVLD), right ventricular end diastolic area (RVEDA), right ventricular end systolic area (RVESA) and right ventricular fractional area change (RVFAC) were evaluated respectively with two-dimensional unenhanced and contrast-enhanced echocardiography. Right ventricular three-dimensional full-volume images were processed and analyzed by TomTec software, and right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV) and right ventricular ejection fraction (RVEF) were measured respectively with three-dimensional unenhanced and contrast-enhanced echocardiography. The measurements of pathological specimen were taken as the gold standard, the accuracies of measuring RVEDVand RVLD by different methods were evaluated. All indexes were measured repeatedly by the same observer and different observers to assess the intraobserver and interobserver reproducibilities of different methods. Results ①The intimal display rate of the right ventricular segments was higher with contrast-enhanced echocardiography than that with unenhanced echocardiography (P<0.05). ②The measurements of RVEDV by three-dimensional contrast-enhanced echocardiography correlated well with the measurements by anatomical specimens. And the correlation was higher (0.916 vs 0.843), the consistency was better than that by unenhanced echocardiography. The measurements of RVLD by two-dimensional contrast-enhanced echocardiography correlated well with the measurements by anatomical specimens. And the correlation was higher (0.928 vs 0.850), the consistency was better than that by unenhanced echocardiography. ③For inter- and intraobservers reproducibilities, the interclass correlation coefficients of RVLD, RVEDV, RVESV, RVEF, RVEDA, RVESA, RVFAC with contrast-enhanced echocardiography were higher and 95% confidence interval ranges were smaller than those with unenhanced echocardiography. Conclusions Contrast-enhanced transthoracic echocardiography can improve the accuracy and repeatability for measurements of right ventricular structure and function, providing a new evaluation method for patients with poor image quality of the right ventricle in clinical practice. Key words: Echocardiography; Ventricular function, right; Ultrasound enhancing agents

Systematic Assessment of the Impact of Ultrasound-Enhancing Agents upon Measurements of Cardiac Size and Function by Echocardiography

Echocardiography with an ultrasound-enhancing contrast agent (CON) is a powerful tool for identifying the endocardial border. However, the precise relationship of measurements obtained from CON to the reference values of two-dimensional unenhanced echocardiography (BASL) remains undefined, especially regarding wall thickness. The aim of this study was to systematically determine the differences between unenhanced and enhanced images for a broad range of left ventricular (LV) measurements and to define reference values for the relationship between the two methods. We examined the echocardiograms of 624 consecutive patients in whom CON was performed for clinical indications. We excluded 192 patients in whom studies were technically difficult for measurement by either or both methods. Echocardiograms were from standard parasternal and apical views according to American Society of Echocardiography guidelines. Recordings were measured for wall thickness and chamber dimension in 343 patients and for LV volumes and ejection fraction in 212 patients. LV wall thickness measurements were systematically reduced with a bias of 0.2cm with limits of agreement (LOA) from -0.5 to 0.16cm in interventricular septal thickness, and from -0.46 to 0.13cm in posterior wall thickness in CON. LV dimensions and volumes systematically increased with a bias of 0.2cm (LOA, -0.19 to 0.58cm) and 14 to 16mL (LOA, -11.9 to 42.8mL), respectively. LV ejection fraction systematically decreased with a bias of 3.4% (LOA, -13.5% to 6.8%) in CON compared to BASL. All differences showed normal distribution in the Kolmogorov-Smirnov test. CON yields significantly different measurements of cardiac size and function compared to unenhanced imaging. These data define the systematic differences in measurements between CON and BASL images; the range of differences is narrow. These differences may influence management when the measurement value is a borderline.

Contrast echocardiography in daily clinical practice.

Ultrasound contrast agents have unique acoustic properties that enable them to enhance the cardiac blood flow and thus are used broadly in modern echocardiography laboratories for salvage of nondiagnostic studies, improving accuracy and reducing variability even in the presence of adequate image quality. Contrast echocardiography is also used as an adjunctive technique when unenhanced echocardiography falls short in the differentiation of cardiac structural abnormalities such as cardiac masses. Ultrasound contrast agents are pure intravascular tracers. Development of innovative ultrasound imaging techniques has led to myocardial perfusion imaging with contrast echocardiography. Although currently an off-label indication, it has been shown that perfusion imaging with contrast echocardiography adds incremental value to stress echocardiography in the detection of coronary artery disease. Moreover, it can be used for assessment of myocardial viability. In this paper we briefly discuss the basics of contrast echocardiography and its use in daily clinical practice.

Analysis of Left Ventricular Volumes and Function: A Multicenter Comparison of Cardiac Magnetic Resonance Imaging, Cine Ventriculography, and Unenhanced and Contrast-Enhanced Two-Dimensional and Three-Dimensional Echocardiography

Contrast echocardiography improves accuracy and reduces interreader variability on left ventricular (LV) functional analyses in the setting of two-dimensional (2D) echocardiography. The need for contrast imaging using three-dimensional (3D) echocardiography is less defined. The aim of this multicenter study was to define the accuracy and interreader agreement of unenhanced and contrast-enhanced 2D and 3D echocardiography for the assessment of LV volumes and ejection fraction (EF). A multicenter, open-label study was conducted including 63 patients, using intrasubject comparisons to assess the agreement of unenhanced and contrast-enhanced 2D and 3D echocardiography as well as calibrated biplane cine ventriculography with cardiac magnetic resonance for the determination of LV volumes and EF. Each of the imaging techniques used to define LV function was assessed by two independent, off-site readers unaware of the results of the other imaging techniques. LV end-systolic and end-diastolic volumes were underestimated by 2D and 3D unenhanced echocardiography compared with cardiac magnetic resonance. Contrast enhancement resulted in similar significant increases in LV volumes on 2D and 3D echocardiography. The mean percentage of interreader variability for LV EF was reduced from 14.3% (95% confidence interval [CI], 11.7%-16.8%) for unenhanced 2D echocardiography and 14.3% (95% CI, 9.7%-18.9%) for unenhanced 3D echocardiography to 8.0% (95% CI, 6.3%-9.7%; P < .001) for contrast-enhanced 2D echocardiography and 7.4% (95% CI, 5.7%-9.1%; P < .01) for contrast-enhanced 3D echocardiography and thus to a similar level as for cardiac magnetic resonance (7.9%; 95% CI, 5.4%-10.5%). A similar effect was observed for interreader variability for LV volumes. Contrast administration on 3D echocardiography results in improved determination of LV volumes and reduced interreader variability. The use of 3D echocardiography requires contrast application as much as 2D echocardiography to reduce interreader variability for volumes and EF.

Contrast echocardiography to assess left ventricular volume and function in Beagle dogs: Comparison with 3-Tesla dual source parallel cardiac magnetic resonance imaging

This study was performed to evaluate the effect and feasibility of contrast echocardiography (CE) compared with unenhanced echocardiography (UE) and cardiac magnetic resonance imaging (CMRI) to assess left ventricular (LV) volume and function, including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) in six healthy Beagles.When the dogs were conscious, LV measurements using CE were significantly higher than those obtained using UE, except for EF, and were similar to the values obtained using CMRI. Additionally, EDV, SV, and EF obtained using UE from anesthetized dogs were significantly lower than those obtained using CE or CMRI. Measurements of EDV, SV and EF using CE were not significantly different from the corresponding measurements obtained using CMRI (31.13±2.18 vs. 32.88±1.17mL, 18.41±1.25 vs. 17.92±0.96mL, 59.29±2.29% vs. 53.33±1.69%, respectively). Inter-observer agreements for UE (0.74±0.05) were lower than those for CE (0.80±0.04) and CMRI (0.92±0.03). In conclusion, LV function was assessed reproducibly using CE, and the measurements obtained were consistent with reference standard measurements obtained using CMRI. Measurements made using CE agreed more closely with CMRI than those made using UE.

Comparison of left ventricular volumes and ejection fraction by monoplane cineventriculography, unenhanced echocardiography and cardiac magnetic resonance imaging

Right-anterior-oblique (RAO) monoplane cineventriculography is usually applied in cardiac catheter labs to assess the left ventricular (LV) function. However, it is uncertain whether this technique is reliable in clinical routine. Unenhanced two-dimensional echocardiography was reported to underestimate left ventricular volumes. The aim of this study was to compare these two conventional techniques with cardiac magnetic resonance imaging (MRI), the present gold standard for the determination of LV function, to evaluate whether the results from the conventional techniques are reliable and in accordance with each other. Seventy-two patients were retrospectively recruited and analysis of the three techniques was performed. Compared with MRI, RAO cineventriculography underestimated LV end-systolic volumes (ESV), and overestimated LV ejection fraction (EF); two-dimensional echocardiography underestimated LV end-diastolic volume (EDV) and EF. Correlation coefficients on EDV, ESV, and EF were 0.8806, 0.9201, and 0.8864 between echocardiography and MRI (P < 0.01, for all), followed by 0.7718, 0.8835, and 0.7785, between cineventriculography and MRI (P < 0.01, for all), and 0.7006, 0.7680, and 0.7644 between cineventriculography and echocardiography (P < 0.01, for all). Echocardiography and MRI showed the highest inter-technique correlation coefficients, and the narrowest Bland-Altman limits of agreement for EDV, ESV and EF. EDV, ESV and EF determined by RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography and MRI were in high accordance with each other, with wide variances between the techniques. Although not interchangeable, RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography, and cardiac MRI are reliable tools in clinical routine for the assessment of LV volumes and function.

Improved prediction of outcome by contrast echocardiography determined left ventricular remodelling parameters compared to unenhanced echocardiography in patients following acute myocardial infarction

Contrast echocardiography has been shown to be a more accurate method of assessing left ventricular (LV) remodelling compared with unenhanced echocardiography after acute myocardial infarction (AMI). However, whether this translated into improved prediction of outcome is not known. Accordingly, a total of 89 consecutive patients undergoing contrast echocardiography and unenhanced echocardiography 7 to 10 days after AMI and reperfusion therapy were followed up for cardiac death (CD) and AMI. LV ejection fraction (LVEF), LV end-systolic volume (ESV), and LV end-diastolic volume were assessed by the two methods independently. Outcome data were obtained (mean 46 +/- 16 months).There were 15 (17%) events (eight CDs and seven AMIs). LVEF and ESV with contrast echocardiography were found to be independent multivariable predictors of CD (P = 0.04 and P = 0.02, respectively) and CD or AMI (P = 0.02 and P = 0.01, respectively). Furthermore, LVEF and ESV with contrast echocardiography provided incremental information for the prediction of CD (P = 0.004 and P = 0.004, respectively) and CD or AMI (P = 0.02 and P = 0.03, respectively). Contrast echocardiography provided improved prediction of outcome compared with unenhanced echocardiography following AMI.

Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography

This paper examines the evidence for contrast echocardiography, both for improving assessment of left ventricular structure and function compared with unenhanced echocardiography and for the identification of myocardial perfusion. Based on the evidence, recommendations are proposed for the clinical use of contrast echocardiography.

Acute Mortality in Hospitalized Patients Undergoing Echocardiography With and Without an Ultrasound Contrast Agent: Results in 18,671 Consecutive Studies

We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent. A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Luke's Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Luke's Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures. Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography exhibited higher clinical acuity, and more significant comorbidities. Approximately 0.4% of hospitalized patients die within 24 h of echocardiography. There is no increased mortality risk associated with Definity-enhanced examinations, despite evidence for higher clinical acuity and more comorbid conditions in patients undergoing contrast studies.

Analysis of myocardial perfusion or myocardial function for detection of regional myocardial abnormalities. An echocardiographic multicenter comparison study using myocardial contrast echocardiography and 2D echocardiography

Echocardiography based myocardial perfusion imaging and regional wall motion analysis are used for evaluation of coronary artery disease and regional myocardial abnormalities. This study sought to compare myocardial contrast echocardiography (MCE) and 2D echocardiography with regard to interobserver variability and detection of regional myocardial abnormalities. In 70 patients evenly distributed between three ejection fraction groups based on biplane cineventriculography ( > 55%, 35-55%, < 35%), unenhanced and contrast enhanced 2D echocardiography and myocardial contrast echocardiography (MCE; SonoVue; Bracco) were performed. Regional wall motion and myocardial perfusion were assessed referring to a 16 segment model. Interobserver agreement (IOA) among 2 readers was determined within each imaging modality. To define a standard of truth for the presence of segmental myocardial disease an independent expert-panel decision was obtained based on clinical data, ECG, coronary angiography and blinded information from the imaging modalities. Regional wall motion assessment was possible in 98.1% of segments using contrast enhanced 2D echocardiography and in 87.2% using unenhanced 2D echocardiography (p < 0.001), while perfusion assessment was possible in 90.1% of segments (p < 0.001). IOA on presence of any regional wall motion abnormality expressed as Kappa coefficient was 0.71 (95% CI 0.53-0.89) for contrast enhanced echocardiography and 0.37 (95% CI 0.14-0.59) for unenhanced echocardiography. IOA on presence of any perfusion abnormality was 0.53 (95% CI 0.34-0.73). For MCE there was high IOA for the apical segments (kappa = 0.57) and lower IOA for the basal segments (kappa=0.14), while no such gradient was found for the IOA on wall motion abnormalities. Mean accuracy to detect expert-panel defined myocardial abnormalities was 80.6% for unenhanced echocardiography, 85.0% for contrast enhanced 2D echocardiography and 80.6% for MCE. MCE is inferior to contrast enhanced 2D echocardiography with regard to visibility of all LV segments and appears slightly inferior with regards to IOA, while both are superior to unenhanced 2D echocardiography. The methods demonstrated high accuracy in detection of panel defined regional myocardial abnormalities.

Analysis of Regional Left Ventricular Function by Cineventriculography, Cardiac Magnetic Resonance Imaging, and Unenhanced and Contrast-Enhanced Echocardiography: A Multicenter Comparison of Methods

To define the use of cineventriculography, cardiac magnetic resonance imaging (cMRI), and unenhanced and contrast-enhanced echocardiography for detection of left ventricular (LV) regional wall motion abnormalities (RWMA). Detection of RWMA is integral to the evaluation of LV function. In 100 patients, cineventriculography and unenhanced and contrast-enhanced echocardiography were performed. Fifty-six of the patients underwent additional cMRI. RWMA were assessed referring to a 16-segment model for cMRI, unenhanced and contrast echocardiography. Cineventriculography was evaluated on a 7-segment model. Hypokinesia in one or more segments defined presence of RWMA. Interobserver agreement among three readers was determined within each imaging modality. Intermethod agreement between imaging modalities was analyzed. A standard of truth for the presence of RWMA was obtained by an independent expert panel decision (EPD) based on clinical data, electrocardiogram, coronary angiography, and blinded information from the imaging modalities. Sixty-seven patients were found to have an RWMA by EPD. 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. Contrast enhancement compared to unenhanced echocardiography improved agreement of echocardiography related to cMRI (kappa 0.46 vs. 0.29) and related to cineventriculography (kappa 0.59 vs. 0.28). Accuracy to detect EPD-defined RWMA was highest for contrast echocardiography, followed by cMRI, unenhanced echocardiography, and cineventriculography. Analysis of RWMA is characterized by considerable interobserver variability even using high-quality imaging modalities. Interobserver agreement on RWMA and accuracy to detect panel-defined RWMA is good using contrast echocardiography.

Should contrast be routinely used for echocardiographic assessment of left ventricular function? A matter of appropriateness

This editorial refers to ‘Assessment of systolic left ventricular function. A multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast enhanced echocardiography’† by R. Hoffmann et al ., on page 607 Hoffmann et al. 1 present data showing that contrast-enhanced echocardiography, compared with unenhanced echocardiography, provides more accurate determination of left ventricular ejection fraction and significantly improves the correlation with cineventriculography and magnetic resonance imaging (MRI). Certainly, the most important question arising from this study is whether contrast injection should be routinely recommended for echocardiographic assessment of left ventricular function, as suggested by the study results. The authors did not discuss this question, nor did they state any clinical implications, thereby leaving the question open to public discussion. We would like to offer the following considerations. Because most heart diseases affect the left ventricle, assessment of left ventricular volumes and function is of critical importance. Several diagnostic approaches have proved their usefulness for assessing left ventricular function, including cineventriculography, echocardiography, MRI, and radionuclide angiography. However, providing quantitative estimates of left ventricular volume, all these approaches have their limitations, and their accuracy and feasibility have been the subject of countless studies. Of the four approaches mentioned, echocardiography has become the most widely used diagnostic technique for assessment of left ventricular function, because of its unrivalled … *Corresponding author. Tel: +49 201 723 4808; fax: +49 201 723 5408. E-mail address : thomas.buck{at}uni-essen.de

Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography

To assess the agreement of left ventricular ejection fraction (LVEF) determinations from unenhanced echocardiography, contrast-enhanced echocardiography, magnetic resonance imaging (MRI), and cineventriculography as well as the inter-observer agreement for each method. In 120 patients, with evenly distributed EF-groups (> 55, 35-55, < 35%), cineventriculography, unenhanced echocardiography with second harmonic imaging, and contrast echocardiography at low mechanical index with iv administration of SonoVue were performed. In addition, cardiac MRI at 1.5 T using a steady-state free precession sequence was performed in a subset of 55 patients. On-site, and two blinded off-site assessments were performed for unenhanced and contrast echocardiography, cineventriculography, and MRI according to pre-defined standards. Intra-class correlation coefficients (ICCs) were determined to assess inter-observer reliability between all three readers (i.e. one on-site and two off-site). EF was 56.2 +/- 18.3% by cineventriculography, 54.1 +/- 12.9% by MRI, 50.9 +/- 15.3% by unenhanced echocardiography, and 54.6 +/- 16.8% by contrast echocardiography. Correlation on EF between cineventriculography and echocardiography increased from 0.72 with unenhanced echocardiography to 0.83 with contrast echocardiography (P < 0.05). Similarly, correlation on EF between MRI and echocardiography increased from 0.60 with unenhanced echocardiography to 0.77 with contrast echocardiography (P < 0.05). The inter-observer reliability ICC was 0.91 (95% CI 0.88-0.94) in contrast echocardiography, followed by cardiac MRI (0.86; 95% CI 0.80-0.92), cineventriculography (0.80; 95% CI 0.74-0.85), and unenhanced echocardiography (0.79; 95% CI 0.74-0.85). Unenhanced echocardiography resulted in slight underestimation of EF and only moderate correlation compared with cineventriculography and MRI. Contrast echocardiography resulted in more accurate EF and significantly improved correlation with cineventriculography and MRI. Contrast echocardiography significantly improved inter-observer agreement on EF compared with unenhanced echocardiography. Inter-observer reliability on EF using contrast echocardiography reaches a level comparable to MRI and is better than those obtained by cineventriculography.

Emerging clinical applications for contrast echocardiography

SonoVue (Bracco, Milan, Italy) and the other last-generation ultrasound contrast agents (USCAs) have been shown to improve the detection of the endocardial border during rest and stress echocardiography in patients with impaired transthoracic image quality, thus allowing greater accuracy and precision in the assessment of both global and regional left ventricular function. Very exciting is the use of the last-generation USCAs as blood flow tracers to obtain non-invasive images of the myocardium that reflect myocardial perfusion (myocardial contrast echocardiography [MCE]). From preliminary results it appears that NICE may offer diagnostic information additive to and independent of that obtainable with unenhanced echocardiography, and may play a major role in the evaluation, management and follow-up of patients with coronary artery disease.

Diagnostic efficacy of sonoVue

SonoVue is a second-generation ultrasound contrast agent consisting of phospholipid-stabilized microbubbles filled with sulfur hexafluoride, with outstanding stability and resistance to pressure. The efficacy of SonoVue (0.5, 1, 2, 4 mL) was compared with Albunex (doses 0.08 and 0.22 mL/kg) in patients with suspected ischemic disease and suboptimal endocardial-border delineation on unenhanced echocardiography at rest. All the doses resulted in significantly greater increases compared with Albunex in left-ventricular endocardial-border delineation score as well as in the duration of clinically useful contrast effect. The utility of SonoVue in diagnosing ischemic heart disease was also evaluated during pharmacologic stress (arbutamine or dobutamine). SonoVue produced significant increases from baseline in endocardial-border delineation score both at rest and during pharmacologic stress. The possibility of detecting myocardial perfusion defects using SonoVue-enhanced power Doppler and gray-scale harmonic contrast echocardiography associated with continuous and intermittent imaging was assessed in patients with coronary artery disease. The results obtained were comparable with corresponding 99mTc sestamibi single-photon emission computed tomography images. An effective cardiovascular assessment of a patient should also include the evaluation of carotid vessels, intracranial circulation, and renal arteries. SonoVue provided significant improvements in the evaluation of the Doppler signal in terms of diagnosis agreement with reference imaging modality especially for intracranial vessels. The safety profile of SonoVue was evaluated in 1,406 patients. The incidence of adverse events was 10.4%, the great majority of which were of mild intensity and resolved without consequences.