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Marfan syndrome is named after Antoine Marfan, who described a 5-year-old child with congenital elongation of the digits and other skeletal abnormalities in 1896. While Marfan syndrome is a systemic connective tissue disorder predominantly involving the skeletal, cardiovascular, and ocular systems, the cardiovascular system presents the most life-threatening complications. Most cardiovascular pathologies surround the left ventricular outflow tract and aorta, with aortic dissection requiring emergent surgical management to the progression of mitral regurgitation requiring elective surgery. Intensive care management, along with a tailored approach to the surgical management of a patient with Marfan syndrome, is critical to their survival. Current surgical operations for patients include aortic root surgery, valve-sparing root replacements, aortic root replacements with conduits, and mitral valve repairs. Further research is necessary to determine the molecular, endovascular, pharmaceutical, and surgical management of Marfan syndrome. This review attempts to concisely discuss the diagnosis, complications, and medical and intensive care management of Marfan syndrome while further divulging on the surgical management of those with this disease process., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None

Partial heart transplantation (PHT) has emerged as a new treatment strategy to correct unrepairable heart valve dysfunction in pediatric patients. PHT selectively replaces the dysfunctional components of the recipient's heart and spares the native ventricles. As a result, the transplant biology of PHTs differs from heart transplants. Notably, donor hearts that are unsuitable for whole heart transplantation can be used, graft preservation can be prolonged and immunosuppression levels can be lowered. These nuances of PHT transplant biology have important implications for organizational aspects of PHT clinical application.

Pediatric valvar heart disease continues to be a topic of interest due to the common and severe clinical manifestations. Problems with heart valve replacement, including lack of adaptive valve growth and accelerated structural valve degeneration, mandate morbid reoperations to serially replace valve implants. Homologous or homograft heart valves are a compelling option for valve replacement in the pediatric population but are susceptible to structural valve degeneration. The immunogenicity of homologous heart valves is not fully understood, and mechanisms explaining how implanted heart valves are attacked are unclear. It has been demonstrated that preservation methods determine homograft cell viability and there may be a direct correlation between increased cellular viability and a higher immune response. This consists of an early increase in human leukocyte antigen (HLA)-class I and II antibodies over days to months posthomograft implantation, followed by the sustained increase in HLA-class II antibodies for years after implantation. Cytotoxic T lymphocytes and T-helper lymphocytes specific to both HLA classes can infiltrate tissue almost immediately after implantation. Furthermore, increased HLA-class II mismatches result in an increased cell-mediated response and an accelerated rate of structural valve degeneration especially in younger patients. Further long-term clinical studies should be completed investigating the immunological mechanisms of heart valve rejection and their relation to structural valve degeneration as well as testing of immunosuppressant therapies to determine the needed immunosuppression for homologous heart valve implantation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Domestic swine ( Sus scrofa domesticus ) are important translational models for cardiovascular transplant studies. This can be attributed to the anatomic and physiologic similarities of their cardiovascular system to humans. Transplant studies frequently employ clinically relevant immunosuppression regimens to prevent organ rejection postoperatively. Immunosuppression can lead to opportunistic infection, including presentations that are novel or poorly described in immunocompetent hosts. In this study, we describe the first case of Mycoplasma hyorhinis -induced endocarditis affecting the pulmonary valve in a juvenile, immunosuppressed pig following a partial heart transplantation procedure. Clinical signs of infection began at 15 d postoperation, were consistent with a variety of infectious agents, including Mycoplasma hyorhinis , and included lethargy, respiratory signs, and elevated white blood cell counts. By 28 d post procedure, lameness and soft tissue swelling around the left tarsus developed. Joint fluid obtained by arthrocentesis was PCR positive for Mycoplasma hyorhinis and negative for other tested pathogens. Despite antimicrobial treatment, the transplanted pulmonary valve developed leaflet thickening, stenosis, and insufficiency starting at 30 d after the procedure. At 86 d posttransplantation, the pig reached experimental endpoints and was humanely euthanized for necropsy and histopathology. The pulmonary valve had numerous dark red vegetative expansions of all 3 leaflets. Postmortem testing of a vegetative lesion was positive for Mycoplasma hyorhinis , confirming the etiologic agent responsible for endocarditis. Mycoplasma hyorhinis -induced endocarditis of an orthotopic transplanted pulmonary valve has yet to be described in swine. This case report demonstrates that infections following immunosuppression may present with novel or undercharacterized clinical signs.

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., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression., Aims: Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non-human primates., Materials & Methods: This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon., Results: Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non-human primate partial heart xenotransplantation., Discussion: Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open-heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open-heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation., Conclusions: Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest with the exception of KGMB who is an owner and employee of Tissue Testing Technologies LLC. The Company is developing procedures for banking of tissues for clinical applications., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Introduction: Partial heart transplants are a new type of pediatric transplant that replace defective heart valves with the parts of matched donor hearts containing the necessary valves. Short-term outcomes of partial heart transplants are excellent, but long-term outcomes are unknown. In order to predict the long-term outcomes of partial heart transplants, we evaluated long-term growth and function of semilunar heart valves transplanted in infancy as part of a heart transplant., Methods: All children who underwent infant heart transplantation at a single center from 1997 to 2014 were included in this study. Children in whom echocardiograms after heart transplantation and after 10 years were not available for review were excluded. The echocardiograms were reviewed by two authors to analyze semilunar valve annulus diameters, Z-scores, peak valve gradients, and valve regurgitation. Statistical difference was determined using two-tailed, paired sample t-tests with Bonferroni correction for multiple comparisons., Results: Data from 15 patients were analyzed. The aortic valve annulus averaged 1.3 cm (range 0.7-1.8 cm) immediately after transplantation and grew to an average of 1.7 cm (range 1.4-2.3 cm) after 10 years (p < .001). After 10 years, the aortic valve peak gradient avereraged 5.1 mmHg (range 2.1-15.5 mmHg) and none of the valves had more than trivial regurgitation. The pulmonary valve annulus averaged 1.5 cm (range 1.1-2.5 cm) immediately after transplantation and grew to an average of 2.1 cm (range 1.0-2.9 cm) after 10 years (p < .001). After 10 years, the pulmonary valve peak gradient averaged 4.3 mmHg (range 1.1-13.8 mmHg), and 7% of valves had moderate regurgitation., Discussion: Semilunar heart valves transplanted in infancy as part of a heart transplant demonstrate statistically significant growth and excellent function after 10 years. This predicts excellent long-term outcomes of partial heart transplants., (© 2024 Wiley Periodicals LLC.)

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., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Aim: Use of microaxial mechanical circulatory support (MCS) has been reported for severe graft rejection or dysfunction after heart transplantation (HTx). We aimed to assess utilization patterns of microaxial MCS after HTx in adolescents (ages 18 and younger) and adults (ages 19 and older)., Methods: Electronic search was performed to identify all relevant studies on post-HTx use of microaxial support in adults and adolescents. A total of 18 studies were selected and patient-level data were extracted for statistical analysis., Results: All patients ( n =23), including adults ( n =15) and adolescents ( n =8), underwent Impella (Abiomed, Danvers, MA) microaxial MCS after HTx. Median age was 36 [IQR 18-56] years (Adults, 52 [37-59]; adolescents, 16 [15-17]). Primary right ventricular graft dysfunction was an indication exclusively seen in the adults 40% (6/15), while acute graft rejection was present in 46.7% (7/15) of adults. Median time after transplant was 9 [0-32] months (Adults, 4 [0-32]; adolescents, 11 [4.5, 45]). Duration of Impella support was comparable between adults and adolescents (5 [2.5-8] vs 6 [5-8] days, p  = 0.38). Overall improvement was observed both in median LV ejection fraction (23.5% [11.3-28] to 42% [37.8-47.3], p  < 0.01) and cardiac index (1.8 [1.2-2.6] to 3 [2.5-3.1], p  < 0.01). Retransplantation was required in four adolescents (50%, 4/8). Survival to discharge was achieved by 60.0% (9/15) of adults and 87.5% (7/8) of adolescents respectively ( p  = 0.37)., Conclusion: Indications for microaxial MCS appear to vary between adult and adolescent patients. Overall improvement in LVEF and cardiac index was observed, however, with suboptimal survival to discharge., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The treatment of neonates with irreparable heart valve dysfunction remains an unsolved problem because there are no heart valve implants that grow. Therefore, neonates with heart valve implants are committed to recurrent implant exchanges until an adult-sized valve can fit., Objective: To deliver the first heart valve implant that grows., Design, Setting, and Participants: Case report from a pediatric referral center, with follow-up for more than 1 year. Participants were a recipient neonate with persistent truncus arteriosus and irreparable truncal valve dysfunction and a donor neonate with hypoxic-ischemic brain injury., Intervention: First-in-human transplant of the part of the heart containing the aortic and pulmonary valves., Main Outcomes and Measures: Transplanted valve growth and hemodynamic function., Results: Echocardiography demonstrated adaptive growth and excellent hemodynamic function of the partial heart transplant valves., Conclusions and Relevance: In this child, partial heart transplant delivered growing heart valve implants with a good outcome at age 1 year. Partial heart transplants may improve the treatment of neonates with irreparable heart valve dysfunction.

Partial heart transplantation is the first clinically successful approach to deliver growing heart valve implants. To date, 13 clinical partial heart transplants have been performed. However, turning partial heart transplantation into a routine procedure that is available to all children who would benefit from growing heart valve implants poses formidable logistical challenges. Firstly, a supply for partial heart transplant donor grafts needs to be developed. This challenge is complicated by the scarcity of donor organs. Importantly, the donor pools for orthotopic heart transplants, partial heart transplants and cadaver homografts overlap. Secondly, partial heart transplants need to be allocated. Factors relevant for equitable allocation include the indication, anatomical fit, recipient clinical status and time on the wait list. Finally, partial heart transplantation will require regulation and oversight, which only recently has been undertaken by the Food and Drug Administration, which regulates human cellular and tissue-based products. Overcoming these challenges will require a change in the system. Once this is achieved, partial heart transplantation could open new horizons for children who require growing tissue implants., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

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., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

A transgenic strain of pigs was created to express green fluorescent protein (GFP) ubiquitously using a pCAGG promoter. Here, we characterize GFP expression in the semilunar valves and great arteries of GFP-transgenic (GFP-Tg) pigs. Immunofluorescence was performed to visualize and quantify GFP expression and colocalization with nuclear staining. GFP expression was confirmed in both the semilunar valves and great arteries of GFP-Tg pigs compared to wild-type tissues (aorta, p = 0.0002; pulmonary artery, p = 0.0005; aortic valve; and pulmonic valve, p < 0.0001). The quantification of GFP expression in cardiac tissue allows this strain of GFP-Tg pigs to be used for future research in partial heart transplantation.

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.

Background: Infants with truncus arteriosus typically undergo repair by repurposing the truncal valve as the neo-aortic valve and using a valved conduit homograft for the neo-pulmonary valve. In cases where the native truncal valve is too insufficient for repair, it is replaced, but this is a rare occurrence with a paucity of data, especially in the infant population. Here, we conduct a meta-analysis to better understand the outcomes of infant truncal valve replacement during the primary repair of truncus arteriosus., Methods: We systematically reviewed PubMed, Scopus, and CINAHL for all studies reporting infant (<12 months) truncus arteriosus outcomes between 1974 and 2021. Exclusion criteria were studies which did not report truncal valve replacement outcomes separately. Data extracted included valve replacement type, mortality, and reintervention. Our primary outcome was early mortality, and our secondary outcomes were late mortality and reintervention rates., Results: Sixteen studies with 41 infants who underwent truncal valve replacement were included. The truncal valve replacement types were homografts (68.8%), mechanical valves (28.1%), and bioprosthetic valves (3.1%). Overall early mortality was 49.4% (95% CI: 28.4-70.5). The pooled late mortality rate was 15.3%/year (95% CI: 5.8-40.7). The overall rate of truncal valve reintervention was 21.7%/year (95% CI: 8.4-55.7)., Conclusions: Infant truncal valve replacement has poor early and late mortality as well as high rates of reintervention. Truncal valve replacement therefore remains an unsolved problem in congenital cardiac surgery. Innovations in congenital cardiac surgery, such as partial heart transplantation, are required to address this.

The current standard of care for pediatric patients with unrepairable congenital valvular disease is a heart valve implant. However, current heart valve implants are unable to accommodate the somatic growth of the recipient, preventing long-term clinical success in these patients. Therefore, there is an urgent need for a growing heart valve implant for children. This article reviews recent studies investigating tissue-engineered heart valves and partial heart transplantation as potential growing heart valve implants in large animal and clinical translational research. In vitro and in situ designs of tissue engineered heart valves are discussed, as well as the barriers to clinical translation.

Many young adults require heart valve replacements. Current options for valve replacement in adults include mechanical valves, bioprosthetic valves, or the Ross procedure. Of these, mechanical and bioprosthetic valves are the most common options, although mechanical valve usage predominates in younger adults due to durability, while bioprosthetic valve usage predominates in older adults. Partial heart transplantation is a new method of valvular replacement that can deliver durable and self-repairing valves and allow adult patients freedom from anticoagulation therapy. This procedure involves transplantation of donor heart valves only, permitting expanded utilization of donor hearts as compared with orthotopic heart transplantation. In this review, we discuss the potential benefits of this procedure in adults who elect against the anticoagulation regimen required of mechanical valve replacements, although it has not yet been clinically established. Partial heart transplantation is a promising new therapy for the treatment of pediatric valvular dysfunction. This is a novel technique in the adult population with potential utility for valve replacement in young patients for whom anticoagulation therapy is problematic, such as women who wish to become pregnant, patients with bleeding disorders, and patients with active lifestyles.

Background: Tourniquets have been modified and used for centuries to occlude blood flow to control hemorrhage. More recently, the occlusion of peripheral vessels has been linked to resultant increases in blood pressure, which may provide additional therapeutic potential, particularly during states of low cardiac output., Objective: The objective of this study was to investigate a causal relationship between tourniquet application and blood pressure in healthy adults., Methods: Healthy adult volunteers were recruited to participate in this IRB-approved study. Each participant met inclusion criteria and demonstrated baseline normotension. Brachial cuff blood pressure and heart rate were recorded pre- and post-tourniquet application to the bilateral legs., Results: Twenty-seven adults aged 22 to 35 years participated and were included in analysis. The average systolic blood pressure was 122 ± 7 mmHg, diastolic blood pressure was 72 ± 9 mmHg, and heart rate was 70 ± 13 bpm. Following bilateral tourniquet application over the femoral vasculature, we observed a statistically significant increase in systolic (7 mmHg, p < 0.001) and diastolic (4 mmHg, p = 0.05) blood pressures with no significant change in heart rate (2 bpm, p > 0.05)., Conclusions: The elevations in systolic and diastolic blood pressures establish a dependent relationship between tourniquet application to the lower extremities and blood pressure elevation. These results may support new indications for tourniquet-use or extremity vessel occlusion in settings of hemodynamic instability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Congenital heart defects are the most common type of birth defects in humans and frequently involve heart valve dysfunction. The current treatment for unrepairable heart valves involves valve replacement with an implant, Ross pulmonary autotransplantation, or conventional orthotopic heart transplantation. Although these treatments are appropriate for older children and adults, they do not result in the same efficacy and durability in infants and young children for several reasons. Heart valve implants do not grow with the. Ross pulmonary autotransplants have a high mortality rate in neonates and are not feasible if the pulmonary valve is dysfunctional or absent. Furthermore, orthotopic heart transplants invariably fail from ventricular dysfunction over time. Therefore, the treatment of irreparable heart valves in infants and young children remains an unsolved problem. The objective of this single-arm, prospective study is to offer an alternative solution based on a new type of transplant, which we call "partial heart transplantation." Partial heart transplantation differs from conventional orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. Similar to Ross pulmonary autotransplants and conventional orthotopic heart transplants, partial heart transplants contain live cells that should allow it to grow with the recipient child. Therefore, partial heart transplants will require immunosuppression. The risks from immunosuppression can be managed, as seen in conventional orthotopic heart transplant recipients. Stopping immunosuppression will simply turn the growing partial heart transplant into a non-growing homovital homograft. Once this homograft deteriorates, it can be replaced with a durable adult-sized mechanical implant. The protocol for our single-arm trial is described. The ClinicalTrials.gov trial registration number is NCT05372757., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rajab et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Cardiac arrest is the leading cause of natural death in the United States, and most surviving patients suffer from neurological dysfunction. Although this is recognized as a problem, there have been very few changes to the cardiopulmonary resuscitation (CPR) procedure. Tourniquets have been recognized for their ability to increase truncal blood pressure and have been shown to improve CPR outcomes in animal models. However, the relationship between tourniquet application and blood pressure elevation has not been adequately explored in healthy human adults., Objectives: The objective of this study is to demonstrate that bilateral, non-invasive, peripheral vascular occlusion in the thighs results in an increased proximal systolic blood pressure ≥ 10 mmHg., Methods: This is a single-center, non-blinded clinical trial. Volunteers will be screened for eligibility at least 24 hours before the day of the trial. On the day of the trial, volunteers will undergo an informed consent process. If they choose to participate in the trial after informed consent, their baseline blood pressure will be measured. Volunteers will then have a Combat Application Tourniquet (CAT) applied to each thigh, and the windlasses will be tightened by IRB-approved personnel. Once no pulse can be felt in the lower extremity, blood pressure will be measured in the arm. This will be replicated three times, and the tourniquets will be loosened between trials to allow the volunteers to rest. Any complications that arise during the trial will be handled by the physician that is present., Analysis: Changes in systolic blood pressure and diastolic blood pressure will be analyzed using a Shapiro-Wilk test. Then, a one-way repeated measures analysis of variance (ANOVA) will be performed with a Holm-Sidak post-hoc test to determine the mean differences. The significance level will be set to 5% for statistical significance., Registry and Registration Number: Clinicaltrials.gov, NCT05324306., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The trial sponsor and primary investigator disclose their involvement as inventors in patent application no. 206085-0104-P1US. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Seigler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pigs, or Sus scrofa domestica, are commonly used animal models in translational transplantation research due to their anatomical, physiological, and immunological similarities to humans. In solid organ transplantation studies, immunosuppressive medications may be administered to pigs to prevent rejection. We provide an overview of the immunosuppressive regimens used in allogeneic solid organ transplantation in pigs, including heart, lung, kidney, bowel and cotransplanted organs and focus on the use of tacrolimus, mycophenolate mofetil, and corticosteroids., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The treatment of babies with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve implants. However, orthotopic heart transplants are known to grow with recipients., Aim: Partial heart transplantation is a new approach to delivering growing heart valve implants, which involves transplantation of the part of the heart containing the valves only. In this review, we discuss the benefits of this procedure in children with unrepairable valve dysfunction., Conclusion: Partial heart transplantation can be performed using donor hearts with poor ventricular function and slow progression to donation after cardiac death. This should ameliorate donor heart utilization and avoid both primary orthotopic heart transplantation in children with unrepairable heart valve dysfunction and progression of these children to end-stage heart failure., (© 2022 Wiley Periodicals LLC.)

The success of cardiopulmonary resuscitation (CPR) is critically dependent on the maintenance of myocardial and cerebral perfusion; therefore, preferential perfusion of these vital organs over non-vital vascular beds, such as the extremities, is desirable. We propose that compression of the femoral and/or brachial arteries during CPR improves resuscitation outcomes.

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., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery transfer is a critical step of the arterial switch operation (ASO) for transposition of the great arteries (TGA). Strategies for coronary transfer include open transfer before neoaortic anastomosis and closed transfer after neoaortic anastomosis. This study reports outcomes of ASO with closed coronary transfer at a single institution., Methods: A retrospective analysis was performed of patients undergoing ASO for TGA from November 2006 to September 2015. Closed coronary transfer was universally employed. Patients were assigned to simple vs complex coronary anatomy groups. The primary outcome was overall survival. Secondary outcomes included reoperation-free survival, coronary reintervention, and aortic insufficiency., Results: Ninety-six consecutive patients underwent ASO for TGA. Median follow-up was 5.8 years. Thirty-five (36%) patients had complex coronary anatomy, which was associated with significantly longer cardiopulmonary bypass and aortic cross-clamp time. Overall survival was 97.4%, and reoperation-free survival was 83.6%. There was no difference in survival or reoperation-free survival of patients with simple vs complex coronary anatomy. Hispanic ethnicity, side-by-side great arteries, and urgent or emergent operation were significantly associated with the composite outcome of reoperation or mortality. There were no coronary interventions after ASO, and the incidence of moderate or greater aortic insufficiency was 2.1% at hospital discharge and 1.5% in follow-up., Conclusions: Closed coronary transfer during ASO has excellent short-term and midterm results. Despite variable and often complex coronary anatomy, coronary ischemic events after ASO are avoidable. Closed coronary transfer has a low risk of aortic valve injury or insufficiency., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Hill, Walkowiak, Head, Kwon, Kavarana and Rajab.)

Background: Bronchial artery revascularization (BAR) during lung transplantation has been hypothesized to improve early tracheal healing and delay the onset of bronchiolitis obliterans syndrome (BOS). We aimed to assess the outcomes of BAR after lung transplantation., Methods: Electronic search in Ovid Medline, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane Controlled Trials Register (CCTR) databases was performed to identify all relevant studies published about lung transplantation with BAR. Studies discussing lung transplantation utilizing BAR were included while those without outcome data such as BOS and survival were excluded. Cohort-level data were extracted and pooled for analysis. A binary outcome meta-analysis of proportions with logit transformation was conducted. Newcastle-Ottawa scale was used for risk of bias assessment., Results: Seven studies were selected for the analysis comprising 143 patients. Mean patient age was 47 (95% CI: 40-55) years. Sixty-one percent (48-72%) were male. Seventy-three percent (65-79%) of patients underwent double lung transplant while 27% (21-25%) underwent single lung transplant. In patients with postoperative angiography, successful BAR was demonstrated in 93% (82-97%) of all assessed conduits. The 30-day/in-hospital mortality was 6% (3-11%). Seventy-nine percent (63-89%) of patients were free from rejection at three months. Eighty-three percent (29-98%) of patients were free from signs of airway ischemia at three and six months. Pooled survival at one year and five years was 87% (78-92%) and 71% (46-87%), respectively, with a mean follow-up time of 21 (3-38) months. Pooled freedom from bronchiolitis obliterans was 86% (77-91%) at two years., Conclusions: While this systematic review and meta-analysis is limited by the available surgeons, institutions, and papers discussing a highly specialized technique, it does show that BAR is a viable technique to minimize BOS and early anastomotic intervention following lung transplantation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-213/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)