Association of procurement technique with organ yield and cost following donation after circulatory death.

Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.

Importance of social vulnerability on long-term outcomes after heart transplantation.

The relationship between social determinants of health and outcomes after heart transplantation has not been examined. The social vulnerability index (SVI) uses United States census data to determine the social vulnerability of every census tract based on 15 factors. This retrospective study seeks to examine the impact of SVI on outcomes after heart transplantation. Adult heart recipients who received a graft between 2012 and 2021 were stratified into SVI percentiles of <75% and SVI of ≥75%. The primary endpoint was survival. The median SVI was 48% (interquartile range: 30%-67%) among 23 700 recipients. One-year survival was similar between groups (91.4 vs 90.7%, log-rank P = .169); however, 5-year survival was lower among individuals living in vulnerable communities (74.8% vs 80.0%, P < .001). This finding persisted despite risk adjustment for other factors associated with mortality (survival time ratio 0.819, 95% confidence interval: 0.755-0.890, P < .001). The incidences of 5-year hospital readmission (81.4% vs 75.4%, P < .001) and graft rejection (40.3% vs 35.7%, P = .004) were higher among individuals living in vulnerable communities. Individuals living in vulnerable communities may be at increased risk of mortality after heart transplantation. These findings suggest there is an opportunity to focus on these recipients undergoing heart transplantation to improve survival.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Simultaneous ex vivo normothermic preservation of liver and heart grafts from a donation after circulatory death donor.

Normothermic machine perfusion of organs is growing in popularity and has been used for both abdominal and thoracic organ preservation before transplantation. The use of normothermic machine perfusion for donation after cardiac death organs can reduce cold ischemia time and help prevent ischemia-related complications. We present a successful case of a donation after cardiac death procurement with both liver and heart allografts preserved by normothermic machine perfusion. Both allografts were perfused without complications and transplanted successfully. As the technology continues to become more prevalent, the situation described will become more commonplace, and we offer a view of the future in transplantation.

DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells.

DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis.

KEY POINTS: Despite growing interest in right ventricular form and function in diseased states, there is a paucity of data regarding characteristics of right ventricular function - namely contractile and lusitropic reserve, as well as ventricular-arterial coupling, in the healthy heart during rest, as well as submaximal and peak exercise. Pressure-volume analysis of the right ventricle, during invasive cardiopulmonary exercise testing, demonstrates that that the right heart has enormous contractile reserve, with a three- or fourfold increase in all metrics of contractility, as well as myocardial energy production and utilization. The healthy right ventricle also demonstrates marked augmentation in lusitropy, indicating that diastolic filling of the right heart is not passive. Rather, the right ventricle actively contributes to venous return during exercise, along with the muscle pump. Ventricular-arterial coupling is preserved during submaximal and peak exercise in the healthy heart. ABSTRACT: Knowledge of right ventricular (RV) function has lagged behind that of the left ventricle and historically, the RV has even been referred to as a 'passive conduit' of lesser importance than its left-sided counterpart. Pressure-volume (PV) analysis is the gold standard metric of assessing ventricular performance. We recruited nine healthy sedentary individuals free of any cardiopulmonary disease (42 ± 12 years, 78 ± 11 kg), who completed invasive cardiopulmonary exercise testing during upright ergometry, while using conductance catheters inserted into the RV to generate real-time PV loops. Data were obtained at rest, two submaximal levels of exercise below ventilatory threshold, to simulate real-world scenarios/activities of daily living, and maximal effort. Breath-by-breath oxygen uptake was determined by indirect calorimetry. During submaximal and peak exercise, there were significant increases in all metrics of systolic function by three- to fourfold, including cardiac output, preload recruitable stroke work, and maximum rate of pressure change in the ventricle (dP/dtmax ), as well as energy utilization as determined by stroke work and pressure-volume area. Similarly, the RV demonstrated a significant, threefold increase in lusitropic reserve throughout exercise. Ventricular-arterial coupling, defined by the quotient of end-systolic elastance and effective arterial elastance, was preserved throughout all stages of exercise. Maximal pressures increased significantly during exercise, while end-diastolic volumes were essentially unchanged. Overall, these findings demonstrate that the healthy RV is not merely a passive conduit, but actively participates in cardiopulmonary performance during exercise by accessing an enormous amount of contractile and lusitropic reserve, ensuring that VA coupling is preserved throughout all stages of exercise.

Cardiac Perforation by Migrated Fractured Strut of Inferior Vena Cava Filter Mimicking Acute Coronary Syndrome.

We present a rare late complication after inferior vena cava filter (IVC) placement. A 52-year-old woman with an IVC presented with sudden onset of chest pain. Cardiac catheterisation and echocardiography revealed an embolised IVC filter strut penetrating the right ventricle. Endovascular retrieval was considered but deemed unsafe due to proximity to the right coronary artery and concern for migration to pulmonary circulation. Urgent removal of the strut was performed via sternotomy. The postoperative course was uneventful. Two weeks later, she was asymptomatic. Minimally invasive approaches have been described for retrieval of intact IVC filters that have migrated to the right heart but not for embolised filter fragments. We recommend traditional sternotomy as the preferred method of retrieval as it limits the likelihood of further migration or trauma.

Biology and Conservation of the Taiwanese Humpback Dolphin, Sousa chinensis taiwanensis.

The humpback dolphins of the eastern Taiwan Strait were first discovered scientifically in 2002 and since then have received much research attention. We reviewed all information published in peer-reviewed scientific journals on these dolphins and where appropriate and available, peer-reviewed scientific workshop reports and graduate theses were also examined. Recent evidence demonstrated that this population warranted recognition as a subspecies, Sousa chinensis taiwanensis. It is found in a highly restricted and linear strip of coastal waters along central western Taiwan. Numbering fewer than 80 individuals and declining, five main threats (fisheries interactions, habitat loss and degradation, loss of freshwater to estuaries within their habitat, air and water pollution, and noise) threaten the future existence of this subspecies. These dolphins have cultural and religious importance and boast the highest level of legal protection for wildlife in Taiwan. However, despite enormous efforts by local and international non-governmental groups urging immediate conservation actions, there have been no real government efforts to mitigate any existing threats; instead, some of these threats have worsened. Based on recent studies, we suggest the IUCN Red List status be revised to Critically Endangered CR 2a(ii); D for the subspecies.

Comparison of Indo-Pacific humpback dolphin (Sousa chinensis) whistles from two areas of western Peninsular Malaysia.

Differences in the acoustic variables of whistles emitted by Indo-Pacific humpback dolphins (Sousa chinensis) from two coastal locations along western Peninsular Malaysia were investigated. Duration, frequency, and frequency modulation variables were extracted from and used to characterize recordings of free-ranging humpback dolphins that were made using a broadband towed hydrophone. A total of 960 whistles from Matang Mangroves and 823 whistles from Langkawi Island were used in analyses. The whistles of Malaysian humpback dolphins covered frequencies from 1231 to 27 120 Hz with durations from 0.010-1.575 s. Significant multivariate differences were found in whistles emitted between locations. Significant differences were also found between dolphins of the two locations in their whistle duration, frequency modulation, and all frequency variables except for minimum frequency, which is likely under morphological constraints. The differences in whistles may be related to adaptations to the local acoustic habitat or unique whistles may have developed due to social interactions within each location, or broader scale differences resulting from geographic separation between the locations.

Noteworthy in Cardiothoracic Surgery 2023.

Noteworthy in Cardiothoracic Surgery 2023 summarizes a few of the most high-impact trials and provocative trends in cardiothoracic surgery and transplantation this past year. Transplantation using organs procured from donation after circulatory death (DCD) continues to increase, and the American Society of Transplant Surgeons released recommendations on best practices in 2023. We review a summary of data on the impact of DCD on heart and lung transplantation. There has been increased interest in extracorporeal life support (ECLS), particularly after the COVID-19 pandemic, and we review the results of the highly discussed ECLS-SHOCK trial, which randomized patients in cardiogenic shock with planned revascularization to ECLS vs usual care. With improving survival outcomes in complex aortic surgery, there is a need for higher-quality evidence to guide which cooling and cerebral perfusion strategies may optimize cognitive outcomes in these patients. We review the short-term outcomes of the GOT ICE trial (Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest), a multicenter, randomized controlled trial of three different nadir temperatures, evaluating outcomes in cognition and associated changes in functional magnetic resonance imaging. Finally, both the Society of Thoracic Surgeons (STS) and the American College of Cardiology, American Heart Association, American College of Chest Physicians and Heart Rhythm Society (ACC/AHA/ACCP/HRS) updated atrial fibrillation guidelines in 2023, and we review surgically relevant updates to the guidelines and the evidence behind them.

Post-transplant survival after normothermic regional perfusion versus direct procurement and perfusion in donation after circulatory determination of death in heart transplantation.

BACKGROUND: Since 2019, the annual transplantation rate of hearts donated following circulatory death (DCD) has increased significantly in the United States. The 2 major heart procurement techniques following circulatory death are direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). Post-transplant survival for heart recipients has not been compared between these 2 techniques. METHODS: This observational study uses data on adult heart transplants from donors after circulatory death from January 1, 2019 to December 31, 2021 in the Scientific Registry of Transplant Recipients. We identified comparable transplant cases across procurement types using propensity-score matching and measured the association between procurement technique and 1-year post-transplant survival using Kaplan-Meier and Cox proportional hazards model stratefied by matching pairs. RESULTS: Among 318 DCD heart transplants, 216 (68%) were procured via DPP, and 102 (32%) via NRP. Among 22 transplant centers that accepted circulatory-death donors, 3 used NRP exclusively, and 5 used both procurement techniques. After propensity-score matching on recipient and donor factors, there was no significant difference in 1-year post-transplant survival (93.1% for NRP vs 91.1% for DPP, p = 0.79) between procurement techniques. CONCLUSIONS: NRP and DPP procurements are associated with similar 1-year post-transplant survival. If NRP is ethically permissible and improves outcomes for abdominal organs, it should be the preferred procurement technique for DCD hearts.

Characterization of pulmonary arterial stiffness using cardiac MRI.

Pulmonary arterial stiffness (PAS) is a pathologic hallmark of all types of pulmonary hypertension (PH). Cardiac MRI (CMR), a gold-standard imaging modality for the evaluation of pulmonary flow, biventricular morphology and function has been historically reserved for the longitudinal clinical follow-up, PH phenotyping purposes, right ventricular evaluation, and research purposes. Over the last two decades, numerous indices combining invasive catheterization and non-invasive CMR have been utilized to phenotype the character and severity of PAS in different types of PH and to assess its clinically prognostic potential with encouraging results. Many recent studies have demonstrated a strong role of CMR derived PAS markers in predicting long-term clinical outcomes and improving currently gold standard risk assessment provided by the REVEAL calculator. With the utilization of a machine learning strategies, strong diagnostic and prognostic performance of CMR reported in multicenter studies, and ability to detect PH at early stages, the non-invasive assessment of PAS is on verge of routine clinical utilization. In this review, we focus on appraising important CMR studies interrogating PAS over the last 20 years, describing the benefits and limitations of different PAS indices, and their pathophysiologic relevance to pulmonary vascular remodeling. We also discuss the role of CMR and PAS in clinical surveillance and phenotyping of PH, and the long-term future goal to utilize PAS as a biomarker to aid with more targeted therapeutic management.

Prolonged travel time to transplantation center is associated with poor outcomes following heart transplantation.

BACKGROUND: This study aims to examine the impact of home-to-transplantation center travel time as a potential barrier to healthcare accessibility. METHODS: Observational study examined adult heart transplant recipients who received a graft between 2012 and 2022 in the United States. Travel time was calculated using the Google Distance Matrix API between the recipient's residence and transplantation center. A multivariable parametric survival model was fitted to minimize confounding bias. RESULTS: Among the 25,923 recipients that met the selection criteria, the median travel time was 51 â€‹min and 95 â€‹% of recipients lived within a 5-h radius of their center. White recipients experienced longer median travel times (62 â€‹min, p â€‹< â€‹0.001) compared to Black (36 â€‹min) or Hispanic (40 â€‹min) recipients. A travel time of 1-2 â€‹h (survival time ratio [STR] 0.867, p â€‹= â€‹0.035) or >2 â€‹h (STR 0.873, p â€‹= â€‹0.026) away from the transplantation center was independently associated with lower long-term survival rates. CONCLUSION: Extended travel times to transplantation centers may negatively impact long-term survival outcomes for heart transplant recipients, suggesting the need to address this potential barrier to healthcare accessibility.

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.

Biosymbiotic haptic feedback - Sustained long term human machine interfaces.

Haptic technology permeates diverse fields and is receiving renewed attention for VR and AR applications. Advances in flexible electronics, facilitate the integration of haptic technologies into soft wearable systems, however, because of small footprint requirements face challenges of operational time requiring either large batteries, wired connections or frequent recharge, restricting the utility of haptic devices to short-duration tasks or low duty cycles, prohibiting continuously assisting applications. Currently many chronic applications are not investigated because of this technological gap. Here, we address wireless power and operation challenges with a biosymbiotic approach enabling continuous operation without user intervention, facilitated by wireless power transfer, eliminating the need for large batteries, and offering long-term haptic feedback without adhesive attachment to the body. These capabilities enable haptic feedback for robotic surgery training and posture correction over weeks of use with neural net computation. The demonstrations showcase that this device class expands use beyond conventional brick and strap or epidermally attached devices enabling new fields of use for imperceptible therapeutic and assistive haptic technologies supporting care and disease management.