Richard D. Schaub

Assessing acute platelet adhesion on opaque metallic and polymeric biomaterials with fiber optic microscopy.

The degree of platelet adhesion and subsequent thrombus formation is an important measure of biocompatibility for cardiovascular biomaterials. Traditional methods of quantifying platelet adhesion often are limited by the need for direct optical access, limited spatial resolution, or the lack of temporal resolution. We have developed a new imaging system that utilizes fiber optics and fluorescence microscopy for the quantification of platelet adhesion. This fiber optic remote microscope is capable of imaging individual fluorescently labeled platelets in whole blood on opaque surfaces. Using this method, platelet adhesion was quantified on a series of metallic [low-temperature isotropic carbon (LTIC); titanium alloy (Ti); diamond-like carbon (DLC); oxidized titanium alloy (TiO); and polycrystalline diamond (PCD)] and polymeric [woven Dacron (WD)] collagen-impregnated Dacron (HEM), expanded polytetrafluoroethylene (ePTFE), and denucleated ePTFE (dePTFE)] biomaterials designed for use in cardiovascular applications. These materials were perfused with heparinized whole human blood in an in vitro parallel plate flow chamber. Platelet adhesion after 5 min of perfusion ranged from 3.7 +/- 1.0 (dePTFE) to 16.8 +/- 1.5 (WD) platelets/1000 micrometer. The temporal information revealed by these studies provides a comparative measure of the acute thrombogenicity of these materials as well as some insight into their long-term hemocompatibilities. Also studied here were the effects of wall shear rate and axial position on platelet adhesion. A predicted increase in platelet adhesion with increased wall shear rate and a trend toward a decrease in platelet adhesion with increased axial distance was observed with the fiber optic microscope. Future applications for this imaging technique may include the long-term evaluation of thrombosis in blood-contacting devices in vitro and, in animal models, in vivo.

Blood biocompatibility analysis in the setting of ventricular assist devices.

Ventricular assist devices (VADs) are increasingly applied to support patients with advanced cardiac failure. While the benefit of VADs in supporting this patient group is clear, substantial morbidity and mortality occur during the VAD implant period due to thromboembolic and infective complications. Efforts at the University of Pittsburgh aimed at evaluating the blood biocompatibility of VADs in the clinical, animal, and in vitro setting over the past decade are summarized. Emphasis is placed on understanding the mechanisms of thrombosis and thromboembolism associated with these devices.

Left Ventricular Assist Device Malfunctions: It Is More Than Just the Pump

Background: Reports of left ventricular assist device (LVAD) malfunction have focused on pump thrombosis. However, the device consists of the pump, driveline, and peripherals, all of which are potentially subject to failure. Methods: Prospectively collected data were reviewed for all LVAD device malfunctions (DMs) occurring in rotary LVADs implanted at a single center between April 2004 and May 2016. Durable LVADs included 108 Heartmate II (HM II) and 105 HeartWare VAD (HVAD). DM data were categorized according to device type and into categories related to the component that failed: (1) controller, (2) peripheral components, and (3) implantable blood pump or its integral electric driveline. Pump-related events were analyzed as pump-specific (suspected or confirmed thrombosis) or nonpump-specific (driveline failure). DM rates were reported as events per 1000 patient-days, and Cox proportional hazard models were used for time-to-event analyses. Cumulative rates of malfunction were examined for the main components of each type of LVAD. Results: Types of DM included controller failure (30%), battery failure (19%), or patient cable failure (14%), whereas only 13% were because of pump failure. DMs were more common in the HM II device (3.73 per 1000 patient-days versus 3.06 per 1000 patient-days for the HVAD, P<0.01). A higher rate of pump-specific malfunctions was discovered in those implanted with an HM II versus an HVAD (0.55 versus 0.39, respectively; P<0.01) and peripheral malfunctions (2.32 versus 1.78 for the HM II and HVAD, respectively; P<0.01); no difference occurred in the incidence of controller DM between the 2 LVADs. Patients with HVAD were 90% free of a pump-specific malfunction at 3 years compared with 56% for the HM II (log-rank P<0.003). Only 74% of the patients with HM II were free of pump thrombosis at 3 years compared with 90% of the patients with HVAD. Freedom from failure of the integrated driveline was 79% at 3 years for the HM II but 100% for the HVAD (log-rank P<0.02). Conclusions: Device malfunction is much broader than pump failure alone and occurs for different components at different rates based on the type of LVAD.

Bariatric surgery for a patient with a HeartMate II ventricular assist device for destination therapy

A patient with a HeartMate II left ventricular assist device who had a body mass index of 52 needed gastric bypass surgery in order to qualify for a heart transplant. Unlike previous experience in which the surgery was performed at the implant hospital, the gastric bypass surgery in this case was performed at a bariatric center of excellence that was a separate facility from the implant hospital. The artificial heart program of the University of Pittsburgh Medical Center worked with the bariatric center of excellence in scheduling the gastric bypass surgery using a multidisciplinary team approach at 2 hospitals to coordinate safe, high-quality patient care in a unique situation.

A new fiber optic probe for cellular visualization.

Thrombus formation within artificial organs has been shown, at least in part, to be caused by retarded or stagnant blood flow. The goal of this work was to develop a magnifying fiber optic probe capable of visualizing particle flow and cellular deposition in a physiologically relevant cellular suspension (blood). The probe has minimal cross sectional area to allow for access to confined areas and to minimize flow disturbance. The probe consists of a germanium oxide fiber optic bundle and a gradient index imaging lens. Fluorescent microspheres of 48 microns, 7 microns, and 3 microns in diameter were imaged after deposition on to a cover slip. The flow (1.44 mm/sec) of 3 microns microspheres suspended in buffer alone and with red cell hematocrits of 10%, 25% and 45% were also visualized. To investigate the potential for this probe to detect ongoing thrombosis, fluorescently labeled human platelets were observed depositing on surfaces from a stagnant platelet rich buffer. These initial data suggest that this probe may offer a technique for the visualization of blood cell adhesion on the interior of artificial organs and the local quantification of flow in such devices.

Using non-invasive quantitative echocardiography during weaning trials to assess left ventricular recovery on mechanical assist devices

compare pulsatile and nonpulsatile flow generated by LVADs with outflow to the ascending aorta and descending aorta. Methods: An in vitro mock circulatory loop, driven by either a pulsatile or a nonpulsatile LVAD was anastomosed to transparent aortic models at either ascending or descending aortic position. The aortic valve was kept closed modeling no native cardiac output. Normal saline was used as a blood substitute. Methylene blue dye was injected to illustrate flow patterns in the ascending aorta and aortic arch. Dye washout time was used as a marker of flow stagnation and potential thrombogenicity. Cardiac output, afterload and coronary flow were measured. Results: Dye washout times for 5 L/min flow rate were 2.0 0.8, 2.0 0.7, 5.0 0.8, and 8.0 4.4 sec for pulsatile ascending (PA), continuous ascending (CA), pulsatile descending (PD), and continuous descending (CD), respectively. Coronary flow was 265, 312, 310, and 286 ml/min for PA, CA, PD, and CD, respectively. Dye washout times for 4 L/min flow rate were 3.0 1.0, 3.0 0.8, 14.0 3.8, and 25.0 9.1 sec for PA, CA, PD, and CD, respectively. Coronary flow was 210, 240, 225, and 233 ml/min for PA, CA, PD, and CD, respectively. Conclusion: LVAD descending aortic anastomosis and retrograde aortic flow is associated with significantly increased (P 0.001) flow stagnation in the ascending aorta. This may increase the risk for thromboembolism in patients solely relying on retrograde aortic flow. There were no differences in coronary flow across the study groups.