Low Ventricular Stiffness Is Associated With Suboptimal Outcomes in Patients With a Single Right Ventricle After the Fontan Operation: A Novel Phenotype.

BACKGROUND: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes. METHODS AND RESULTS: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, ß, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL-1; P=0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P=0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was ß (P=0.038). CONCLUSIONS: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

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.

Bacteria Endocarditis Caused by Mycoplasma hyorhinis in a Juvenile, Immunosuppressed Pig (Sus scrofa domesticus) following Partial Heart Transplantation.

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.

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.

Calcium Chloride Infusions are Not Associated with Improved Outcomes in Neonates Undergoing Cardiac Operations.

Neonatal cardiac performance is dependent on calcium delivery to the myocardium. Little is known about the use and impact of calcium chloride infusions in neonates who undergo cardiac surgery. We hypothesized that the use of calcium chloride infusions would decrease the doses required of traditional inotropic and vasoactive medications by supporting cardiac output in this patient population. We performed a single-institution, retrospective, cohort study. All neonates (≤ 30 days old) undergoing cardiac surgery from 06/01/2015 through 12/31/2018 were included. Patients were divided into two groups: those who received postoperative calcium chloride infusions (calcium group) and those who did not (control group). The primary outcome was the occurrence of a maximum Vasoactive Inotropic Score (VIS) > 15 in the first 24 h following surgery. One hundred and thirty-five patients met inclusion criteria. Sixty-six patients received postoperative calcium infusions and 69 patients did not. Gestational age, weight at surgery, age at surgery, surgical complexity and cardiopulmonary bypass times were similar between groups. Forty-two (70%) patients receiving calcium had a postoperative maximum VIS > 15 compared with 38 (55%) patients not on a calcium infusion (p = 0.08). There were no differences in postoperative length of ventilation, time to enteral feeding, hospital LOS, or operative mortality between groups. Calcium chloride infusions in neonates who underwent cardiac surgery did not decrease exposure to other inotropic and vasoactive agents in the first 24 post-operative hours or improve patient outcomes.

Prophylactic Physostigmine for Extreme and Refractory Adult Emergence Delirium, Aimed at Increasing Patient Safety and Reducing Health Care Workplace Violence: A Case Report.

Emergence delirium is a well-known phenomenon that may be encountered after general anesthesia. A common approach to this issue is to risk stratify patients preoperatively and treat them postoperatively if emergence delirium occurs. We present the case of a patient with Barrett esophagus and a history of severe and refractory emergence delirium, who was successfully treated prophylactically with physostigmine, resulting in decreased risk of harm to the patient, trauma to the perioperative staff, and a safer and more positive recovery.

Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass: Randomized Controlled Trial.

BACKGROUND: The efficacy of intraoperative corticosteroids to improve outcomes following congenital cardiac operations remains controversial. OBJECTIVES: The purpose of this study was to determine whether intraoperative methylprednisolone improves post-operative recovery in neonates undergoing cardiac surgery. METHODS: Neonates undergoing cardiac surgery with cardiopulmonary bypass at 2 centers were enrolled in a double-blind randomized controlled trial of methylprednisolone (30 mg/kg) or placebo after the induction of anesthesia. The primary outcome was a previously validated morbidity-mortality composite that included any of the following events following surgery before discharge: death, mechanical circulatory support, cardiac arrest, hepatic injury, renal injury, or rising lactate level (>5 mmol/l). RESULTS: Of the 190 subjects enrolled, 176 (n = 81 methylprednisolone, n = 95 placebo) were included in this analysis. A total of 27 (33%) subjects in the methylprednisolone group and 40 (42%) in the placebo group reached the primary study endpoint (odds ratio [OR]: 0.63; 95% confidence interval [CI]: 0.31 to 1.3; p = 0.21). Methylprednisolone was associated with reductions in vasoactive inotropic requirements and in the incidence of the composite endpoint in subjects undergoing palliative operations (OR: 0.38; 95% CI: 0.15 to 0.99; p = 0.048). There was a significant interaction between treatment effect and center. In this analysis, methylprednisolone was protective at 1 center, with an OR: 0.35 (95% CI: 0.15 to 0.84; p = 0.02), and not so at the other center, with OR: 5.13 (95% CI: 0.85 to 30.90; p = 0.07). CONCLUSIONS: Intraoperative methylprednisolone failed to show an overall significant benefit on the incidence of the composite primary study endpoint. There was, however, a benefit in patients undergoing palliative procedures and a significant interaction between treatment effect and center, suggesting that there may be center or patient characteristics that make prophylactic methylprednisolone beneficial.

Decline in ventricular function as a result of general anesthesia in pediatric heart transplant recipients.

Echocardiography is frequently performed under anesthesia during procedures such as cardiac catheterization with EMB in pediatric HTx recipients. Anesthetic agents may depress ventricular function, resulting in concern for rejection. The aim of this study was to compare ventricular function as measured by echocardiography before and during GA in 17 pediatric HTx recipients. Nearly all markers of ventricular systolic function were significantly decreased under GA, including EF (-4.2% ±1.2, P < .01) and RV FAC (-0.05 ± 0.02, P = .04). Subjects in the first post-transplant year (n = 9) trended toward a more significant decrease in EF vs those beyond the first post-transplant year (n = 8; -6.0% ±1.2 vs -2.1 ± 2.0, P = .1). This information quantifies a decline in biventricular function that should be expected in pediatric HTx recipients while under GA and can assist the transplant clinician in avoiding unnecessary treatment of transient GA-induced ventricular dysfunction.