Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

BACKGROUND: Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP). METHODS: Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses. RESULTS: Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. CONCLUSIONS: A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

BACKGROUND AND AIMS: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR). METHODS AND RESULTS: In this retrospective, single-center study, 1071 adult patients who underwent an MVR between 2004 and 2018 were stratified into five BMI groups (<20, 20-24.9, 25-29.9, 30-34.9, >35). Cox proportional hazard regression models were used to determine the association between BMI and all-cause mortality. Patients who were underweight had significantly higher all-cause mortality rates at the longest follow-up (median 8.2 years) than patients with normal weight (p = 0.01). Patients who were in the obese group had significantly higher readmission rates due to myocardial infarction (MI) at the longest follow-up (p = 0.017). Subgroup analysis revealed a significant increase in long-term all-cause mortality for female patients who were underweight. Significant changes in left atrial size, mitral valve peak and mean gradients were seen in all BMI groups. CONCLUSIONS: For patients undergoing mitral valve replacement, BMI is unrelated to operative outcomes except for patients who are underweight.

Mitral Valve Repair in Patients with Chronic Kidney Disease: Long-Term Outcomes and Cardiac Remodeling.

OBJECTIVES: Literature examining mitral valve repair (MVr) outcomes in patients with chronic kidney disease (CKD) is largely limited to short-term outcomes and percutaneous approaches. This study is the first to present long-term outcomes of mortality and morbidity with paired cardiac remodeling data from patients with CKD undergoing surgical MVr. DESIGN: A retrospective, observational, comparative study. SETTING: Single-center university hospital. PARTICIPANTS: Patients with varying stages of CKD undergoing MVr from 2004 to 2018. INTERVENTIONS: Patients were grouped by estimated glomerular filtration (eGFR) rate and followed for a maximum of 15 years. Long-term outcomes and measures of cardiac remodeling were then compared between the groups. MEASUREMENTS AND MAIN RESULTS: The primary outcome was all-cause mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodeling. Every 10-unit increase in eGFR was associated with a significant reduction in all-cause mortality at 5 years (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.67-0.98, p = 0.028), 10 years (HR: 0.82, 95% CI: 0.72-0.94, p = 0.004), and at 15 years (HR: 0.78, 95% CI: 0.69-0.88, p < 0.001). The moderate CKD group had significantly higher rates of all-cause mortality at 15 years (HR: 3.38, 95% CI: 1.28-8.98, p = 0.014). eGFR was a significant predictor for residual moderate-to-severe mitral regurgitation at 1 year (HR: 0.74, 95% CI: 0.57-0.96, p = 0.024). There was positive cardiac remodeling following MVr in patients with CKD with a significant reduction in left ventricular size and left atrium volume. CONCLUSIONS: In patients with CKD undergoing MVr, eGFR is a predictor of decreased long-term survival and residual mitral regurgitation at 1 year. Further investigation is required to optimize postoperative outcomes in this patient population.

Oxidative stress and related metabolic alterations are induced in ex situ perfusion of donated hearts regardless of the ventricular load or leukocyte depletion.

We sought to determine the role of donor blood circulating leukocytes in mediating oxidative stress and inflammation during normothermic ex situ heart perfusion (ESHP). Normothermic ESHP allows preservation of donated heart in a perfused, dynamic state, preventing ischemia. However, the cardiac function declines during ESHP, limiting the potential of this method for improvement of the outcomes of transplantation and expanding the donor pool. Extracorporeal circulation-related oxidative stress plays a critical role in the functional decline of the donor heart. Hearts from domestic pigs were perfused in working mode (WM, whole blood-based or leukocyte-depleted blood-based perfusate) or nonworking mode. Markers of oxidative stress and responsive glucose anabolic pathways were induced in the myocardium regardless of left ventricular load. Myocardial function during ESHP as well as cardioprotective mechanisms were preserved better in WM. Leukocyte-depleted perfusate did not attenuate tissue oxidative stress or perfusate proinflammatory cytokines and did not improve functional preservation. Although ESHP is associated with ongoing oxidative stress and metabolic alteration in the myocardium, preserved cardioprotective mechanisms in WM may exert beneficial effects. Leukocyte depletion of the perfusate may not attenuate inflammation and oxidative stress effectively or improve the functional preservation of the heart during ESHP.

Family perspectives of ex situ heart perfusion.

BACKGROUND: Pediatric patients awaiting a heart transplant have high waitlist mortality. Several strategies have been utilized to decrease waiting times, but a mortality risk still exists. New medical technologies may improve waiting times and associated mortality. Ex situ heart perfusion (ESHP) is one such technology, which can decrease the impact of cold ischemia on the donor heart and allow for a longer out-of-body time. Adoption of such technology in pediatric heart transplantation will require support from end users, including patient and families. The aim of this qualitative study was to report the perspectives of families with experience related to pediatric HTx toward ESHP. METHODS: Semistructured interviews were conducted with 12 parents or guardians of children who were awaiting or received heart transplantation. Interviews were transcribed, and data were analyzed using qualitative content analysis. RESULTS: Participants expressed varied awareness and knowledge of ESHP. Independent of their understanding of ESHP, all purported that ESHP was an excellent idea and that this technology should be implemented in the pediatric population. They did not identify fundamentally different ethical issues or concerns for ESHP being used relative to other medical technologies. Overall, most participants described consent processes for ESHP should be like any other procedure. All agreed that the surgeon should continue to describe the overall health of the donor heart, provide their medical recommendations, and allow families to have the final say. CONCLUSIONS: The concepts described by the parents and guardians are important in moving this novel technology forward. This information will serve the basis for knowledge translation that will provide educational resources to broaden the understanding and reach of ESHP.

Barriers and misconceptions of ex situ heart perfusion in pediatric donation.

BACKGROUND: Despite efforts, pediatric HTx candidates continue to have high waitlist mortality due to limited donor availability. However, there is a significant number of offered hearts not used due to concerns of viability. ESHP is a method for continuous perfusion of the donor heart that allows assessment and extended out-of-body time. It is imperative to understand healthcare stakeholders' perspectives on ESHP for implementation. Therefore, the aims of this qualitative study were to: (1) Explore pediatric stakeholders' perspectives toward ESHP; and (2) Identify barriers to widespread adoption of this technology. METHODS: Virtual focus groups were completed with pediatric HTx healthcare professional stakeholders. Following transcription of audio-recordings, the material was analyzed using content analysis. RESULTS: Four focus groups were completed with 17 participants, representing 12 institutions and three countries. Focus groups revealed varied understanding of both current and potential uses of ESHP. Participants did see the potential benefits of extending out-of-body time for and the ability to evaluate donor heart quality. However, concerns were expressed relating to patient selection, wait-list times, post-HTx outcomes, adverse events, and technical issues. These were felt to be important to understand in order to justify the costs of ESHP and impact on the healthcare system. CONCLUSIONS: This project represents the first qualitative formative evaluation of ESHP in pediatrics. The knowledge gained from stakeholders will form the basis for education initiatives, clinical trial design, and roll-out of new ESHP technologies designed for pediatrics.

Ex situ heart perfusion for optimization of pediatric donor organ utilization: Attitudes and perceptions.

BACKGROUND: Children with heart failure have the highest mortality while awaiting transplantation. Ex situ heart perfusion (ESHP), a method for continuous perfusion of the donor heart, has the potential to improve access to transplant by increasing travel distance between donor and recipient. An adult ESHP device is currently available, but as of yet there is no pediatric device. The aim of this study was to evaluate current knowledge of ESHP among pediatric heart transplant practitioners, define potential barriers, and identify uses of this novel technology. METHODS: An electronic survey was developed to assess perspectives of international pediatric heart transplant stakeholders (n = 68) on ESHP. Select questions were analyzed to evaluate for associations between groups of respondents and patterns of response. RESULTS: Most respondents were familiar but <10% had clinically utilized ESHP. There was optimism that ESHP could decrease waitlist mortality. Respondents were concerned about potential device malfunction and lack of long-term outcomes. There were no differences found in terms of ESHP familiarity among age groups, practitioner center volume, country of work, or discipline. CONCLUSIONS: ESHP has the potential to expand the pediatric heart donor pool and decrease waitlist mortality. More education on outcomes and risks/benefits is needed in order to promote widespread adoption.

Predicting outcomes following short-term ventricular assist device implant with the MELD-XI score.

BACKGROUND: Short-term continuous flow (STCF) ventricular assist devices (VADs) are utilized in adults with cardiogenic shock; however, mortality remains high. Previous studies have found that high pre-operative MELD-XI scores in durable VAD patients are associated with mortality. The use of the MELD-XI score to predict outcomes in STCF-VAD patients has not been explored. We sought to determine the relationship between MELD-XI and outcomes in adults with STCF-VADs. METHODS: This was a retrospective review of adults implanted with STCF-VADs between 2009 and 2019. Receiver operating characteristic (ROC) analysis was performed to predict outcomes and Kaplan-Meier analysis was done to assess survival. RESULTS: Seventy-nine patients were included with a median MELD-XI score of 21.2 (IQR 13.5, 27.0). Patients with an unsuccessful wean from support (p < 0.001) or major post-operative bleeding (p = 0.03) had significantly higher pre-implant MELD-XI scores. The optimal MELD-XI cut-point for mortality was 24.9 with 27.8 for major bleeding. Survival was worse among patients in the high-risk MELD-XI group, however, not statistically significant (p = 0.09). Prior ECMO support, but not MELD-XI, was an independent predictor of unsuccessful wean (p = 0.03). CONCLUSIONS: Pre-operative MELD-XI score was a moderate predictor of unsuccessful wean with limited utility in predicting bleeding in patients on STCF-VAD support. This scoring system may be useful in the clinical setting for pre-implant risk stratification and counseling among patients and outcomes.

Percutaneous Treatment of Ascending Aortic Obstruction in a Young Child After Orthotopic Heart Transplantation.

We report a case of a 14-month-old child with ascending aortic obstruction (AAO) post cardiac transplantation, who underwent successful percutaneous ascending aortic stent angioplasty. Congenital or acquired AAO is typically treated with surgical augmentation. The experience with percutaneous techniques is limited and often avoided due to challenges with equipment stability and proximity to coronary arteries and aortic valve leaflets. This case highlights that a percutaneous approach to relief of AAO is a feasible alternative even in small children utilizing a newer pre-mounted stent.

Recellularized bovine pericardium with autologous mesenchymal stem cells reduces immune activation.

INTRODUCTION: Current bioprosthetic heart valve replacement options are limited by structural valvular deterioration (SVD) due to an immune response to the xenogenic scaffold. Autologous mesenchymal stem cell (MSC) recellularization is a method of concealing xenogenic scaffolds, preventing recipient immune recognition of xenogenic tissue heart valves, and potentially leading to reduction in SVD incidence. The purpose of this study is to examine the effects of autologous MSC recellularized tissue on the immune response of human whole blood to bovine pericardium (BP). We hypothesized that autologous MSC recellularization of BP will result in reduced pro-inflammatory cytokine production equivalent to autologous human pericardium. METHODS: Bone marrow, human pericardium, and whole blood were collected from adult patients undergoing elective cardiac surgery. Decellularized BP underwent recellularization with autologous MSCs, followed by co-incubation with autologous whole blood. Immunohistochemical, microscopic, and quantitative immune analysis approaches were used. RESULTS: We demonstrated that native BP, exposed to human whole blood, results in significant TNF-α and IL1ß production. When decellularized BP is recellularized with autologous MSCs and exposed to whole blood, there is a significant reduction in TNF-α and IL1ß production. Importantly, recellularized BP exposed to whole blood had similar production of TNF-α and IL1ß when compared to autologous human pericardium exposed to human whole blood. CONCLUSION: Our results suggest that preventing initial immune activation with autologous MSC recellularization may be an effective approach to decrease the recipient immune response, preventing recipient immune recognition of xenogeneic tissue engineered heart valves, and potentially leading to reduction in SVD incidence.

Coronary Artery Revascularization in Heart Transplant Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the primary cause of late mortality after heart transplantation. We look to provide a comprehensive review of contemporary revascularization strategies in CAV. METHODS: PubMed and Web of Science were systematically searched by 3 authors. 1,870 articles were initially screened and 24 were included in this review. RESULTS: PCI is the main revascularization technique utilized in CAV. The pooled estimates for restenosis significantly favored DES over BMS (OR 4.26; 95% CI: 2.54-7.13; p < 0.00001; I2 = 4%). There were insufficient data to quantitatively compare mortality following DES versus BMS. There was no difference in short-term mortality between CABG and PCI. In-hospital mortality was 0.0% for CABG and ranged from 0.0 to 8.34% for PCI. One-year mortality was 8.0% for CABG and 5.0-25.0% for PCI. CABG had a potential advantage at 5 years. Five-year mortality was 17.0% for CABG and ranged from 14 to 40.4% following PCI. Select measures of postoperative morbidity trended toward superior outcomes for CABG. CONCLUSION: In CAV, PCI is the primary revascularization strategy utilized, with DES exhibiting superiority to BMS regarding postoperative morbidity. Further investigation into outcomes following CABG in CAV is required to conclusively elucidate the superior management strategy in CAV.

Ventricular assist device support following pediatric heart transplantation.

BACKGROUND: VAD support for early graft failure after HTx is a rare event in pediatrics. METHODS: We retrospectively describe our single-center experience with post-HTx VAD support in a cohort of patients transplanted between 01/05 and 12/20. RESULTS: Nine patients underwent VAD insertion in the early post-HTx period [median age 6.1 years (Range 0.3-20.3), median weight 17.6 kg (Range 3.5-65.0), and congenital heart disease (67%)]. Of the nine patients with early graft failure, almost half (44%) were implanted after 2015 and all of these patients had a pre-HTx plan for possible post-transplant VAD insertion. Time to VAD implant was a median of 0 day (Range 0-11). Total time on VAD support was a median of 12 days (Range 3.0-478.0). Two-thirds (n = 6; 67%) of the patients were weaned from support, retransplanted (11%) and two patients died (22%). In all of the patients where post-HTx VAD was anticipated there was 100% survival. CONCLUSIONS: In this small patient series, post-HTx VAD was a useful measure in selected patients especially with pre-HTx planning. However, more shared experiences to verify these findings are needed.

The effects of body mass index on long-term outcomes and cardiac remodeling following mitral valve repair surgery.

BACKGROUND: Previous literature has demonstrated equivalent or improved survival post mitral valve (MV) surgery amongst patients with obesity when compared to their normal-weight counterparts. This relationship is poorly understood and the impact of body mass index (BMI) on cardiac remodeling has not been established. METHODS: In this retrospective, single-center study, we sought to identify the impact that BMI may have on long-term outcomes and cardiac remodeling post-MV repair. Outcomes were compared between patients of varying BMI undergoing MV repair between 2004 and 2018. The primary outcome was mortality and secondary outcomes included stroke, myocardial infarction, reoperation of the MV, rehospitalization, and cardiac remodeling. RESULTS: A total of 32 underweight, 249 normal weight, 249 overweight, 121 obese, and 50 morbidly obese patients were included in this study. Underweight patients had increased mortality at longest follow-up. Patients with morbid obesity were found to have higher rates of readmission for heart failure. Only underweight patients did not demonstrate a significant reduction in LVEF. Patients with normal weight and overweight had a significant reduction in left atrial size, and patients with obesity had a significant reduction in MV area. CONCLUSIONS: An obesity paradox has been identified in cardiac surgery. While patients with obesity have higher rates of comorbidities preoperatively, their rates of mortality are equivalent or even superior to those with lower BMI. The results of our study confirm this finding with patients of high BMI undergoing MV repair demonstrating equivalent rates of morbidity to their normal BMI counterparts. While the obesity paradox has been relatively consistent in the literature, the understanding of its cause and long-term impacts are not well understood. Further focused investigation is necessary to elucidate the cause of this relationship.

A review of the immune response stimulated by xenogenic tissue heart valves.

Valvular heart disease continues to afflict millions of people around the world. In many cases, the only corrective treatment for valvular heart disease is valve replacement. Valve replacement options are currently limited, and the most common construct utilized are xenogenic tissue heart valves. The main limitation with the use of this valve type is the development of valvular deterioration. Valve deterioration results in intrinsic permanent changes in the valve structure, often leading to hemodynamic compromise and clinical symptoms of valve re-stenosis. A significant amount of research has been performed regarding the incidence of valve deterioration and determination of significant risk factors for its development. As a result, many believe that the underlying driver of valve deterioration is a chronic immune-mediated rejection process of the foreign xenogenic-derived tissue. The underlying mechanisms of how this occurs are an area of ongoing research and active debate. In this review, we provide an overview of the important components of the immune system and how they respond to xenografts. A review of the proposed mechanisms of xenogenic heart valve deterioration is provided including the immune response to xenografts. Finally, we discuss the role of strategies to combat valve degeneration such as preservation protocols, epitope modification and decellularization.

Heart donation and transplantation after circulatory determination of death: expert guidance from a Canadian consensus building process.

Controlled donation after circulatory determination of death (DCD), where death is determined after cardiac arrest, has been responsible for the largest quantitative increase in Canadian organ donation and transplants, but not for heart transplants. Innovative international advances in DCD heart transplantation include direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). After death is determined, DPP involves removal and reanimation of the arrested heart on an ex situ organ perfusion system. Normothermic regional perfusion involves surgically interrupting (ligating the aortic arch vessels) brain blood flow after death determination, followed by restarting the heart and circulation in situ using extracorporeal membrane oxygenation. The objectives of this Canadian consensus building process by a multidisciplinary group of Canadian stakeholders were to review current evidence and international DCD heart experience, comparatively evaluate international protocols with existing Canadian medical, legal, and ethical practices, and to discuss implementation barriers. Review of current evidence and international experience of DCD heart donation (DPP and NRP) determined that DCD heart donation could be used to provide opportunities for more heart transplants in Canada, saving additional lives. Although candid discussion identified a number of potential barriers and challenges for implementing DCD heart donation in Canada, it was determined that DPP implementation is feasible (pending regulatory approval for the use of an ex situ perfusion device in humans) and in alignment with current medical guidelines for DCD. Nevertheless, further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

RéSUMé: Le don contrôlé après un décès circulatoire (DDC), cas dans lequel le décès est déterminé après un arrêt cardiaque, est à l'origine de la plus forte augmentation quantitative des dons et des transplantations d'organes au Canada, sauf pour les transplantations cardiaques. Parmi les progrès internationaux novateurs dans la transplantation cardiaque après DDC, citons l'obtention directe et perfusion (ODP) et la circulation régionale normothermique (CRN). Une fois le décès déterminé, l'ODP consiste à retirer et réanimer le cœur arrêté sur un système de perfusion ex situ. La circulation régionale normothermique consiste à interrompre de manière chirurgicale (en ligaturant les vaisseaux de l'arc aortique) le flux sanguin au cerveau après la détermination du décès, puis à redémarrer le cœur et la circulation in situ utilisant l'oxygénation par membrane extracorporelle (ECMO). Les objectifs de ce processus canadien d'établissement de consensus par un groupe multidisciplinaire d'intervenants canadiens étaient d'examiner les données probantes et les expériences internationales actuelles en matière de DDC, d'évaluer comparativement les protocoles internationaux par rapport aux pratiques médicales, juridiques et éthiques canadiennes existantes, et de discuter des obstacles à la mise en œuvre de tels protocoles. L'examen des données probantes et des expériences internationales actuelles en matière de don de cœur après DDC (ODP et CRN) a permis de déterminer que le don de cœur après DDC pourrait être utilisé afin de faire de plus nombreuses transplantations cardiaques au Canada, sauvant ainsi des vies supplémentaires. Bien que des discussions aient permis d'identifier plusieurs obstacles et défis potentiels à la mise en œuvre du don cardiaque après DDC au Canada, il a été déterminé que la mise en œuvre de l'ODP est réalisable (en attente de l'approbation réglementaire pour l'utilisation d'un dispositif de perfusion ex situ chez l'humain) et en accord avec les directives médicales actuelles concernant le DDC. Néanmoins, d'autres travaux sont nécessaires pour évaluer la conformité de la CRN aux politiques canadiennes actuelles de détermination de la mort et pour garantir l'absence de perfusion cérébrale au cours de ce processus.

Impact of sex on cardiac remodeling and long-term outcomes, following mitral valve replacement.

BACKGROUND: Differences in cardiac remodeling after mitral valve (MV) surgery between the sexes is poorly understood. Inferior outcomes for females undergoing MV surgery compared with males have been suggested in the literature, although causative factors behind this discrepancy have not been identified. MATERIALS AND METHODS: In this propensity-matched, retrospective, single-center study, we sought to identify the impact that sex may have on cardiac remodeling and long-term outcomes to better inform clinical decision-making in MV surgical intervention. Outcomes were compared between males and females undergoing MV replacement (MVR) between 2004 and 2018. The primary outcome was cardiac remodeling 1 year postoperatively. Secondary outcomes included mortality, stroke, myocardial infarction (MI), reoperation of the MV, and rehospitalization. RESULTS: A total of 311 males and 311 females were included after propensity matching. Both groups demonstrated significant improvement in left atrial remodeling, although only males demonstrated a significant degree of improved left ventricular remodeling while their female counterparts did not. Mortality rates were relatively equivalent between the two groups, although males were more likely to develop sepsis and require rehospitalization due to MI. CONCLUSIONS: There has been little research exploring the differences in cardiac remodeling between the sexes after MVR. The results of this study have suggested that MVR is equally safe for both sexes and has demonstrated a difference in the heart's ability to remodel after MVR. The significance of this difference has the potential to result in largely different clinical outcomes for males and females. Further study is necessary to fully elucidate this relationship.

Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposal.

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.

The effects of body mass index on outcomes for patients undergoing surgical aortic valve replacement.

BACKGROUND: Most of the studies of obesity and postoperative outcome have looked predominantly at coronary artery bypass grafting with fewer focused on valvular disease. The purpose of this study was to compare the outcomes of patients undergoing aortic valve replacement stratified by body mass index (BMI, kg/m^2). METHODS: The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry captured 4780 aortic valve replacements in Alberta, Canada from January 2004 to December 2018. All recipients were stratified by BMI into five groups (BMI: < 20, 20-24.9, 25-29.9, 30-34.9, and > = 35). Log-rank test and Cox regression were used to examine the crude and adjusted survival differences. RESULTS: Intra-operative clamp time and pump time were similar among the five groups. Significant statistical differences between groups existed for the incidence of isolated AVR, AVR and CABG, hemorrhage, septic infection, and deep sternal infection (p < 0.05). While there was no significant statistical difference in the mortality rate across the BMI groups, the underweight AVR patients (BMI < 20) were associated with increased hazard ratio (1.519; 95% confidence interval: 1.028-2.245) with regards to all-cause mortality at the longest follow-up compared with normal weight patients. CONCLUSION: Overweight and obese patients should be considered as readily for AVR as normal BMI patients.

Discharge and Readmission to the Pediatric Cardiac ICU in Pediatric Patients With Durable Ventricular Assist Devices.

OBJECTIVES: Pediatric patients implanted with a durable ventricular assist device are initially managed in the pediatric cardiac ICU but are eligible for discharge to the ward. Our objectives were to characterize discharge and readmission of ventricular assist device patients to the pediatric cardiac ICU, identify risk factors for readmission, and determine whether discharge or readmission is associated with mortality. DESIGN: Retrospective study. SETTING: Stollery Children's Hospital. PATIENTS: Patients implanted with a durable ventricular assist device at less than 18 years old between 2005 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 44 patients who underwent ventricular assist device implantation at a median age of 3.7 years (interquartile range, 0.6-9.0 yr), with the most common etiology being noncongenital heart disease (76.7%). Median time of total ventricular assist device support was 110.0 days (interquartile range, 42.3-212.3 d) with the median index pediatric cardiac ICU stay being 34.0 days (interquartile range, 19.8-81.0 d). Thirty patients (68.0%) were discharged to the ward with 18 (60.0%) having at least one readmission. The median time to first readmission was 18.0 days (interquartile range, 14.8-109.8 d) with a median of two readmissions per patient (interquartile range, 1.0-3.0). The most common reason for readmission was pump thrombosis (30.4%), followed by neurologic dysfunction (23.9%). There were no statistically significant pre- or post-implant factors associated with readmission, and readmission was not associated with mortality (p = 0.600). Univariate Kaplan-Meier survival analysis indicated that use of pre-implant extracorporeal membrane oxygenation, post-implant continuous renal replacement therapy, as well as failure to be discharged from the index pediatric cardiac ICU stay were associated with mortality. CONCLUSIONS: Readmissions to the pediatric cardiac ICU occurred in 60.0% of pediatric patients on durable ventricular assist devices with the first readmission occurring within a month of discharge from the index pediatric cardiac ICU stay. While readmission was not associated with mortality, lack of discharge from index pediatric cardiac ICU stay was likely due to a worse pre-implant clinical status.

Current techniques and the future of lung preservation.

Although lung transplant remains the only option for patients suffering from end-stage lung failure, donor supply is insufficient to meet demand. Static cold preservation is the most common method to preserve lungs in transport to the recipient; however, this method does not improve lung quality and only allows for 8 h of storage. This results in lungs which become available for donation but cannot be used due to failure to meet physiologic criteria or an inability to store them for a sufficient time to find a suitable recipient. Therefore, lungs lost due to failure to meet physiological or compatibility criteria may be mitigated through preservation methods which improve lung function and storage durations. Ex situ lung perfusion (ESLP) is a recently developed method which allows for longer storage times and has been demonstrated to improve lung function such that rejected lungs can be accepted for donation. Although greater use of ESLP will help to improve donor lung utilization, the ability to cryopreserve lungs would allow for organ banking to better utilize donor lungs. However, lung cryopreservation research remains underrepresented in the literature despite its unique advantages for cryopreservation over other organs. Therefore, this review will discuss the current techniques for lung preservation, static cold preservation and ESLP, and provide a review of the cryopreservation challenges and advantages unique to lungs.