Contrast Enhanced Three Dimensional Echocardiographic Quantification of Right Ventricular Volumes in Repaired Congenital Heart Disease

We propose the novel integration of two echocardiographic technologies - three-dimensional echocardiography using semi-automated right ventricular analysis coupled with the administration of ultrasound enhancing agents - to improve the inter-rater reliability and accuracy of various measures of right ventricular size and function, compared with cardiac MRI.

Patients with repaired congenital heart disease with residual pulmonary insufficiency represent a challenging group of patients with congenital heart disease as they develop progressive right ventricular dilation and failure, increasing the risk for sudden cardiac death and often necessitating pulmonary valve replacement. These patients require close follow-up with serial cardiac imaging; however, the complex three-dimensional structure of these dilated right ventricles renders them difficult to adequately image with traditional two-dimensional echocardiography. Due to these difficulties, cardiac MRI is the current gold standard for assessing right ventricular size and function in these patients. However, cardiac MRI is costly and less accessible for patients than echocardiography. Although initial studies comparing 3D echocardiography with MRI showed that 3D echocardiography underestimates right ventricular size, recent advances in three-dimensional imaging technologies which utilize automated ultrasound "speckle-tracking" and artificial intelligence technology are lessening this inherent bias. Furthermore, the use of commercially-available ultrasound enhancing agents made of lipid microspheres has improved left ventricular endocardial border detection, inter-rater reliability and correlation of 3D echocardiography obtained estimates of left ventricular size and function compared with Cardiac Magnetic Resonance (CMR). However, their use has yet to be applied to the three-dimensional echocardiographic assessment of the right ventricle in congenital heart disease despite their ability to improve right ventricular endocardial border detection with three-dimensional echocardiography in adults. The investigators propose the novel integration of two echocardiographic technologies - three-dimensional echocardiography using semi-automated right ventricular analysis coupled with the administration of ultrasound enhancing agents - to change the paradigm of how clinicians assess the right ventricles of patients with repaired congenital heart disease with residual pulmonary insufficiency. The investigators hypothesize that ultrasound enhancing agents will improve the inter-rater reliability and accuracy of various measures of right ventricular size and function, compared with cardiac MRI, thereby filling an important gap in existing methods for assessing right ventricular function. Lastly, because of the current limitations in assessing right ventricular function in this population, as a secondary aim, the investigators will also assess three-dimensional right ventricular strain -- a novel quantitative surrogate of right ventricular function.

Overall Objectives: To shift the paradigm in the assessment of right ventricular size and function by developing a protocol to assess the right ventricles in patients with repaired congenital heart disease with residual pulmonary insufficiency by integrating the use of three-dimensional echocardiography with semi-automated right ventricular analysis software with the intravenous administration of ultrasound enhancing agents.

Specific Aim 1. To compare the accuracy and inter-rater reliability of 3D echocardiography-based measurements of right ventricular end-diastolic volume, end-systolic volume, and ejection fraction, with and without contrast, with MRI derived values in patients with repaired congenital heart disease with residual pulmonary insufficiency.

Specific Aim 2. To compare the accuracy and inter-rater reliability of 3D echocardiography measurement of right ventricular strain with MRI derived right ventricular (RV) strain in patients with repaired congenital heart disease with residual pulmonary insufficiency.

Eligibility Criteria:
Inclusion Criteria:

1. All patients aged 11 or greater with repaired congenital heart disease and residual pulmonary insufficiency who are referred to Nemours A.I. DuPont Hospital for Children for clinically indicated cardiac MRI will be eligible for inclusion.
2. Informed written consent of parent or legal guardian.
3. Informed written assent of subject, if appropriate.

Exclusion Criteria:

1. Any patients in which Lumason is contraindicated (i.e. prior anaphylactoid reaction) will be ineligible for the clinical ultrasound and ineligible for the study.
2. History of allergic reaction to Lumason, sulfur hexafluoride, sulfur hexafluoride lipid microsphere components, or other ingredients in Lumason (polyethylene glycol, distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na), palmitic acid)
3. Pregnant women will be excluded from the study as well since Lumason has not been studied in pregnancy.