Neelakantan Saikrishnan

Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. Although exact causes and mechanisms of AV calcification are unclear, previous studies suggest that mechanical forces play a role. Since calcium deposits occur almost exclusively on the aortic surfaces of AV leaflets, it has been hypothesized that adverse patterns of fluid shear stress on the aortic surface of AV leaflets promote calcification. The current study characterizes AV leaflet aortic surface fluid shear stresses using Laser Doppler velocimetry and an in vitro pulsatile flow loop. The valve model used was a native porcine valve mounted on a suturing ring and preserved using 0.15% glutaraldehyde solution. This valve model was inserted in a mounting chamber with sinus geometries, which is made of clear acrylic to provide optical access for measurements. To understand the effects of hemodynamics on fluid shear stress, shear stress was measured across a range of conditions: varying stroke volumes at the same heart rate and varying heart rates at the same stroke volume. Systolic shear stress magnitude was found to be much higher than diastolic shear stress magnitude due to the stronger flow in the sinuses during systole, reaching up to 20 dyn/cm2 at mid-systole. Upon increasing stroke volume, fluid shear stresses increased due to stronger sinus fluid motion. Upon increasing heart rate, fluid shear stresses decreased due to reduced systolic duration that restricted the formation of strong sinus flow. Significant changes in the shear stress waveform were observed at 90 beats/min, most likely due to altered leaflet dynamics at this higher heart rate. Overall, this study represents the most well-resolved shear stress measurements to date across a range of conditions on the aortic side of the AV. The data presented can be used for further investigation to understand AV biological response to shear stresses.

Accurate Assessment of Aortic Stenosis A Review of Diagnostic Modalities and Hemodynamics

Aortic valve (AV) stenosis is one of the most common valvular diseases and is the third most common cardiovascular disease in developed countries. It occurs in ≈2.8% of patients ≥75 years of age and can occur because of degenerative calcification and congenital valvular defects such as bicuspid AVs or rheumatic disease.1–3 Calcific aortic stenosis (AS) is associated with increased leaflet stiffness and a narrowed AV orifice, resulting in increased pressure gradients across the valve. The presence of a bicuspid AV significantly increases the risk of AS.4 The natural history of AS is a prolonged asymptomatic period, with progressive reduction of the AV orifice area due to sclerosis initially, culminating in calcific AS. This is accompanied by a corresponding increase in the transaortic pressure gradient (Δ P ) and myocardial pressure overload. Through the preload reserve, the left ventricle (LV) compensates for the increased workload until the sarcomeres stretch to their maximum diastolic length. Once the preload reserve is exhausted, increases in afterload are accompanied by a reduction in stroke volume (SV), resulting in afterload mismatch. Ultimately, this causes LV hypertrophy, associated with an enlargement of cardiac myocytes and increased LV wall thickness.5 Initial diagnosis of AS typically occurs during routine physical examination with the presence of a heart murmur, click, or other abnormal sounds, but undiagnosed patients may experience the onset of severe symptoms such as angina, syncope, and heart failure. Without intervention, patient mortality typically occurs within 5 years of the onset of symptoms.6–11 Multiple studies and reviews have focused on the clinical aspects of this disease, including disease progression, markers of disease severity, treatment guidelines, and outcomes.1–3,6,12–16 Very few reviews have focused on the hemodynamic principles underlying AS and on comparing data obtained across different …

Experimental and numeric investigation of Impella pumps as cavopulmonary assistance for a failing Fontan.

OBJECTIVE This study sought to evaluate the performance of microaxial ventricular assist devices for the purposes of supporting failing Fontan physiology by decreasing central venous pressure. METHODS Three Abiomed Impella pumps (Abiomed, Inc, Danvers, Mass) were evaluated in a mock circulatory system of the Fontan circuit. The local response of pressures and flows to pump function was assessed as a function of pump speed and pulmonary vascular resistance at a high baseline central venous pressure. For one device, subsequent modeling studies were conducted using a lumped parameter model of the single ventricle circuit. RESULTS The left ventricular devices (Impella 2.5, 5.0) were shown to be suboptimal as single device solutions for cavopulmonary support. The small area of these devices relative to vessel diameter led to significant flow recirculation without an obstructive separator in place. Furthermore, downstream pressure augmentation adversely affected the pressure in the superior vena cava. The use of 2 devices would be mandatory for successful support. The right-sided device (Impella RP), whose outflow was positioned in the left pulmonary artery, demonstrated decreased flow recirculation and did not impede superior caval venous flow. Although static pressure is still required to drive flow through the opposite lung, numeric modeling demonstrated the potential for modest but significant improvements in lowering the central venous pressure (2-8 mm Hg). CONCLUSIONS Left-sided microaxial pumps are not well suited for cavopulmonary support because of severe flow recirculation and the need for multiple devices. The right-ventricular Impella device provides improved performance by directing flow into the pulmonary artery, resulting in modest decreases in central venous pressure.

Mechanics of healthy and functionally diseased mitral valves: a critical review.

The mitral valve is a complex apparatus with multiple constituents that work cohesively to ensure unidirectional flow between the left atrium and ventricle. Disruption to any or all of the components-the annulus, leaflets, chordae, and papillary muscles-can lead to backflow of blood, or regurgitation, into the left atrium, which deleteriously effects patient health. Through the years, a myriad of surgical repairs have been proposed; however, a careful appreciation for the underlying structural mechanics can help optimize long-term repair durability and inform medical device design. In this review, we aim to present the experimental methods and significant results that have shaped the current understanding of mitral valve mechanics. Data will be presented for all components of the mitral valve apparatus in control, pathological, and repaired conditions from human, animal, and in vitro studies. Finally, current strategies of patient specific and noninvasive surgical planning will be critically outlined.

Reynolds number effects on scale energy balance in wall turbulence

The scale energy budget utilizes a modified version of the classical Kolmogorov equation of wall turbulence to develop an evolution equation for the second order structure function [R. J. Hill, “Exact second-order structure-function relationships,” J. Fluid Mech. 468, 317 (2002)]. This methodology allows for the simultaneous characterization of the energy cascade and spatial fluxes in turbulent shear flows across the entire physical domain as well as the range of scales. The present study utilizes this methodology to characterize the effects of Reynolds number on the balance of energy fluxes in turbulent channel flows. Direct numerical simulation data in the range Reτ = 300–934 are compared to previously published results at Reτ = 180 [N. Marati, C. M. Casciola, and R. Piva, “Energy cascade and spatial fluxes in wall turbulence,” J. Fluid Mech. 521, 191 (2004)]. The present results show no Reynolds number effects in the terms of the scale energy budget in either the viscous sublayer or buffer regions of t...

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm²) but elevated to its peak during mid to late systole at about 18-20 dyn/cm². Low magnitude shear stress (<5 dyn/cm²) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement.

Transcatheter aortic valve replacements (TAVRs) are a percutaneous alternative to surgical aortic valve replacements and are used to treat patients with aortic valve stenosis. This minimally invasive procedure relies on expansion of the TAVR stent to radially displace calcified aortic valve leaflets against the aortic root wall. However, these calcium deposits can impede the expansion of the device causing distortion of the valve stent and pericardial tissue leaflets. The objective of this study was to elucidate the impact of eccentric TAVR stent distortion on the dynamic deformation of the tissue leaflets of the prosthesis in vitro. Dual-camera stereophotogrammetry was used to measure the regional variation in strain in a leaflet of a TAVR deployed in nominal circular and eccentric (eccentricity index = 28%) orifices, representative of deployed TAVRs in vivo. It was observed that (i) eccentric stent distortion caused incorrect coaptation of the leaflets at peak diastole resulting in a ‘peel-back’ leaflet geometry that was not present in the circular valve and (ii) adverse bending of the leaflet, arising in the eccentric valve at peak diastole, caused significantly higher commissure strains compared with the circular valve in both normotensive and hypertensive pressure conditions (normotension: eccentric = 13.76 ± 2.04% versus circular = 11.77 ± 1.61%, p = 0.0014, hypertension: eccentric = 15.07 ± 1.13% versus circular = 13.56 ± 0.87%, p = 0.0042). This study reveals that eccentric distortion of a TAVR stent can have a considerable impact on dynamic leaflet deformation, inducing deleterious bending of the leaflet and increasing commissures strains, which might expedite leaflet structural failure compared to leaflets in a circular deployed valve.

Peak Mechanical Loads Induced in the In Vitro Edge-to-Edge Repair of Posterior Leaflet Flail

BACKGROUND Percutaneous edge-to-edge mitral valve (MV) repair is a potential therapeutic option for patients presenting with mitral regurgitation, who may not be suitable for surgery. We characterized the edge-to-edge repair forces in a posterior leaflet flail MV model to identify potential modes of mechanical failure. METHODS Porcine MVs were evaluated in two different sizes (Physio II 32 and 40) in a left-side heart simulator under physiologic hemodynamic conditions. Edge-to-edge repair was simulated by suturing miniature force transducers near the free edge of the anterior and posterior leaflets, on the ventricular side, resulting in a double orifice MV. Posterior leaflet flail was created by selective chordal cutting. RESULTS Chordal cutting resulted in posterior leaflet flail and mitral regurgitation; all valves coapted normally before chordal cutting. Peak systolic control forces (size 32, 0.098 ± 0.058 N; size 40, 0.236 ± 0.149 N) were not significantly different from systolic flail forces (size 32, 0.136 ± 0.107 N; size 40, 0.220 ± 0.128 N) for either MV size. No correlation was observed between force magnitude and flail height or width. Peak systolic force was greater (p = 0.08) for the larger MVs (size 40 compared with size 32). Finally, peak diastolic force was significantly smaller (p = 0.04) than peak systolic force regardless of valve size. CONCLUSIONS For the first time, forces imparted on an edge-to-edge MV repair were quantified for a posterior leaflet flail model. Force magnitude was not significantly altered with flail compared with control; it was greatest during peak systole and increased with valve size.

Effects of Targeted Papillary Muscle Relocation on Mitral Leaflet Tenting and Coaptation

BACKGROUND Ischemic mitral valve (MV) repair for patients with severe left ventricular dilation remains challenging. The objective of this study was to investigate the efficacy of papillary muscle (PM) relocation to restore physiologic MV function. METHODS Fresh ovine MVs (n = 6) were studied in a left-heart simulator under physiologic hemodynamics. Ischemic MV disease was simulated by annular dilation and PM displacement. Initial valvular repair was performed with mitral annuloplasty; further PM displacement simulated progressive left ventricular dilation. Basal PM repositioning (Kron procedure), performed to alleviate leaflet tethering, consisted of relocating (1) both PMs toward the commissures; (2) both PMs toward the trigones; (3) the posteromedial PM toward the ipsilateral commissure; and (4) the posteromedial PM toward the ipsilateral trigone. Coaptation length and tenting area were measured using three-dimensional echocardiography as surrogates of MV function. RESULTS Papillary muscle relocation as an adjunct to mitral annuloplasty statistically improved coaptation length and tenting area compared with the disease condition. No statistical differences in coaptation length and tenting area were observed between final repaired conditions and control conditions. No statistical differences were observed between commissural and trigonal repairs at any incremental repair step. Coaptation length and tenting area were plotted against PM distance; the data were fit to linear regressions. CONCLUSIONS In a realistic in vitro model of ischemic left ventricular dilation, apical-basal PM relocation, as an adjunct procedure to mitral annuloplasty, restored optimal MV closure. Trigonal or commissural traction suture location did not significantly affect the degree of restored coaptation. Linear relationships between PM positions and leaflet variables were established, which could be used to inform surgical repairs.