Partial Heart Transplant in Congenital Cardiac Surgery.

This Surgical Innovation outlines the advantages of performing a partial transplant to deliver growing heart valve implants in newborn babies.

Surgical Protocol for Partial Heart Transplantation in Growing Piglets.

Partial heart transplantation is a new approach to deliver growing heart valve implants. Partial heart transplants differ from heart transplants because only the part of the heart containing the necessary heart valve is transplanted. This allows partial heart transplants to grow, similar to the valves in heart transplants. However, the transplant biology of partial heart transplantation remains unexplored. This is a critical barrier to progress of the field. Without knowledge about the specific transplant biology of partial heart transplantation, children with partial heart transplants are empirically treated like children with heart transplants because the valves in heart transplants are known to grow. In order to progress the field, an animal model for partial heart transplantation is necessary. Here, we contribute our surgical protocol for partial heart transplantation in growing piglets. All aspects of partial heart transplantation, including the donor procedure, the recipient procedure, and recipient perioperative care are described in detail. There are important nuances in the conduct of virtually all aspects of open heart surgery that differs in piglets from humans. Our surgical protocol, which is based on our experience with 34 piglets, will allow other investigators to leverage our experience to seek fundamental knowledge about the nature of partial heart transplants. This is significant because the partial heart transplant model in piglets is complex and very resource intensive.

Survival after partial heart transplantation in a piglet model.

Partial heart transplantation (PHT) is a novel surgical approach that involves transplantation of only the part of the heart containing a valve. The rationale for this approach is to deliver growing heart valve implants that reduce the need for future re-operations in children. However, prior to clinical application of this approach, it was important to assess it in a preclinical model. To investigate PHT short-term outcomes and safety, we performed PHT in a piglet model. Yorkshire piglets (n = 14) were used for PHT of the pulmonary valve. Donor and recipient pairs were matched based on blood types. The piglets underwent PHT at an average age of 44 days (range 34-53). Post-operatively, the piglets were monitored for a period of two months. Of the 7 recipient piglets, one mortality occurred secondary to anesthesia complications while undergoing a routine echocardiogram on post-operative day 19. All piglets had appropriate weight gain and laboratory findings throughout the post-operative period indicating a general state of good health and rehabilitation after undergoing PHT. We conclude that PHT has good short-term survival in the swine model. PHT appears to be safe for clinical application.

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.

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.

Ischemia-Reperfusion Injury in Porcine Aortic Valvular Endothelial and Interstitial Cells.

Ischemia-reperfusion injury (IRI) in the myocardium has been thoroughly researched, especially in acute coronary syndrome and heart transplantation. However, our understanding of IRI implications on cardiac valves is still developing. This knowledge gap becomes even more pronounced given the advent of partial heart transplantation, a procedure designed to implant isolated human heart valves in young patients. This study aims to investigate the effects of IRI on aortic valvular endothelial cells (VECs), valvular interstitial cells (VICs), and whole leaflet cultures (no separation of VECs and VICs). We employed two conditions: hypoxic cold storage reperfusion (HCSR) and normothermia (NT). Key markers, secreted protein acidic and cysteine rich (SPARC) (osteonectin), and inducible nitric oxide synthase (iNOS2) were evaluated. In the isolated cells under HCSR, VICs manifested a significant 15-fold elevation in SPARC expression compared to NT (p = 0.0016). Conversely, whole leaflet cultures exhibited a 1-fold increment in SPARC expression in NT over HCSR (p = 0.0011). iNOS2 expression in VECs presented a marginal rise in HCSR, whereas, in whole leaflet settings, there was a 1-fold ascent in NT compared to HCSR (p = 0.0003). Minor escalations in the adhesion molecules intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), E-selection, and P-selection were detected in HCSR for whole leaflet cultures, albeit without statistical significance. Additionally, under HCSR, VICs released a markedly higher quantity of IL-6 and IL-8, with respective p-values of 0.0033 and <0.0001. Interestingly, the IL-6 levels in VECs remained consistent across both HCSR and NT conditions. These insights lay the groundwork for understanding graft IRI following partial heart transplantation and hint at the interdependent dynamic of VECs and VICs in valvular tissue.

Morbidity and Mortality of Heterotopic Partial Heart Transplantation in Rodent Models.

Unrepairable congenital heart valve disease is an unsolved problem in pediatric cardiac surgery because there are no growing heart valve implants. Partial heart transplantation is a new type of transplant that aims to solve this problem. In order to study the unique transplant biology of partial heart transplantation, animal models are necessary. This study aimed to assess the morbidity and mortality of heterotopic partial heart transplantation in rodent models. This study assessed two models. The first model involved transplanting heart valves from donor animals into the abdominal aortic position in the recipient animals. The second model involved transplanting heart valve leaflets into the renal subcapsular position of the recipient animals. A total of 33 animals underwent heterotopic partial heart transplantation in the abdominal aortic position. The results of this model found a 60.61% (n = 20/33) intraoperative mortality rate and a 39.39% (n = 13/33) perioperative mortality rate. Intraoperative mortality was due to vascular complications from the procedure, and perioperative mortality was due to graft thrombosis. A total of 33 animals underwent heterotopic partial heart transplantation in the renal subcapsular position. The results of this model found a 3.03% (n = 1/33) intraoperative mortality rate, and the remaining 96.97% survived (n = 32/33). We conclude that the renal subcapsular model has a lower mortality rate and is technically more accessible than the abdominal aortic model. While the heterotopic transplantation of valves into the abdominal aortic position had significant morbidity and mortality in the rodent model, the renal subcapsular model provided evidence for successful heterotopic transplantation.

A review of animal models for post-operative pericardial adhesions.

Post-operative pericardial adhesions remain a serious complication after cardiac surgery that can lead to increased morbidity and mortality. Fibrous adhesions can destroy tissue planes leading to injury of surrounding vasculature, lengthening of operation time, and increased healthcare costs. While animal models are necessary for studying the formation and prevention of post-operative pericardial adhesions, a standardized animal model for inducing post-operative pericardial adhesions has not yet been established. In order to address this barrier to progress, an analysis of the literature on animal models for post-operative pericardial adhesions was performed. The animal model, method used to induce adhesions, and the time to allow development of adhesions were analyzed. Our analysis found that introduction of autologous blood into the pericardial cavity in addition to physical abrasion of the epicardium caused more severe adhesion formation in comparison to abrasion alone or abrasion with desiccation (vs. abrasion alone p = 0.0002; vs. abrasion and desiccation p = 0.0184). The most common time frame allowed for adhesion formation was 2 weeks, with the shortest time being 10 days and the longest being 12 months. Finally, we found that the difference in adhesion severity in all animal species was similar, suggesting the major determinants for the choice of model are animal size, animal cost, and the availability of research tools in the particular model. This survey of the literature provides a rational guide for researchers to select the appropriate adhesion induction modality, animal model, and time allowed for the development of adhesions.

Physiological Ventricular Simulator for Valve Surgery Training.

Surgical simulation is becoming increasingly important in training cardiac surgeons. However, there are currently no training simulators capable of testing the quality of simulated heart valve procedures under dynamic physiologic conditions. Here we describe a dynamic ventricular simulator, consisting of a 3D printed valve suspension chamber and a model 1423 Harvard apparatus pulsatile pump, which can provide close to physiologic hemodynamic perfusion of porcine aortic roots attached to the valve chamber for education and training in cardiac surgery. The simulator was validated by using it to test aortic valve leaflet repairs (n = 6) and aortic valve replacements (n = 3) that were performed by two trainees. Procedural success could be evaluated by direct visualization of the opening and closing valve, hemodynamic measurements and echocardiography. We conclude that, unlike other methods of simulation, this novel ventricular simulator is able to test the functional efficacy of aortic procedures under dynamic physiologic conditions using clinically relevant echocardiographic and hemodynamic outcomes. While validated for valve surgery, other potential applications include ascending aortic interventions, coronary re-implantation or catheter-based valve replacements.

Diversity in the Adult and Pediatric Heart Transplant Surgeon Workforce between 2000 and 2020.

There is a paucity of literature evaluating trends in the demographic composition of the cardiothoracic surgery workforce. Using the United Network for Organ Sharing database, we retrospectively analyzed the changes in sex, race, and ethnicity of surgeons performing heart transplantations between 2000−2020. Surgeons performing heart transplantations for adult (≥18 years) and pediatric (<18 years) patients between 2000−2020 were identified and stratified by sex (male, female) and by race/ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic of any race). Between 2000−2020, the proportion of non-White and female cardiothoracic surgeons performing adult and pediatric heart transplantations increased. Nevertheless, there remains a lack of diversity in the workforce, particularly when compared to the general United States population.

Ross Operation in Neonates: A Meta-analysis.

BACKGROUND: The Ross operation is the preferred treatment for aortic valve replacement in children. However previous studies indicate that outcomes in neonates are poor. This meta-analysis examines the pooled outcomes of the Ross operation in neonates. METHODS: Four major databases (PubMed/MEDLINE, EMBASE, Scopus, and ScienceDirect) were searched from inception until May 1, 2020 for studies describing outcomes of the Ross operation in neonates. The primary outcome was early mortality, and secondary outcomes were late mortality and mechanical support. Random-effects models were used to account for possible heterogeneity between studies, and continuity corrections were used to include zero total event trials. RESULTS: Eighteen studies comprising outcomes data on 181 neonates were included in the analysis. Meta-analysis showed a pooled early mortality rate of 24% (95% confidence interval, 12%-38%; I2 = 52%, P for heterogeneity = .01). Meta-regression analysis showed that more recently published studies reported significantly worse early mortality (P = .03). The pooled incidence of postoperative mechanical support was 15% (95% confidence interval, 5%-28%; I2 = 28%, P for heterogeneity = .22). No evidence of publication bias was found according to Egger's test (bias coefficient = 0.21, P = .57). CONCLUSIONS: The neonatal Ross operation carries a high early mortality rate. The treatment of unrepairable aortic valves in neonates remains an unsolved problem in congenital cardiac surgery.

Postoperative Outcomes in Infants Undergoing ABO-incompatible Heart Transplantation in the United States.

BACKGROUND: ABO-incompatible heart transplant is a method to increase the infant donor pool. However data on long-term survival and rejection after ABO-incompatible heart transplant in recent era are limited. METHODS: The United Network for Organ Sharing database was queried for infant heart transplants performed from January 2008 to March 2020. Patient demographics and known risk factors for posttransplant mortality were collected. Statistical analysis using Bayesian additive regression trees was performed to evaluate the association of ABO incompatibility and overall survival, graft survival, acute rejection episodes, and length of stay. RESULTS: Of 1368 included infants (age < 1 year), 280 (20.47%) were ABO incompatible. ABO incompatibility was not associated with increased all-cause mortality, acute rejection episodes, or length of stay, whereas extracorporeal membrane oxygenation and intubation status of the recipient at the time of transplantation were associated with increased all-cause mortality and graft failure. Idiopathic cardiomyopathy was associated with a decreased likelihood of posttransplant all-cause mortality. One-, 5-, and 10-year survival rates among compatible vs incompatible transplants were estimated to be 90% vs 88%, 82% vs 79%, and 77% vs 73%, respectively. CONCLUSIONS: ABO-incompatible infant heart transplant does not affect posttransplant survival, incidence of rejection, or postoperative length of stay. Therefore it remains a viable and important strategy to increase the infant donor pool.

Validation of Point-of-Care Ultrasound to Measure Perioperative Edema in Infants With Congenital Heart Disease.

Purpose: Fluid overload is a common post-operative issue in children following cardiac surgery and is associated with increased morbidity and mortality. There is currently no gold standard for evaluating fluid status. We sought to validate the use of point-of-care ultrasound to measure skin edema in infants and assess the intra- and inter-user variability. Methods: Prospective cohort study of neonates (≤30 d/o) and infants (31 d/o to 12 m/o) undergoing cardiac surgery and neonatal controls. Skin ultrasound was performed on four body sites at baseline and daily post-operatively through post-operative day (POD) 3. Subcutaneous tissue depth was manually measured. Intra- and inter-user variability was assessed using intraclass correlation coefficient (ICC). Results: Fifty control and 22 surgical subjects underwent skin ultrasound. There was no difference between baseline surgical and control neonates. Subcutaneous tissue increased in neonates starting POD 1 with minimal improvement by POD 3. In infants, this pattern was less pronounced with near resolution by POD 3. Intra-user variability was excellent (ICC 0.95). Inter-user variability was very good (ICC 0.82). Conclusion: Point-of-care skin ultrasound is a reproducible and reliable method to measure subcutaneous tissue in infants with and without congenital heart disease. Acute increases in subcutaneous tissue suggests development of skin edema, consistent with extravascular fluid overload. There is evidence of skin edema starting POD 1 in all subjects with no substantial improvement by POD 3 in neonates. Point-of-care ultrasound could be an objective way to measure extravascular fluid overload in infants. Further research is needed to determine how extravascular fluid overload correlates to clinical outcomes.

Cellular Viability of Partial Heart Transplant Grafts in Cold Storage.

Congenital heart defects are the most common types of birth defects in humans. Children with congenital heart defects frequently require heart valve replacement with an implant. Unfortunately, conventional heart valve implants do not grow. Therefore, these children are committed to serial re-operations for successively larger implant exchanges. Partial heart transplantation is a new and innovative approach to deliver growing heart valve implants. However, the transplant biology of partial heart transplant grafts remains unexplored. This is a critical barrier for clinical translation. Therefore, we investigated the cellular viability of partial heart transplants in cold storage. Histology and immunohistochemistry revealed no morphological differences in heart valves after 6, 24, or 48 h of cold storage. Moreover, immunohistochemistry showed that the marker for apoptosis activated caspase 3 and the marker for cell division Ki67 remained unchanged after 48 h of cold storage. Finally, quantification of fluorescing resorufin showed no statistically significant decrease in cellular metabolic activity in heart valves after 48 h of cold storage. We conclude that partial heart transplants remain viable after 48 h of cold storage. These findings represent the first step toward translating partial heart transplantation from the bench to the bedside because they have direct clinical implications for the procurement logistics of this new type of transplant.

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.