Safety and feasibility of contrast echocardiography for the evaluation of patients with HeartMate 3 left ventricular assist devices

Safety and feasibility of contrast echocardiography for the evaluation of patients with HeartMate... Abstract Aims Patients with a left ventricular assist device (LVAD) are challenging to evaluate using conventional imaging techniques, such as standard echocardiography (SE). The aim of this pilot study was to evaluate the potential of contrast echocardiography (CE) for the evaluation of the left ventricle (LV). Methods and results This prospective study included 14 ambulatory patients (mean age 58 ± 9 years, 79% male) with a LVAD (all HeartMate 3, Abbott Laboratories, Chicago, IL, USA). Nine (64%) patients had an ischaemic cardiomyopathy, and 5 (36%) had a non-ischaemic cardiomyopathy. All patients underwent SE and CE using intravenous administration of Sonovue contrast agent (Bracco, Milan, Italy). The echocardiograms were assessed by three observers, using a standard 17-segment model of the LV. Left ventricular end-diastolic volume (LVEDV) was assessed using the biplane Simpson method. The contrast agent was well tolerated by all patients, without any side effects. Overall, SE allowed visualization of 57% of LV segments (135/238) and CE allowed visualization of 79% of LV segments (187/238), P < 0.001. Per patient, SE resulted in visualization of 9.6 ± 5.2 segments and CE was able to visualize 13.4 ± 5.8 segments (P < 0.001). Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent. cardiomyopathy, contrast-enhanced echocardiography, HeartMate 3, left ventricular assist device Introduction Left ventricular assist devices (LVADs) are an increasingly used treatment option for patients with advanced heart failure refractory to optimal medical therapy, either as a bridge to cardiac transplantation or destination therapy.1–3 The introduction of the LVAD has resulted in a good long-term survival with substantial improvement in the patient’s quality of life.3 Non-invasive imaging plays an important role in the follow-up of patients with a LVAD, for the evaluation of LV function, monitoring of treatment response, and screening for potential complications.4,5 However, a substantial number of these patients exhibit an impaired image quality or may even deemed unsuitable for conventional imaging techniques including standard echocardiography (SE). Multiple studies have demonstrated that contrast echocardiography (CE) may substantially improve the endocardial border delineation and the evaluation of the LV function.6,7 CE was recently proposed as an imaging modality for the evaluation of the LV in patients with a LVAD, particularly to overcome the limitations of SE.8,9 The aim of the current pilot study was to evaluate the safety, feasibility and potential of CE in patients with a novel continuous-flow LVAD, type HeartMate 3. This a third generation LVAD, with a magnetically levitated impellor, which is a potential source of destruction of echocardiography contrast agents. The hypothesis of this study was that CE use was safe and feasible in patients with HeartMate 3 LVAD to improve visualization of the LV cavity and facilitates the determination of LV size. Methods Patient population and study protocol This prospective study included all patients with a LVAD that underwent CE. The study protocol was approved by the Medical Ethics Committee of the Erasmus Medical Center, Rotterdam, The Netherlands. All patients provided informed consent. Consecutive ambulatory patients with a LVAD (all patients had a HeartMate 3, Abbott Laboratories, Chicago, IL, USA) because of advanced heart failure due to ischaemic or non-ischaemic cardiomyopathy were asked to participate in this prospective pilot study. All patients underwent a SE examination in conjunction with CE. Exclusion criteria were contraindications for the use of ultrasound contrast agent, such as unstable angina, acute cardiac failure, acute endocarditis, known right-to-left shunts, and known allergy for microbubble contrast agents. Echocardiographic acquisition The SE and CE examinations were performed using a Philips EPIQ 7C ultrasound system (Philips Medical Systems, Bothell, USA), with an X5-1 transducer. For SE and CE, a standardized image acquisition protocol based on the American Society of Echocardiography guideline was used.10 In short, parasternal long-axis and short axis views, and apical 4-, 2- and 3-chamber views were obtained using B-mode ultrasound and colour Doppler imaging. For the CE examination, the ultrasound system was switched to its contrast mode. The contrast mode was using amplitude modulation techniques and a mechanical index of 0.1–0.5 to optimize the CE images. CE was performed using intravenous administration of SonoVue™ ultrasound contrast agent (sulphur hexafluoride microbubble suspension, Bracco S.p.A., Milan, Italy). The ultrasound contrast agent was injected in boluses of 0.5 mL, the bolus administration was repeated when necessary up to a total dose of 5.0 mL. During and after contrast administration, the patients were observed for potential side effects or complications and LVAD function parameters were monitored. For both SE and CE, cineclips were digitally stored and reviewed offline. Echocardiographic analysis The SE and CE studies were reviewed offline by three independent observers unaware of the clinical data. A 17-segment model of the LV was used to analyse the LV in three standard views: parasternal long-axis, apical 4- and 2-chamber view. The image quality of each LV segment on the SE and CE clips was independently scored as (i) interpretable or (ii) uninterpretable. If there was a discrepancy in the scores of the independent readers, a consensus was reached. LV end-diastolic dimension (LVEDD) and LV end-diastolic volume (LVEDV) were assessed on the SE and CE datasets using TomTec Arena software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany). The LVEDD was measured from leading edge to leading edge on the parasternal long-axis view. The LVEDV was assessed with the biplane Simpson method using the 4- and 2-chamber apical view. Statistical analyses Statistical analyses were performed using SPSS for Windows (version 17.0, SPSS, Chicago, IL, USA) and Excel (Excel 2003, Microsoft, Redmont, USA). Continuous variables are reported as mean ± standard deviation. Categorical variables are expressed as number (%). The χ2 test was used to evaluate differences between proportions. A P-value <0.05 was considered to indicate a statistically significant difference. Results Patient characteristics The patient characteristics (mean age 58±9 years, range 43–75 years, 11 (79%) men and 3 (21%) women) are summarized in Table 1. The majority of the patients had received a LVAD because of an ischaemic cardiomyopathy (9, 64%), whereas the remaining 5 (36%) patients had a non-ischaemic cardiomyopathy. LVAD implantation was considered as a bridge to transplantation in 8 (57%) patients and a destination therapy in 6 (43%). Table 1 Clinical characteristics of the study population Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Data are presented as numbers of patients (percentages) or as mean ± standard deviation. BMI, body mass index; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; NYHA, New York Heart Association. Table 1 Clinical characteristics of the study population Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Data are presented as numbers of patients (percentages) or as mean ± standard deviation. BMI, body mass index; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; NYHA, New York Heart Association. Safety and feasibility All CE studies were performed without adverse reactions and were well tolerated. None of the patients had signs of an allergic reaction and no known or unknown side effects occurred during or after intravenous administration of the contrast agent. No changes in LVAD function parameters were observed during or after CE. The dose of the contrast agent that was necessary for an adequate CE examination in these patients with an LVAD was not different from the dose that is regularly used in our centre for CE in patients without an LVAD. Hence, there were no signs that the HeartMate 3 LVAD caused a substantial destruction of the contrast agent. Image quality SE resulted in an interpretable visualization of all 17 segments in 2 (14%) patients. In the remaining 12 (86%) patients, visualization of the LV segments was impaired (range 0–16 interpretable segments). Using SE, visualization of 57% (135/238) of LV segments was possible. Per patient, SE leads to interpretable image quality in on average 9.6 ± 5.2 LV segments. CE led to an improvement in the number of interpretable LV segments in 10 (71%) patients. Figure 1 demonstrates an improved visualization of the LV endocardial borders using CE. In 4 (29%) patients, CE did not change the image interpretation. Overall, CE resulted in a significant improvement of image quality, and visualization of 79% (187/238) LV segments was possible (P < 0.001). Per patient, CE yielded visualization of on average 13.4 ± 5.8 LV segments, an improvement of 3.8 ± 2.7 segments as compared to SE. Assessment of LVEDD was possible in all patients, both on SE (LVEDD 66 ± 14 mm) and CE (LVEDD 64 ± 11 mm). Using SE, assessment of LVEDV using the biplane Simpson method was possible in 5/14 (36%) patients on SE, with an average LVEDV of 177 ± 55 mL. In four remaining patients assessment of LVEDV on SE was possible only in the 4-chamber apical view, and in five patients assessment of LVEDV was not possible at all. Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Using CE, assessment of LVEDV was possible in 11/14 (79%) of patients with a LVAD (LVEDV 229 ± 68 mL). In two remaining patients assessment of LVEDV on CE was possible only in the 4-chamber apical view, and in one patient assessment of LVEDV was not possible. Figure 1 View largeDownload slide Standard echocardiography (SE) and corresponding contrast echocardiography (CE) images in a patient with advanced heart failure and a HeartMate 3 LVAD. SE resulted in a poor visualization of the LV, in both 4-chamber (A) and 2 chamber (C) apical views. After intravenous administration of the ultrasound contrast agent, CE yielded an improved visualization of the LV endocardial borders, in both 4-chamber (B) and 2 chamber (D) apical views. See Supplementary data online, Videos of this example. Figure 1 View largeDownload slide Standard echocardiography (SE) and corresponding contrast echocardiography (CE) images in a patient with advanced heart failure and a HeartMate 3 LVAD. SE resulted in a poor visualization of the LV, in both 4-chamber (A) and 2 chamber (C) apical views. After intravenous administration of the ultrasound contrast agent, CE yielded an improved visualization of the LV endocardial borders, in both 4-chamber (B) and 2 chamber (D) apical views. See Supplementary data online, Videos of this example. Discussion The main findings of the present study are: (i) that CE in patients with an LVAD is safe and feasible and (ii) CE significantly improves the visualization of the endocardial borders of the LV. Imaging of the LV and evaluation of LVEDV is clinically relevant to monitor changes in LV function and size in response to therapy and to detect potential complications, such as intracardiac thrombi and blood flow stasis. Continuous-flow LVADs are increasingly being used in patients with advanced heart failure, as a bridge to LV recovery, cardiac transplantation, or as destination therapy.1–3 The evaluation of LV shape, function and intracardiac blood flow in patients with a LVAD may be challenging. SE is currently used as the main imaging method in the evaluation of these patients. The current study demonstrates that SE in these patients is associated with a significantly impaired image quality. Several factors may explain the impaired image quality. First, the LVAD and the inflow and outflow cannulas limit the acoustic window. Second, the device may cause artefacts. Third, patients with a LVAD cannot always be optimally positioned for echocardiography. Finally, additional factors like bandages and concomitant lung disease hinder accurate visualization of segmental and global LV function. Computed tomography has been used in the evaluation of these patients, but this technique is also limited by artefacts caused by the LVAD. Additionally the use of iodinated contrast agent is a limitation of that technique, particularly in those with an impaired renal function. Cardiac magnetic resonance imaging cannot be used because of the metal components of the LVAD. The American Society of Echocardiography and the European Association of Echocardiography have recognized the clinical value of CE and issued position papers providing guidelines.10–12 It has become clear that CE is a safe imaging modality13,14 that may provide improved image quality or information that cannot be obtained by SE in stable and critically ill patients.15,16 Clinical applications of CE include: improvement of LV endocardial border delineation, reduction of variability in assessment of LV volumes and function, increase reader confidence, and assessment of LV structural abnormalities: apical variant of hypertrophic cardiomyopathy, ventricular non-compaction, apical thrombus, aneurysm, pseudo aneurysm, myocardial rupture and intracardiac masses (tumours and thrombi).6,7,10–12 Recently, CE has been proposed, in a case-report8 and a retrospective case series,9 as a potentially useful imaging modality in the evaluation of patients with a LVAD. Moser et al.8 reported the case of a 25-year-old woman with a non-ischaemic cardiomyopathy and a LVAD (HeartMate II). Echocardiography revealed an apical pseudo aneurysm on SE, additional CE demonstrated a bidirectional flow between the LV and the pseudo-aneurysm evident by contrast enhancement. This case demonstrates the critical role of SE and CE in the follow-up of patients with a LVAD to confirm circulatory function and exclude device-related complications. Fine et al.9 retrospectively reviewed the records of 251 patients with a LVAD implantation who received a clinically indicated echocardiogram. Of them, 10 (4%) patients with a LVAD (HeartMate II in 9, Heartmate XVE in 1 patient) underwent a CE study, of whom 2 patients had a repeat CE study. No adverse events or known side-effects occurred during or after CE. These patients underwent a CE because of a suboptimal endocardial border delineation during SE. The use of contrast agent (Definity in 9 and Optison in 3 patients) aided image interpretation in 10 (83%) CE examinations. The current prospective study confirms that CE in patients with a LVAD (all patients had a HeartMate 3) is safe, and can be performed with a regular dose of contrast agent (Sonovue). There were no signs that the LVAD caused a substantial destruction of the contrast agent. This study has clinically relevant implications. This study shows that the SE allowed visualization of 57% of LV segments. After safe and easy intravenous administration of the ultrasound contrast agent, CE resulted in visualization of 79% of LV segments. Moreover, LV size determination could be obtained more often due to improved LV visualization using CE. Clearly, segmental and global LV function and LVEDV are important parameters in patients with a LVAD to monitor alterations in response to therapy and to diagnose potential complications. This study has several limitations. First, because this was a pilot study, the number of patients that was considered was small. Second, potential destruction of the contrast agent by the LVAD was visually assessed and could not be quantitatively assessed. Third, this study was performed with Sonovue contrast agent, and it is not clear whether the results can be extrapolated to CE using other agents. Fourth, all of the patients had a HeartMate 3 LVAD, and it is not sure whether the current results can be extrapolated to patients with other LVAD systems. Fifth, the mentioned contraindications were considered at the time of the study conception and design, recently the contraindications have been removed by the US Food and Drug Administration Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent. Supplementary data Supplementary data are available at European Heart Journal-Cardiovascular Imaging online. Conflict of interest: None declared. References 1 Slaughter MS , Rogers JG , Milano CA , Russell SD , Conte JV , Feldman D et al. Advanced heart failure treated with continuous-flow left ventricular assist device . N Engl J Med 2009 ; 361 : 2241 – 51 . Google Scholar CrossRef Search ADS PubMed 2 Jorde UP , Kushwaha SS , Tatooles AJ , Naka Y , Bhat G , Long JW et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) . J Am Coll Cardiol 2014 ; 63 : 1751 – 7 . Google Scholar CrossRef Search ADS PubMed 3 McIlvennan CK , Magid KH , Ambardekar AV , Thompson JS , Matlock DD , Allen LA. Clinical outcomes after continuous-flow left ventricular assist device: a systematic review . Circ Heart Fail 2014 ; 7 : 1003 – 13 . Google Scholar CrossRef Search ADS PubMed 4 Estep JD , Stainback RF , Little SH , Torre G , Zoghbi WA. The role of echocardiography and other imaging modalities in patients with left ventricular assist devices . JACC Cardiovasc Imaging 2010 ; 3 : 1049 – 64 . Google Scholar CrossRef Search ADS PubMed 5 Ammar KA , Umland MM , Kramer C , Sulemanjee N , Jan MF , Khandheria BK et al. The ABCs of left ventricular assist device echocardiography: a systematic approach . Eur Heart J Cardiovasc Imaging 2012 ; 13 : 885 – 99 . Google Scholar CrossRef Search ADS PubMed 6 Feinstein SB , Coll B , Staub D , Adam D , Schinkel AF , ten Cate FJ et al. Contrast enhanced ultrasound imaging . J Nucl Cardiol 2010 ; 17 : 106 – 15 . Google Scholar CrossRef Search ADS PubMed 7 Schinkel AF , Kaspar M , Staub D. Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis . Int J Cardiovasc Imaging 2016 ; 32 : 35 – 48 . Google Scholar CrossRef Search ADS PubMed 8 Moser AR , Hockman D , Magalski A , Main ML , Khumri TM , Austin BA. Apical pseudoaneurysm following continuous flow left ventricular assist device placement . Circ Heart Fail 2012 ; 5 : e53 – 4 . Google Scholar CrossRef Search ADS PubMed 9 Fine NM , Abdelmoneim SS , Dichak A , Kushwaha SS , Park SJ , Mulvagh SL. Safety and feasibility of contrast echocardiography for LVAD evaluation . JACC Cardiovasc Imaging 2014 ; 7 : 429 – 30 . Google Scholar CrossRef Search ADS PubMed 10 Porter TR , Abdelmoneim S , Belcik JT , McCulloch ML , Mulvagh SL , Olson JJ et al. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography . J Am Soc Echocardiogr 2014 ; 27 : 797 – 810 . Google Scholar CrossRef Search ADS PubMed 11 Mulvagh SL , Rakowski H , Vannan MA , Abdelmoneim SS , Becher H , Bierig SM et al. American Society of Echocardiography consensus statement on the clinical applications of ultrasonic contrast agents in echocardiography . J Am Soc Echocardiogr 2008 ; 21 : 1179 – 201 . Google Scholar CrossRef Search ADS PubMed 12 Senior R , Becher H , Monaghan M , Agati L , Zamorano J , Vanoverschelde JL et al. Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography . Eur J Echocardiogr 2009 ; 10 : 194 – 212 . Google Scholar CrossRef Search ADS PubMed 13 Main ML , Ryan AC , Davis TE , Albano MP , Kusnetzky LL , Hibberd M. Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (multicenter registry results in 4,300,966 consecutive patients) . Am J Cardiol 2008 ; 102 : 1742 – 6 . Google Scholar CrossRef Search ADS PubMed 14 Main ML , Hibberd MG , Ryan A , Lowe TJ , Miller P , Bhat G. Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent . JACC Cardiovasc Imaging 2014 ; 7 : 40 – 8 . Google Scholar CrossRef Search ADS PubMed 15 Reilly JP , Tunick PA , Timmermans RJ , Stein B , Rosenzweig BP , Kronzon I. Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients . J Am Coll Cardiol 2000 ; 35 : 485 – 90 . Google Scholar CrossRef Search ADS PubMed 16 Kurt M , Shaikh KA , Peterson L , Kurrelmeyer KM , Shah G , Nagueh SF et al. Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort . J Am Coll Cardiol 2009 ; 53 : 802 – 10 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. 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Safety and feasibility of contrast echocardiography for the evaluation of patients with HeartMate 3 left ventricular assist devices

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Abstract

Abstract Aims Patients with a left ventricular assist device (LVAD) are challenging to evaluate using conventional imaging techniques, such as standard echocardiography (SE). The aim of this pilot study was to evaluate the potential of contrast echocardiography (CE) for the evaluation of the left ventricle (LV). Methods and results This prospective study included 14 ambulatory patients (mean age 58 ± 9 years, 79% male) with a LVAD (all HeartMate 3, Abbott Laboratories, Chicago, IL, USA). Nine (64%) patients had an ischaemic cardiomyopathy, and 5 (36%) had a non-ischaemic cardiomyopathy. All patients underwent SE and CE using intravenous administration of Sonovue contrast agent (Bracco, Milan, Italy). The echocardiograms were assessed by three observers, using a standard 17-segment model of the LV. Left ventricular end-diastolic volume (LVEDV) was assessed using the biplane Simpson method. The contrast agent was well tolerated by all patients, without any side effects. Overall, SE allowed visualization of 57% of LV segments (135/238) and CE allowed visualization of 79% of LV segments (187/238), P < 0.001. Per patient, SE resulted in visualization of 9.6 ± 5.2 segments and CE was able to visualize 13.4 ± 5.8 segments (P < 0.001). Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent. cardiomyopathy, contrast-enhanced echocardiography, HeartMate 3, left ventricular assist device Introduction Left ventricular assist devices (LVADs) are an increasingly used treatment option for patients with advanced heart failure refractory to optimal medical therapy, either as a bridge to cardiac transplantation or destination therapy.1–3 The introduction of the LVAD has resulted in a good long-term survival with substantial improvement in the patient’s quality of life.3 Non-invasive imaging plays an important role in the follow-up of patients with a LVAD, for the evaluation of LV function, monitoring of treatment response, and screening for potential complications.4,5 However, a substantial number of these patients exhibit an impaired image quality or may even deemed unsuitable for conventional imaging techniques including standard echocardiography (SE). Multiple studies have demonstrated that contrast echocardiography (CE) may substantially improve the endocardial border delineation and the evaluation of the LV function.6,7 CE was recently proposed as an imaging modality for the evaluation of the LV in patients with a LVAD, particularly to overcome the limitations of SE.8,9 The aim of the current pilot study was to evaluate the safety, feasibility and potential of CE in patients with a novel continuous-flow LVAD, type HeartMate 3. This a third generation LVAD, with a magnetically levitated impellor, which is a potential source of destruction of echocardiography contrast agents. The hypothesis of this study was that CE use was safe and feasible in patients with HeartMate 3 LVAD to improve visualization of the LV cavity and facilitates the determination of LV size. Methods Patient population and study protocol This prospective study included all patients with a LVAD that underwent CE. The study protocol was approved by the Medical Ethics Committee of the Erasmus Medical Center, Rotterdam, The Netherlands. All patients provided informed consent. Consecutive ambulatory patients with a LVAD (all patients had a HeartMate 3, Abbott Laboratories, Chicago, IL, USA) because of advanced heart failure due to ischaemic or non-ischaemic cardiomyopathy were asked to participate in this prospective pilot study. All patients underwent a SE examination in conjunction with CE. Exclusion criteria were contraindications for the use of ultrasound contrast agent, such as unstable angina, acute cardiac failure, acute endocarditis, known right-to-left shunts, and known allergy for microbubble contrast agents. Echocardiographic acquisition The SE and CE examinations were performed using a Philips EPIQ 7C ultrasound system (Philips Medical Systems, Bothell, USA), with an X5-1 transducer. For SE and CE, a standardized image acquisition protocol based on the American Society of Echocardiography guideline was used.10 In short, parasternal long-axis and short axis views, and apical 4-, 2- and 3-chamber views were obtained using B-mode ultrasound and colour Doppler imaging. For the CE examination, the ultrasound system was switched to its contrast mode. The contrast mode was using amplitude modulation techniques and a mechanical index of 0.1–0.5 to optimize the CE images. CE was performed using intravenous administration of SonoVue™ ultrasound contrast agent (sulphur hexafluoride microbubble suspension, Bracco S.p.A., Milan, Italy). The ultrasound contrast agent was injected in boluses of 0.5 mL, the bolus administration was repeated when necessary up to a total dose of 5.0 mL. During and after contrast administration, the patients were observed for potential side effects or complications and LVAD function parameters were monitored. For both SE and CE, cineclips were digitally stored and reviewed offline. Echocardiographic analysis The SE and CE studies were reviewed offline by three independent observers unaware of the clinical data. A 17-segment model of the LV was used to analyse the LV in three standard views: parasternal long-axis, apical 4- and 2-chamber view. The image quality of each LV segment on the SE and CE clips was independently scored as (i) interpretable or (ii) uninterpretable. If there was a discrepancy in the scores of the independent readers, a consensus was reached. LV end-diastolic dimension (LVEDD) and LV end-diastolic volume (LVEDV) were assessed on the SE and CE datasets using TomTec Arena software (TomTec Imaging Systems GmbH, Unterschleissheim, Germany). The LVEDD was measured from leading edge to leading edge on the parasternal long-axis view. The LVEDV was assessed with the biplane Simpson method using the 4- and 2-chamber apical view. Statistical analyses Statistical analyses were performed using SPSS for Windows (version 17.0, SPSS, Chicago, IL, USA) and Excel (Excel 2003, Microsoft, Redmont, USA). Continuous variables are reported as mean ± standard deviation. Categorical variables are expressed as number (%). The χ2 test was used to evaluate differences between proportions. A P-value <0.05 was considered to indicate a statistically significant difference. Results Patient characteristics The patient characteristics (mean age 58±9 years, range 43–75 years, 11 (79%) men and 3 (21%) women) are summarized in Table 1. The majority of the patients had received a LVAD because of an ischaemic cardiomyopathy (9, 64%), whereas the remaining 5 (36%) patients had a non-ischaemic cardiomyopathy. LVAD implantation was considered as a bridge to transplantation in 8 (57%) patients and a destination therapy in 6 (43%). Table 1 Clinical characteristics of the study population Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Data are presented as numbers of patients (percentages) or as mean ± standard deviation. BMI, body mass index; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; NYHA, New York Heart Association. Table 1 Clinical characteristics of the study population Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Characteristic Data Age (year) 58 ± 9 Men 11 (79) Height (cm) 179 ± 9 Weight (kg) 80 ± 14 BMI (kg/m2) 25 ± 4 INTERMACS Class 1–3 8 (57) INTERMACS Class 4–7 6 (43) NYHA Class 3 7 (50) NYHA Class 4 7 (50) Ischaemic cardiomyopathy 9 (64) Non-ischaemic cardiomyopathy 5 (36) Paroxysmal atrial fibrillation 6 (43) Ventricular tachycardia 11 (79) Percutaneous coronary intervention 7 (50) Coronary bypass surgery 2 (14) Data are presented as numbers of patients (percentages) or as mean ± standard deviation. BMI, body mass index; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; NYHA, New York Heart Association. Safety and feasibility All CE studies were performed without adverse reactions and were well tolerated. None of the patients had signs of an allergic reaction and no known or unknown side effects occurred during or after intravenous administration of the contrast agent. No changes in LVAD function parameters were observed during or after CE. The dose of the contrast agent that was necessary for an adequate CE examination in these patients with an LVAD was not different from the dose that is regularly used in our centre for CE in patients without an LVAD. Hence, there were no signs that the HeartMate 3 LVAD caused a substantial destruction of the contrast agent. Image quality SE resulted in an interpretable visualization of all 17 segments in 2 (14%) patients. In the remaining 12 (86%) patients, visualization of the LV segments was impaired (range 0–16 interpretable segments). Using SE, visualization of 57% (135/238) of LV segments was possible. Per patient, SE leads to interpretable image quality in on average 9.6 ± 5.2 LV segments. CE led to an improvement in the number of interpretable LV segments in 10 (71%) patients. Figure 1 demonstrates an improved visualization of the LV endocardial borders using CE. In 4 (29%) patients, CE did not change the image interpretation. Overall, CE resulted in a significant improvement of image quality, and visualization of 79% (187/238) LV segments was possible (P < 0.001). Per patient, CE yielded visualization of on average 13.4 ± 5.8 LV segments, an improvement of 3.8 ± 2.7 segments as compared to SE. Assessment of LVEDD was possible in all patients, both on SE (LVEDD 66 ± 14 mm) and CE (LVEDD 64 ± 11 mm). Using SE, assessment of LVEDV using the biplane Simpson method was possible in 5/14 (36%) patients on SE, with an average LVEDV of 177 ± 55 mL. In four remaining patients assessment of LVEDV on SE was possible only in the 4-chamber apical view, and in five patients assessment of LVEDV was not possible at all. Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Using CE, assessment of LVEDV was possible in 11/14 (79%) of patients with a LVAD (LVEDV 229 ± 68 mL). In two remaining patients assessment of LVEDV on CE was possible only in the 4-chamber apical view, and in one patient assessment of LVEDV was not possible. Figure 1 View largeDownload slide Standard echocardiography (SE) and corresponding contrast echocardiography (CE) images in a patient with advanced heart failure and a HeartMate 3 LVAD. SE resulted in a poor visualization of the LV, in both 4-chamber (A) and 2 chamber (C) apical views. After intravenous administration of the ultrasound contrast agent, CE yielded an improved visualization of the LV endocardial borders, in both 4-chamber (B) and 2 chamber (D) apical views. See Supplementary data online, Videos of this example. Figure 1 View largeDownload slide Standard echocardiography (SE) and corresponding contrast echocardiography (CE) images in a patient with advanced heart failure and a HeartMate 3 LVAD. SE resulted in a poor visualization of the LV, in both 4-chamber (A) and 2 chamber (C) apical views. After intravenous administration of the ultrasound contrast agent, CE yielded an improved visualization of the LV endocardial borders, in both 4-chamber (B) and 2 chamber (D) apical views. See Supplementary data online, Videos of this example. Discussion The main findings of the present study are: (i) that CE in patients with an LVAD is safe and feasible and (ii) CE significantly improves the visualization of the endocardial borders of the LV. Imaging of the LV and evaluation of LVEDV is clinically relevant to monitor changes in LV function and size in response to therapy and to detect potential complications, such as intracardiac thrombi and blood flow stasis. Continuous-flow LVADs are increasingly being used in patients with advanced heart failure, as a bridge to LV recovery, cardiac transplantation, or as destination therapy.1–3 The evaluation of LV shape, function and intracardiac blood flow in patients with a LVAD may be challenging. SE is currently used as the main imaging method in the evaluation of these patients. The current study demonstrates that SE in these patients is associated with a significantly impaired image quality. Several factors may explain the impaired image quality. First, the LVAD and the inflow and outflow cannulas limit the acoustic window. Second, the device may cause artefacts. Third, patients with a LVAD cannot always be optimally positioned for echocardiography. Finally, additional factors like bandages and concomitant lung disease hinder accurate visualization of segmental and global LV function. Computed tomography has been used in the evaluation of these patients, but this technique is also limited by artefacts caused by the LVAD. Additionally the use of iodinated contrast agent is a limitation of that technique, particularly in those with an impaired renal function. Cardiac magnetic resonance imaging cannot be used because of the metal components of the LVAD. The American Society of Echocardiography and the European Association of Echocardiography have recognized the clinical value of CE and issued position papers providing guidelines.10–12 It has become clear that CE is a safe imaging modality13,14 that may provide improved image quality or information that cannot be obtained by SE in stable and critically ill patients.15,16 Clinical applications of CE include: improvement of LV endocardial border delineation, reduction of variability in assessment of LV volumes and function, increase reader confidence, and assessment of LV structural abnormalities: apical variant of hypertrophic cardiomyopathy, ventricular non-compaction, apical thrombus, aneurysm, pseudo aneurysm, myocardial rupture and intracardiac masses (tumours and thrombi).6,7,10–12 Recently, CE has been proposed, in a case-report8 and a retrospective case series,9 as a potentially useful imaging modality in the evaluation of patients with a LVAD. Moser et al.8 reported the case of a 25-year-old woman with a non-ischaemic cardiomyopathy and a LVAD (HeartMate II). Echocardiography revealed an apical pseudo aneurysm on SE, additional CE demonstrated a bidirectional flow between the LV and the pseudo-aneurysm evident by contrast enhancement. This case demonstrates the critical role of SE and CE in the follow-up of patients with a LVAD to confirm circulatory function and exclude device-related complications. Fine et al.9 retrospectively reviewed the records of 251 patients with a LVAD implantation who received a clinically indicated echocardiogram. Of them, 10 (4%) patients with a LVAD (HeartMate II in 9, Heartmate XVE in 1 patient) underwent a CE study, of whom 2 patients had a repeat CE study. No adverse events or known side-effects occurred during or after CE. These patients underwent a CE because of a suboptimal endocardial border delineation during SE. The use of contrast agent (Definity in 9 and Optison in 3 patients) aided image interpretation in 10 (83%) CE examinations. The current prospective study confirms that CE in patients with a LVAD (all patients had a HeartMate 3) is safe, and can be performed with a regular dose of contrast agent (Sonovue). There were no signs that the LVAD caused a substantial destruction of the contrast agent. This study has clinically relevant implications. This study shows that the SE allowed visualization of 57% of LV segments. After safe and easy intravenous administration of the ultrasound contrast agent, CE resulted in visualization of 79% of LV segments. Moreover, LV size determination could be obtained more often due to improved LV visualization using CE. Clearly, segmental and global LV function and LVEDV are important parameters in patients with a LVAD to monitor alterations in response to therapy and to diagnose potential complications. This study has several limitations. First, because this was a pilot study, the number of patients that was considered was small. Second, potential destruction of the contrast agent by the LVAD was visually assessed and could not be quantitatively assessed. Third, this study was performed with Sonovue contrast agent, and it is not clear whether the results can be extrapolated to CE using other agents. Fourth, all of the patients had a HeartMate 3 LVAD, and it is not sure whether the current results can be extrapolated to patients with other LVAD systems. Fifth, the mentioned contraindications were considered at the time of the study conception and design, recently the contraindications have been removed by the US Food and Drug Administration Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent. Supplementary data Supplementary data are available at European Heart Journal-Cardiovascular Imaging online. Conflict of interest: None declared. References 1 Slaughter MS , Rogers JG , Milano CA , Russell SD , Conte JV , Feldman D et al. Advanced heart failure treated with continuous-flow left ventricular assist device . N Engl J Med 2009 ; 361 : 2241 – 51 . Google Scholar CrossRef Search ADS PubMed 2 Jorde UP , Kushwaha SS , Tatooles AJ , Naka Y , Bhat G , Long JW et al. Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support) . J Am Coll Cardiol 2014 ; 63 : 1751 – 7 . Google Scholar CrossRef Search ADS PubMed 3 McIlvennan CK , Magid KH , Ambardekar AV , Thompson JS , Matlock DD , Allen LA. Clinical outcomes after continuous-flow left ventricular assist device: a systematic review . Circ Heart Fail 2014 ; 7 : 1003 – 13 . Google Scholar CrossRef Search ADS PubMed 4 Estep JD , Stainback RF , Little SH , Torre G , Zoghbi WA. The role of echocardiography and other imaging modalities in patients with left ventricular assist devices . JACC Cardiovasc Imaging 2010 ; 3 : 1049 – 64 . Google Scholar CrossRef Search ADS PubMed 5 Ammar KA , Umland MM , Kramer C , Sulemanjee N , Jan MF , Khandheria BK et al. The ABCs of left ventricular assist device echocardiography: a systematic approach . Eur Heart J Cardiovasc Imaging 2012 ; 13 : 885 – 99 . Google Scholar CrossRef Search ADS PubMed 6 Feinstein SB , Coll B , Staub D , Adam D , Schinkel AF , ten Cate FJ et al. Contrast enhanced ultrasound imaging . J Nucl Cardiol 2010 ; 17 : 106 – 15 . Google Scholar CrossRef Search ADS PubMed 7 Schinkel AF , Kaspar M , Staub D. Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis . Int J Cardiovasc Imaging 2016 ; 32 : 35 – 48 . Google Scholar CrossRef Search ADS PubMed 8 Moser AR , Hockman D , Magalski A , Main ML , Khumri TM , Austin BA. Apical pseudoaneurysm following continuous flow left ventricular assist device placement . Circ Heart Fail 2012 ; 5 : e53 – 4 . Google Scholar CrossRef Search ADS PubMed 9 Fine NM , Abdelmoneim SS , Dichak A , Kushwaha SS , Park SJ , Mulvagh SL. Safety and feasibility of contrast echocardiography for LVAD evaluation . JACC Cardiovasc Imaging 2014 ; 7 : 429 – 30 . Google Scholar CrossRef Search ADS PubMed 10 Porter TR , Abdelmoneim S , Belcik JT , McCulloch ML , Mulvagh SL , Olson JJ et al. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography . J Am Soc Echocardiogr 2014 ; 27 : 797 – 810 . Google Scholar CrossRef Search ADS PubMed 11 Mulvagh SL , Rakowski H , Vannan MA , Abdelmoneim SS , Becher H , Bierig SM et al. American Society of Echocardiography consensus statement on the clinical applications of ultrasonic contrast agents in echocardiography . J Am Soc Echocardiogr 2008 ; 21 : 1179 – 201 . Google Scholar CrossRef Search ADS PubMed 12 Senior R , Becher H , Monaghan M , Agati L , Zamorano J , Vanoverschelde JL et al. Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography . Eur J Echocardiogr 2009 ; 10 : 194 – 212 . Google Scholar CrossRef Search ADS PubMed 13 Main ML , Ryan AC , Davis TE , Albano MP , Kusnetzky LL , Hibberd M. Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (multicenter registry results in 4,300,966 consecutive patients) . Am J Cardiol 2008 ; 102 : 1742 – 6 . Google Scholar CrossRef Search ADS PubMed 14 Main ML , Hibberd MG , Ryan A , Lowe TJ , Miller P , Bhat G. Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent . JACC Cardiovasc Imaging 2014 ; 7 : 40 – 8 . Google Scholar CrossRef Search ADS PubMed 15 Reilly JP , Tunick PA , Timmermans RJ , Stein B , Rosenzweig BP , Kronzon I. Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients . J Am Coll Cardiol 2000 ; 35 : 485 – 90 . Google Scholar CrossRef Search ADS PubMed 16 Kurt M , Shaikh KA , Peterson L , Kurrelmeyer KM , Shah G , Nagueh SF et al. Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort . J Am Coll Cardiol 2009 ; 53 : 802 – 10 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Jul 26, 2017

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