Abstract 18776: Could Early Direct Detection of Left Ventricular Assist Device Thrombus Reduce Thrombotic Complications
Background: Treatment of advanced heart failure with implantable LVADs continues to increase. However, LVADs can be associated with serious complications: bleeding, infection, and thrombosis.
Objective: To develop a sensitive image-guided approach to localize and quantify early thrombus accumulation in titanium LVADs permitting earlier clinical intervention to minimize thrombotic events.
Materials: A monomeric bifunctional ligand with a fibrin-specific peptide, a short spacer, and 99mTc chelating amino acid sequence (F1A) was developed and compared with a tetrameric (PEG2000) analogue (F4A).
Results: 99mTc attenuation by the LVAD titanium (1mm) was 23%. 99mTc-F1A affinity to fibrin was Kd~10 nM. The 99mTc-F4A probe could not be competitively displaced by F1A up to 120,000:1. In vitro 99mTc-F1A binding to fibrin clot was interfered heavily by plasma (p < 0.05); whereas, 99mTc-F4A was unaffected (p > 0.05). The pharmacokinetic half-life of 99mTc-F4A was faster (124±41min, p < 0.05) than 99mTc-F1A (176±26min). Biodistribution studies showed that 99mTc-F1A and 99mTc-F4A have rapid renal elimination with negligible liver or spleen accumulation. In mice with carotid thrombus 99mTc-F4A provided robust signal (0.93±0.11) that was competitively reduced by 35% (p < 0.05) with unlabeled F4A (3:1 blockade). In an LVAD (10,000 RPM) mock circulatory loop (1:1, PBS: plasma), 99mTc-F4A rapidly bound to phantom fibrin clots in 2 min (p < 0.05), whereas 99mTc-F1A accumulation was negligible. LVADs from patients without clinical suspicion of pump thrombus were operated at 9,400 RPM in the mock loop. 99mTc-F4A circulated 30 min and bound to fibrin along the outlet cannula in 3 of 4 devices studied to date (Figure).
Conclusion: 99mTc-F4A is a high-avidity prototype probe to localize thrombus in LVADs. This may allow earlier clinical intervention to minimize thrombotic complications and the need for pump exchange.
Author Disclosures: G. Cui: None. W. Akers: None. M.J. Scott: None. J.S. Allen: None. A.H. Schmieder: None. S.C. Silvestry: Consultant/Advisory Board; Modest; Heartware. Consultant/Advisory Board; Significant; Thoratec. A. Itoh: None. K. Paranandi: None. Y. Tia: None. S. Achilefu: None. G.A. Ewald: None. G.M. Lanza: Other Research Support; Modest; Philips Research Hamburg. Other; Modest; Ocean NanoTech, LLC has licensed WU IP.
- © 2014 by American Heart Association, Inc.