Bivalirudin anticoagulation for cardiopulmonary bypass during cardiac surgery.

INTRODUCTION: Heparin is the primary anticoagulant for cardiopulmonary bypass (CPB) support during cardiac surgery. While widely used, ∼2% of cardiac surgery patients develop heparin-induced thrombocytopenia (HIT) and 4-26% develop heparin resistance. Bivalirudin is an alternative anticoagulant mainly used for percutaneous coronary interventions. Given the challenges associated with heparin anticoagulation, we conducted a review to explore the use of bivalirudin for CPB surgery. METHODS: PubMed and Embase scoping review included 2 randomized controlled trials, a retrospective comparison study, 3 pilot studies, and 30 case reports. To provide a contemporary series, we searched for articles published from 2010 to 2023. Our review included studies from both adult and pediatric populations. RESULTS: While data is limited, bivalirudin seems to supply similar effectiveness and safety as heparin for CPB anticoagulation. Across the three comparative studies, the heparin cohorts had a 0-9% mortality rate and 0-27% rate of major bleeding/reoperation compared to a 0-3% mortality and 0-6% major bleeding/reoperation rate for the bivalirudin cohorts. Bivalirudin was successfully used as an anticoagulant in a wide range of CPB surgeries (e.g., heart transplants, ventricular assisted device placements, and valve repairs). Successful patient outcomes were reported with bivalirudin infusion of ∼2 mg/kg/hour, activated clotting time monitoring (target >400 s or 2.5× baseline), use of cardiotomy suctions, minimization of stagnant blood, and post-bypass modified ultrafiltration. CONCLUSION: Bivalirudin is a safe and effective anticoagulant for CPB, especially for patients with HIT or heparin resistance. Further comparative research is called for to optimize bivalirudin utilization for CPB during cardiac surgery.

ECMO support in SARS-CoV2 multisystem inflammatory syndrome in children in a child.

In this report, we describe the case of a 5-year-old male with SARS-CoV-2 associated MIS-C with progressive respiratory failure and vasoplegic shock requiring extracorporeal support. At presentation, reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 was negative, however, SARS-CoV2 antibody testing was positive. Multiple inflammatory markers and cardiac biomarkers were elevated. Echocardiogram demonstrated mildly depressed left ventricular function and no coronary anomalies noted. The patient required mechanical ventilation, vasopressors, and eventually extracorporeal membrane oxygenation (ECMO) for profound circulatory shock and progressive respiratory failure. During his clinical course, recovery of cardiac function was demonstrated however, a middle cerebral artery infarct and left frontal subarachnoid hemorrhage was suffered which ultimately the patient succumbed to. To the best of our knowledge, this is the youngest previously healthy child who had multi-system hyperinflammatory syndrome requiring ECMO support and the first case of SARS-CoV-2 related pediatric stroke.Clinical Trial Registration: None.

Aspergillus aortitis & aortic valve endocarditis after coronary surgery.

The authors report a case of Aspergillus aortitis and aortic valve endocarditis that developed after coronary artery bypass surgery resulting in recurrent, embolic, bilateral lower extremity ischemia. This necessitated multiple lower extremity embolectomies followed by redo-sternotomy, extensive annular debridement, root reconstruction with a modified Bentall technique, and hemiarch replacement. This case highlights the challenges in diagnosis and management of this rare disease entity and some of its devastating complications.

Non-anastomotic failure of woven Dacron tube grafts in the thoracic aorta in young adults.

BACKGROUND: Dacron tube grafts have been used in the surgical management of cardiovascular disease since the 1970s. Complications at the site of the anastomosis have been well described. Non-anastomotic failure is far less common. We present a series of four patients who presented with complications of non-anastomotic failure of woven Dacron tube grafts. METHODS: A retrospective chart review of four patients who presented to our institution between March 2014 and March 2017 with clinical complications of a Dacron tube graft was conducted. RESULTS: All four patients underwent a staged surgical repair for an interrupted aortic arch between the years of 1988 and 2001. All four patients underwent revision of their original interposition graft (Gore-Tex, W.L. Gore & Associates, Flagstaff, AZ) with implantation of a Hemashield woven Dacron tube graft (Maquet, Rastatt, Germany). From 13 to 22 years postimplant of the Dacron tube graft, all patients presented with symptoms or clinical evidence of primary graft failure. Two patients underwent urgent surgical intervention and did not survive. One patient underwent attempted surgical intervention, which was aborted in the setting of profuse bleeding, and ultimately had an endovascular rescue of the tube graft with a Zenith Alpha endograft (Cook Medical, Bloomington, IN). One patient underwent elective endovascular intervention prior to onset of symptoms. CONCLUSION: Non-anastomotic failure of woven Dacron tube grafts can occur in the thoracic aorta in young adults and may be managed with endovascular techniques.

The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth.

Substance P and its truncated receptor exert oncogenic effects. The high production of substance P in breast cancer cells (BCCs) is caused by the enhancement of tachykinin (TAC)1 translation by cytosolic factor. In vitro translational studies and mRNA stabilization analyses indicate that BCCs contain the factor needed to increase TAC1 translation and to stabilize the mRNA. Prediction of protein folding, RNA-shift analysis, and proteomic analysis identified a 40 kDa molecule that interacts with the noncoding exon 7. Western blot analysis and RNA supershift identified Musashi 1 (Msi1) as the binding protein. Ectopic expression of TAC1 in nontumorigenic breast cells (BCs) indicates that TAC1 regulates its stability by increasing Msi1. Using a reporter gene system, we showed that Msi1 competes with microRNA (miR)130a and -206 for the 3' UTR of exon 7/TAC1. In the absence of Msi1 and miR130a and -206, reporter gene activity decreased, indicating that Msi1 expression limits TAC1 expression. Tumor growth was significantly decreased when nude BALB/c mice were injected with Msi1-knockdown BCCs. In summary, the RNA-binding protein Msi1 competes with miR130a and -206 for interaction with TAC1 mRNA, to stabilize and increase its translation. Consequently, these interactions increase tumor growth.

Early Outcomes With HeartWare HVAD as Bridge to Transplant in Children: A Single Institution Experience.

The HeartWare HVAD has been used as a bridge to cardiac transplantation in the pediatric population. We describe outcomes following HeartWare HVAD implantation at a single center. A retrospective chart review was performed of all HeartWare HVAD implants performed at our institution between May 2013 and March 2015. Eight children between the ages of 9 and 17 years underwent HVAD implantation as a bridge to transplant (N = 7 cardiomyopathy, N = 1 complex single ventricle). There was one operative death in the complex single ventricle patient. Seven patients (87%) were successfully bridged to transplant. Median time of support was 24.5 days (range, 6-91 days). All transplanted patients are alive and well at a median follow-up of 448 days. Our results demonstrated that mechanical support with HeartWare HVAD is feasible in patients of varying sizes (from older children to adolescents).

Utilization of the Impella 2.5 micro-axial pump in children for acute circulatory support.

Percutaneous circulatory support is widely available for use in adult patients. Options remain limited in the pediatric population due to limitations of vessel and patient size, resulting in the use of more invasive means of circulatory support. We present a case series of pediatric patients in whom the Impella 2.5 axial flow pump was able to be placed utilizing a hybrid approach that allowed for adequate distal perfusion while providing successful short-term hemodynamic support.

Surgical Repair of a Left Main Coronary Artery to Right Ventricle Fistula in a Neonate.

We describe the case of a newborn male with a large fistula from the left main coronary artery to the right ventricle. This case illustrates a rare congenital coronary artery fistula and its successful surgical management in the neonatal period.

Partial upper median sternotomy for anterior aortopexy for innominate artery compression syndrome: a case series.

Background: Innominate artery compression syndrome (IAS) is caused by an abnormally originating innominate artery compressing the trachea anteriorly. One option to relieve such compression is an anterior aortopexy (AA). We describe our technique of an AA via a partial upper median sternotomy. Case Description: Nine consecutive patients underwent AA for IAS via a partial upper median sternotomy from July 2017 to November 2020 at two US teaching hospitals. The median age was 9 months [interquartile range (IQR), 3-16.5 months]. The male to female ratio was 1.25. All patients had >70% compression by flexible bronchoscopy. Two patients had previous surgeries. The median follow-up was 6 months (IQR, 4-8.5 months). The indications for the operation were: acute life-threatening events (ALTEs) (4/9 patients), recurrent intubation (4/9), and severe stridor with >70% luminal reduction (1/9). Technical success (defined as ≤20% residual stenosis) was achieved in 78% (7/9) of the patients. The two patients with unsuccessful AAs required either a tracheal resection or an innominate artery reimplantation. Both achieved full symptom resolution. Overall, 78% (7/9) of patients experienced full symptom resolution. Of the two patients without full symptom resolution, one had mild stridor at 6 months post-operation. The other patient without full resolution is awaiting further vocal cord surgery for an associated glottic pathology. Conclusions: A partial upper sternotomy provides a very versatile approach to an AA for IAS. In addition to facilitating an adequate AA, a partial upper sternotomy provides options for direct tracheal surgery or an innominate artery reimplantation in case an optimal result is not obtained by an AA.

Early Outcomes of Pulmonary Valve Replacement With the Edwards Inspiris Resilia Pericardial Bioprosthesis.

BACKGROUND: Controversy regarding the optimal pulmonary valve substitute remains, with no approved surgical valve for pulmonary valve replacement (PVR). Furthermore, unfavorable anatomy often precludes transcatheter PVR in patients with congenital heart disease. We therefore sought to evaluate the feasibility of the Edwards Inspiris pericardial aortic bioprosthesis in the pulmonary position in pediatric and adult patients requiring PVR. METHODS: Data from consecutive patients who underwent PVR from February 2019 to February 2021 at our institution were retrospectively reviewed. Postoperative adverse events included paravalvular or transvalvular leak, endocarditis, explant, thromboembolism, valve thrombosis, valve-related bleeding, hemolysis, and structural valve degeneration. Progression of valve gradients was assessed from discharge to 30 days and one year. RESULTS: Of 24 patients with median age of 26 years (interquartile range [IQR]: 17-33; range: 4-60 years), 22 (91.7%) patients had previously undergone tetralogy of Fallot repair and 2 (8.3%) patients had undergone double-outlet right ventricle repair in the neonatal period or infancy. All patients had at least mild right ventricular (RV) dilatation (median RV end-diastolic volume index 161.4, IQR: 152.3-183.5 mL/m2) and at least moderate pulmonary insufficiency (95.8%) or stenosis (8.3%). Median cardiopulmonary bypass and cross-clamp times were 71 (IQR: 63-101) min and 66 (IQR: 60-114) min, respectively. At a median postoperative follow-up of 2.5 years (IQR: 1.4-2.6; range: 1.0-3.0 years), there were no mortalities, valve-related reoperations, or adverse events. Postoperative valve gradients and the severity of pulmonary regurgitation did not change significantly over time. CONCLUSIONS: At short-term follow-up, the bioprosthesis in this study demonstrated excellent safety and effectiveness for PVR. Further studies with longer follow-up are warranted.

Recurrent Pediatric Respiratory Distress From a Challenging Vascular Anomaly: The Uncrossing Operation for Circumflex Aorta.

The authors report a case of circumflex aorta causing persistent respiratory distress in a 9-year-old boy who had previously undergone vascular ring division and multiple aortopexies. The uncrossing operation was performed, with symptomatic relief of both posterior and right-sided tracheal compression from the transverse aorta and right aortic arch, respectively.

An indirect role for oncomir-519b in the expression of truncated neurokinin-1 in breast cancer cells.

Neurokinin 1 (NK1) encodes full-length (NK1-FL) and truncated (NK1-Tr) receptors, with distinct 3' UTR. NK1-Tr exerts oncogenic functions and is increased in breast cancer (BC). Enhanced transcription of NK1 resulted in higher level of NK1-Tr. The 3' UTR of these two transcripts are distinct with NK1-Tr terminating at a premature stop codon. NK1-Tr mRNA gained an advantage over NK1-FL with regards to translation. This is due to the ability of miR519B to interact with sequences within the 3' UTR of NK1-FL, but not NK1-Tr since the corresponding region is omitted. MiR519b suppressed the translation of NK1-FL in T47D and MDA-MB-231 resulting in increased NK1-Tr protein. Cytokines can induce the transcription of NK1. However, our studies indicated that translation appeared to be independent of cytokine production by the BC cells (BCCs). This suggested that transcription and translation of NK1 might be independent. The findings were validated in vivo. MiR-519b suppressed the growth of MDA-MB-231 in 7/10 nude BALB/c. In total, increased NK1-Tr in BCCs is due to enhanced transcription and suppressed translation of NK1-FL by miR-519b to reduced tumor growth. In summary, we report on miRNA as a method to further regulate the expression of a spiced variant to promote oncogenesis. In addition, the findings have implications for therapy with NK1 antagonists. The oncogenic effect of NK1-Tr must be considered to improve the efficacy of current drugs to NK1.

Cardiac transplantation in adult congenital heart disease: a narrative review.

Background and Objective: As more children with congenital heart disease survive to adulthood, adult congenital heart disease (ACHD) prevalence will increase (currently ~1 million US patients). Heart failure (HF) accounts for 26-42% of ACHD deaths. The rate of ACHD heart transplantations (ACHD HTx) is also increasing. We describe the ACHD HTx recipient/candidate cohort, analyze ACHD HTx outcomes, identify ACHD HTx specific challenges, and discuss opportunities to better serve more patients with ACHD HF. Methods: PubMed literature search including articles published from 2010-2023. Reviewed 89 studies, 67 included. Our search focused on the challenges of ACHD HTx and potential solutions. Key Content and Findings: ACHD HTx recipients are young [median age 35 years, interquartile range (IQR): 24-46 years]. 87-95% of ACHD HTx recipients had prior cardiac surgery. The most common underlying diagnoses include transposition of the great arteries (31%) and Fontan/Glenn circulation (28%). 63% of listed ACHD HTx candidates received a transplant within one year of listing. Post-transplant 1-year survival is 80%, 5-year survival 74%, and 10-year survival 59%. There are 4 unique ACHD HTx challenges: (I) difficulty in assessing pulmonary hypertension, resulting in some centers selecting oversized donor hearts. However, selecting oversized hearts does not improve post-operative mortality and could prolong waitlist time. (II) Increased immunologic sensitization, increasing rejection risk. Desensitization therapy has enabled sensitized HTx recipients to enjoy outcomes similar to non-sensitized recipients. (III) Procedural complexity with ~30% of cases requiring additional surgical reconstruction. Detailed multidisciplinary planning, extensive imaging, and transferring the patient into the operating room early can help manage the complexities and reduce organ ischemic time. (IV) Increased intraoperative bleeding due to patients' surgical histories and circulatory collaterals. Preoperative collateral coil embolization and select utilization of hypothermic circulatory arrest can help reduce bleeding. Additional Fontan specific challenges include extensive great artery repair, liver failure, plastic bronchitis, and protein loss enteropathy. Finally, given limited donor heart availability, mechanical circulatory support is a promising technology for patients with ACHD HF. Conclusions: The prevalence of ACHD HTx is slowly but steadily increasing. The operational complexity of ACHD HTx can be managed, and the majority of recipients have excellent outcomes (59% 10-year survival).

Norwood Aneurysm: Report of a Rare Phenomenon.

An 18-year-old male with complex single-ventricle physiology status post-3-stage palliation developed a large Norwood aneurysm (77 × 67 mm). The patient underwent a successful surgical reconstruction. Care providers must be aware of this rare complication and provide appropriate surveillance.

Complex Repair of Anomalous Left Coronary Artery From the Pulmonary Artery in a 55-Year-Old Patient.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a congenital malformation that classically presents within the first year of life. Few patients survive into adulthood, and initial presentation after the fourth decade of life is rare. We describe a 55-year-old woman who presented after cardiac arrest. She initially refused surgery and underwent automated implantable cardioverter defibrillator placement, followed later by surgical repair involving reimplantation of the left coronary artery to the aorta and pulmonary artery reconstruction using interposition grafts. We report this late presentation of ALCAPA and successful surgical management.

Pericardiectomy for Successful Treatment of Constrictive Pericarditis in a Pediatric Patient.

A 15-year-old girl with history of asthma and obesity presented with recurrent anasarca without systolic heart failure or significant renal disease. She was diagnosed with constrictive pericarditis and successfully underwent pericardiectomy with pericardial stripping and a waffle procedure. (Level of Difficulty: Advanced.).

Transcriptomes and metabolism define mouse and human MAIT cell populations.

Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus using single-cell RNA sequencing and phenotypic and metabolic analyses. We showed that the predominant mouse subset, which produced IL-17 (MAIT17), and the subset that produced IFN-γ (MAIT1) had not only greatly different transcriptomes but also different metabolic states. MAIT17 cells in different organs exhibited increased lipid uptake, lipid storage, and mitochondrial potential compared with MAIT1 cells. All these properties were similar in the thymus and likely acquired there. Human MAIT cells in lung and blood were more homogeneous but still differed between tissues. Human MAIT cells had increased fatty acid uptake and lipid storage in blood and lung, similar to human CD8 T resident memory cells, but unlike mouse MAIT17 cells, they lacked increased mitochondrial potential. Although mouse and human MAIT cell transcriptomes showed similarities for immature cells in the thymus, they diverged more strikingly in the periphery. Analysis of pet store mice demonstrated decreased lung MAIT17 cells in these so-called "dirty" mice, indicative of an environmental influence on MAIT cell subsets and function.

Long-term Results Using Glutaraldehyde-treated Homograft Pericardium in Congenital Heart Surgery.

BACKGROUND: This study reports the long-term outcomes using glutaraldehyde-treated cryopreserved homograft pericardium (CPH) in neonates, infants, children, and young adults undergoing congenital cardiac surgery. METHODS: A retrospective review was performed of all patients at a single institution (Rady Children's Hospital, San Diego, CA) who had undergone surgical implantation with CPH between 2006 and 2016. The study identified 134 consecutive patients who underwent implantation of a total of 276 patches. The baseline demographic characteristics, primary cardiac diagnosis, surgical characteristics, operative reports, and postoperative catheterization and reoperation reports were analyzed. The use of CPH was categorized by specific anatomic insertion site. RESULTS: The median age at patch implantation was 1.47 years (range, 1 day to 31.6 years). The numbers and locations of patch use were 124 for pulmonary arterial repair, 57 for repair of the aorta, 49 for septal repair, and 43 at other sites. At a median follow-up of 5.29 years, 9 patients had died (6.7%), but none of those deaths were related to CPH. Twelve patients (8.96%) underwent reoperations, and 18 patients (13.4%) underwent catheter interventions at sites of CPH implantation. The 10-year freedom from patch-induced reoperation and catheter intervention rates were 88.5% and 86.9%, respectively. Overall patch failure-free survival was 85.8% and 79.0% at 5 and 10 years, respectively. CONCLUSIONS: The use of CPH patch in the surgical correction of congenital heart disease is effective and durable, as evidenced by the low reintervention rates. These results are comparable to the early and midterm outcomes of other similarly used surgical patches.

Pseudoaneurysm of Innominate Artery Graft Stump in an Infant.

Innominate artery grafts are often utilized in pediatric cardiac surgery and very rarely lead to complications, including infection. Here, we present a unique case of an infant who underwent repair of coarctation of the aorta and hypoplastic arch using a GORE-TEX graft (W. L. Gore and Associates, Newark, DE) for antegrade cerebral perfusion. The graft subsequently became infected with Pseudomonas and formed a pseudoaneurysm with resultant tracheal compression. The presentation, diagnosis, and management of this mycotic pseudoaneurysm are described.