Award Date

5-1-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdisciplinary Programs

First Committee Member

Thessa Hilgenkamp

Second Committee Member

Brach Poston

Third Committee Member

Samantha John

Fourth Committee Member

Jenny Kent

Number of Pages

143

Abstract

BACKGROUND: This dissertation presents a comprehensive echocardiographic evaluation of cardiac structure, function, and ventricular-arterial coupling in adults with Down syndrome (Ds). Individuals with Down syndrome are living longer due to significant improvements in medical care and early surgical repair of congenital heart defects; however, cardiovascular disease remains a leading cause of mortality in this population. Despite this, detailed cardiac assessment of adults with Down syndrome without congenital heart defects remains underrepresented in cardiovascular research, with most existing literature focusing on pediatric populations or congenital anomalies.AIMS: The primary objective of this research was to compare cardiac structure, systolic and diastolic function, and ventricular-arterial coupling between adults with Down syndrome and age- and activity-matched adults without Down syndrome. METHODS: This study used a cross-sectional design including 40 adults with Down syndrome and 20 adults without Down syndrome, aged 18-35, with similar low physical activity levels. Comprehensive baseline echocardiographic examinations were performed by a certified Registered Diagnostic Cardiac Sonographer (RDCS) following the American Society of Echocardiography guidelines. Measurements were obtained using multiple echocardiographic views (parasternal long axis, parasternal short axis, apical four-chamber, apical two-chamber, and apical five-chamber) and various imaging modalities (2-D imaging, M-mode, Tissue Doppler Imaging, and Simpson's biplane) to acquire a comprehensive assessment of cardiac dimensions, volumes, velocities, and functional parameters. RESULTS: The first study (Chapter 2) focused on cardiac size and systolic function, showing that adults with Down syndrome had significantly smaller left ventricular internal diameters during diastole (LVIDd) and systole (LVIDs), smaller left ventricular end-systolic volumes indexed to body surface area (LVESVI), and smaller left atrial dimensions (LAD) and volumes indexed to body surface area (LAVI) compared to adults without Down syndrome. In this study, adults with Down syndrome had lower diastolic blood pressure and lower stroke volume than adults without Down syndrome. Despite having smaller internal diameters and volumes, adults with Down syndrome demonstrated higher ejection fractions and fractional shortening, suggesting compensatory mechanisms that help maintain cardiac output. The second study (Chapter 3) examined diastolic function, demonstrating that adults with Down syndrome had significantly reduced lateral Tissue Doppler Imaging (TDI) of early diastolic myocardial velocity (Em), suggesting impaired myocardial relaxation during early diastole. Conversely, they exhibited higher mitral inflow velocity (eV), indicating a compensatory mechanism for rapid ventricular filling. These findings suggest altered diastolic mechanics characterized by reduced myocardial relaxation velocities and increased early filling velocities, reflecting a complex pattern of diastolic function. The third study (Chapter 4) provided novel insights into ventricular-arterial coupling (VAC) in adults with Down syndrome using the non-invasive single-beat method described by Chen et al. Adults with Down syndrome had significantly lower VAC ratios, faster pre-ejection times (PEP), and shorter normalized systolic durations (tNd) compared to adults without Down syndrome. These parameters suggest that in this study, adults with Down syndrome spent less time in systole, generated left ventricular pressure more rapidly, and exhibited a different balance between ventricular and arterial function than adults without Down syndrome. The findings of this dissertation reveal a unique cardiac phenotype in adults with Down syndrome characterized by smaller cardiac dimensions and volumes, compensatory systolic hyperfunction, altered diastolic mechanics, and a distinct ventricular-arterial coupling profile. These findings suggest that adults with Down syndrome maintained cardiac output at rest through several compensatory mechanisms: (1) higher ejection fraction and fractional shortening to maximize stroke volume from smaller ventricular dimensions, and volumes (2) increased early mitral inflow velocities to optimize diastolic filling despite reduced myocardial relaxation, and (3) rapid pressure generation during a shortened systolic period. Lower diastolic blood pressure in adults with Down syndrome may be an additional physiological factor that could impact cardiac function in this population. Lower diastolic blood pressure could decrease coronary perfusion during diastole and reduce preload due to diminished venous return, necessitating the compensatory mechanisms observed in this study. This challenges the traditional view that lower blood pressure is universally beneficial and suggests that lower diastolic blood pressure in adults with Down syndrome may contribute to a complex pattern of cardiovascular compensatory mechanisms. CONCLUSION: This dissertation provides several key contributions to the field. First, it challenges the conventional interpretation that a higher ejection fraction indicates superior cardiac function, demonstrating that a higher ejection fraction in adults with Down syndrome reflects a compensatory mechanism to maintain cardiac output despite smaller cardiac dimensions and volumes. Second, it showed that adults with Down syndrome had impaired myocardial relaxation partially offset by increased early filling velocities. Third, it provides the first comprehensive assessment of ventricular-arterial coupling in adults with Down syndrome. These findings potentially have clinical implications, and clinicians should consider a comprehensive evaluation of structural parameters, diastolic function, and ventricular-arterial coupling to assess cardiovascular health in adults with Down syndrome thoroughly. Future research should explore whether the cardiac compensatory mechanisms observed in this study evolve with aging and whether they contribute to the increased cardiovascular mortality seen in older adults with Down syndrome. Longitudinal studies incorporating advanced echocardiographic techniques, such as 3D imaging and strain analysis, would provide valuable insights into this population's cardiac function. Additional investigation of the underlying mechanisms of increased cardiac contractility, including assessment of endothelial function and biomarkers of myocardial stress, would further enhance our understanding of cardiovascular physiology in adults with Down syndrome. In conclusion, this dissertation illustrates that adults with Down syndrome exhibited a distinct cardiac phenotype characterized by smaller cardiac dimensions and volumes, compensatory hypercontractile systolic function, altered diastolic mechanics, and less efficient ventricular-arterial coupling. These adaptations assist in maintaining cardiac output at rest but may lead to reduced cardiac reserve. This research establishes a foundation for improved cardiovascular assessment and care in this expanding adult population by providing a more nuanced understanding of cardiac function in adults with Down syndrome.

Keywords

cardiac function; cardiac size; cardiac ultrasound; Down syndrome; Echocardiogram; ventricular-arterial coupling

Disciplines

Investigative Techniques | Medical Neurobiology | Medicine and Health Sciences | Neuroscience and Neurobiology | Neurosciences

File Format

PDF

File Size

1142 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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Available for download on Monday, May 15, 2028


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