Calcific Aortic Stenosis-A Review on Acquired Mechanisms of the Disease and Treatments.

Calcific aortic stenosis is a progressive disease that has become more prevalent in recent decades. Despite advances in research to uncover underlying biomechanisms, and development of new generations of prosthetic valves and replacement techniques, management of calcific aortic stenosis still comes with unresolved complications. In this review, we highlight underlying molecular mechanisms of acquired aortic stenosis calcification in relation to hemodynamics, complications related to the disease, diagnostic methods, and evolving treatment practices for calcific aortic stenosis.

In Vivo Pressurization of the Zebrafish Embryonic Heart as a Tool to Characterize Tissue Properties During Development.

Cardiac morphogenesis requires an intricate orchestration of mechanical stress to sculpt the heart as it transitions from a straight tube to a multichambered adult heart. Mechanical properties are fundamental to this process, involved in a complex interplay with function, morphology, and mechanotransduction. In the current work, we propose a pressurization technique applied to the zebrafish atrium to quantify mechanical properties of the myocardium under passive tension. By further measuring deformation, we obtain a pressure-stretch relationship that is used to identify constitutive models of the zebrafish embryonic cardiac tissue. Two-dimensional results are compared with a three-dimensional finite element analysis based on reconstructed embryonic heart geometry. Through these steps, we found that the myocardium of zebrafish results in a stiffness on the order of 10 kPa immediately after the looping stage of development. This work enables the ability to determine how these properties change under normal and pathological heart development.

Effect of Left and Right Coronary Flow Waveforms on Aortic Sinus Hemodynamics and Leaflet Shear Stress: Correlation with Calcification Locations.

Coronary flow induces hemodynamic alterations in the aortic sinus region. The objectives of this study are to: (1) investigate the differences among sinus hemodynamics and leaflet wall shear stresses engendered by the left versus right versus non-coronary flow and (2) correlate respective wall shear stresses with leaflet calcification in patients. A left heart simulator flow loop with a tunable coronary circuit provided physiological coronary flow waveforms corresponding to the left coronary cusp case (LCC), right coronary cusp case (RCC), and non-coronary cusp case (NCC). High spatio-temporal resolution particle image velocimetry was conducted to quantify leaflet wall shear stress and sinus vorticity fields and to measure aortic leaflet tip kinematics. Thirty-one patients with severe calcific aortic valve disease were segmented from CT data for the calcific volumes in their respective left, right, and non-coronary cusps. Leaflet tip position during systole shows the RCC has a wider leaflet opening compared to LCC and NCC. Velocity and vorticity fields combined with leaflet position data show that sinus vorticity is diminished (peak ~ 43 s-1) in the LCC while RCC and NCC maintain high vorticity (~ 1200 and ~ 950 s-1 respectively). WSS magnitudes greater than 0.3 Pa show 20 and 81% greater occurrences in the LCC and RCC respectively compared to NCC. Significant differences [X2 (2, n = 31) = 7.31, p = 0.0258] between the calcification levels in each cusp of the patient population. Coronary flow differences between LCC, RCC, and NCC show significant impact on leaflet kinematics and sinus flow hemodynamics. Clinical data correlations of the coronary flow cases indicate the left coronary cusp has a higher likelihood of calcification compared to the right.

Right ventricle in hypoplastic left heart syndrome exhibits altered hemodynamics in the human fetus.

Hypoplastic left heart syndrome (HLHS) represents approximately 9% of all congenital heart defects and is one of the most complex, with the left side of the heart being generally underdeveloped. Numerous studies demonstrate that intracardiac fluid flow patterns in the embryonic and fetal circulation can impact cardiac structural formation and remodeling. This highlights the importance of quantifying the altered hemodynamic environment in congenital heart defects, like HLHS, relative to a normal heart as it relates to cardiac development. Therefore, to study human cardiovascular fetal flow, computational fluid dynamic simulations were performed using 4D patient-specific ultrasound scans in normal and HLHS hearts. In these simulations, we find that the HLHS right ventricle exhibits a greater cardiac output than normal; yet, hemodynamics are relatively similar between normal and HLHS right ventricles. Overall, this study provides detailed quantitative flow patterns for HLHS, which has the potential to guide future prevention and therapeutic interventions, while more immediately providing additional functional detail to cardiologists to aid in decision making.