Impact of Cytomegalovirus on Survival After Heart Transplant: analysis of 20,000 Patients from the UNOS Registry Data

Background: Left Ventricular Assist Device (LVAD) pump thrombosis (PT) is a devastating complication of mechanical circulatory support. The diagnosis of LVAD thrombus is difficult in vivo, often only suggested by markers of hemolysis and echocardiographic features, which lack sensitivity. We sought to test a probe with high avidity anti-fibrin 99mTc to localize and quantify thrombus within the high shear environment of titanium axial-flow pumps. Methods: Monomeric bifunctional ligands with a fibrin-specific peptide, a short spacer, and technetium chelating amino acid sequence (F1A) were covalently inter-coupled via a 4-arm-PEG2000 tetramer to form F4A. Each was radiolabeled with 99mTc using the IsoLink procedure. We collected 20 explanted HeartMate II LVADs, of which 9 were explanted for suspected pump thrombosis and 11 were explanted during heart transplant or exchange for other complications. Ex-vivo imaging of explanted pumps was conducted in plasma using a mock circulatory loop running at 9400 RPM for 30 minutes as has previously been described. After imaging the devices were sent to the manufacturer for disassembly and thorough inspection for thrombus. Results: The majority of patients were male (85%) with a mean age of 54.1 6 9.8 and a median INTERMACS profile of 2. The median time of LVAD support prior to explant was 7.6 6 7.2 months. Of the 9 patients exchanged for suspected pump thrombosis all had undetectable haptoglobin levels and mean LDH levels of 3520 6 2596. All 9 had CT scans prior to LVAD exchange without any visualized thrombus or kinking of the inflow or outflow cannulas. Two of the pumps have been disassembled and inspected by the manufacturer. Both pumps were in patients with suspected pump thrombosis and both the pumps had thrombus found on SPECT imaging and on visual inspection (Figure 1A and 1B). Conclusions: A novel, fibrin-specific 99mTc small tetrameric probe offers the potential to detect, localize, and quantify intra-LVAD thrombus noninvasively. Once verified in a large cohort this agent offers the opportunity to diagnose LVAD pump thrombosis at an earlier stage. Definite and early diagnosis may confer therapeutic options to avoid pump failure and/or costly and morbid LVAD exchange.