Biological Response to Sintered Titanium in Left Ventricular Assist Devices: Pseudoneointima, Neointima, and Pannus.

Titanium alloys have traditionally been used in blood-contacting cardiovascular devices, including left ventricular assist devices (LVADs). However, titanium surfaces are susceptible to adverse coagulation, leading to thrombogenesis and stroke. To improve hemocompatibility, LVAD manufacturers introduced powder sintering on blood-wetted surfaces in the 1980s to induce endothelialization. This technique has been employed in multiple contemporary LVADs on the pump housing, as well as the interior and exterior of the inflow cannula. Despite the wide adoption of sintered titanium, reported biologic response over the past several decades has been highly variable and apparently unpredictable-including combinations of neointima, pseudoneoimtima, thrombus, and pannus. We present a history of sintered titanium used in LVAD, a review of accumulated clinical outcomes, and a synopsis of gross appearance and composition of various depositions found clinically and in animal studies, which is unfortunately confounded by the variability and inconsistency in terminology. Therefore, this review endeavors to introduce a unified taxonomy to harmonize published observations of biologic response to sintered titanium in LVADs. From these data, we are able to deduce the natural history of the biologic response to sintered titanium, toward development of a deterministic model of the genesis of a hemocompatible neointima.

High-speed visualization of ingested, ejected, adherent, and disintegrated thrombus in contemporary ventricular assist devices.

Biocompatibility of ventricular assist devices (VADs) has been steadily improving, yet the rate of neurological events remains unacceptably high. Recent speculation for elevated stroke rates centers on ingestion of thrombi originating upstream of the pump, such as in the ventricle or left atrial appendage. These thrombi may be ejected by the VAD or become deposited within the blood flow pathway, presenting serious complications to the patient. This study was performed to visualize and quantify the degree of disruption, adherence, and disintegration of thrombi that are ingested by the three most implanted VADs: the HeartMate II, HeartMate 3, and HVAD. Clot analogs of varying microstructure compositions (red, white) and sizes (0.5, 1, 2 cm3 ) were synthesized in vitro based on clinical explant data. These were introduced individually into an in vitro flow loop with a transparent replica of the HMII, HM3, and HVAD operated at nominal steady flow (2.3-4.0 L/min). High-speed videography (up to 10 000 fps) revealed the ingestion, disruption, ejection, and adherence of thrombus fragments. Thromboemboli of varying compositions and sizes were observed mechanically attaching to components in all 3 VAD models. In some instances, ingested thrombi physically obstructed portions of the blood flow path; 18% (3 of 17 total) of red thrombi adhered to the inflow straightener of the transparent HMII. In the HVAD model, fewer than 4% of clots were adherent or trapped within the pump, irrespective of microstructure or initial volume. In comparison, 100% (4 of 4 total) of 1-cm3 white (fibrin) clots became lodged within the transparent HM3 while, in contrast, less than 5% of macerated red clots (3 of 63 total) of the same volume were adherent inside the pump. A significant proportion of ingested thrombi were macerated into infinitesimal fragments; 84% and 74% of 2-cm3 red thrombi in the HVAD and HM3 models, respectively, were found to have disintegrated upon ingestion. However, large emboli were also discharged from both centrifugal VADs; these fragments, ranging from 0.01 to 0.29 cm3 regardless of microstructure and original volume, may be capable of occluding an intracranial vessel. Therefore, ingested thrombus may explain, in part, elevated stroke rates in contemporary blood pumps in the absence of adherent pump thrombosis.

Classification of the Frequency, Severity, and Propagation of Thrombi in the HeartMate II Left Ventricular Assist Device.

Computational fluid dynamics has become a dynamic tool in the development of ventricular assist devices (VADs) and as a predictor of thrombosis within these pumps. The genesis of thrombi could be in loco, due to deposition within the VAD, or upstream such as the left atrial appendage or inside the left ventricle. To calibrate our group's computational model, a retrospective analysis of 29 explanted HeartMate II (HMII) VADs due to suspected pump thrombosis (PT) from the University of Michigan was conducted. Thrombi in these pumps were characterized by their frequency, composition, severity, and physical distribution in five regions of the blood flow pathway. The outlet bearing/stator region had the highest frequency of deposition (≈72%), and the preponderance of thrombi appeared white and unlaminated in their microstructure. Conversely, 41.3% of VADs showed thrombus on the fore bearing of the HMII, and these formations tended to be red and laminated, indicating they formed in layers over time. Furthermore, the majority of clots observed in the fore bearing and outlet bearing/stator regions were partially occlusive in nature. Fourteen VADs presented PT in multiple regions and analysis of the data showed a statistically significant correlation (p < 0.01) between deposition in the fore bearing and subsequent thrombosis in the outlet bearing/stator; however, no other regions exhibited statistically significant correlations. This gives credence to the hypothesis that thrombi do not occur independently in multiple regions of the blood flow pathway in the HMII but may propagate downstream.

Characterizing the HeartMate II Left Ventricular Assist Device Outflow Using Particle Image Velocimetry.

Ventricular assist devices (VADs) are implanted in patients with a diseased ventricle to maintain peripheral perfusion as a bridge-to-transplant or as destination therapy. However, some patients with continuous flow VADs (e.g., HeartMate II (HMII)) have experienced gastrointestinal (GI) bleeding, in part caused by the proteolytic cleavage or mechanical destruction of von Willebrand factor (vWF), a clotting glycoprotein. in vitro studies were performed to measure the flow located within the HMII outlet cannula under both steady and physiological conditions using particle image velocimetry (PIV). Under steady flow, a mock flow loop was used with the HMII producing a flow rate of 3.2 L/min. The physiological experiment included a pulsatile pump operated at 105 BPM with a ventricle filling volume of 50 mL and in conjunction with the HMII producing a total flow rate of 5.0 L/min. Velocity fields, Reynolds normal stresses (RNSs), and Reynolds shear stresses (RSSs) were analyzed to quantify the outlet flow's potential contribution to vWF degradation. Under both flow conditions, the HMII generated principal Reynolds stresses that are, at times, orders of magnitude higher than those needed to unfurl vWF, potentially impacting its physiological function. Under steady flow, principal RNSs were calculated to be approximately 500 Pa in the outlet cannula. Elevated Reynolds stresses were observed throughout every phase of the cardiac cycle under physiological flow with principal RNSs approaching 1500 Pa during peak systole. Prolonged exposure to these conditions may lead to acquired von Willebrand syndrome (AvWS), which is accompanied by uncontrollable bleeding episodes.