Abstract

Background: 99mTc-F4A is a tetrameric, fibrin-specific probe characterized in vitro, in mice and in left ventricular assist devices (LVAD) explanted from patients. Objective: To survey the incidence and spatial distribution of thrombus by 99mTc-F4A signal intensity in LVADs removed for pump exchange (n=9) or heart transplant (n=11) in an early cohort of patients. Methods: LVADs excised from patients were rewired and operated (~9,400 RPM) in a mock circulatory loop (1/2 tygon, 200ml, 50:50, PBS: plasma; heparin). 99mTc-F4A (500μCi) was injected into the loop, circulated for 30 min. Activity was localized within LVADs by NanoSPECT/CT. Results: The median time of LVAD support prior to explant was 7.6 ± 7.2 months. Thrombus was detected in 19/20 LVADs by high 99mTc-F4A signal and corroborated by gross pathology in 4 LVADs by the manufacturer. 99mTc-F4A signal was scored as strong, weak, or none, and was assessed for the inlet cannula (metallic and Gor-Tex tubing segments), the inlet stator/bearing, turbine, outlet bearing, and outlet cannula regions. Inlet cannulas were available for 8/20 LVADs with 7/8 having thrombus. Strong signal was noted in 4/7 of the metallic segment and in 5/7 of the Gor-Tex segments. 99mTc-F4A signal occurred around the inlet bearing in 8/20 LVADs and the outlet bearing region in 5/20 LVADs, but the incidence of thrombus within the axial turbine was negligible. Thrombus was observed in the outlet cannula in 10/20 pumps. (Fig) Strong 99mTc-F4A signal was noted most often at the inlet bearing 75% (6/8) and in outlet cannulas 50% (5/10). Strong signal was noted in 13/20 LVADs in at least one location. Of 5/20 LVADs with multiple deposits, 4/5 of these pumps had a strong 99mTc-F4A signal. Conclusion: These initial ex vivo survey data reveal a high incidence of LVAD thrombus in exchanged and routinely transplanted LVADs. 99mTc-F4A imaging may offer a sensitive and specific diagnostic tool to noninvasively assess and better manage LVAD thrombus.

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