SPECT imaging of lung ischemia-reperfusion injury using [99mTc]cFLFLF for molecular targeting of formyl peptide receptor 1.

Primary graft dysfunction after lung transplantation, a consequence of ischemia-reperfusion injury (IRI), is a major cause of morbidity and mortality. IRI involves acute inflammation and innate immune cell activation, leading to rapid infiltration of neutrophils. Formyl peptide receptor 1 (FPR1) expressed by phagocytic leukocytes plays an important role in neutrophil function. The cell surface expression of FPR1 is rapidly and robustly upregulated on neutrophils in response to inflammatory stimuli. Thus, we hypothesized that use of [99mTc]cFLFLF, a selective FPR1 peptide ligand, would permit in vivo neutrophil labeling and noninvasive imaging of IRI using single-photon emission computed tomography (SPECT). A murine model of left lung IRI was utilized. Lung function, neutrophil infiltration, and SPECT imaging were assessed after 1 h of ischemia and 2, 12, or 24 h of reperfusion. [99mTc]cFLFLF was injected 2 h before SPECT. Signal intensity by SPECT and total probe uptake by gamma counts were 3.9- and 2.3-fold higher, respectively, in left lungs after ischemia and 2 h of reperfusion versus sham. These values significantly decreased with longer reperfusion times, correlating with resolution of IRI as shown by improved lung function and decreased neutrophil infiltration. SPECT results were confirmed using Cy7-cFLFLF-based fluorescence imaging of lungs. Immunofluorescence microscopy confirmed cFLFLF binding primarily to activated neutrophils. These results demonstrate that [99mTc]cFLFLF SPECT enables noninvasive detection of lung IRI and permits monitoring of resolution of injury over time. Clinical application of [99mTc]cFLFLF SPECT may permit diagnosis of lung IRI for timely intervention to improve outcomes after transplantation.

Long term employment following heart transplantation in the United States.

BACKGROUND: Employment is an important metric of post-transplant functional status and the quality of life yet remains poorly described after heart transplant. We sought to characterize the prevalence of employment following heart transplantation and identify patients at risk for post-transplant unemployment. METHODS: Adults undergoing single-organ heart transplantation (2007-2016) were evaluated using the UNOS database. Univariable analysis was performed after stratifying by employment status at 1-year post-transplant. Fine-Gray competing risk regression was used for risk adjustment. Cox regression evaluated employment status at 1 year with mortality. RESULTS: Of 10,132 heart transplant recipients who survived to 1 year and had follow-up, 22.0% were employed 1-year post-transplant. Employment rate of survivors increased to 32.9% by year 2. Employed individuals were more likely white (70.8% vs 60.4%, p < 0.01), male (79.6% vs 70.7% p < 0.01), held a job at listing/transplant (37.6% vs 7.6%, p < 0.01), and had private insurance (79.1% vs 49.5%, p < 0.01). Several characteristics were independently associated with employment including age, employment status at time of listing or transplant, race and ethnicity, gender, insurance status, education, and postoperative complications. Of 1,657 (14.0%) patients employed pretransplant, 58% were working at 1-year. Employment at 1year was independently associated with mortality with employed individuals having a 26% decreased risk of mortality. CONCLUSION: Over 20% of heart transplant patients were employed at 1 year and over 30% at 2 years, while 58% of those working pretransplant had returned to work by 1-year. While the major predictor of post-transplant employment is preoperative employment status, our study highlights the impact of social determinants of health.

Burden of Tricuspid Regurgitation in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Tricuspid regurgitation (TR) is associated with poor outcomes after cardiac surgery. Guidelines recommend correction of severe TR in patients undergoing left-sided valve surgery but not coronary artery bypass graft surgery (CABG). We sought to evaluate impact of TR on outcomes after CABG. METHODS: All patients (n = 28,027) undergoing CABG in The Society of Thoracic Surgeons (STS) regional database (2011 to 2018) were stratified by TR severity. Primary outcomes included major morbidity or mortality, which were compared using univariate analysis. RESULTS: Of patients undergoing CABG, 4837 (17%) had mild, 800 (3%) had moderate, and 81 (0.29%) had severe TR. Increased severity was associated with higher rate of preoperative heart failure (none 5162 [23.4%] vs mild 1697 [35%] vs moderate 427 [53%] vs severe 54 [67%], P < .001] and STS predicted risk of mortality (1.0 [0.6 to 1.9) vs 1.4 [0.8 to 2.9] vs 2.8 [1.4 to 5.4] vs 6.2 [2.2 to 11.4], P < .001). Increasing severity was associated with higher postoperative rate of renal failure (426 [1.9%] vs 145 [3%] vs 58 [7.3%] vs 7 [8.6%], P < .001), prolonged ventilation (1652 [7.5%] vs 495 [10.2%] vs 153 [19.1%] vs 22 [27.2%], P < .001), and mortality (344 [1.6%] vs 132 [2.7%] vs 58 [7.3%] vs 9 [11.1%], P < .001). After risk adjustment, mild, moderate, and severe TR remained associated with increased morbidity and mortality (all P < .05). CONCLUSIONS: Increasing TR severity, although independently associated with higher surgical risk, is not accounted for entirely by STS risk calculator. This highlights the importance of TR on operative risk and supports consideration of concurrent tricuspid intervention for patients with significant TR undergoing CABG.