Anticoagulant independent mechanical heart valves: viable now or still a distant holy grail.

Valvular heart disease remains a large public health problem for all societies; it attracts the attention of public health organizations, researchers and governments. Valve substitution is an integral part of the treatment for this condition. At present, the choice of valve prosthesis is either tissue or mechanical. Tissue valves have become increasingly popular in spite of unresolved problems with durability, hemodynamics, cost and need for anticoagulation therapy. As a consequence, mechanical valve innovation has virtually ceased; the last successful mechanical design is 25 years old. We postulate that with improved technology, knowledge and experience gained over the last quarter century, the best possible solution to the problem of valve substitution can be achieved with a mechanical valve that is anticoagulant independent, durable, hemodynamically and cost efficient. At present, it is possible to design, test and produce a valve that can accomplish these goals.

Are anticoagulant independent mechanical valves within reach-fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models.

BACKGROUND: Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. METHODS: Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. RESULTS: Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). CONCLUSIONS: Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach.

Thrombogenic potential of transcatheter aortic valve implantation with trivial paravalvular leakage.

BACKGROUND: Significant paravalvular leakage after transcatheter aortic valve implantation (TAVI) correlates with increased morbidity and mortality, but adverse consequences of trivial paravalvular leakage have stimulated few investigations. Using a unique method distinctly different from other diagnostic approaches, we previously reported elevated backflow velocities of short duration (transients) in mechanical valve closure. In this study, similar transients were found in a transcatheter valve paravalvular leakage avatar. METHODS: Paravalvular leakage rate (zero to 58 mL/second) and aortic valve incompetence (volumetric back flow/forward flow; zero to 32%) were made adjustable using a mock transcatheter aortic valve device and tested in quasi-steady and pulsatile flow test systems. Projected dynamic valve area (PDVA) from the back illuminated mock transcatheter aortic valve device was measured and regional backflow velocities were derived by dividing volumetric flow rate by the PDVA over the open and closing valve phase and the total closed valve area derived from backflow leakage. RESULTS: Aortic incompetence from 1-32% generated negative backflow transients from 8 to 267 meters/second, a range not dissimilar to that measured in mechanical valves with zero paravalvular leakage. Optimal paravalvular leakage was identified; not too small generating high backflow transients, not too large considering volume overload and cardiac energy loss caused by defective valve behavior and fluid motion. CONCLUSIONS: Thrombogenic potential of transcatheter aortic valves with trivial aortic incompetence and high magnitude regional backflow velocity transients was comparable to mechanical valves. This may have relevance to stroke rate, asymptomatic microembolic episodes and indications for anticoagulation therapy after transcatheter valve insertion.

Importance of shear in prosthetic valve closure dynamics.

BACKGROUND AND AIM OF STUDY: The results of recent hematological studies have suggested that, under non-physiological flow conditions, circulating procoagulant proteins activate the coagulation cascade. In the present study, in-vitro estimates of flow transients at or near the time of valve closure, including regional backflow velocity (RBV, m/s), flow acceleration (m/s2), and rate of acceleration (jerk, m/s3), have shed new light on the blood-damage potential of prosthetic valves. METHODS: Several prosthetic valves were tested in a pulse duplicator under simulated cardiac conditions. A unique prototype subsystem (Leonardo(VSI)) was used to measure the projected dynamic valve areas (PDVAs) from backlit valves. The regional flow velocity was derived by dividing the time-dependent volumetric flow rate by the PDVA. The flow acceleration and jerk were subsequently obtained as time derivatives of the flow velocity. RESULTS: Current mechanical valves have overt flow transients at valve closure, relating to leaflet nonresponse to flow deceleration and residual PDVA. In contrast, tissue valves initiate closure during the flow deceleration phase, and seal when closed, thus preventing supra-physiological backflow transients. The estimated average RBV transients at or near closure ranged from 45 to 162 m/s for mechanical valves, and from 3 to 10 m/s (i.e., ca. 93% less) for tissue valves. The average derived flow acceleration and jerk transients ranged from +2,235 to -1,786xg and from +10.8 x 106 to -7.5 x 10(6) m/s3 for mechanical valves, respectively, and were substantially lower for tissue valves (ca. 90-99% less). CONCLUSION: The study results implicate that RBV transients at or near mechanical valve closure, and not the forward or closed flow phase, as being primary to the shear-induced activation of the coagulation cascade. Results obtained in vitro for an experimental trileaflet mechanical valve (Triflo) were tested only in the aortic site similar to those obtained with tissue valves.

Biointegration and growth of porcine valved pulmonary conduits in a sheep model.

As there is currently no suitable valved pulmonary conduit for small children, porcine conduits treated by the L-Hydro process were implanted into 9 newborn lambs to investigate growth potential. Of the 8 survivors, 7 were kept alive for 12 months after implantation. The diameter of the conduit and gradient across the valve were evaluated at surgery and at 3 and 9 months postoperatively using bidirectional echocardiographic and angiographic methods. After sacrifice, histological and radiological analyses were performed. The mean weight of the animals was 4.2 +/- 1.1 kg at implantation and 43.1 +/- 6.2 kg at sacrifice. There was a significant increase in mean valve area from 139.9 +/- 18.0 mm2 at implantation to 443.5 +/- 89.2 mm2 at 12 months. Pre-sacrifice angiography showed no transvalvular gradient, and radiographic analysis did not reveal significant conduit wall or leaflet calcification in any of the animals. Histological examination of the grafts demonstrated total integration, with native-like intact valve leaflets. Thus functional evaluation, echocardiography, and histology demonstrated growth of the grafts with completely endothelialized and apparently normal pulmonary valve leaflets without calcification.