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ORIGINAL ARTICLE The Feasibility and Clinical Utility of Microsphere Contrast-enhanced Transthoracic Echocardiography in Adult Congenital Heart Disease David G. Platts, MBBS, MD, FRACP, FCSANZ, FESC, FASE,*† Natalie F.A. Kelly, Masters of Cardiac Ultrasound, B Ex Sc,* Vishva A. Wijesekera, MBChB, FRACP,‡ Abhishek Sengupta, MBBS,§ Kylie Burns, MBBS, FRACP,‡ Darryl J. Burstow, MBBS, FRACP,*† Thomas Butler, MBBS, FRACP,* Dorothy J. Radford, MBBS, MD, FRCP(E), FRACP,*†‡ and Mugur Nicolae, MD, FRACP*‡ *Department of Echocardiography, ‡Adult Congenital Heart Service, and §Cardiology Department, The Prince Charles Hospital, Brisbane, Queensland, Australia; †School of Medicine, The University of Queensland, Brisbane, Queensland, Australia ABSTRACT
Background. Transthoracic echocardiography (TTE) plays a key role in adult congenital heart disease (ACHD). However, a significant number of studies are nondiagnostic due to poor image quality. Enhancement of the blood pool-tissue interface with contrast-enhanced TTE (CE-TTE) can improve image quality in suboptimal studies. The aim of this analysis was to evaluate feasibility and clinical utility of CE-TTE in the assessment of patients with ACHD. Methods. A retrospective analysis of all CE-TTE performed in ACHD patients at our institution from August 2007 to May 2014 was performed. Endocardial definition scores (EDS) for each segment in the right and left ventricles were graded pre- and postcontrast imaging, as 1 = good, 2 = suboptimal, 3 = not seen. The endocardial border definition score index (EBDSI) was also calculated pre- and postcontrast imaging. Results. Twenty patients with ACHD had 24 CE. Summation data for all ventricular EDS for unenhanced TTE vs. CE-TTE imaging was: EDS 1 = 136 vs. 314, EDS 2 = 119 vs. 72, EDS 3 = 162 vs. 31, respectively. Wilcoxon matched-pairs rank-signed test showed a significant ranking difference (improvement) pre- and postcontrast for the combined ventricular data (P < .0001) and the individual left and right ventricular data (all P < .0001). The EBDSI for combined ventricular data using CE-TTE was significantly lower than for noncontrast imaging (1.23 ± 0.49 vs. 2.06 ± 0.62, P < .0001). There was one minor contrast adverse reaction. Conclusions. CE-TTE resulted in significantly improved right and left ventricular endocardial definition and improved EDBSI. CE-TTE should be viewed as an additional imaging technique that is available to help assess patients with ACHD, especially those with nondiagnostic images. Key Words. Transthoracic Echocardiography; Contrast Microspheres; Adult Congenital Heart Disease
Introduction
C
ongenital heart disease is a common cardiac disorder, with an annual incidence approximately 1 in 100 live births.1 Prior to corrective surgery being performed in a successful manner, complex congenital lesions had a high early mortality. However, with significant improvements in © 2015 Wiley Periodicals, Inc.
patient management, this group of cardiac patients are now living into adult life.2–4 It is estimated that there are approximately 2 million people alive with congenital heart disease in the United States and at least 1 million of these are over the age of 18 years.5 These patients with adult congenital heart disease (ACHD) require specialized care through dedicated ACHD clinics as well as multidisciCongenit Heart Dis. 2015;••:••–••
2 plinary care provided by personnel trained in ACHD. One such discipline is echocardiography, which has a key role to play in diagnosis, serial monitoring, detection of complications, and assessing response to therapy in ACHD.6,7 Transthoracic echocardiography (TTE) is a safe, noninvasive, and well-tolerated investigation that provides information about cardiac structure and function in a timely and cost-effective manner.8–10 However, in approximately 20% of adult TTEs, the image quality is suboptimal, rendering the images nondiagnostic.11–13 In light of the complex nature of ACHD patients, the rate of nondiagnostic TTE may be higher, though there is no published data to confirm this. Contrast-enhanced TTE (CE-TTE) using intravenously administered contrast microsphere agents is a well accepted imaging modality used to convert a nondiagnostic TTE into a diagnostic TTE, by enhancing the blood poolmyocardial interface and improving endocardial definition.14,15 However, the role of CE-TTE in the ACHD population has not been a focus of attention. Currently, these contrast agents are also contraindicated in the presence of an intracardiac shunt. This analysis sought to assess the feasibility and clinical utility of using CE-TTE in patients with a heterogeneous group of ACHD.
Methods
A retrospective analysis of all CE-TTE performed in patients with ACHD was performed (from August 2007 to May 2014). Patients were included if they had congenital heart disease and had survived into adulthood. Conventional valvular or myocardial congenital defects seen in adult cardiac practice, such as a bicuspid aortic valve or ventricular noncompaction, were excluded from the analysis. All patients had a standard unenhanced TTE prior to a contrast-enhanced study, by a sonographer trained and experienced in scanning patients with ACHD. The CE-TTE was performed by a contrast and ACHD-trained sonographer and interpreted by a single expert reader in contrastenhanced transthoracic imaging. Conventional contrast-specific imaging was performed during the administration of the contrast agent Definity (Lantheus Medical Imaging, Billerica, MA, USA). This agent is a perflutren microsphere contrast agent with a mean diameter of 1.1 to 3.3 μ,16 consisting of an outer tri-lipid shell and an inner gaseous core of the biologically inert gas, octofluoropropane. Congenit Heart Dis. 2015;••:••–••
Platts et al. Following activation of the contrast agent, one vial of contrast consisting of 1.3 mL was diluted with normal saline to either 10 mL or 50 mL. If diluted to 10 mL, the contrast was administered as intermittent boluses of approximately 0.5–1.0 mL. If the contrast was diluted to 50 mL, it was administered as an infusion, using an Alaris GH Plus infusion pump (CareFusion, San Diego, CA, USA), starting at 150 mL/hour and up-titrated to optimize the contrast image. The following parameters were collected: patient demographics, diagnosis, indication for CE-TTE, method of contrast administration, presence of any implantable cardiac device, description of any adverse reactions and diagnostic information obtained. The conventional left-sided ventricle was imaged in conventional apical four, two, and three views. The endocardial definition scores (EDS) for each segment was graded pre- and postcontrast imaging, using the conventional scoring system of 1 = good, 2 = suboptimal, 3 = not seen. The endocardial border definition score index (EBDSI) was also calculated pre- and postcontrast imaging, by dividing the sum of the endocardial definition scores by the number of segments graded. A normal EBDSI is one, with worsening image quality resulting in increasingly higher scores. For systemic and conventional (pulmonic) right ventricular assessment of EDS, imaging was optimized to view the right ventricle from an apical acoustic window. The right ventricle was then divided into two halves down its long axis. Each half (free wall and septal) was then split into threethirds (basal, mid, and apical segments). This generated six right ventricular segments for evaluation. In those patients with a systemic right ventricle, analysis was only performed in an equivalent apical four chamber view, to enable standardization across a heterogeneous group of pathologies. Continuous variables were expressed as mean ± one standard deviation. Comparison between the continuous variables was performed using a paired t-test. Categorical variables were expressed as absolute values. Comparison between the categorical variables for EDS was performed using the Wilcoxon signed-rank test. A P value of
ORIGINAL ARTICLE The Feasibility and Clinical Utility of Microsphere Contrast-enhanced Transthoracic Echocardiography in Adult Congenital Heart Disease David G. Platts, MBBS, MD, FRACP, FCSANZ, FESC, FASE,*† Natalie F.A. Kelly, Masters of Cardiac Ultrasound, B Ex Sc,* Vishva A. Wijesekera, MBChB, FRACP,‡ Abhishek Sengupta, MBBS,§ Kylie Burns, MBBS, FRACP,‡ Darryl J. Burstow, MBBS, FRACP,*† Thomas Butler, MBBS, FRACP,* Dorothy J. Radford, MBBS, MD, FRCP(E), FRACP,*†‡ and Mugur Nicolae, MD, FRACP*‡ *Department of Echocardiography, ‡Adult Congenital Heart Service, and §Cardiology Department, The Prince Charles Hospital, Brisbane, Queensland, Australia; †School of Medicine, The University of Queensland, Brisbane, Queensland, Australia ABSTRACT
Background. Transthoracic echocardiography (TTE) plays a key role in adult congenital heart disease (ACHD). However, a significant number of studies are nondiagnostic due to poor image quality. Enhancement of the blood pool-tissue interface with contrast-enhanced TTE (CE-TTE) can improve image quality in suboptimal studies. The aim of this analysis was to evaluate feasibility and clinical utility of CE-TTE in the assessment of patients with ACHD. Methods. A retrospective analysis of all CE-TTE performed in ACHD patients at our institution from August 2007 to May 2014 was performed. Endocardial definition scores (EDS) for each segment in the right and left ventricles were graded pre- and postcontrast imaging, as 1 = good, 2 = suboptimal, 3 = not seen. The endocardial border definition score index (EBDSI) was also calculated pre- and postcontrast imaging. Results. Twenty patients with ACHD had 24 CE. Summation data for all ventricular EDS for unenhanced TTE vs. CE-TTE imaging was: EDS 1 = 136 vs. 314, EDS 2 = 119 vs. 72, EDS 3 = 162 vs. 31, respectively. Wilcoxon matched-pairs rank-signed test showed a significant ranking difference (improvement) pre- and postcontrast for the combined ventricular data (P < .0001) and the individual left and right ventricular data (all P < .0001). The EBDSI for combined ventricular data using CE-TTE was significantly lower than for noncontrast imaging (1.23 ± 0.49 vs. 2.06 ± 0.62, P < .0001). There was one minor contrast adverse reaction. Conclusions. CE-TTE resulted in significantly improved right and left ventricular endocardial definition and improved EDBSI. CE-TTE should be viewed as an additional imaging technique that is available to help assess patients with ACHD, especially those with nondiagnostic images. Key Words. Transthoracic Echocardiography; Contrast Microspheres; Adult Congenital Heart Disease
Introduction
C
ongenital heart disease is a common cardiac disorder, with an annual incidence approximately 1 in 100 live births.1 Prior to corrective surgery being performed in a successful manner, complex congenital lesions had a high early mortality. However, with significant improvements in © 2015 Wiley Periodicals, Inc.
patient management, this group of cardiac patients are now living into adult life.2–4 It is estimated that there are approximately 2 million people alive with congenital heart disease in the United States and at least 1 million of these are over the age of 18 years.5 These patients with adult congenital heart disease (ACHD) require specialized care through dedicated ACHD clinics as well as multidisciCongenit Heart Dis. 2015;••:••–••
2 plinary care provided by personnel trained in ACHD. One such discipline is echocardiography, which has a key role to play in diagnosis, serial monitoring, detection of complications, and assessing response to therapy in ACHD.6,7 Transthoracic echocardiography (TTE) is a safe, noninvasive, and well-tolerated investigation that provides information about cardiac structure and function in a timely and cost-effective manner.8–10 However, in approximately 20% of adult TTEs, the image quality is suboptimal, rendering the images nondiagnostic.11–13 In light of the complex nature of ACHD patients, the rate of nondiagnostic TTE may be higher, though there is no published data to confirm this. Contrast-enhanced TTE (CE-TTE) using intravenously administered contrast microsphere agents is a well accepted imaging modality used to convert a nondiagnostic TTE into a diagnostic TTE, by enhancing the blood poolmyocardial interface and improving endocardial definition.14,15 However, the role of CE-TTE in the ACHD population has not been a focus of attention. Currently, these contrast agents are also contraindicated in the presence of an intracardiac shunt. This analysis sought to assess the feasibility and clinical utility of using CE-TTE in patients with a heterogeneous group of ACHD.
Methods
A retrospective analysis of all CE-TTE performed in patients with ACHD was performed (from August 2007 to May 2014). Patients were included if they had congenital heart disease and had survived into adulthood. Conventional valvular or myocardial congenital defects seen in adult cardiac practice, such as a bicuspid aortic valve or ventricular noncompaction, were excluded from the analysis. All patients had a standard unenhanced TTE prior to a contrast-enhanced study, by a sonographer trained and experienced in scanning patients with ACHD. The CE-TTE was performed by a contrast and ACHD-trained sonographer and interpreted by a single expert reader in contrastenhanced transthoracic imaging. Conventional contrast-specific imaging was performed during the administration of the contrast agent Definity (Lantheus Medical Imaging, Billerica, MA, USA). This agent is a perflutren microsphere contrast agent with a mean diameter of 1.1 to 3.3 μ,16 consisting of an outer tri-lipid shell and an inner gaseous core of the biologically inert gas, octofluoropropane. Congenit Heart Dis. 2015;••:••–••
Platts et al. Following activation of the contrast agent, one vial of contrast consisting of 1.3 mL was diluted with normal saline to either 10 mL or 50 mL. If diluted to 10 mL, the contrast was administered as intermittent boluses of approximately 0.5–1.0 mL. If the contrast was diluted to 50 mL, it was administered as an infusion, using an Alaris GH Plus infusion pump (CareFusion, San Diego, CA, USA), starting at 150 mL/hour and up-titrated to optimize the contrast image. The following parameters were collected: patient demographics, diagnosis, indication for CE-TTE, method of contrast administration, presence of any implantable cardiac device, description of any adverse reactions and diagnostic information obtained. The conventional left-sided ventricle was imaged in conventional apical four, two, and three views. The endocardial definition scores (EDS) for each segment was graded pre- and postcontrast imaging, using the conventional scoring system of 1 = good, 2 = suboptimal, 3 = not seen. The endocardial border definition score index (EBDSI) was also calculated pre- and postcontrast imaging, by dividing the sum of the endocardial definition scores by the number of segments graded. A normal EBDSI is one, with worsening image quality resulting in increasingly higher scores. For systemic and conventional (pulmonic) right ventricular assessment of EDS, imaging was optimized to view the right ventricle from an apical acoustic window. The right ventricle was then divided into two halves down its long axis. Each half (free wall and septal) was then split into threethirds (basal, mid, and apical segments). This generated six right ventricular segments for evaluation. In those patients with a systemic right ventricle, analysis was only performed in an equivalent apical four chamber view, to enable standardization across a heterogeneous group of pathologies. Continuous variables were expressed as mean ± one standard deviation. Comparison between the continuous variables was performed using a paired t-test. Categorical variables were expressed as absolute values. Comparison between the categorical variables for EDS was performed using the Wilcoxon signed-rank test. A P value of
