TY - JOUR AU1 - , van den Bosch, A.E. AU2 - Meijboom,, F.J. AU3 - McGhie,, J.S. AU4 - Roos-Hesselink,, J.W. AU5 - Ten Cate,, F.J. AU6 - Roelandt,, J.R.T.C. AB - Abstract Background: Contrast echocardiography improves endocardial border detection of the left ventricle. Whether this is also true for the right ventricle (RV) is unknown. The aim of this study is to assess whether the use of contrast (Sonovue™) echocardiography has additional value in RV endocardial border visualisation (EBV), and whether it has impact on the echocardiographic judgement of RV function. Methods: Twenty adult patients with congenital heart disease were imaged using second harmonic two-dimensional echocardiography with and without contrast. Two independent observers analysed EBV of 13 RV wall segments in each patient. EBV was graded for each wall segment from 0 to 3 (0 = not visible, 3 = optimal visualisation). Results: EBV improved in all patients with contrast echocardiography compared to second harmonic imaging (mean EBV 1.00±0.77 with second harmonics, 2.13±0.75 with contrast, P <0.0001). The benefit was most evident in the near-field images. In 55% of the patients visual estimation of RV function changed with contrast echocardiography. Conclusion: The use of contrast echocardiography is superior to second harmonic imaging for RV EBV. Improved EBV may allow more accurate assessment of RV dimensions and function. echocardiography, contrast media, right ventricle, congenital heart defects 1 Introduction Contrast echocardiography has proved to be of additional value over conventional two-dimensional echocardiography in the assessment of left ventricular border detection and left ventricular function. 1–3 So far the right ventricle (RV) has not been systematically studied with contrast echocardiography. Especially in congenital heart disease, assessment of RV function is an important determinant that strongly influences clinical outcome. In these patients echocardiographic imaging is challenging. 4,5 The acoustic window is often restricted because of multiple cardiac surgeries in the past, and poor near-field resolution makes it difficult to assess the anterior wall of the RV. Despite the continued progress in diagnostic ultrasonography such as the use of second harmonic imaging and high-frequency transducers, restrictions to image quality still remain. 6 Moreover, RV shape and dimensions vary substantially between different types of congenital heart disease. Of special interest are those patient groups that are notorious for RV dysfunction: tetralogy of Fallot (ToF) and transposition of the great arteries (TGA) post-Mustard or Senning operation. In the latter condition, the morphological RV acts as a systemic ventricle and contrast echocardiography is only possible with contrast agents which pass the lungs. 7 Adequate serial assessment of RV size and function is essential for timely detection of RV deterioration and to consider optimal timing for possible re-intervention. The aim of this study is to assess whether contrast echocardiography has additional value in the endocardial border identification of an RV that functions as a systemic ventricle. Does it have an advantage over recently developed techniques such as second harmonic imaging? As a comparison those patients were studied for whom RV function is considered to be very important, but with the RV in a normal subpulmonary position: patients with ToF. 2 Methods 2.1 Patients Twenty consecutive patients with congenital heart disease who were seen at our outpatient clinic, were asked to participate in the study. The purpose of the study was explained and possible negative side effects were mentioned. All patients agreed. In 10 patients the RV functions as a systemic ventricle: eight patients had TGA corrected using a Mustard operation and two patients had a congenitally corrected TGA. The other 10 patients had ToF with total surgical correction in childhood. No additional cardiac defects were present. There were 14 males (70%) and six females (30%) with a mean age of 31 years, range 18–54 years, at the time of the study. Six patients (30%) with ToF had severe pulmonary regurgitation. All 20 patients had dilated RV. 2.2 Echocardiography All patients underwent echocardiographic assessment using two modalities: second harmonic and contrast imaging. The imaging protocol was completed within half an hour. Echocardiography was performed with a Hewlett–Packard Sonos 5500 (Hewlett–Packard Co., Andover, MA) with a broadband transducer. Second harmonic imaging was done with a transmit/receive frequency of 1.6/3.2 MHz and a mechanical index of 1.6. Contrast imaging was performed with a transmit/receive frequency of 1.6/3.2 MHz and a mechanical index of 0.4. Gain settings were optimised for each subject. Images obtained from the apical four-chamber and parasternal short-axis (apical, medial and basal) view were stored as single cardiac cycles on magneto-optical disk for off-line analysis. 2.3 Contrast agent Sonovue ® (sulphur hexafluoride) was used as contrast agent. 8 Sonovue was prepared according to the manufacturer's recommendation by mixing with 5-ml saline. The bubble concentration is in the range 1–5×10 8 microbubbles per ml. The solution was injected as series of multiple boluses (0.2–0.4 ml) in a peripheral vein and flushed with saline. Not more than 5 ml of contrast agent was needed for an optimal study. After a bolus injection of the contrast agent, the RV cavity fills rapidly with high intensity contrast signals, maximum reached within 5–10 s. These high intensity signals give initially attenuation (decrease in the intensity of sound due to absorption) of the basal and medial segments. When attenuation subsides the entire RV is opacified and all segments can be visualised. There were no complications such as shock, hypotension, or arrhythmia associated with contrast medium injection. 2.4 Right ventricular wall segmentation according to echocardiographic images We analysed the anterior and posterior endocardial walls of the RV in short-axis images recorded at three levels: apical, medial and basal ( Fig. 1 ). With this method, the RV is divided into six segments: 1, posteroapical; 2, posteromedial; 3, posterobasal; 4, anteroapical; 5, anteromedial; 6, anterobasal. Three other segments (apical, medial and basal) viewed from an apical four-chamber position were also evaluated. The interventricular septum forms one of the walls of the RV and was evaluated in the four echocardiographic images. In total, the endocardial border visualisation (EBV) of the RV was evaluated for 13 segments. Assessment of RV function was judged on an ordinal scale by visual estimation of both second harmonics and contrast images, and graded into normal, moderately or severely reduced. Figure 1 Open in new tabDownload slide Right ventricular segmentation according to echocardiographic images. The RV in parasternal short-axis images recorded at three equivalent levels: apical, medial and basal, and the apical four-chamber view. Right ventricular segments: 1, posteroapical; 2, posteromedial; 3, posterobasal; 4, anteroapical; 5, anteromedial; 6, anterobasal. From a four-chamber view: 7, four-chamber apical; 8, four-chamber medial; 9, four-chamber basal. The interventricular septum segments: 10, apical septum; 11, medial septum; 12, basal septum and 13, four-chamber septum. Figure 1 Open in new tabDownload slide Right ventricular segmentation according to echocardiographic images. The RV in parasternal short-axis images recorded at three equivalent levels: apical, medial and basal, and the apical four-chamber view. Right ventricular segments: 1, posteroapical; 2, posteromedial; 3, posterobasal; 4, anteroapical; 5, anteromedial; 6, anterobasal. From a four-chamber view: 7, four-chamber apical; 8, four-chamber medial; 9, four-chamber basal. The interventricular septum segments: 10, apical septum; 11, medial septum; 12, basal septum and 13, four-chamber septum. 2.5 Echocardiographic analysis All loops were reviewed in dynamic format and in random order by two independent observers. The EBV of each RV segment was graded: 0, not visible; 1, barely visible (myocardial boundaries undefined); 2, visible (endocardial boundaries defined) and 3, optimal (excellent delineation of endocardial border). Composite scores for each subject and view were computed by averaging the segmental scores and were also used to calculate a total and regional endocardial visualisation index (EVI). This is the mean EBV score for all segments (T-EVI) and per region (apical, medial and basal). 2.6 Statistical analysis The segmental endocardial visualisation scores were compared between imaging modalities with the Student's t -test. Repeat analysis was performed on the subgroup of patients with the lowest and highest overall second harmonics imaging score. Interobserver agreement was assessed with the Student's t -test. Data were presented as the mean value (SD) unless otherwise stated. Statistical significance was considered to be P value <0.05. Results In all 20 patients, the study protocol was completed and no complications occurred. 3.1 Endocardial border visualisation Total 236 (91%) of 260 RV wall segments and interventricular septum segments were available for qualitative analysis. In seven patients, it was technically impossible to obtain parasternal short-axis images at all levels. Results of the EBV for the right ventricular segments, second harmonics vs contrast mode, are given in Table 1 . In 11 of the 13 RV segments there is a significant ( P <0.05) improvement of the EBV. As shown in Fig. 2 , contrast echocardiography improved the EBV in all patients (100%). Representative still frames that were extracted from dynamic image loops for second harmonic and contrast mode are shown in Fig. 3 . Figure 2 Open in new tabDownload slide Mean EBV score for all RV segments for each patient. Figure 2 Open in new tabDownload slide Mean EBV score for all RV segments for each patient. Figure 3 Open in new tabDownload slide Two-dimensional echocardiography still frames. Panels A and B show second harmonics and contrast images recorded in the four-chamber view. Panels C and D show second harmonics and contrast images of parasternal short-axis view. Note improved visualisation of RV endocardial border and RV trabeculation (arrow) with contrast echocardiography. The contrast images show enhanced visualisation of apical segment and anterior wall of the RV. Figure 3 Open in new tabDownload slide Two-dimensional echocardiography still frames. Panels A and B show second harmonics and contrast images recorded in the four-chamber view. Panels C and D show second harmonics and contrast images of parasternal short-axis view. Note improved visualisation of RV endocardial border and RV trabeculation (arrow) with contrast echocardiography. The contrast images show enhanced visualisation of apical segment and anterior wall of the RV. Table 1 Endocardial border visualisation (EBV) score for RV segments RV segments . Second harmonics . Contrast echocardiography . P -value . . Observer 1 . Observer 2 . Observer 1 . Observer 2 . . Posteroapical 0.8 0.8 2.1 2.2 <0.0001 Anteroapical 0.7 0.8 2.5 2.5 <0.0001 Four-chamber apex 0.8 1.0 2.2 2.5 <0.0001 Posteromedial 1.0 1.1 2.1 2.2 <0.0001 Anteromedial 0.9 0.9 2.3 2.4 <0.0001 Four-chamber medial 1.3 1.5 2.2 2.1 <0.0001 Posterobasal 1.0 1.1 2.0 2.3 <0.0001 Anterobasal 0.6 0.7 2.4 2.3 <0.0001 Four-chamber basal 1.4 1.5 1.2 1.4 0.20 Septum apical 1.9 1.7 1.9 1.9 0.38 Medial 2.1 1.9 2.5 2.2 0.0007 Basal 2.1 1.9 2.4 2.1 0.009 Four-chamber septum 2.1 1.9 2.7 2.6 <0.0001 RV segments . Second harmonics . Contrast echocardiography . P -value . . Observer 1 . Observer 2 . Observer 1 . Observer 2 . . Posteroapical 0.8 0.8 2.1 2.2 <0.0001 Anteroapical 0.7 0.8 2.5 2.5 <0.0001 Four-chamber apex 0.8 1.0 2.2 2.5 <0.0001 Posteromedial 1.0 1.1 2.1 2.2 <0.0001 Anteromedial 0.9 0.9 2.3 2.4 <0.0001 Four-chamber medial 1.3 1.5 2.2 2.1 <0.0001 Posterobasal 1.0 1.1 2.0 2.3 <0.0001 Anterobasal 0.6 0.7 2.4 2.3 <0.0001 Four-chamber basal 1.4 1.5 1.2 1.4 0.20 Septum apical 1.9 1.7 1.9 1.9 0.38 Medial 2.1 1.9 2.5 2.2 0.0007 Basal 2.1 1.9 2.4 2.1 0.009 Four-chamber septum 2.1 1.9 2.7 2.6 <0.0001 Mean value EBV score for each RV segment for second harmonic imaging and contrast echocardiography. Open in new tab Table 1 Endocardial border visualisation (EBV) score for RV segments RV segments . Second harmonics . Contrast echocardiography . P -value . . Observer 1 . Observer 2 . Observer 1 . Observer 2 . . Posteroapical 0.8 0.8 2.1 2.2 <0.0001 Anteroapical 0.7 0.8 2.5 2.5 <0.0001 Four-chamber apex 0.8 1.0 2.2 2.5 <0.0001 Posteromedial 1.0 1.1 2.1 2.2 <0.0001 Anteromedial 0.9 0.9 2.3 2.4 <0.0001 Four-chamber medial 1.3 1.5 2.2 2.1 <0.0001 Posterobasal 1.0 1.1 2.0 2.3 <0.0001 Anterobasal 0.6 0.7 2.4 2.3 <0.0001 Four-chamber basal 1.4 1.5 1.2 1.4 0.20 Septum apical 1.9 1.7 1.9 1.9 0.38 Medial 2.1 1.9 2.5 2.2 0.0007 Basal 2.1 1.9 2.4 2.1 0.009 Four-chamber septum 2.1 1.9 2.7 2.6 <0.0001 RV segments . Second harmonics . Contrast echocardiography . P -value . . Observer 1 . Observer 2 . Observer 1 . Observer 2 . . Posteroapical 0.8 0.8 2.1 2.2 <0.0001 Anteroapical 0.7 0.8 2.5 2.5 <0.0001 Four-chamber apex 0.8 1.0 2.2 2.5 <0.0001 Posteromedial 1.0 1.1 2.1 2.2 <0.0001 Anteromedial 0.9 0.9 2.3 2.4 <0.0001 Four-chamber medial 1.3 1.5 2.2 2.1 <0.0001 Posterobasal 1.0 1.1 2.0 2.3 <0.0001 Anterobasal 0.6 0.7 2.4 2.3 <0.0001 Four-chamber basal 1.4 1.5 1.2 1.4 0.20 Septum apical 1.9 1.7 1.9 1.9 0.38 Medial 2.1 1.9 2.5 2.2 0.0007 Basal 2.1 1.9 2.4 2.1 0.009 Four-chamber septum 2.1 1.9 2.7 2.6 <0.0001 Mean value EBV score for each RV segment for second harmonic imaging and contrast echocardiography. Open in new tab Improvement of EBV for each region (apical, medial and basal) is expressed in the EVI. The advantage of contrast imaging is best seen in the apical segments (A-EVI was 0.82±0.78 with second harmonics and 2.34±0.70 with contrast); this is due to a decrease in near-field artefacts. Medial EVI (M-EVI) increased from 1.07±0.72 with second harmonics to 2.19±0.53 with contrast. The increase of visualisation was less in the basal segments (B-EVI was 1.07±0.81 with second harmonics and 1.90±0.91 with contrast); this is based on the low EBV score in the basal four-chamber segment. The interventricular septum segments had good visualisation with second harmonic imaging (septum-EVI 1.9±0.37), but still EBV improved with contrast (septum-EVI 2.27±0.5). The overall quality of the endocardial visualisation, reflected by the total EVI (T-EVI), was significantly higher in the contrast mode images: 1.00±0.77 with second harmonics vs 2.13±0.75 with contrast. The EVI for the subjects ( n = 9) with the poorest acoustic windows are shown in Table 2 . These subjects had a markedly limited quality of echocardiographic images, as demonstrated by an overall EVI of 0.54±0.59 with second harmonics. In majority of the segments, the EBV improved with contrast echocardiography. The enhanced ability of contrast echocardiography was best noticeable in the apical segments (A-EVI 0.22±0.42 with second harmonics to 2.28±0.69 with contrast). Table 2 Endocardial visualisation index (EVI) in patients with poor and good quality of the echocardiographic images with second harmonics . Second harmonics . Contrast echocardiography . P -value . EVI<1.0 with second harmonics ( n = 9) Total-EVI 0.54 ± 0.59 2.10 ± 0.76 <0.0001 EVI ≥ 1.0 with second harmonics ( n = 11) Total-EVI 1.29 ± 0.72 2.21 ± 0.71 <0.0001 . Second harmonics . Contrast echocardiography . P -value . EVI<1.0 with second harmonics ( n = 9) Total-EVI 0.54 ± 0.59 2.10 ± 0.76 <0.0001 EVI ≥ 1.0 with second harmonics ( n = 11) Total-EVI 1.29 ± 0.72 2.21 ± 0.71 <0.0001 Excluding the interventricular septum segments. Open in new tab Table 2 Endocardial visualisation index (EVI) in patients with poor and good quality of the echocardiographic images with second harmonics . Second harmonics . Contrast echocardiography . P -value . EVI<1.0 with second harmonics ( n = 9) Total-EVI 0.54 ± 0.59 2.10 ± 0.76 <0.0001 EVI ≥ 1.0 with second harmonics ( n = 11) Total-EVI 1.29 ± 0.72 2.21 ± 0.71 <0.0001 . Second harmonics . Contrast echocardiography . P -value . EVI<1.0 with second harmonics ( n = 9) Total-EVI 0.54 ± 0.59 2.10 ± 0.76 <0.0001 EVI ≥ 1.0 with second harmonics ( n = 11) Total-EVI 1.29 ± 0.72 2.21 ± 0.71 <0.0001 Excluding the interventricular septum segments. Open in new tab The EVI scores for the subjects ( n = 11) with moderate to good acoustic windows (T-EVI of 1.29±0.72 with second harmonics) are shown in Table 2 . Even in patients with a good acoustic window, contrast echocardiography improves the visualisation in all segments (T-EVI 2.10±0.71 with contrast). There was no difference in the visualisation scores between the patients with TGA and the patients with corrected ToF. 3.2 Right ventricular function We evaluated the RV function by visual estimation on both second harmonic images and after contrast injection. RV function obtained from second harmonic images: seven patients (35%) had severely reduced, seven patients (35%) had moderately reduced, five patients (15%) had a moderate to good and only one patient had a good RV function. After contrast injection, the evaluation of right ventricular function changed in 11 patients (55%) (five patients with TGA; six patients with ToF). All 11 patients were judged to have a better RV function than was assumed on the second harmonic images. In eight patients RV function judged on contrast images changed from moderately reduced to moderate/good and in three patients from severely reduced to moderately reduced. Our results show no significant difference for interobserver agreement for visualisation of the endocardial border. 4 Discussion 4.1 Endocardial border visualisation of the right ventricle This study shows that in all patients visualisation of RV endocardial border was better with contrast echocardiography. A substantial improvement of EBV was realised in the majority of the RV segments with contrast echocardiography and is expressed in a significantly higher T-EVI. Although, the interventricular septum segments have good visualisation with second harmonics, contrast echocardiography enables an improved visualisation by opacification of both RV and LV. This makes evaluation of the interventricular septal wall motion and wall thickness more accurate. 4.2 Advantages of contrast imaging With transthoracic echocardiography, imaging limitations occur as a result of partly retrosternal position of the RV and interposition of non-cardiac structures. In the near-field images, especially the apex in the four-chamber view and the anterior wall of the RV in the parasternal cross-sections, contrast echocardiography gives a significantly better visibility of the endocardial border. As shown in Table 1 , the four-chamber basal segment visualisation does not improve. Delineation of the endocardium with high echogenicity at baseline (e.g. basal lateral segment) significantly declined after contrast injection. Acoustic shadowing in the basal segments counterbalances the benefits of contrast enhancement. The evaluation of EBV in patients with a very limited acoustic window is particularly challenging. We found the largest improvement of EBV score in patients with poor echocardiography imaging. This shows that the contrast echocardiography is most effective in patients with poor fundamental image quality. The EBV also improved in the patients with good echocardiographic image quality, due to a better visibility of the trabeculations of the RV. However, the added value of contrast echo is less dramatic than seen in poor echocardiographic image quality. This emphasises that good EBV by echocardiography can only be acquired with contrast. By improving EBV with contrast imaging, the visual estimation of RV function could be more accurate. 1,9,10 Presumable is that RV function is underestimated with second harmonic imaging. 4.3 Clinical implications Contrast echocardiography improves EBV, which facilitates more accurate assessment of RV wall motion and therefore better judgement of RV function. The improvement in image quality narrows the interpretative range, thus allows greater accuracy and precision in the assessment of both global and regional RV functions. Accordingly, contrast imaging is indicated in all echocardiographic studies where judgement of RV function is essential. This finding may have important clinical implications, especially in congenital heart disease, where RV function often plays a crucial role. We experienced that contrast echocardiography is easily used in the clinical setting and appears to be a safe diagnostic method. The characteristics of Sonovue and its safety profile have already been reported in several reports. 11 In this study, we experienced no complication of Sonovue. 4.4 Study limitations This study only represents our initial clinical experience in a limited number of patients ( n = 20) with congenital heart disease. The segmentation of the RV endocardial was done according to the standard echocardiographic images. This segmentation does not represent anatomic boundaries (infundibular, free wall, diaphragmatic and septal) and the RV outflow tract was not included. RV segments obtained in the apical four-chamber view might correspond with segments obtained in the short-axis views. This phenomenon could not be avoided. The RV segmentation can only be used for evaluation of echocardiographic images obtained in the same view. 5 Conclusions We conclude that contrast echocardiography is superior to second harmonic imaging alone for EBV of the RV. In the near-field images, especially the apex in the four-chamber position and the anterior wall of the RV contrast imaging give a significantly better visibility of the endocardial border. Contrast imaging provides us with more reliable information for the assessment of the RV dimension and function in patients with congenital heart disease. It is a safe, reproducible and relatively cheap noninvasive technique that can easily be performed by the bedside in any cardiology outpatient clinic. References 1 Paelinck B.P. , Kasprzak J.D. . 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Contrast echocardiography: current and future applications , J Am Soc Echocardiogr , 2000 , vol. 13 4 (pg. 331 - 342 ) Google Scholar Crossref Search ADS PubMed WorldCat 11 Bokor D. , Chambers J.B. , Rees P.J. , Mant T.G. , Luzzani F. , Spinazzi A. . Clinical safety of SonoVue, a new contrast agent for ultrasound imaging, in healthy volunteers and in patients with chronic obstructive pulmonary disease , Invest Radiol , 2001 , vol. 36 2 (pg. 104 - 109 ) Google Scholar Crossref Search ADS PubMed WorldCat Copyright © 2003, The European Society of Cardiology TI - Enhanced visualisation of the right ventricle by contrast echocardiography in congenital heart disease JF - European Heart Journal - Cardiovascular Imaging DO - 10.1016/S1525-2167(03)00048-9 DA - 2004-03-01 UR - https://www.deepdyve.com/lp/oxford-university-press/enhanced-visualisation-of-the-right-ventricle-by-contrast-qHmzY5pWgx SP - 104 EP - 110 VL - 5 IS - 2 DP - DeepDyve ER -