Ikechukwu Okafor

The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus

Background: Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon. Methods: Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus). Results: SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (R2=0.7, P<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. Conclusions: Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.

The Effect of Valve-in-Valve Implantation Height on Sinus Flow

Valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) has proven to be a successful treatment for high risk patients with failing aortic surgical bioprostheses. However, thrombus formation on the leaflets of the valve has emerged as a major issue in such procedures, posing a risk of restenosis, thromboembolism, and reduced durability. In this work we attempted to understand the effect of deployment position of the transcatheter heart valve (THV) on the spatio-temporal flow field within the sinus in VIV-TAVR. Experiments were performed in an in vitro pulsatile left heart simulator using high-speed Particle Image Velocimetry (PIV) to measure the flow field in the sinus region. The time-resolved velocity data was used to understand the qualitative and quantitative flow patterns. In addition, a particle tracking technique was used to evaluate relative thrombosis risk via sinus washout. The velocity data demonstrate that implantation position directly affects sinus flow patterns, leading to increased flow stagnation with increasing deployment height. The particle tracking simulations showed that implantation position directly affected washout time, with the highest implantation resulting in the least washout. These results clearly demonstrate the flow pattern and flow stagnation in the sinus is sensitive to THV position. It is, therefore, important for the interventional cardiologist and cardiac surgeon to consider how deployment position could impact flow stagnation during VIV-TAVR.

Role of Mitral Annulus Diastolic Geometry on Intraventricular Filling Dynamics

The mitral valve (MV) is a bileaflet valve positioned between the left atrium and ventricle of the heart. The annulus of the MV has been observed to undergo geometric changes during the cardiac cycle, transforming from a saddle D-shape during systole to a flat (and less eccentric) D-shape during diastole. Prosthetic MV devices, including heart valves and annuloplasty rings, are designed based on these two configurations, with the circular design of some prosthetic heart valves (PHVs) being an approximation of the less eccentric, flat D-shape. Characterizing the effects of these geometrical variations on the filling efficiency of the left ventricle (LV) is required to understand why the flat D-shaped annulus is observed in the native MV during diastole in addition to optimizing the design of prosthetic devices. We hypothesize that the D-shaped annulus reduces energy loss during ventricular filling. An experimental left heart simulator (LHS) consisting of a flexible-walled LV physical model was used to characterize the filling efficiency of the two mitral annular geometries. The strength of the dominant vortical structure formed and the energy dissipation rate (EDR) of the measured fields, during the diastolic period of the cardiac cycle, were used as metrics to quantify the filling efficiency. Our results indicated that the O-shaped annulus generates a stronger (25% relative to the D-shaped annulus) vortical structure than that of the D-shaped annulus. It was also found that the O-shaped annulus resulted in higher EDR values throughout the diastolic period of the cardiac cycle. The results support the hypothesis that a D-shaped mitral annulus reduces dissipative energy losses in ventricular filling during diastole and in turn suggests that a symmetric stent design does not provide lower filling efficiency than an equivalent asymmetric design.

The hemodynamic effects of acute aortic regurgitation into a stiffened left ventricle resulting from chronic aortic stenosis

Acute aortic regurgitation (AR) post-chronic aortic stenosis is a prevalent phenomenon occurring in patients who undergo transcatheter aortic valve replacement (TAVR) surgery. The objective of this work was to characterize the effects of left ventricular diastolic stiffness (LVDS) and AR severity on LV performance. Three LVDS models were inserted into a physiological left heart simulator. AR severity was parametrically varied through four levels (ranging from trace to moderate) and compared with a competent aortic valve. Hemodynamic metrics such as average diastolic pressures (DP) and reduction in transmitral flow were measured. AR index was calculated as a function of AR severity and LVDS, and the work required to make up for lost volume due to AR was estimated. In the presence of trace AR, higher LVDS had up to a threefold reduction in transmitral flow (13% compared with 3.5%) and a significant increase in DP (2-fold). The AR index ranged from ∼42 to 16 (no AR to moderate AR), with stiffer LVs having lower values. To compensate for lost volume due to AR, the low, medium, and high LVDS models were found to require 5.1, 5.5, and 6.6 times more work, respectively. This work shows that the LVDS has a significant effect on the LV performance in the presence of AR. Therefore, the LVDS of potential TAVR patients should be assessed to gain an initial indication of their ability to tolerate post-procedural AR.

Atrial systole enhances intraventricular filling flow propagation during increasing heart rate

Diastolic fluid dynamics in the left ventricle (LV) has been examined in multiple clinical studies for understanding cardiac function in healthy humans and developing diagnostic measures in disease conditions. The question of how intraventricular filling vortex flow pattern is affected by increasing heart rate (HR) is still unanswered. Previous studies on healthy subjects have shown a correlation between increasing HR and diminished E/A ratio of transmitral peak velocities during early filling (E-wave) to atrial systole (A-wave). We hypothesize that with increasing HR under constant E/A ratio, E-wave contribution to intraventricular vortex propagation is diminished. A physiologic in vitro flow phantom consisting of a LV physical model was used for this study. HR was varied across 70, 100 and 120 beats per minute (bpm) with E/A of 1.1-1.2. Intraventricular flow patterns were characterized using 2D particle image velocimetry measured across three parallel longitudinal (apical-basal) planes in the LV. A pair of counter-rotating vortices was observed during E-wave across all HRs. With increasing HR, diminished vortex propagation occurred during E-wave and atrial systole was found to amplify secondary vorticity production. The diastolic time point where peak vortex circulation occurred was delayed with increasing HR, with peak circulation for 120bpm occurring as late as 90% into diastole near the end of A-wave. The role of atrial systole is elevated for higher HR due to the limited time available for filling. Our baseline findings and analysis approach can be applied to studies of clinical conditions where impaired exercise tolerance is observed.

A physiologic flow phantom for the evaluation of 4D flow MRI in the left ventricle

Background 4D PCMR has the potential to help in understanding the direct relationship between fluid and structure interaction within the cardiovascular system, to allow for 3D visualization of blood flow patterns in the heart, and to make direct wall shear stress measurements. However, the wide dynamic range of velocities in the left ventricle (LV, range of 0-200 cm/s) can create difficulties when optimizing acquisition protocols, especially when attempting to measure complex flow features during filling and diastasis. Additionally, there is no reference standard method to validate velocity flow and wall shear stress measurements. Here we describe our experience with a custom-built MRI compatible physiologic left heart flow phantom which can be used to optimize acquisition parameters, and can be used in the lab to make velocity measurements with particle image velocimetry (PIV).