Faculty Bibliography

We aimed to investigate myocardial temperatures of allografts after removal from cold static storage (CSS) and the relationship between temperature and early outcomes of heart transplantation (HT). Between January and September 2024, 22 allografts preserved with CSS underwent prospective temperature measurements at the left ventricular free wall (LVFW) and interventricular septum; preservation solution temperatures were also measured. Median LVFW temperature was 4.0°C, septal temperature was 3.9°C, and solution temperature was 3.7°C. LVFW and septal temperatures were significantly correlated (p < 0.001), as were septal and solution temperatures (p = 0.03). Ischemic time inversely correlated with solution temperature (p = 0.021), and septal thickness correlated with septal temperature (p = 0.04). One patient developed severe primary graft dysfunction, and 30-day recipient and graft survival were 100% (22/22). We conclude that CSS maintains myocardial temperatures near 4°C, and it can achieve excellent post-HT outcomes with a low incidence of PGD.

OBJECTIVE:Post-cardiopulmonary bypass (post-CPB) vasoplegia syndrome (VS) is associated with a dysregulated inflammatory response and a higher morbidity and mortality, but the molecular pathways involved have been incompletely identified. We used multiplexed proteomic and transcriptomic analyses and targeted biochemical assays to identify the inflammatory and metabolic mediators that characterize post-CPB VS. METHODS:16 matched pairs of VS+ and VS- patients were analyzed pre-CPB and post-CPB for comparative proteomic and transcriptomic differences, with gene ontology (GO) pathway enrichment. Circulating NO metabolites (NOx), acetylcholine (ACh), and choline acetyltransferase (ChAT) levels were measured and correlated with VS. RESULTS:Baseline proteomic analysis demonstrated elevated TNF, IL-1R1 and IL-17RA in VS+ patients, with the activation of inflammatory cytokine, leukocyte activation, and NO biosynthesis pathways. Analysis of temporal pre-to-post-CPB proteomic changes in VS+ patients demonstrated post-CPB elevation IL17A, CXCL2, and VEGFR/FLT, and decreased immune resolving proteins. Post-CPB proteomic analysis demonstrated differential activation of leukocyte trafficking, T-cell differentiation, IL-6, and IL-17 pathways in VS+ patients. Transcriptomic analysis demonstrated post-CPB activation of cellular response to hypoxia, cellular stress response, and decreased response to angiotensin pathways. Circulating NOx, ACh, and ChAT levels were elevated pre-CPB in VS+ patients and increased further post-CPB. Pre-CPB ACh had a 99% AUC correlation with post-CPB VS+. CONCLUSIONS:We demonstrated increased baseline cardiovascular inflammation in VS+ patients, which predisposed them to a dysregulated response to CPB, and we identified CPB-induced activation of IL-17 skewed multi-cytokine inflammatory pathways and endothelial activation as mechanistic mediators of post-CPB VS. Circulating ACh was identified as a potential biomarker.

OBJECTIVE/UNASSIGNED:Mid-to-distal tracheal surgery for cancer can be safely performed minimally invasively with a one-day length of stay, avoiding a guardian chin suture, and ensuring a R0 resection in select patients. METHODS/UNASSIGNED:This is a retrospective technical review of the largest series to date of patients with mid-to-distal tracheal cancers. All were offered a right robotic approach using veno-venous extracorporeal membrane oxygenation (VV ECMO) support via percutaneous right internal jugular vein and right common femoral vein access. RESULTS/UNASSIGNED:From May 2019 to April 2024, five consecutive patients (3 men, 2 women; aged 11, 29, 37, 40, and 74 years) presented with a mid-to-distal tracheal cancer. All underwent right robotic mid-distal tracheal resections on VV ECMO for primary tracheal cancers. All patients had an end-to-end tracheal anastomosis and R0 resection and all avoided: systemic heparinization, suprahyoid release maneuvers and a postoperative guardian chin stitch. Median operative time was 258 min (range 227-292). All patients tolerated the operations well and were discharged home on the morning of postoperative day 1. There was no minor or major morbidity, no 30 or 90-day mortality, and no re-admissions. Two patients complained of cough. All had R0 resections and to date none have evidence of recurrent disease or stricture. CONCLUSION/UNASSIGNED:Resection of mid-to-distal primary tracheal cancers can be performed safely and efficiently via a right robotic approach while on VV ECMO with little to no morbidity or mortality and require only an overnight hospital stay. The techniques used to perform the operation and achieve these results are described.

BACKGROUND:Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients. METHODS:We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls. RESULTS:Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death. CONCLUSIONS:Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.

BACKGROUND:Studies have not explored consciousness during deep hypothermic circulatory arrest (DHCA). However, as studies in cardiac arrest have identified a spectrum of consciousness, we sought to establish the feasibility of studying consciousness during DHCA. METHODS:This was a prospective study across 10 hospitals with 36 DHCA patients undergoing thoracic aortic aneurysm repair or pulmonary endarterectomy. A tablet computer delivered audiovisual stimuli (images and names of three fruits) using headphones during each procedure as a potential test of implicit learning and explicit recall. We also established electroencephalography (EEG) and near-infrared spectroscopy (NIRS) to measure electrocortical markers of consciousness and cerebral oxygenation. Post-procedure interviews were carried out to test patients' ability to recall the audiovisual stimuli as well other explicit memories. PRIMARY OUTCOMES/METHODS:1) Feasibility of establishing tests of explicit recall and implicit learning, 2) Electroencephalography testing during DHCA. SECONDARY OUTCOMES/RESULTS:1) Signs of explicit recall of memories or implicit learning, and 2) identification of electrocortical biomarkers of consciousness during DHCA. RESULTS:Overall, 29/36 (81%) had the tablet set up. All 36 had NIRS and EEG set up, but 9 (25%) had useable EEG data, and 23 (66%) NIRS data. Delta EEG waves were observed during circulatory arrest in 3/9 (33%) patients, while 1/9 (11%) had theta waves just prior to circulatory arrest. All others showed isoelectric pattern. 35/36 (97%) agreed to follow up interviews. None had explicit recall of the names of the three fruits, but 3/36 (9%) correctly guessed them as a potential sign of implicit learning and 3 (9%) recalled other memories including events around the procedure and themes consistent with a recalled experience of death. CONCLUSIONS:A spectrum of consciousness and awareness, including signs of implicit learning and electrocortical biomarkers of consciousness may be present during DHCA, despite absence of visible signs of consciousness. This can be further used to help explain the negative psychological outcomes that cardiac arrest survivors face.

BACKGROUND/UNASSIGNED:Donation after circulatory death (DCD) with cardiopulmonary bypass for thoracoabdominal normothermic regional perfusion (TA-NRP) has led to increased use of donor hearts. Rejection rates and long-term survival outcomes are not known. METHODS/UNASSIGNED:A single-center retrospective cohort review of patients who underwent DCD heart transplantation from January 2020 to December 2023 was performed. Donor and recipient characteristics, operative characteristics, and posttransplantation outcomes were analyzed. Subgroup analysis comparing co-localized vs distant donors and recipients was performed. The primary end point was 1-year survival. Secondary end points included incidences of primary graft dysfunction (PGD), cardiac allograft vasculopathy (CAV), rejection rate, and overall mortality. Our TA-NRP protocol has remained the same, consisting of sternotomy, ligation of aortic arch vessels, establishment of cardiopulmonary bypass, reintubation, resuscitation of the heart, and cold static storage during transport. RESULTS/UNASSIGNED:< .005) ischemia times, without any other differences. CONCLUSIONS/UNASSIGNED:Outcomes after DCD heart transplantation using TA-NRP remain encouraging with acceptable rates of rejection, PGD, CAV, and survival at 1 year.

OBJECTIVE/UNASSIGNED:Anticoagulation monitoring in patients supported on extracorporeal membrane oxygenation is challenging given the risks of both bleeding and thrombotic complications. Based on our early clinical experience, we revised our heparin protocol by reducing our target anti-factor Xa assay from 0.3 to 0.7 U/mL to 0.15 to 0.5 U/mL, while instituting a partial thromboplastin time cutoff of 70 seconds. We evaluated the impact of this change on bleeding/thrombotic complications. METHODS/UNASSIGNED:A single-center retrospective study of adult patients on extracorporeal membrane oxygenation support was conducted from January 2015 to August 2022. Patients were stratified into groups based on protocol revision: Pre-Revision (2015-2018) or Post-Revision (2019-2022). Our primary end point was the incidence of bleeding/thrombotic complications. Time in therapeutic range was calculated to determine protocol adherence. Poisson regression was performed to correlate time in therapeutic range with the likelihood of complication. RESULTS/UNASSIGNED:008). CONCLUSIONS/UNASSIGNED:A modified heparin monitoring protocol defined by a lower therapeutic anti-factor Xa assay target and a set partial thromboplastin time cutoff correlated with decreases in bleeding/thrombotic complications in patients on extracorporeal membrane oxygenation.

Perspective Statement: Beyond the Society of Thoracic Surgery's (STS) quality metrics, many other operative measures, such as completeness of revascularization, and patient care measures add quality and value for patients undergoing coronary artery bypass surgery; and Enhanced Recovery after Surgery (ERAS) protocols have improved patient experience and recovery, leading to better outcomes and significant healthcare savings.

As we approach the five-year anniversary of the 2018 heart allocation system in the United States, it is imperative to consider the changing landscape of mechanical circulatory support and the strategies used to bridge patients into heart transplants. This manuscript reviews the history of the heart allocation system, as well as the conditions that led to its multiple revisions. We discuss initial outcomes following the implementation of the new allocation system, including the impact on waitlist mortality and post-transplant outcomes. We also give special consideration to changes in bridging strategies using venoarterial extracorporeal membrane oxygenation (VA ECMO), intra-aortic balloon pumps, and durable left ventricular assist devices (LVADs).