Why partial heart transplantation could be regulated as organ transplantation.

Partial heart transplant (PHT) is a recent clinical innovation involving the transplantation of a segment of the heart (valves) directly from the deceased donor into the recipient patient. This procedure holds out the possibility of significant benefit, especially for pediatric patients because these grafts show growth potential after transplant, reducing or eliminating the current need for repeat procedures. The clinical process for donation and transplant of partial heart (PH) grafts generally follows an organ clinical pathway; however, the Food and Drug Administration has recently stated its intent to regulate PH as tissues, raising a host of regulatory considerations. PHT requires donor testing and eligibility determinations within a short, clinically viable timeframe and, similar to organ transplant, involves donor-recipient matching. Waitlist allocation policies that are a regulatory focus of the Organ Procurement and Transplantation Network including equity and efficiency may become relevant. Oversight of PHT by the Organ Procurement and Transplantation Network could be accomplished through interpretation of the vascular composite allograft definition or through designation by the US Department of Health and Human Services of PH grafts as organs. While some clinical questions remain unanswered, it is important to carefully address these regulatory considerations to support the emergence of this innovation and ensure the continued trust of the donating public and the patients who may benefit from PHT.

Partial heart transplantation: Growing heart valve implants for children.

Heart valves serve a vital hemodynamic function to ensure unidirectional blood flow. Additionally, native heart valves serve biological functions such as growth and self-repair. Heart valve implants mimic the hemodynamic function of native heart valves, but are unable to fulfill their biological functions. We developed partial heart transplantation to deliver heart valve implants that fulfill all functions of native heart valves. This is particularly advantageous for children, who require growing heart valve implants. This invited review outlines the past, present and future of partial heart transplantation.

The impact of heart valve and partial heart transplant models on the development of banking methods for tissues and organs: A concise review.

Cryopreserved human heart valves fill a crucial role in the treatment for congenital cardiac anomalies, since the use of alternative mechanical and xenogeneic tissue valves have historically been limited in babies. Heart valve models have been used since 1998 to better understand the impact of cryopreservation variables on the heart valve tissue components with the ultimate goals of improving cryopreserved tissue outcomes and potentially extrapolating results with tissues to organs. Cryopreservation traditionally relies on conventional freezing, employing cryoprotective agents, and slow cooling to sub-zero centigrade temperatures; but it is plagued by the formation of ice crystals and cell damage upon thawing. Researchers have identified ice-free vitrification procedures and developed a new rapid warming method termed nanowarming. Nanowarming is an emerging method that utilizes targeted application of energy at the nanoscale level to rapidly rewarm vitrified tissues, such as heart valves, uniformly for transplantation. Vitrification and nanowarming methods hold great promise for surgery, enabling the storage and transplantation of tissues for various applications, including tissue repair and replacement. These innovations have the potential to revolutionize complex tissue and organ transplantation, including partial heart transplantation. Banking these grafts addresses organ scarcity by extending preservation duration while preserving biological activity with maintenance of structural fidelity. While ice-free vitrification and nanowarming show remarkable potential, they are still in early development. Further interdisciplinary research must be dedicated to exploring the remaining challenges that include scalability, optimizing cryoprotectant solutions, and ensuring long-term viability upon rewarming in vitro and in vivo.

Donor supply for partial heart transplantation in the United States.

BACKGROUND: Congenital heart disease (CHD) is the most common cause of birth defects worldwide. Valvular defects are a common form of CHDs, and, at this time, treatment options for children with unrepairable valve disease are limited. Issues with anticoagulation, sizing, and lack of growth in valve replacement options can lead to high mortality rates and incidence of reoperations. Partial heart transplantation, or transplantation of fresh valve allografts, has recently been described as a strategy to provide a durable and non-thrombogenic alternative to conventional prostheses and provide growth potential in pediatric patients. METHODS: The United Network for Organ Sharing (UNOS) database was queried to analyze the number of pediatric donor hearts that were not recovered but had viable valves (n = 3565) between January 2010 and September 2021. Recoverable valves were grouped by donor age: infants (age < 1 year), toddlers (age ≥1 and <3 years), and children (age ≥3 and <18 years). Demographic characteristics of donors were analyzed between age groups. RESULTS: Infants, toddlers, and children had a total of 344, 465, and 2756 hearts with recoverable valves, respectively, over the study period, representing an average of 29, 39, and 230 hearts with recoverable valves per year. CONCLUSION: The results of our study identify the minimum donor supply for partial heart transplantation. The actual number is likely higher because it includes hearts not entered in the UNOS database and domino transplants from orthotopic heart transplant recipients. Partial heart transplantation is logistically feasible as there are recoverable valves available for all age groups, fulfilling a clinical need in pediatric patients with unrepairable valve disease.

A proposed objective scale for extracorporeal membrane oxygenation circuit thrombosis.

Patients undergoing extracorporeal membrane oxygenation (ECMO) are susceptible to thrombosis, which is a major cause of death and morbidity. However, there is no objective ECMO thrombosis grading scale to standardize evaluation, guide treatment, and facilitate further research. In this letter, we propose an objective grading scale for ECMO circuit thrombosis based on physical characteristics and location within the circuit. This ECMO thrombosis scale will allow for protocolized escalation of ECMO thrombosis treatment, ranging from watchful observation, intensified anticoagulation, and circuit exchange.

Partial heart xenotransplantation: A research protocol in non-human primates.

Partial heart transplantation is a new type of transplant that delivers growing heart valve replacements for babies. Partial heart transplantation differs from orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. It also differs from homograft valve replacement because viability of the graft is preserved by tissue matching, minimizing donor ischemia times, and recipient immunosuppression. This preserves partial heart transplant viability and allows the grafts to fulfill biological functions such as growth and self-repair. These advantages over conventional heart valve prostheses are balanced by similar disadvantages as other organ transplants, most importantly limitations in donor graft availability. Prodigious progress in xenotransplantation promises to solve this problem by providing an unlimited source of donor grafts. In order to study partial heart xenotransplantation, a suitable large animal model is important. Here we describe our research protocol for partial heart xenotransplantation in nonhuman primates.

Left Superior Vena Cava Draining to Left Atrium: A Case Report, Review of the Literature, and Classification.

Persistent left superior vena cava (PLSVC) draining to the left atrium (LA) is a rare congenital abnormality that is often asymptomatic and found incidentally on imaging. PLSVC is usually described alongside other congenital defects, such as septal defects, tetralogy of fallot, and aortic coarctation. PLSVC to LA with an atrial septal defect is known as Raghib syndrome, but to our knowledge PLSVC to LA without an atrial septal defect or right superior vena cava has not been described in the literature. Here, we report the presentation of a patient with PLSVC-LA without ASD and propose a classification system for this subset of congenital heart defects to help guide clinical and surgical management of these patients.

Effect of cardiac graft rejection on semilunar valve function: implications for heart valve transplantation.

BACKGROUND: The treatment of neonates with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve replacements. Heart valve transplantation is a potential approach to deliver growing heart valve replacements. Therefore, we retrospectively analysed the semilunar valve function of orthotopic heart transplants during rejection episodes. METHODS: We included children who underwent orthotopic heart transplantation at our institution and experienced at least one episode of rejection between 1/1/2010 and 1/1/2020. Semilunar valve function was analysed using echocardiography at baseline, during rejection and approximately 3 months after rejection. RESULTS: Included were a total of 31 episodes of rejection. All patients had either no (27) or trivial (4) aortic insufficiency prior to rejection. One patient developed mild aortic insufficiency during a rejection episode (P = 0.73), and all patients had either no (21) or trivial (7) aortic insufficiency at follow-up (P = 0.40). All patients had mild or less pulmonary insufficiency prior to rejection, which did not significantly change during (P = 0.40) or following rejection (P = 0.35). Similarly, compared to maximum pressure gradients across the valves at baseline, which were trivial, there was no appreciable change in the gradient across the aortic valve during (P = 0.50) or following rejection (P = 0.42), nor was there any meaningful change in the gradient across the pulmonary valve during (P = 0.55) or following rejection (P = 0.91). CONCLUSIONS: This study demonstrated that there was no echocardiographic evidence of change in semilunar valve function during episodes of rejection in patient with heart transplants. These findings indicate that heart valve transplants require lower levels of immune suppression than orthotopic heart transplants and provide partial foundational evidence to justify future research that will determine whether heart valve transplantation may deliver growing heart valve replacements for children.

Smart materials in cardiovascular implants: Shape memory alloys and shape memory polymers.

Smart materials have intrinsic properties that change in a controlled fashion in response to external stimuli. Currently, the only smart materials with a significant clinical impact in cardiovascular implant design are shape memory alloys, particularly Nitinol. Recent prodigious progress in material science has resulted in the development of sophisticated shape memory polymers. In this article, we have reviewed the literature and outline the characteristics, advantages, and disadvantages of shape memory alloys and shape memory polymers which are relevant to clinical cardiovascular applications, and describe the potential of these smart materials for applications in coronary stents and transcatheter valves.

Outcome of Repeat Pulmonary Metastasectomy.

Pulmonary metastasectomy is a well-established contribution to the cure of oligometastatic cancers, but its exact effectiveness is poorly understood. Here we report the outcomes of repeat pulmonary metastasectomy from a multicenter trial. This retrospective study included patients who underwent re-do metastasectomies between January 2010 and December 2014. The exclusion criterion was metastasectomy without curative intent. We reviewed medical files of 621 consecutive patients who underwent initial pulmonary metastasectomy. Of those, 64 patients underwent repeat metastasectomies, and these patients were included in the analysis. All the 64 patients underwent a second metastasectomy, later 35 of them underwent a third metastasectomy, 12 underwent a fourth metastasectomy, and 6 underwent a fifth metastasectomy. The total number of re-do metastasectomies was 181. The median overall survival among the patients undergoing re-do metastasectomy was 66.0 ± 3.8 months. Three and 5-year survival rates were 82.3% and 63.3%, respectively. The 5-year survival rates were 63.3% after the first, 50.9% after the second, 74.4% after the third, 83.3% after the fourth, and 60.0% after the fifth metastasectomy. We conclude that at the current stage of knowledge, there is an indication for repeat re-do metastasectomy with curative intent.

Decellularized scaffolds for tissue engineering: Current status and future perspective.

Based on Organ Procurement and Transplantation Network data as of December 2019, more than 113 000 patients require an organ transplantation, yet, over the course of this past year, only 36 000 patients received a transplant. This discrepancy between those that need a donor organ and those that receive one remains one of medicine's biggest challenges. Multiple solutions, both biologic and artificial, have been proposed to mitigate this difference. One of the most promising approaches to generate bioartificial organs for transplantation involves re-seeding decellularized scaffolds with appropriate cells. Decellularization involves physical, chemical, or biological methods that typically require intimate contact of various decellularization solutions with each cell. Consequently, conventional submersion decellularization has been limited to simple tissues such as heart valves. The invention of perfusion decellularization was a breakthrough that allowed the generation of tissue-engineered scaffolds from tissues with higher structural organization and entire organs. Such scaffolds are composed of a myriad of extracellular matrix (ECM) components that include collagen, elastin, proteoglycans, and glycoproteins. Together, these components allow the scaffolds to fulfill specialized functions, such as structural functions as well as biological functions including the regulation of cellular processes and extracellular molecules. These specialized functions of decellularized scaffolds can increasingly be harnessed for applications in tissue engineering.

Techniques for lung transplantation in the rat.

The rat is an important model organism for lung transplantation research. Orthotopic rat lung transplantation is a complex procedure, which requires advanced microsurgical techniques. This technical paper describes in detail highly reproducible intraoperative microsurgical techniques and peri-operative management, including the donor procedure, recipient anesthetic management, the recipient operation and anticipated peri-operative complications.

Management of a young patient with dextrocardia, atrial septal defect, and Eisenmenger syndrome with venous-venous extracorporeal membrane oxygenation and heart-lung transplantation.

Dextrocardia is a rare congenital condition which presents important challenges for surgical management. We discuss a patient with dextrocardia, atrial septal defect, and Eisenmenger syndrome, which ultimately led to decompensated end-stage lung disease and heart-lung transplant. Venous-venous extracorporeal membrane oxygenation was an important strategy to bridge the patient until donor organs became available. Transplantation of a heart-lung block allowed for the treatment of the patient's underlying congenital heart defect, anatomic reversal of dextrocardia with appropriate venous and arterial connections, and management of pulmonary damage from pulmonary hypertension.

Comparison of heart transplant outcomes between recipients with pulsatile- vs continuous-flow LVAD.

OBJECTIVE: Continuous-flow (CF) left ventricular assist devices (LVADs) have replaced pulsatile flow (PF) LVADs irrespective of concerns from the physiologic changes/morbidity secondary to lack of pulsatility. Data comparing posttransplant outcomes in patients with CF vs PF LVADs are limited and conflicting. We used the Organ Procurement and Transplant Network database to compare posttransplant outcomes between CF and PF LVAD patients. METHODS: From 1 January 2005 to 31 December 2011, 3449 adult patients underwent primary heart alone transplantation. The cohort was restricted to 2741 recipients with LVAD at the time of transplant and divided into two groups: PF (Heartmate XVE) (n = 705) and CF (Heartmate II, HeartWare HVAD, and Jarvik 2000) (n = 2036). Endpoints were 30-day freedom from graft failure, 1-, and 5-year patient survival. Propensity score matching identified 705 pairs for adjusted comparisons. RESULTS: Among propensity-matched patients, 30-day freedom from graft failure after heart transplantation (PF = 94.8% vs CF = 95.2%, P > .7), and 1-, and 5-year patient survival (PF; 87.5% vs CF; 88.9%, P = .4, and PF;75.7% vs CF;77.5%, P = .3) were not different. CONCLUSION: Survival and freedom from graft failure after heart transplantation is similar between CF and PF LVADs. These findings are relevant as the use of CF devices increases despite physiologic changes related to the absence of pulsatility.

Bioengineering Human Lung Grafts on Porcine Matrix.

OBJECTIVE: Bioengineering of viable, functional, and implantable human lung grafts on porcine matrix. SUMMARY BACKGROUND DATA: Implantable bioartificial organ grafts could revolutionize transplant surgery. To date, several milestones toward that goal have been achieved in rodent models. To make bioengineered organ grafts clinically relevant, scaling to human cells and graft size are the next steps. METHODS: We seeded porcine decellularized lung scaffolds with human airway epithelial progenitor cells derived from rejected donor lungs, and banked human umbilical vein endothelial cells. We subsequently enabled tissue formation in whole organ culture. The resulting grafts were then either analyzed in vitro (n = 15) or transplanted into porcine recipients in vivo (n = 3). RESULTS: By repopulating porcine extracellular matrix scaffolds with human endothelial cells, we generated pulmonary vasculature with mature endothelial lining and sufficient anti-thrombotic function to enable blood perfusion. By repopulating the epithelial surface with human epithelial progenitor cells, we created a living, functioning gas exchange graft. After surgical implantation, the bioengineered lung grafts were able to withstand physiological blood flow from the recipient's pulmonary circulation, and exchanged gases upon ventilation during the 1-hour observation. CONCLUSIONS: Engineering and transplantation of viable lung grafts based on decellularized porcine lung scaffolds and human endothelial and epithelial cells is technically feasible. Further graft maturation will be necessary to enable higher-level functions such as mucociliary clearance, and ventilation-perfusion matching.

The Use of Lidocaine Containing Cardioplegia in Surgery for Adult Acquired Heart Disease.

BACKGROUND: Del Nido cardioplegia, a crystalloid-based solution with lidocaine as a key element, is given as a single dose and has been used successfully in congenital cardiac surgery. HYPOTHESIS: We retrospectively compared a lidocaine containing "modified del Nido" solution with our standard whole blood cardioplegia to investigate its safety and efficacy in adult cardiac surgery. METHODS: From June 1, 2013 to December 30, 2013, we used a single dose of lidocaine containing cardioplegia (LC group) in 92 consecutive operations. Propensity matching analysis was undertaken to compare the outcomes of such patients with those who underwent their surgery by the same surgeon using standard whole blood cardioplegia (WB group), n = 396. Propensity score matching yielded 79 pairs of patients. RESULTS: After propensity matching, LC and WB groups were similar in baseline operative characteristics including cross-clamp time (LC: 65 minutes [range 54 to 89] vs. WB: 70 minutes [54 to 86], p = 0.993). Postoperative outcomes were similar including inotropic requirements (30.4% [24/72] vs. 25.3% [20/72], p < 0.60), median ventilation time (4.7 hours vs. 5.3, p < 0.74) and median length of stay was seven days for both groups (p < 0.82). Despite higher median postoperative, 24-hour CK-MB levels LC group (LC:22.3 ng/ml, range [15.6 to 40.3] vs. WB:18.4 ng/ml [13.9 to 28.2], p = 0.040), operative and one-year mortality were comparable among study groups (both p > 0.798). CONCLUSIONS: Lidocaine containing cardioplegia appears to be safe in adults undergoing cardiac procedure when administered for the first 60 minutes of aortic cross clamping. Higher CK-MB levels did not translate into adverse clinical outcomes.