The safe addition of nitric oxide to the sweep gas of the extracorporeal membrane oxygenation circuit in a pediatric cardiac intensive care unit.

Background: Nitric Oxide (NO) is a naturally occurring modulator of inflammation found in the human body. Several studies in the pediatric cardiothoracic surgery literature have demonstrated some beneficial clinical effects when NO is added to the sweep gas of the cardiopulmonary bypass circuit.Purpose: Our primary aim was to determine the safety of incorporating nitric oxide into the oxygenator sweep gas of the extracorporeal membrane oxygenation (ECMO) circuit. Secondarily, we looked at important clinical outcomes, such as survival, blood product utilization, and common complications related to ECMO.Methods: We performed a single center, retrospective review of all patients at our institution who received ECMO between January 1, 2017 and March 31, 2023. We began additing NO to the ECMO sweep gas in 2019. Results: There were no instances of clinically significant methemoglobinemia with the addition of NO to the sweep gas (0% vs 0%, p = 1). The median daily methemoglobin level was higher in those who received NO via the sweep gas when compared to those who did not (1.6 vs 1.1, p = <0.001). Conclusions: The addition of NO to the sweep gas of the ECMO circuit is safe.

15-Year Analysis of Surgical Approaches and Outcomes for Coarctation in 132 Neonates and Infants.

A variety of surgical approaches exist to treat aortic coarctation in neonates and infants. Our institutional approach is designed to match the surgical approach to the individual anatomy of the patient. The objective of this study is to evaluate operative characteristics and outcomes of all neonates and infants who underwent surgical repair of coarctation of the aorta or hypoplastic aortic arch at University of Florida from 2006 to 2021, inclusive, either in isolation or with concomitant repair of atrial septal defect (ASD) and/or ventricular septal defect (VSD). A retrospective review was performed of 132 patients aged 0-1 year who underwent surgical repair of aortic coarctation or hypoplastic aortic arch between 2006 and 2021, inclusive, either in isolation or with concomitant repair of ASD and/or VSD. Patients were divided into two groups based on the surgical approach: Group 1 = Median Sternotomy and Group 2 = Left Lateral Thoracotomy. Continuous variables are presented as median (minimum-maximum); categorical variables are presented as N (%). The most common operative technique in Group 1 was end-to-side reconstruction with ligation of the aortic isthmus. The most common operative technique in Group 2 was extended end-to-end repair. Operative Mortality was one patient (1/132 = 0.76%). Transcatheter intervention for recurrent coarctation was performed in seven patients (7/132 = 5.3%). Surgical re-intervention for recurrent coarctation was performed in three patients (3/132 = 2.3%). From these data, one can conclude that a strategy of matching the surgical approach to the anatomy of neonates and infants who underwent surgical repair of aortic coarctation or hypoplastic aortic arch, either in isolation or with concomitant repair of ASD and/or VSD, is associated with less than 1% Operative Mortality and less than 3% recurrent coarctation requiring reoperation.

Nosocomial Infections in Adults Receiving Extracorporeal Membrane Oxygenation: A Review for Infectious Diseases Clinicians.

Over the past ten years, there has been a rapid expansion in the use of extracorporeal membrane oxygenation (ECMO) in the care of patients with refractory cardiac or respiratory failure. Infectious diseases clinicians must reconcile conflicting evidence from limited studies as they develop practices at their own institutions, which has resulted in considerably different practices globally. This review describes infection control and prevention as well as antimicrobial prophylaxis strategies in this population. Data on diagnostics and treatment for patients receiving ECMO with a focus on diagnostic and antimicrobial stewardship is then examined. This review summarizes gaps in the current ECMO literature and proposes future needs, including developing clear definitions for infections and encouraging transparent reporting of practices at individual facilities in future clinical trials.

A single-institutional experience with 36 children less than 5 kilograms supported with the Berlin Heart: Comparison of congenital versus acquired heart disease.

OBJECTIVES: We reviewed outcomes in all 36 consecutive children <5 kg supported with the Berlin Heart pulsatile ventricular assist device at the University of Florida, comparing those with acquired heart disease (n = 8) to those with congenital heart disease (CHD) (n = 28). METHODS: The primary outcome was mortality. The Kaplan-Meier method and log-rank tests were used to assess group differences in long-term survival after ventricular assist device insertion. T-tests using estimated survival proportions were used to compare groups at specific time points. RESULTS: Of 82 patients supported with the Berlin Heart at our institution, 49 (49/82 = 59.76%) weighed <10 kg and 36 (36/82 = 43.90%) weighed <5 kg. Of 36 patients <5 kg, 26 (26/36 = 72.22%) were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 36 patients <5 kg was [days]: median = 109, range = 4-305.) Eight out of 36 patients <5 kg had acquired heart disease, and all eight [8/8 = 100%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 8 patients <5 kg with acquired heart disease was [days]: median = 50, range = 9-130.) Twenty-eight of 36 patients <5 kg had congenital heart disease. Eighteen of these 28 [64.3%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 28 patients <5 kg with congenital heart disease was [days]: median = 136, range = 4-305.) For all 36 patients who weighed <5 kg: 1-year survival estimate after ventricular assist device insertion = 62.7% (95% confidence interval = 48.5-81.2%) and 5-year survival estimate after ventricular assist device insertion = 58.5% (95% confidence interval = 43.8-78.3%). One-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3-99.9%) in acquired heart disease and 55.6% (95% confidence interval = 39.5-78.2%) in CHD, P = 0.036. Five-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3-99.9%) in acquired heart disease and 48.6% (95% confidence interval = 31.6-74.8%) in CHD, P = 0.014. CONCLUSION: Pulsatile ventricular assist device facilitates bridge to transplantation in neonates and infants weighing <5 kg; however, survival after ventricular assist device insertion in these small patients is less in those with CHD in comparison to those with acquired heart disease.

Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts.

BACKGROUND: Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals. METHODS: Eight 39-55 kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and two liters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean ± Standard Deviation (Median, Minimum-Maximum). RESULTS: Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 ± 1.8 (44, 42-46) versus 44 ± 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 ± 0 (360, 360-360) versus 141 ± 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 ± 0 (8, 8-8) versus 16.5 ± 4.2 (16, 12-16).In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% ± 14.95% (48.5%, 33%-63%) and 41.25% ± 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% ± 5.9% (57%, 50%-67%) and 60.4% ± 7.7% (61.5%, 51.9%-67%), respectively. CONCLUSION: The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.

Venovenous extracorporeal membrane oxygenation neck cannulation in an infant.

In this video tutorial, we present neck cannulation for venovenous extracorporeal membrane oxygenation using a crescent right atrial double lumen cannula in a 4-kg baby.

Epstein Barr virus-directed T-cell therapy for refractory EBV-PTLD in a toddler post Orthotopic heart transplantation.

Epstein-Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post-transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV-directed T cells in rituximab-refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV-PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV-directed T-cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV-directed T-cell therapy for management and associated pitfalls.

The biological role and future therapeutic uses of nitric oxide in extracorporeal membrane oxygenation, a narrative review.

BACKGROUND: Nitric oxide (NO) is a gas naturally produced by the human body that plays an important physiological role. Specifically, it binds guanylyl cyclase to induce smooth muscle relaxation. NO's other protective functions have been well documented, particularly its protective endothelial functions, effects on decreasing pulmonary vascular resistance, antiplatelet, and anticoagulation properties. The use of nitric oxide donors as vasodilators has been known since 1876. Inhaled nitric oxide has been used as a pulmonary vasodilator and to improve ventilation perfusion matching since the 1990s. It is currently approved by the United States Food and Drug Administration for neonates with hypoxic respiratory failure, however, it is used off-label for acute respiratory distress syndrome, acute bronchiolitis, and COVID-19. PURPOSE: In this article we review the currently understood biological action and therapeutic uses of NO through nitric oxide donors such as inhaled nitric oxide. We will then explore recent studies describing use of NO in cardiopulmonary bypass and extracorporeal membrane oxygenation and speculate on NO's future uses.

Defining the Spectrum of Hypoplastic Left Heart Syndrome (HLHS).

The 2021 International Paediatric and Congenital Cardiac Code and the Eleventh Revision of the International Classification of Diseases provide the following definition for hypoplastic left heart syndrome (HLHS): "Hypoplastic left heart syndrome (HLHS) is defined as a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch." Although HLHS with intact ventricular septum (HLHS + IVS) and HLHS with ventricular septal defect (HLHS + VSD) are different cardiac phenotypes, both of these lesions are part of the spectrum of HLHS.

Quality analysis of publicly available information about hypoplastic left heart syndrome.

PURPOSE: Publicly available health information is increasingly important for patients and their families. While the average US citizen reads at an 8th-grade level, electronic educational materials for patients and families are often advanced. We assessed the quality and readability of publicly available resources regarding hypoplastic left heart syndrome (HLHS). METHODS: We queried four search engines for "hypoplastic left heart syndrome", "HLHS", and "hypoplastic left ventricle". The top 30 websites from searches on Google, Yahoo!, Bing, and Dogpile were combined into a single list. Duplicates, commercial websites, physician-oriented resources, disability websites, and broken links were removed. Websites were graded for accountability, content, interactivity, and structure using a two-reviewer system. Nonparametric analysis of variance was performed. RESULTS: Fifty-two websites were analysed. Inter-rater agreement was high (Kappa = 0.874). Website types included 35 hospital/healthcare organisation (67.3%), 12 open access (23.1%), 4 governmental agency (7.7%), and 1 professional medical society (1.9%). Median total score was 19 of 39 (interquartile range = 15.8-25.3): accountability 5.5 of 17 (interquartile range = 2.0-9.3), content 8 of 12 (interquartile range = 6.4-10.0), interactivity 2 of 6 (interquartile range = 2.0-3.0), and structure 3 of 4 (interquartile range = 2.8-4.0). Accountability was low with 32.7% (n = 17) of sites disclosing authorship and 26.9% (n = 14) citing sources. Forty-two percent (n = 22) of websites were available in Spanish. Total score varied by website type (p = 0.03), with open access sites scoring highest (median = 26.5; interquartile range = 20.5-28.6) and hospital/healthcare organisation websites scoring lowest (median = 17.5; interquartile range = 13.5-21.5). Score differences were driven by differences in accountability (p = 0.001) - content scores were similar between groups (p = 0.25). Overall readability was low, with median Flesch-Kincaid Grade Level of 11th grade (interquartile range = 10th-12th grade). CONCLUSIONS: Our evaluation of popular websites about HLHS identifies multiple opportunities for improvement, including increasing accountability by disclosing authorship and citing sources, enhancing readability by providing material that is understandable to readers with the full spectrum of educational background, and providing information in languages besides English, all of which would enhance health equity.

Outcomes of Children Supported With Pulsatile Paracorporeal Ventricular Assist Device: Congenital Versus Acquired Heart Disease.

BACKGROUND: We reviewed the outcomes of 82 consecutive pediatric patients (less than 18 years of age) supported with the Berlin Heart ventricular assist device (VAD), comparing those with congenital heart disease (CHD; n = 44) with those with acquired heart disease (AHD; n = 37). METHODS: The primary outcome was mortality after VAD insertion. Kaplan-Meier methods and log-rank tests were used to assess group differences in long-term survival. RESULTS: Forty-four CHD patients were supported (age: median = 65 days, range = 4 days-13.3 years; weight [kg]: median = 4, range = 2.4-42.3). Ten biventricular CHD patients were supported with eight biventricular assist devices (BiVADs), one left ventricular assist device (LVAD) only, and one LVAD converted to BiVAD, while 34 univentricular CHD patients were supported with single ventricle-ventricular assist devices (sVADs). In CHD patients, duration of VAD support was [days]: median = 134, range = 4-554. Of 44 CHD patients, 28 underwent heart transplantation, 15 died on VAD, and one was still on VAD. Thirty-seven AHD patients were supported (age: median = 1.9 years, range = 27 days-17.7 years; weight [kg]: median = 11, range = 3.1-112), including 34 BiVAD and 3 LVAD. In AHD patients, duration of VAD support was [days]: median = 97, range = 4-315. Of 37 AHD patients, 28 underwent transplantation, three died on VAD, five weaned off VAD (one of whom underwent heart transplantation 334 days after weaning), and one was still on VAD. One-year survival after VAD insertion was 59.9% (95% CI = 46.7%-76.7%) in CHD and 88.6% (95% CI = 78.8%-99.8%) in AHD, P = .0004. Five-year survival after VAD insertion was 55.4% (95% CI = 40.8%-75.2%) in CHD and 85.3% (95% CI = 74.0%-98.2%) in AHD, P = .002. CONCLUSIONS: Pulsatile VAD facilitates bridge-to-transplantation in neonates, infants, and children with CHD; however, survival after VAD insertion is worse in patients with CHD than in patients with AHD.

Utilization of the percutaneous left ventricular support as bridge to heart transplantation across the United States: In-depth UNOS database analysis.

BACKGROUND: Intra-aortic balloon pump (IABP) and Impella device utilization as a bridge to heart transplantation (HTx) have risen exponentially. We aimed to explore the influence of device selection on HTx outcomes, considering regional practice variation. METHODS: A retrospective longitudinal study was performed on a United Network for Organ Sharing (UNOS) registry dataset. We included adult patients listed for HTx between October 2018 and April 2022 as status 2, as justified by requiring IABP or Impella support. The primary end-point was successful bridging to HTx as status 2. RESULTS: Of 32,806 HTx during the study period, 4178 met inclusion criteria (Impella n = 650, IABP n = 3528). Waitlist mortality increased from a nadir of 16 (in 2019) to a peak of 36 (in 2022) per thousand status 2 listed patients. Impella annual use increased from 8% in 2019 to 19% in 2021. Compared to IABP, Impella patients demonstrated higher medical acuity and lower success rate of transplantation as status 2 (92.1% vs 88.9%, p < 0.001). The IABP:Impella utilization ratio varied widely between regions, ranging from 1.77 to 21.31, with high Impella use in Southern and Western states. However, this difference was not justified by medical acuity, regional transplant volume, or waitlist time and did not correlate with waitlist mortality. CONCLUSIONS: The shift in utilizing Impella as opposed to IABP did not improve waitlist outcomes. Our results suggest that clinical practice patterns beyond mere device selection determine successful bridging to HTx. There is a critical need for objective evidence to guide tMCS utilization and a paradigm shift in the UNOS allocation system to achieve equitable HTx practice across the United States.

Never too early: the impact of a shadowing programme in paediatric and congenital cardiac surgery for undergraduate college students.

PURPOSE: Diversification of the medical and cardiothoracic surgical workforce represents an ongoing need. A congenital cardiac surgery shadowing programme for undergraduate students was implemented at the University of Florida Congenital Heart Center. METHODS: Students shadowing in the Congenital Heart Center from 17 December 2020 through 20 July 2021 were sent a survey through Qualtrics to evaluate the impact of their shadowing experience. The main objectives of the survey were to determine the personal relationship(s) of the students to physicians prior to shadowing, how the presence or absence of physicians in the family of a given student related to the exposure of the student to a medical setting prior to shadowing, and the interest of the students in medicine and cardiothoracic surgery prior to and after the shadowing experience. Survey responses included "Yes/No" questions, scaled responses using a Likert scale, selection lists, and free text responses. When applicable, t-tests were utilised to assess differences between student groups. RESULTS: Of the 37 students who shadowed during the study period, 26 (70%) responded. Most students were female (58%, n = 15), and the mean age was 20.9 ± 2.4 years. Students spent a mean duration of 95 ± 138 hours shadowing providers as part of the shadowing programme. Likert scale ratings of interest in the professions of medicine, surgery, and cardiothoracic surgery all increased after the shadowing experience (p < 0.01). Students with a family member in medicine had more clinical exposure prior to the shadowing programme (p < 0.01). CONCLUSION: A surgical shadowing programme at a Congenital Heart Center may have an important formative impact on the views of undergraduate students regarding potential careers in surgery and medicine. Additionally, students without family members in medicine tend to have less prior exposure to medicine and could likely benefit more from this type of shadowing programme.

Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study.

BACKGROUND: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. OBJECTIVES: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. METHODS: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. RESULTS: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. CONCLUSION: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

An Analysis of 186 Transplants for Pediatric or Congenital Heart Disease: Impact of Pretransplant VAD.

BACKGROUND: We reviewed our management strategy and outcome data for all 181 patients with pediatric or congenital heart disease who received 186 heart transplants from January 1, 2011, to March 1, 2022, and evaluated the impact of pretransplant ventricular assist device (VAD). METHODS: Continuous variables are presented as mean (SD); median [interquartile range] (range). Categorical variables are presented as number (percentage). Univariable associations with long-term mortality were assessed with Cox proportional hazards models. Impact of pretransplant VAD on survival was estimated with multivariable models. RESULTS: Pretransplant VAD was present in 53 of 186 transplants (28.5%). Patients with VAD were younger (years): 4.8 (5.6); 1 [0.5-8] (0.1-18) vs 12.1 (12.7); 10 [0.7-17] (0.1-58); P = .0001. Patients with VAD had a higher number of prior cardiac operations: 3.0 (2.3); 2 [1-4] (1-12) vs 1.8 (1.9); 2 [0-3] (0-8); P = .0003. Patients with VAD were also more likely to receive an ABO-incompatible transplant: 10 of 53 (18.9%) vs 9 of 133 (6.8%); P = .028. Univariable associations with long-term mortality included: In multivariable analysis, pretransplant VAD did not impact survival while controlling for each one of the factors shown in univariable analysis to be associated with long-term mortality. Kaplan-Meier 5-year survival (95% CI) was 85.8% (80.0%-92.1%) for all patients, 84.3% (77.2%-92.0%) without pretransplant VAD, and 91.1% (83.1%-99.9%) with pretransplant VAD. CONCLUSIONS: Our single-institution analysis of 181 patients receiving 186 heart transplants for pediatric or congenital heart disease over 11.25 years reveals similar survival in patients with (n = 51) and without (n = 130) pretransplant VAD. The presence of a pretransplant VAD is not a risk factor for mortality after transplantation for pediatric or congenital heart disease.