Management of Unrepaired Tetralogy of Fallot in an 86-Year-Old Patient Undergoing Transcatheter Aortic Valve Replacement.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, typically requiring early treatment in infancy. Untreated TOF is associated with poor survival, with most uncorrected patients not surviving beyond the third decade. Here, we present a unique case of an 86-year-old female with uncorrected TOF who underwent a transcatheter aortic valve replacement (TAVR) procedure due to severe aortic stenosis (AS). The patient's TOF was identified during infancy, and she was categorized as an acyanotic "pink baby." Notably, the first palliative surgery for TOF was performed in 1944, when the patient was seven years old. The patient never underwent corrective surgery for TOF and continued to lead a symptom-free life until she developed severe AS later in life. The TAVR procedure significantly improved her symptoms, illustrating the importance of considering alternative etiologies for symptoms in elderly patients with uncorrected TOF and AS. In addition, we underscore the anesthetic management during TAVR, specifically highlighting the challenges addressed, such as the utilization of general anesthesia with transesophageal echocardiography (TEE) and the placement of a pulmonary artery (PA) catheter.

Selective Deletion of Heparan Sulfotransferase Enzyme, Ndst1, in Donor Endothelial and Myeloid Precursor Cells Significantly Decreases Acute Allograft Rejection.

Early damage to transplanted organs initiates excess inflammation that can cause ongoing injury, a leading cause for late graft loss. The endothelial glycocalyx modulates immune reactions and chemokine-mediated haptotaxis, potentially driving graft loss. In prior work, conditional deficiency of the glycocalyx-modifying enzyme N-deacetylase-N-sulfotransferase-1 (Ndst1f/f TekCre+) reduced aortic allograft inflammation. Here we investigated modification of heparan sulfate (HS) and chemokine interactions in whole-organ renal allografts. Conditional donor allograft Ndst1 deficiency (Ndst1-/-; C57Bl/6 background) was compared to systemic treatment with M-T7, a broad-spectrum chemokine-glycosaminoglycan (GAG) inhibitor. Early rejection was significantly reduced in Ndst1-/- kidneys engrafted into wildtype BALB/c mice (Ndst1+/+) and comparable to M-T7 treatment in C57Bl/6 allografts (P < 0.0081). M-T7 lost activity in Ndst1-/- allografts, while M-T7 point mutants with modified GAG-chemokine binding displayed a range of anti-rejection activity. CD3+ T cells (P < 0.0001), HS (P < 0.005) and CXC chemokine staining (P < 0.012), gene expression in NFκB and JAK/STAT pathways, and HS and CS disaccharide content were significantly altered with reduced rejection. Transplant of donor allografts with conditional Ndst1 deficiency exhibit significantly reduced acute rejection, comparable to systemic chemokine-GAG inhibition. Modified disaccharides in engrafted organs correlate with reduced rejection. Altered disaccharides in engrafted organs provide markers for rejection with potential to guide new therapeutic approaches in allograft rejection.