Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R2 = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.

Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Investigation of Cerebral Mitochondrial Injury in a Porcine Survivor Model of Carbon Monoxide Poisoning.

INTRODUCTION: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). One of the glaring gaps is the lack of rigorous experimental models that may recapitulate survivors of acute CO poisoning in the early phase. The primary objective of this preliminary study is to use our advanced swine platform of acute CO poisoning to develop a clinically relevant survivor model to perform behavioral assessment and MRI imaging that will allow future development of biomarkers and therapeutics. METHODS: Four swine (10 kg) were divided into two groups: control (n = 2) and CO (n = 2). The CO group received CO at 2000 ppm for over 120 min followed by 30 min of re-oxygenation at room air for one swine and 150 min followed by 30 min of re-oxygenation for another swine. The two swine in the sham group received room air for 150 min. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. Following exposures, all surviving animals were observed for a 24-h period with neurobehavioral assessment and imaging. At the end of the 24-h period, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. RESULTS: While a preliminary ongoing study, animals in the CO group showed alterations in cerebral metabolism and cellular function in the acute exposure phase with possible sustained mitochondrial changes 24 h after the CO exposure ended. CONCLUSIONS: This preliminary research further establishes a large animal swine model investigating survivors of CO poisoning to measure translational metrics relevant to clinical medicine that includes a basic neurobehavioral assessment and post exposure cellular measures.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Hereditary haemorrhagic telangiectasia and SMAD4 mutation in a patient with complex single ventricle heart disease.

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient's staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

The Early History of the Congenital Heart Surgeons' Society.

The concept of a new organization for congenital heart surgeons in North America to discuss their difficult cases and offer each other potential solutions began in 1973. This article pays tribute to the founders of the Congenital Heart Surgeons' Society and offers insight into the desire of these surgeons to improve clinical outcomes for children with congenital heart disease.

The Academic Impact of Congenital Heart Surgeons' Society (CHSS) Studies.

PURPOSE: We reviewed all 64 articles ever published by The Congenital Heart Surgeons' Society (CHSS) Data Center to estimate the academic impact of these peer-reviewed articles. MATERIALS AND METHODS: The Congenital Heart Surgeons' Society has performed research based on 12 Diagnostic Inception Cohorts. The first cohort (Transposition) began enrolling patients on January 1, 1985. We queried PubMed to determine the number of publications that referenced each of the 64 journal articles generated by the datasets of the 12 Diagnostic Inception Cohorts that comprise the CHSS Database. Descriptive summaries of the data were tabulated using mean with standard deviation and median with range. RESULTS: Sixty-four peer-reviewed papers have been published based on the CHSS Database. Fifty-nine peer-reviewed articles have been published based on the 12 Diagnostic Inception Cohorts, and five additional articles have been published based on Data Science. Excluding the recently established Diagnostic Inception Cohort for patients with Ebstein malformation of tricuspid valve, the number of papers published per cohort ranged from 1 for coarctation to 11 for transposition of the great arteries. The 11 articles generated from the CHSS Transposition Cohort were referenced by a total of 111 articles (median number of references per journal article = 9 [range = 0-22, mean = 10.1]). Overall, individual articles were cited by an average of 11 (mean), and a maximum of 41 PubMed-listed publications. Overall, these 64 peer-reviewed articles based on the CHSS Database were cited 692 times in PubMed-listed publications. The first CHSS peer-reviewed article was published in 1987, and during the 35 years from 1987 to 2022, inclusive, the annual number of CHSS publications has ranged from 0 to 7, with a mean of 1.8 publications per year (median = 1, mode = 1). CONCLUSION: Congenital Heart Surgeons' Society studies are widely referenced in the pediatric cardiac surgical literature, with over 10 citations per published article. These cohorts provide unique information unavailable in other sources of data. A tool to access this analysis is available at: [https://data-center.chss.org/multimedia/files/2022/CAI.pdf].

Historical Accounts of Congenital Heart Surgery.

We present historical accounts of congenital heart surgery since the early 1900s, as our specialty evolved from individual heroic efforts into an established and sophisticated surgical specialty with consistent and excellent results. We highlight colleagues and intrepid pioneers who have strived to solve seemingly insurmountable problems during this remarkable journey and celebrate continued success into the 21st century with surgical advances that have resulted in innovative operations, database inquiries, quality measures, new techniques of medical illustration, and the establishment of the Congenital Heart Surgeons' Society, which has become the leading organization dedicated to congenital heart surgery in North America.

The Congenital Heart Surgeons' Society Presidents and Their Contributions.

The Congenital Heart Surgeons' Society (CHSS) was founded by 16 congenital heart surgeons in 1973, who endeavored to share their clinical advances in an informal setting that would stimulate honest and forthright discussions. As the Society grew, prospective studies were organized from a centralized data center that was established and based first in Birmingham, Alabama, thence to Toronto, and recently in a collaboration between Toronto and the Cleveland Clinic. These studies formed the basis for a myriad of outcomes reports that favorably impacted surgical results. The Kirklin-Ashburn Fellowship was created and endowed by the membership which has been successful in training many congenital heart surgeons. The CHSS was then incorporated into a 501(c) (3) not-for-profit organization with bylaws, officers, and committees in 2002. Increased membership followed. The CHSS has become the face of congenital heart surgery in North America by affiliating with the World Journal for Pediatric and Congenital Heart Surgery, having one designated member on the American Board of Thoracic Surgery, and hosting joint meetings with the European Congenital Heart Surgeons Association. Since 2002, 11 presidents have been elected for two-year terms and have guided the advances that have been achieved by the CHSS. Their contributions and achievements are highlighted in chronological order.

Indexed oxygen delivery during pediatric cardiopulmonary bypass is a modifiable risk factor for postoperative acute kidney injury.

BACKGROUND: Acute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort. METHODS: This was a retrospective analysis of patients under 1 year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk. RESULTS: We included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve = 0.66, 95% CI = 0.60 - 0.72, sensitivity = 56.1%, specificity = 69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve = 0.65, 95% CI = 0.58 - 0.72, sensitivity = 52.6%, specificity = 74.6%). CONCLUSION: Indexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Background: Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Methods: Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. Results: During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. Conclusions: This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Pediatric Extracorporeal Cardiopulmonary Resuscitation: Development of a Porcine Model and the Influence of Cardiopulmonary Resuscitation Duration on Brain Injury.

Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group (P=0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4-7.4] versus CPR30: 7.5 [IQR 7.4-7.5], P=0.022), higher lactate (CPR60: 6.8 [IQR 6.8-11] versus CPR30: 4.2 [IQR 4.1-4.3] mmol/L; P=0.012), and higher ICP (CPR60: 19.3 [IQR 11.7-29.3] versus CPR30: 7.9 [IQR 6.7-9.3] mm Hg; P=0.037). Both groups had greater mitochondrial injury than shams (CPR60: P<0.001; CPR30: P<0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.

Impact of the Southern Thoracic Surgical Association James W. Brooks Scholarship.

BACKGROUND: Medical students and general surgery residents often do not get exposure to cardiothoracic surgery (CTS) because of a decreased emphasis on CTS rotations during their training. The Southern Thoracic Surgical Association (STSA) began offering the Brooks Scholarship to medical students in 2010 and general surgery residents in 2014 to promote CTS. This study examines the impact of the scholarship. METHODS: We examined the history of the award and how STSA administers the award. Next we examined the impact of the award by evaluating the number of medical students and residents who are tracked to complete a CTS program. Finally we performed an analysis of the academic output of the awardees who have completed or were tracked to complete a CTS program. RESULTS: The scholarship was developed to honor the memory of past STSA President Dr James W. Brooks. The award is administered through the STSA scholarship committee and provides medical students and residents funds to attend the STSA annual meeting and the opportunity to spend time with a mentor during the meeting. Eighty-eight percent of medical student recipients (21/24) and 100% of general surgery resident recipients (15/15) have completed or are on track to complete a CTS program. The 36 recipients going into CTS have published a total of 823 papers and 9240 articles have cited those papers. CONCLUSIONS: The STSA medical student and general surgery Brooks scholarship awards were associated with completing or pursuing a career in CTS. STSA should continue the Brooks scholarship to attract talented medical students and residents to CTS.

Incidence of postoperative seizures in neonates following cardiac surgery with regional cerebral perfusion and deep hypothermic circulatory arrest.

Objectives: Historically, our center has primarily used deep hypothermic circulatory arrest, but in recent years some surgeons have selectively used regional cerebral perfusion as an alternative. We aimed to compare the incidence of postoperative electroencephalographic seizure incidence in neonates undergoing surgery with regional cerebral perfusion and deep hypothermic circulatory arrest. Methods: A retrospective analysis was performed in neonates who underwent surgery between 2012 and 2022 with either deep hypothermic circulatory arrest or regional cerebral perfusion with routine postoperative continuous electroencephalography monitoring for 48 hours. Propensity matching was performed to compare postoperative seizure risk between the 2 groups. Results: Among 1136 neonates undergoing cardiac surgery with cardiopulmonary bypass, regional cerebral perfusion was performed in 99 (8.7%) and deep hypothermic circulatory arrest in 604 (53%). The median duration of regional cerebral perfusion was 49 minutes (interquartile range, 38-68) and deep hypothermic circulatory arrest was 41 minutes (interquartile range, 31-49). The regional cerebral perfusion group had significantly longer total support, cardiopulmonary bypass, and aortic crossclamp times. Overall seizure incidence was 11% (N = 76) and 13% (N = 35) in the most recent era (2019-2022). The unadjusted seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 64, 11%). After propensity matching, the seizure incidence was similar in neonates undergoing regional cerebral perfusion (N = 12, 12%) and deep hypothermic circulatory arrest (N = 37, 12%) (odds ratio, 0.97; 95% CI, 0.55-1.71; P = .92). Conclusions: In this contemporary single-center experience, the incorporation of regional cerebral perfusion did not result in a change in seizure incidence in comparison with deep hypothermic circulatory arrest. However, unmeasured confounders may have impacted these findings. Further studies are needed to determine the impact, if any, of regional cerebral perfusion on postoperative seizure incidence.