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Background: Complications following the Fontan procedure include prolonged pleural drainage and readmission for effusions. To address these complications, a post-Fontan management pathway was implemented with primary goals of reducing chest tube duration/reinsertion rates and decreasing hospital length of stay and readmissions., Methods: Fontan patients were identified by retrospective chart review (2017-2019) to obtain baseline data for chest tube duration/reinsertion rates, hospital length of stay, and readmission rates for effusion. A post-Fontan management pathway was implemented (2020-2021) utilising post-operative vasopressin, nasal cannula oxygen until chest tube removal, and discharge regimen of three times daily diuretics, sildenafil, and afterload reducing medications. Patients were followed to evaluate primary outcomes., Results: The pre- and post-pathway groups were similar in single ventricle morphology, demographics, and pre-operative haemodynamics. Forty-three and 36 patients were included in the pre- and post-pathway cohorts, respectively. There were statistically significant reductions in chest tube duration (8 vs. 5 days, p ≤ 0.001), chest tube output on post-operative day 4 (20.4 vs. 9.9 mL/kg/day, p = 0.003), and hospital readmission rates for effusion (13[30%] vs. 3[8%], p = 0.02) compared to baseline. There was an absolute reduction in hospital length of stay (11 vs. 9.5 days, p = 0.052). When combining average cost savings for the Fontan hospitalisations, readmissions for effusion, and cardiac catheterisations within 6 months of Fontan completion, there was a $325,144 total cost savings for 36 patients following pathway implementation., Conclusion: Implementation of a post-Fontan management pathway resulted in significant reductions in chest tube duration and output, and readmission rates for effusion in the perioperative period. more...

Collaborative multicenter research has significantly increased our understanding of fetal Ebstein anomaly, delineating risk factors for adverse outcomes as well as predictors of postnatal management. These data are incorporated into prenatal care and therapeutic strategies and inform family counseling and delivery planning to optimize care. This report details the translation of findings from multicenter studies into multidisciplinary prenatal care for a fetus with Ebstein anomaly, supraventricular tachycardia, and a circular shunt, including transplacental therapy to control arrhythmias and achieve ductal constriction, informed and coordinated delivery room management, and planned univentricular surgical palliation. more...

Background: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection., Methods: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance., Results: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection., Conclusion: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance., (© 2024 Wiley Periodicals LLC.) more...

Objective: To identify risk factors for aortopulmonary collateral (APC) development and assess the impact of severe APCs in children undergoing staged single ventricle palliation., Methods: Children undergoing a bidirectional Glenn operation between January 1, 2016, and March 31, 2021, at our center were included. All underwent angiography prior to Glenn and Fontan; APC flow was graded on a scale of 0 (no appreciable collateral flow) to 4 (severe burden). Demographic data, congenital diagnosis, clinical history, and outcomes were stratified by Glenn assessment; Fontan outcomes were stratified by pre-Fontan grade., Results: Sixty patients met the inclusion criteria, all of whom had angiographic evidence of APCs. There were 7 transplants and 9 deaths in the cohort. There were no significant differences in demographics among the patients. Right ventricular morphology was more common in patients with severe pre-Glenn collaterals (24 of 44 vs 2 of 6 vs 7 of 8; P  = .014). Longer stage 1 aortic cross-clamp duration was associated with greater severity pre-Glenn (44 minutes vs 34 minutes vs 66 minutes; P  = .023). Patients with grade 3 pre-Glenn collaterals more commonly required transplantation than those with grade 1 collaterals ( P  < .001) and had lower overall transplant-free survival than those with grade 1 ( P  = .005) or grade 2 ( P  = .04) collaterals., Conclusions: The ubiquity of APCs in this study demonstrates their prevalence in single ventricle disease. Right ventricular morphology and prolonged aortic cross-clamp duration are associated with higher burden. Greater severity was associated with decreased transplant-free survival. These data emphasize the negative long-term impact of these collaterals., (© 2023 The Author(s).) more...

Background: During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure., Methods: We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish and Drosophila models were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further., Results: Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identified RTTN , the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient's condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes., Conclusions: This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role for RTTN in perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease. more...

We describe a 35-month-old girl with a complex congenital heart defect including double-inlet left ventricle who presented with an occluded ductal stent. We performed pulmonary artery unifocalization and central shunt placement to bridge to Fontan or as final palliation. Anticipating a prolonged role for the shunt, we used a novel approach to aortopulmonary shunt construction consisting of a stent-restricted shunt that allows extended shunt longevity through an ability to "grow" with the patient's somatic growth. This technique demonstrates a safe way to dilate aortopulmonary shunts without repeated open surgical intervention., (© 2023 The Authors.) more...

Objectives: Donor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients., Methods: Pediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated., Results: A total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively)., Conclusions: Donor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.) more...

Partial anomalous pulmonary venous return is a rare congenital heart defect that can escape detection until adulthood and can be misdiagnosed as pulmonary hypertension and managed with vasodilators before the anomaly is identified. This report describes the cases of 3 patients with pulmonary hypertension whose hemodynamics and symptoms improved after repair of anomalous veins. Anomalous pulmonary veins are difficult to identify on a transthoracic echocardiogram, so a high index of suspicion and early use of additional imaging modalities are important to avoid a delayed diagnosis and progression to irreversible disease., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Background: Congenitally corrected transposition of the great arteries (ccTGA) has many management strategies, with the emergence of anatomic repair increasing the available surgical options. Contemporary surgical practices have not been described in multicenter analyses. This study describes the distribution of heart surgery in patients with ccTGA and defines contemporary outcomes in a large multicenter cohort., Methods: Index cardiovascular operations in patients with primary or fundamental diagnosis of ccTGA were identified in The Society of Thoracic Surgeons Congenital Heart Surgery Database from 2010 to 2019. Operations of interest were combined into mutually exclusive groups designating overall ccTGA management strategies. Outcomes were defined with standard Society of Thoracic Surgeons Congenital Heart Surgery Database definitions. Pearson χ 2 and Kruskal-Wallis tests were used for statistical comparisons., Results: One hundred one centers performed 985 index operations, with anatomic repair the most common approach. Twenty-six centers performed more than 10 operations. Atrial switch plus Rastelli operations had the highest rate of operative mortality (8.4%) and major complications (38.2%). Heart transplant operations had the longest postoperative length of stay among survivors (18 days [interquartile range, 13.5-26])., Conclusions: Patients with ccTGA remain a challenging cohort, with significant diversity in the operations used and a substantial burden of operative mortality and morbidity., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Background: Obesity increases the risk of post-operative arrhythmias in adults undergoing cardiac surgery, but little is known regarding the impact of obesity on post-operative arrhythmias after CHD surgery., Methods: Patients undergoing CHD surgery from 2007 to 2019 were prospectively enrolled in the parent study. Telemetry was assessed daily, with documentation of all arrhythmias. Patients aged 2-20 years were categorised by body mass index percentile for age and sex (underweight <5, normal 5-85, overweight 85-95, and obese >95). Patients aged >20 years were categorised using absolute body mass index. We investigated the impact of body mass index category on arrhythmias using univariate and multivariate analysis., Results: There were 1250 operative cases: 12% underweight, 65% normal weight, 12% overweight, and 11% obese. Post-operative arrhythmias were observed in 38%. Body mass index was significantly higher in those with arrhythmias (18.8 versus 17.8, p = 0.003). There was a linear relationship between body mass index category and incidence of arrhythmias: underweight 33%, normal 38%, overweight 42%, and obese 45% (p = 0.017 for trend). In multivariate analysis, body mass index category was independently associated with post-operative arrhythmias (p = 0.021), with odds ratio 1.64 in obese patients as compared to normal-weight patients (p = 0.036). In addition, aortic cross-clamp time (OR 1.007, p = 0.002) and maximal vasoactive-inotropic score in the first 48 hours (OR 1.03, p = 0.04) were associated with post-operative arrhythmias., Conclusion: Body mass index is independently associated with incidence of post-operative arrhythmias in children after CHD surgery. more...

Background: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest., Methods: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA., Results: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001)., Conclusion: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients., (© 2022 Wiley Periodicals LLC.) more...

Background: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored., Objective: Explore the relationship between ncfDNA and clinical events in heart transplant recipients., Methods: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints., Results: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection., Conclusions: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) more...

We report the case of an 18-year-old male patient with a history of bicuspid aortic valve with severe aortic insufficiency who had undergone a Ross procedure 1 year prior but subsequently developed stenosis of the pulmonary homograft necessitating conduit replacement. His postoperative course was complicated by acute respiratory distress syndrome. Bronchoscopy revealed significant mucus plugging without identification of contributing pathogen. Further evaluation revealed a history of electronic cigarette use not identified preoperatively and thought to be largely contributory to his postoperative complications. This case highlights the importance of screening preoperatively for electronic cigarette use and counseling on cessation before surgical procedures., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Autograft root dilation is common after the unsupported Ross procedure. In the absence of valvar incompetence, and with the perception that dissection is exceedingly rare, expectant management of autograft aneurysm is common practice. Autograft dissection may not be as rare as thought though, as at this point 7 case reports have accrued that describe autograft dissection requiring urgent operative intervention. All had a bicuspid native aortic valve. Bicuspid aortic valve has been shown to be associated with an intrinsic, histologically demonstrated pulmonary arteriopathy, possibly contributing to autograft root dilation and dissection. Autograft root dilation can no longer be regarded as benign, especially in patients with bicuspid aortic valve. Mounting evidence further validates the practice of externally supporting the Ross autograft. For patients who have had an unsupported Ross procedure, mounting evidence may support earlier intervention for autograft root dilation and aneurysm. more...

Background: Diaphragm paralysis (DP) complicates the postoperative course of neonates and infants undergoing cardiac surgery. Events causing DP remain poorly understood, and preventive strategies remain elusive. This retrospective cohort analysis aims to test the hypothesis that chest tubes in contact with the phrenic nerve in the pleural apex may cause pressure palsy., Methods: In late 2018, the chest tube positioning strategy was changed so as to avoid a putative "danger zone" configuration, defined as (1) the chest tube looping apicomedially at the level of the second right intercostal space, and (2) wedging of chest tube tip against pericardium. A preintervention and postintervention analysis of 531 patients from 2012 to 2019 was performed to evaluate any association of chest tube position or duration in place with DP. Univariable and multivariable analyses were carried out, with significance set a priori at P < .05., Results: The preintervention group comprised 488 patients, of whom 32 (6.6%) had RDP. The postintervention group comprised 43 patients, none of whom had DP. Multivariable analysis of the entire cohort revealed chest tube positioning in the danger zone as the only significant association with RDP (odds ratio, 4.22; 95% confidence interval, 1.57-11.33; P < .05)., Conclusions: Chest tubes that occupy the right superior pleural space are associated with increased risk of DP., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.) more...

Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies. Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level. While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease. Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis. The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS. High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure. RNA-Seq was used to identify regulation of N-glycan related enzymes. The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis. In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures. In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group. Three sialylated N-glycans showed common elevation in AS independent of age. On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages. Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS. This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.) more...

Background: Adults with congenital heart disease (CHD) awaiting heart transplant (HT) have higher mortality and waitlist removal due to clinical deterioration than those without CHD. The selective use of non-lung donors (NLD) to recover donor pulmonary vasculature to assist in graft implantation may be a contributing factor and is supported by consensus statements despite the recent use of pericardium or graft material as an alternative in pulmonary vascular reconstruction. The impact of selecting NLD for CHD recipients on wait time and mortality has not been evaluated., Methods/results: In the United Network for Organ Sharing (UNOS) Registry, 1271 HT recipients age ≥ 18 with CHD were identified between 1987 and 2016, 68% of which had NLDs. Prior to HT, NLD recipients were significantly less likely to be listed UNOS Status 1A, require mechanical ventilation, or intra-aortic balloon pump support. There was no difference in mean waitlist time (254 vs. 278 days, p = .31), 1-year mortality (82% vs. 80%, p = .81; adjusted odds ratio 1.32, 95% confidence interval [CI] 0.96-1.83, p = .08), or overall mortality (adjusted hazard ratio 1.08, 95% CI 0.86-1.36, p = .48) between recipients from NLD and concomitant lung donors., Conclusions: Adult CHD patients who are less critically ill or listed at a lower status are more likely to receive HT from NLD. There is no overall mortality benefit associated with this practice. While specific cases may necessitate waiting for NLD, programs need to re-evaluate whether this should remain a more widespread practice among CHD patients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) more...

Background: Aortic arch reobstruction is a common complication after aortic repair, with rates of reintervention varying from 0% to 40%, depending on the disease and the institution. This study aimed to determine the reintervention rate in children undergoing aortic arch repair using a tailored autologous pericardial patch at our center (Monroe Carell, Jr Children's Hospital at Vanderbilt, Nashville, TN)., Methods: This retrospective study examined all patients operated on by a single surgeon for aortic arch reconstruction through sternotomy, from 2011 to 2018, with 1 year of follow-up. Our data set was analyzed for normality by using the Shapiro-Wilk test, and nonparametric statistical methods were used. Kaplan-Meier survival analysis was performed, IBM SPSS software version 23 was used to perform all statistical analysis., Results: A total of 171 patients met inclusion criteria. Twenty-three (13.5%) patients underwent aortic arch reinterventions during the study period, 17 (9.9%) catheter based and 3 (1.8%) surgical. Three patients (1.8%) had both. Freedom from reintervention at 1-year follow-up for the univentricular and biventricular patients was 82.1% and 89.4% (P = .174), respectively. To assess the growth of the aortic arch over time, cardiac catheterization measurements were used to index different parts of the aortic arch against the descending aorta. Ascending-to-descending aortic arch measurements revealed that the pre-Glenn median was 2.0 (interquartile range, 1.8 to 2.2), whereas the pre-Fontan median was 2.5 (interquartile range, 2.2 to 2.7) (P < .05)., Conclusions: There was no significant difference in reintervention rates between biventricular and univentricular arches, and catheterization measurements showed significant growth of the arch over time. The use of a tailored autologous pericardial patch for aortic arch repair is comparable to other reported methods of arch repair., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Objectives: Infants undergoing congenital heart surgery require central venous lines which can be achieved by various combinations of transthoracic lines, percutaneous-indwelling central catheters and tunneled Broviac catheters. Transthoracic lines are removed by protocol prior to cardiac intensive care unit discharge (risk of bleeding), at which time percutaneous-indwelling central catheters are placed. Transdiaphragmatic tunneled Broviac catheters placed at the time of sternotomy, remain in place until hospital discharge, when they are safely removed at bedside. We characterized actual cost profiles associated with strategies that do versus do not include tunneled Broviac catheters., Methods: From January 2014 to December 2016, we identified a study population of 220 consecutive patients under 1 year of age undergoing congenital heart surgery. Cost data were acquired from our electronic patient system interface database and office of finance. Our cohort was divided into 2 groups, tunneled Broviac catheter and nontunneled Broviac catheter. We calculated the total cost associated with each groups' central venous lines, propensity matched, and used the Mann-Whitney U test to analyze the results., Results: Eighty-three (37.7%) of the 220 patients had tunneled Broviac catheters. The tunneled Broviac catheter group had 4 percutaneous-indwelling central catheter insertions and 6 radiological interventions while the nontunneled Broviac catheter group had 90 percutaneous-indwelling central catheters and 203 radiologic interventions. After propensity score matching, both groups were reduced to 82 patients and sum, median and interquartile range cost for tunneled Broviac catheters and nontunneled Broviac catheters was $17,351.84, $159.76 (128-159.76) versus $72,809.32, $1277.26 (31.76-1277.26), P < .02 respectively., Conclusions: Tunneled Broviac catheters, placed routinely at cardiac surgery, incur lower costs than the conventional combination of transthoracic lines and percutaneous-indwelling central catheters. The cost-effectiveness is achieved by reducing the number of percutaneous-indwelling central catheters and associated radiologic interventions., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.) more...

Background: Endomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. The quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multicenter prospective blinded study (DNA-Based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to the total amount of cfDNA present in a blood sample., Methods: A total of 241 heart transplant patients were recruited from 7 centers. Age at transplant ranged from 8 days to 73 years, with 146 subjects <18 years and 95 ≥18 years. All the patients were followed for at least 1 year, with blood samples drawn at routine and for-cause biopsies. A total of 624 biopsy-paired samples were included for analysis through a commercially available cfDNA assay (myTAI HEART , TAI Diagnostics Inc.). A blinded analysis of repeated measures compared the outcomes using receiver operating characteristic (ROC) curves. All primary clinical end-points were monitored at 100%. All analysis and conclusions were reviewed by both an independent external oversight committee and the National Institutes of Health-mandated DTRT steering committee., Results: DF in acute cellular rejection (ACR) 1R/2R (n = 15) was higher than ACR 0R (n = 42) (p = 0.02); DF in antibody-mediated rejection pAMR1 (n = 8) and pAMR2 (n = 12) (p = 0.05) were higher than pAMR0 (n = 466) (p = 0.04 and p = 0.05 respectively). An optimal DF threshold was determined by the use of an ROC analysis, which ruled out the presence of either ACR or antibody-mediated rejection., Conclusions: The cell-free DNA DF holds promise as a non-invasive diagnostic test to rule out acute rejection in both adult and pediatric heart transplant populations., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.) more...

As a result of improvements in care for patients with congenital heart disease (CHD), >90% of children born with CHD are expected to survive to adulthood. For those adults, heart failure (HF) is the leading cause of death. Advances in recognition of, and treatments for, these patients continue to improve. Specifically, adults with CHD are candidates for both heart transplantation and mechanical circulatory support. However, challenges remain that require investigation to improve outcomes., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.) more...

Objectives: Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants., Design: Single-center prospective observational cohort pilot study., Setting: Pediatric cardiac ICU at a tertiary children's hospital., Patients: Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion., Intervention: None., Measurements and Main Results: Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008)., Conclusions: Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes. more...

Background: Turner syndrome (TS) is a genetic syndrome characterized by monosomy X (45,XO) in phenotypic females and is commonly associated with congenital heart disease. We sought to describe the distribution, mortality, and morbidity of congenital heart surgery in TS and compare outcomes to individuals without genetic syndromes., Methods: The Society of Thoracic Surgeons Congenital Heart Surgery Database was used to evaluate index cardiovascular operations performed from 2000 to 2017 in pediatric patients (aged 0-18 years) with and without TS. Analyses were stratified by the most common operations, including coarctation repair, aortic arch repair, partial anomalous pulmonary venous return repair, Norwood, superior cavopulmonary anastomosis (Glenn), and Fontan., Results: Included were 780 operations in TS and 62,659 operations in controls. The most common TS operations were coarctation repair in 274 (35%), aortic arch repair in 116 (15%), and Norwood in 59 (8%). Compared with controls, TS patients had lower weight-for-age Z-scores across all operations (P < .01 for all); however, operative mortality rates did not differ significantly. The chylothorax rate was higher in TS after coarctation repair (8.8% vs 2.8%, P < .001) and Norwood (22% vs 8.1%, P < .001). The median (interquartile range) postoperative length of stay was longer in TS for coarctation repair (6.5 [5.0-15.5] days vs 5.0 [4.0-9.0] days, P < .001), aortic arch repair (15.0 [8.0-27.5] days vs 11.0 [7.0-21.0] days, P = .004), and Glenn (9.0 [6.0-16.0] days vs 6.0 [5.0-11.0] days, P = .013)., Conclusions: Turner syndrome patients most commonly underwent operations for left-sided obstructive lesions. Despite increased morbidity for select operations, TS was not associated with increased operative mortality., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Background: Sympathetically-associated hypertension after coarctation repair is a common problem often requiring anti-hypertensive infusions in an intensive care unit. Epidurals suppress sympathetic output and can reduce blood pressure but have not been studied following coarctation repair in children. We sought to determine whether epidurals for coarctation repair in children were associated with decreased requirement for postoperative anti-hypertensive infusions, if they were associated with changes in hospital course, or with complications., Methods: In this observational retrospective cohort study, we evaluated all patients age 1-18 years undergoing coarctation repair at our institution during a 10-year period and compared the requirement for postoperative anti-hypertensive infusions in patients with and without epidurals using an anti-hypertensive dosing index (ADI) incorporating total dose-hours of all anti-hypertensive infusions (primary outcome). We also assessed intensive care unit (ICU) and hospital length of stay, discharge on oral anti-hypertensive medication, and complications potentially related to epidurals (secondary outcomes)., Results: Children undergoing coarctation repair with epidurals had decreased requirements for postoperative anti-hypertensive infusions compared to children without epidurals (cumulative ADI 65.0 [28.5-130.3] v. 157.0 [68.6-214.7], p = 0.021; mean ADI 49.0 [33.3-131.2] v. 163.0 [66.6-209.8], p = 0.01). After multivariable cumulative logit mixed-effects regression analysis, mean ADI was decreased in patients with epidurals throughout the postoperative period ( p < 0.001). Patients with epidurals were 1.6 years older and weighed 10.6 kg more than patients without epidurals but were otherwise comparable. Epidural complications included pruritus (three patients), agitation (one patient), somnolence (one patient), and transient orthostatic hypotension (one patient). Duration of intensive care unit admission, duration of hospital stays, and requirement for anti-hypertensive medication at discharge were similar in patients with and without epidurals., Conclusions: This is the first study of children receiving an epidural for surgical repair of aortic coarctation via open thoracotomy. In this small, single-institution, observational retrospective cohort study, epidurals for coarctation repair in children were associated with decreased postoperative anti-hypertensive infusion requirements. Epidurals were not associated with length of ICU or hospital stay, or with discharge on anti-hypertensive medication. No significant epidural complications were noted. Prospective study of larger populations will be necessary to confirm these associations, address causality, verify safety, and assess other effects. more...

A 38-year-old female with tricuspid atresia and normally related great arteries, initially palliated with Björk modified Fontan, and ultimately converted to extracardiac conduit Fontan, with a history of ventricular tachycardia and hepatitis C virus (HCV) treated with sofosbuvir/ledipasvir, was referred to our center for consideration of combined heart and liver transplantation. The patient's blood group was O with panel reactive antibodies of 52%. She consented to consideration of HCV-positive donors. Fifteen days later, an HCV-positive donor was identified, and she underwent heart transplantation with pulmonary artery reconstruction performed jointly by adult and pediatric transplant surgeons. To our knowledge, this the first time an HCV-positive donor heart has been to transplant an adult with congenital heart disease. more...

Background: The number of adult congenital heart disease (ACHD) patients requiring heart transplantation (HT) continues to grow, and if they survive the first year after transplant, their long-term survival is at least equivalent to non-ACHD patients. The 1-year survival of ACHD patients with HT remains lower than non-ACHD patients. We evaluated the affect of transplant center volume on 1-year survival of ACHD patients. We analyzed United Network of Organ Sharing patients (age ≥18 years) who underwent their first orthotopic HT between January 1, 2000, and December 31, 2015, to assess the association between transplant center volume and 1-year survival of ACHD patients., Results: We identified 827 ACHD patients at 113 centers who underwent HT during the study period. The average age of the recipients and donors was 36 ± 13 years (60% men and 84% Caucasian) and 28 ± 11 (63% men and 66% Caucasian), respectively. Of the ACHD patients undergoing HT, 27% (n = 60) were done at low-volume centers, 30% (n = 10) were reported at high-volume centers, and the remaining (n = 43) were at medium-volume centers. A total of 96 patients died within 30 days, including 37 (16.7%) at low-volume, 37 (10.2%) at medium-volume, and 22 (9.0%) at high-volume centers (p = 0.019). The average unadjusted Kaplan-Meier 30-day survival at low-volume centers was 83% ± 2%, which was significantly lower than medium-volume (90% ± 1%) and high-volume (91% ± 2%) centers (log-rank p < 0.05). Within 1 year, 154 patients had died, including 56 (36.4%) at low-volume, 60 (38.9%) at medium-volume, and 38 (24.7%) at high-volume centers (p = 0.011). Average unadjusted Kaplan-Meier 1-year survival at low-volume centers was 75% ± 3%, which was significantly lower than medium-volume (83% ± 2%) and high-volume (84% ± 2%) centers (log-rank p < 0.05)., Conclusions: The 30-day and 1-year survival of ACHD patients undergoing HT is partly influenced by overall transplant center volume and, potentially, volume of ACHD HTs, with low-volume centers performing poorly relative to medium-volume and high-volume centers. The role of peri-operative care and multidisciplinary management in improving survival at low-volume centers required further investigations., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.) more...

Deep hypothermia for the operative correction of congenital cardiac lesions protects hypoperfused organs, mostly because of its effect on lowering metabolic demand and oxygen requirement. Deleterious cerebral and extracranial side effects of deep hypothermia itself calls for a reexamination of the therapeutic value of hypothermia, and has led to the development of alternative perfusion strategies. Here we describe the potential advantages of milder hypothermia over deep hypothermia and our method of a practical and reproducible implementation of multisite perfusion under mild hypothermia (32°C)., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...

Background: Transplant-free survival for single right ventricle (RV) lesions remains less than 70% at 3 years. Arrhythmia burden, influence of shunt type at Norwood procedure (RV-to-pulmonary artery shunt [RVPAS] versus Blalock-Taussig shunt [BTS]), and implications for mortality risk are not well defined., Methods: The authors performed a single-center retrospective analysis of patients with single RV lesions enrolled in a prospective study of arrhythmias after congenital heart surgery., Results: Fifty-eight patients received a RVPAS and 62 received a BTS, with a median follow-up of 773 days. Overall arrhythmia incidence was 78%, two-thirds of which prompted intervention. Among all types of arrhythmias, only ventricular arrhythmias (VAs) differed by shunt type, which were more common in patients receiving an RVPAS (29% RVPAS versus 14% BTS; p = 0.049). The majority of VAs were transient (69% less than 1 minute), and typically occurred early post-Norwood procedure (median 12 days). No additional variables were associated with development of VAs. Shunt type did not influence transplant-free survival. Within the entire cohort, there was a trend toward increased mortality with prior history of VA (odds ratio, 2.90; 95% confidence interval, 0.99 to 8.90; p = 0.052). For interstage survivors to Glenn palliation, any VA associated with a 14-fold increased risk of death or transplant (hazard ratio, 14.00; 95% confidence interval, 3.66 to 53.40; p < .001). No other tachyarrhythmia or bradyarrhythmia was associated with mortality., Conclusions: In this cohort with single RV lesions and prospective rhythm surveillance, patients receiving an RVPAS at Norwood surgery had an increased incidence of VAs compared with patients with a BTS. VAs correlated with late mortality in patients who survived the interstage period., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

We describe a strategy aimed at maximizing the safety and minimizing the thrombogenicity of central venous lines for neonates with congenital heart defects. Our method involves the use of a tunneled technique to place a 4.2 Fr single-lumen (Broviac) catheter in the subpericardial space, with minimal intravascular course and a tip placed in the lower right atrium. Using this technique, we potentially eliminated the requirement for percutaneous placement of central venous lines postoperatively as well as potentially decreased the risk of intrapericardial bleeding associated with transthoracic lines. more...

Background: Neonatal aortic arch reconstruction, typically performed with deep hypothermia and selective cerebral perfusion, leaves splanchnic organ protection dependent on hypothermia alone. A simplified method of direct in-field descending aortic perfusion during neonatal arch reconstruction permits the avoidance of deep hypothermia. We hypothesize that direct splanchnic perfusion at mild hypothermia provides improved or equivalent safety compared with deep hypothermia and may contribute to postoperative extracardiac organ recovery., Methods: Included were 138 biventricular patients aged younger than 90 days undergoing aortic arch reconstruction with cardiopulmonary bypass. Patients were grouped according to perfusion method A (selective cerebral perfusion with deep hyperthermia at 18° to 20°C) or method B (selective cerebral perfusion and splanchnic perfusion at 30° to 32°C). Patient characteristics and perioperative clinical and serologic data were analyzed. Significance was assigned for p of less than 0.05., Results: Of the 138 survivors, 63 underwent method A and 75 underwent method B. The median age at operation was 8.5 days (range, 6 to 15 days), and median weight was 3.2 kg (range, 2.8 to 3.73 kg), with no significant differences between groups. Cardiopulmonary bypass times were comparable between the two perfusion methods (p = 0.255) as were the ascending aortic cross-clamp times (p = 0.737). The postoperative glomerular filtration rate was significantly different between our groups (p = 0.028 to 0.044), with method B achieving a higher glomerular filtration rate. No significant differences were seen in ventilator time, postoperative length of stay, fractional increase of postoperative serum creatinine over preoperative serum creatinine, and postoperative lactate., Conclusions: A simplified method of direct splanchnic perfusion during neonatal aortic arch reconstruction avoids the use of deep hypothermia and provides renal protection at least as effective as deep hypothermia., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

We report a novel method of constructing an extracardiac bidirectional inferior cavopulmonary anastomosis. Our patient was a 4-month-old girl with complex single-ventricle anatomy and a small-caliber superior vena cava. A direct anastomosis from the inferior vena cava to the main pulmonary artery was constructed by using all autologous tissue. The resulting pathway remained patent and exhibited growth with age. Furthermore, a pulmonary arteriovenous malformation did not develop. This case demonstrates how a bidirectional inferior cavopulmonary anastomosis is feasible in the human and can provide similar hemodynamic results as the bidirectional superior cavopulmonary anastomosis., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Hypoplastic left heart syndrome (HLHS) has been associated with germline mutations in 12 candidate genes and a recurrent somatic mutation in HAND1 gene. Using targeted and whole exome sequencing (WES) of heart tissue samples from HLHS patients, we sought to estimate the prevalence of somatic and germline mutations associated with HLHS. We performed Sanger sequencing of the HAND1 gene on 14 ventricular (9 LV and 5 RV) samples obtained from HLHS patients, and WES of 4 LV, 2 aortic, and 4 matched PBMC samples, analyzing for sequence discrepancy. We also screened for mutations in the 12 candidate genes implicated in HLHS. We found no somatic mutations in our HLHS cohort. However, we detected a novel germline frameshift/stop-gain mutation in NOTCH1 in a HLHS patient with a family history of both HLHS and hypoplastic right heart syndrome (HRHS). Our study, involving one of the first familial cases of single ventricle defects linked to a specific mutation, strengthens the association of NOTCH1 mutations with HLHS and suggests that the two morphologically distinct single ventricle conditions, HLHS and HRHS, may share a common molecular and cellular etiology. Finally, somatic mutations in the LV are an unlikely contributor to HLHS. more...