Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children.

OBJECTIVE: This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children. DESIGN/METHODS: This is a retrospective chart review of a single institution comprising patients aged 0 to 18 years old with congenital heart disease. Patients must have received either PCC or rFVIIa after coming off CPB. Our primary efficacy endpoint is time in the operating room from off-CPB to pediatric intensive care unit admission. Our primary safety endpoint is thrombosis through 30 days. RESULTS: Our primary efficacy outcome was significantly shorter in the PCC group compared with the rFVIIa group (P < .0001). Similarly, secondary efficacy outcomes of packed red blood cell administration, chest tube output, and transfusion exposures all significantly favored PCC administration. However, CPB time was significantly longer, and body temperatures were significantly lower, in the rFVIIa group. Safety outcomes, including our primary safety outcome of thrombosis through 30 days, were similar between the two groups. CONCLUSION: This study questions whether PCC could be favored over rFVIIa for hemostasis in children with congenital heart disease following CPB surgery. In addition, this study has found no difference when comparing PCC and rFVIIa in terms of safety outcomes, particularly thrombosis events. There are several limitations to this study due to the retrospective nature of the design and the differences between the two study groups. Despite the limitations, this study suggests that relatively early administration of PCC could be favored over delayed administration of rFVIIa to control recalcitrant post-CPB bleeding in the operating room.

The Supported vs Unsupported Ross in Pediatric Patients: Neoaortic Root and Ventricular Function.

BACKGROUND: The supported Ross is used to mitigate the neoaortic root dilation that has been described with the unsupported Ross. There is limited literature assessing the efficacy of the supported Ross in young patients. In this study, the fate of the neoaortic root was compared in the supported and unsupported Ross procedure in adolescent patients. METHODS: A retrospective review was performed of patients who underwent the Ross procedure between 1996 and 2019. An analysis was conducted of patients aged 10 to 18 years who underwent the supported and unsupported Ross operation, without a Konno enlargement, to assess for longitudinal echocardiographic changes. Given differences in follow-up time, both regression analysis and Mann-Whitney nonparametric tests were used to correct for time from discharge to most recent follow-up. RESULTS: The median follow-up time for supported and unsupported Ross patients without a Konno enlargement was 2.90 years (0.21-13.03 years) and 12.13 years (2.63-19.47 years), respectively. Unsupported Ross patients experienced a higher rate of change per year in the aortic annulus (P = .003 and P = .014) and aortic sinus (P = .002 and P = .002) diameters, respectively. There was no significant difference in the rate of change of end-diastolic left ventricular internal diameter (P = .703 and P = .92) and aortic insufficiency (P = .687 and P = .215) between the supported and unsupported Ross patients. CONCLUSIONS: Progressive dilation of the neoaortic root in unsupported Ross patients is significantly mitigated with the supported Ross with excellent stability. The supported Ross is safe and effective and may play an increasing role in the management of children with aortic disease.

Nuclear Cell-Free DNA Predicts Adverse Events After Pediatric Cardiothoracic Surgery.

BACKGROUND: Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. METHODS: This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. RESULTS: Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). CONCLUSIONS: This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.

2640 Meters Closer to the Stars: Does High Altitude Affect Fontan Results?

BACKGROUND: Risk factors for and postoperative results of the Fontan operation in patients living at high altitude (>2500 meters above sea level) in the Andean region remain unknown. This study was conducted to evaluate immediate postoperative outcomes and to assess short- and long-term functional class after the Fontan operation. METHODS: From June 2003 to February 2019, 104 patients receiving the Fontan procedure at 2640 meters (8661 feet) above sea level were retrospectively studied. Preoperative catheterization, intraoperative variables, and postoperative outcomes were described. Functional class was evaluated in patients living permanently below (group I) and at or higher than 2500 meters (8202 feet) above sea level (group II). Risk factors for mortality were analyzed. RESULTS: Median age at operation was 8.5 ± 4.4 years; pulmonary artery pressure, 16.2 ± 3.6 mm Hg; end-diastolic systemic ventricular pressure, 13.3 ± 3.8 mm Hg; and pulmonary vascular resistance index, 2.1 (interquartile range, 07-3.7) Wood units. Chest tube duration was 8.5 (6-12) days. Mortality was 4.8%, with 0 in the last 5 years. Higher preoperative pulmonary pressure (16.2 ± 3.6 mm Hg vs 21.2 ± 3.40 mm Hg; P = .01), aortic cross-clamp time (P < .001), and renal failure (P < .01) were associated with mortality. Functional class improved to class I in 86.4%. Overall survival was 90.7% at 10 years of follow-up. CONCLUSIONS: Increased pulmonary pressure and pulmonary vascular resistance index are directly related to high altitude. The Fontan-Kreutzer operation performed at high altitude in the Andean region is feasible with good results. We routinely fenestrate all cases to avoid dysfunction in the early postoperative period. Functional status is adequate after the operation.

Outcomes Following Surgery to Address Shone Syndrome in Children.

BACKGROUND: Shone syndrome is characterized by coincident mitral valve stenosis and left ventricular outflow tract obstruction. Although first described in 1963, little research has expounded surgical outcomes. We sought to evaluate our experience with this cohort, emphasizing outcomes including mortality, morbidity, and cardiac function. METHODS: A retrospective chart review of 46 patients who underwent operation for Shone syndrome between 1990 and May 2018 was conducted. Index operations included 32 repairs of the left ventricular outflow tract, four mitral valve repair/replacements, nine combined repairs, and one non-Shone's repair. Median age at index procedure was 22 days (2 days-10 years). Mean follow-up was 9.1 years (2 months-21 years), and 70 additional operations (51 reoperations) were required. Three patients were lost to follow-up. RESULTS: Overall survival was 95.7% with two late deaths. Freedom from death or transplant was 93.5%. Thirteen (28.3%) patients remained free from reoperation. Thirty-three patients required 51 reoperations of the left ventricle outflow tract (n = 12), mitral valve (n = 16), combined repairs (n = 21), and transplant (n = 1). At most recent follow-up, patients exhibited mitral stenosis (n = 21), aortic stenosis (n = 7), and diminished LV function (n = 2). CONCLUSION: Surgical correction of Shone's offers excellent survival benefit, but reoperation burden is high, with >70% of patients requiring reintervention in the follow-up period. A total of 65% of patients developed recurrent obstruction of left ventricular inflow or outflow, however, ventricular function is preserved in the majority of patients. All but one patient had no functional deficits, classified as New York Heart Association I with > 60% requiring no medication.

Impact of Valve Type (Ross vs. Mechanical) on Health-Related Quality of Life in Children and Young Adults with Surgical Aortic Valve Replacement.

BACKGROUND: The impact of aortic valve replacement (AVR) type on health-related quality of life (HRQOL) in adolescents and young adults is unclear, but may vary depending on need for anticoagulation or re-intervention. We sought to determine the differences in HRQOL following AVR with either the Ross procedure or mechanical AVR in this young population. METHODS: Patients 14-35 years old and at least 1 year post-AVR were included. HRQOL was assessed using the Short Form-36 (SF-36). Valve-specific concerns regarding anticoagulation and reoperation were also assessed. Clinical outcome data were obtained by chart review. RESULTS: A total of 51 patients were enrolled: 24 (47%) Ross and 27 (53%) mechanical AVR. Ross patients were younger at time of AVR (16 vs. 22 years, p < 0.01) and study enrollment (23.7 vs 29.5 years, p < 0.01). Median follow-up from AVR to study enrollment was similar (5.4 years for Ross vs. 5.6 years for mechanical, p = 0.62). At last follow-up, clinical outcomes including cardiac function, functional class, and aortic valve re-intervention rates were similar between groups, although mechanical valve patients had more bleeding events (p = 0.012). SF-36 scores were generally high for the entire cohort, with no significant difference between groups in any domain. Mechanical AVR patients reported more concern about frequency of blood draws (p < 0.01). Concern for reoperation was similar between both groups. CONCLUSION: Despite more bleeding events and concern about the frequency of blood draws, adolescents and young adults with mechanical AVR reported similarly high levels of HRQOL compared to those following Ross AVR.

Interventions Associated With Treatment of Low Cardiac Output After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Both cardiac output (CO) and systemic vascular resistance (SVR) contribute to hemodynamic vulnerability. Simultaneous measures of mean arterial pressure and somatic regional near infrared spectroscopy saturation can classify complex hemodynamics into 4 distinct states, with a low-CO state of higher risk. We sought to identify interventions associated with low-CO state occupancy and transition. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis. Associations of static and dynamic support levels and state classifications over 48 postoperative hours were tested between states and across transitions using mixed regression methods in a quasi-experimental design. RESULTS: Data from 10,272 hours in 214 patients were analyzed. A low-CO state was observed in 142 patients for 1107 hours. Both low CO and extracorporeal membrane oxygenation had increased mortality risk. The low-CO state was characterized by lower milrinone but higher catecholamine dose. Successful transition out of low CO was associated with increased milrinone dose and hemoglobin concentration. Increasing milrinone and hemoglobin levels predicted reduced risk of low CO in future states. CONCLUSIONS: Bivariate classification objectively defines hemodynamic states and transitions with distinct support profiles. Maintaining or increasing inodilator and hemoglobin levels were associated with improved hemodynamic conditions and were predictive of successful future transitions from the low-CO state.

Innominate Vein Turn-down Procedure for Failing Fontan Circulation.

After the Fontan, systemic venous hypertension induces pathophysiologic changes in the lymphatic system that can result in complications of pleural effusion, ascites, plastic bronchitis, and protein losing enteropathy. Advances in medical therapy and novel interventional approaches have not substantially improved the poor prognosis of these complications. A more physiological approach has been developed by decompression of the thoracic duct to the lower pressure common atrium with a concomitant increase of preload. Diverting the innominate vein to the common atrium increases the transport capacity of the thoracic duct, which in most patients enters the circulation at the left subclavian-jugular vein junction. Contrary to the fenestrated Fontan circulation, in which the thoracic duct is drained into the high pressure Fontan circulation, turn down of the innominate vein to the common atrium effectively decompresses the thoracic duct to the lower pressure system with "diastolic suctioning" of lymph. Innominate vein turn-down may be considered for medical-refractory post-Fontan lymphatic complications of persistent chylothorax, plastic bronchitis, and protein losing enteropathy. Prophylactic innominate vein turn-down may also be considered at time of the Fontan operation for patients that are higher risk for lymphatic complications.

Mitral Valve Surgery in Neonates, Infants, and Children: Surgical Approach, Outcomes, and Predictors.

The surgical treatment of mitral disease in pediatrics is challenging. Managing diversity in patient anatomy, growth, and the need for long-term anticoagulation requires trade-offs between imperfect solutions. We sought to assess our approach to pediatric mitral valve surgery and identify predictors associated with mortality and recurrent mitral disease. The medical records, echocardiograms, and operative reports of all patients who underwent surgical intervention on the mitral valve from January 2000 to April 2016 were reviewed. A total of 143 patients underwent mitral valve surgery, 64 of which were neonates or infants (ages 10-355 days) and 79 of which were children (ages 1-17.8 years). Neonates and infants had a higher preoperative New York Heart Association heart failure classification in comparison to children (P < 0.001) with a less severe degree of mitral valve insufficiency (P = 0.007). Postoperative outcomes for primary repair patients (n = 133) demonstrated significant differences in recurrence of mitral valve disease, with 38% of neonates/infants and 21% of children affected (P = 0.028). Five-year rates of mortality or transplant were 22% (8%, 33%) in neonates and infants compared to 4% (0%, 10%) in children, P = 0.013. Mitral valve surgery in neonates and infants is particularly high risk and is associated with higher rate of recurrence and reintervention early. However, if successful early, mitral valve repair in neonates and infants can result in a durable freedom from reintervention that parallels freedom from reintervention in older children undergoing repair. Further understanding of mechanisms of failure and better matching of anatomic substrate to strategy is needed.

Identification of Time-Dependent Risks of Hemodynamic States After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Hemodynamic changes result from interaction of cardiac output (CO) and systemic vascular resistance (SVR). We sought to identify time-dependent changes in postoperative hemodynamic states and their associations with mortality. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis of mean arterial pressure and somatic regional near-infrared spectroscopic oximetry saturation. State classifications over 48 postoperative hours were modelled using multinomial logistic regressions for association with mortality. RESULTS: Data from 9614 of 10,272 hours in 214 patients were analyzed. Operative survival was 91%. The predominant state was high CO (46% time). Low CO state without extracorporeal membrane oxygenation (ECMO) was found in 52% of patients for 9.7% time. ECMO was employed in 24 (11.2%) patients for 10.4% time. State stability was 33%, with high SVR the least stable (17%) and high CO the most stable (53%). Transition from high CO increased in hours 1 to 12, mainly to low SVR. Transition to low CO was 18.4%, increasing in hours 1 to 12, mainly from high SVR. The transition risk to ECMO was 0.32%, and 0.74% during hours 1 to 12, only from low CO. Both low CO and ECMO had increased mortality risk. CONCLUSIONS: Bivariate classification defines hemodynamic states with distinct physiologic, transition, and mortality risk profiles. High SVR state was unstable. Transition to ECMO occurred only from low CO, while the low SVR and high CO states were safest.

Norwood Procedure-Difficulty in Weaning From Cardiopulmonary Bypass and Implications for Outcomes.

Difficulty weaning from cardiopulmonary bypass (CPB) or the need to return to CPB (collectively D-CPB) may occur after the Norwood procedure. We sought to evaluate the relationship between D-CBP and survival. This was a retrospective chart review of all patients undergoing a Norwood procedure at our institution during the interval 2005-2017. Primary outcome was survival for the Norwood procedure. Secondary outcomes included various measures of morbidity. Successful wean from CBP (S-CPB) was defined as no need to return to full-flow CPB during the initial definitive wean or after separation from CPB; otherwise, the classification was difficulty with wean (D-CBP). Successful rescue in the D-CPB group was defined as not requiring extracorporeal life support either in the operating room or within the first 3 postoperative days. Of the 196 patients in the cohort, 49 were D-CPB. Survival for S-CPB was 92.5% (136/147) vs 71.4% (35/49) for D-CPB (P = 0.001). Major morbidity occurred in 29.9% (44/147) in S-CPB vs 69.4% (34/49) in D-CPB (P < 0.001). With multivariable analysis, D-CPB was significantly associated with mortality (odds ratio = 8.09; confidence interval 2.72-24.05; P < 0.001). Successful rescue occurred in 30 of 49 patients in the D-CPB group and demonstrated survival similar to the S-CPB group. In the Norwood patient, D-CPB is an important intraoperative event and prognostic factor for mortality and morbidity. Successful rescue appears to ameliorate the impact of D-CPB on survival.

Evolving understanding of total artificial heart support of young infants and children.

BACKGROUND: We have developed a new method of total artificial heart (TAH) support for young patients, and here share our preliminary results and evolving understanding. METHODS: This report is a retrospective chart review of all patients <10 kg who received a TAH at our institution from May 2017 to the time of this report. RESULTS: Our cohort includes 5 patients. Two had single-ventricle circulation, 1 of whom had undergone a Glenn procedure and was revised back to a Sano shunt. Four were on extracorporeal life support for longer than 10 days, 3 with an open chest. In these 3 patients, the TAH was a salvage operation. Centrifugal pumps were used for 2 patients and pulsatile pumps for 3 patients. Three patients survived to transplantation and discharge, with support times of 79, 44, and 96 days; in these patients, the duration of follow-up from discharge to the time of this report was 687, 19, and 8 days, respectively, and all patients were well. For the pulsatile pumps, in the first patient we placed valved conduits for inflow connections. For the second patient, we omitted the valved conduits and oversized the pumps to avoid full fill; yet, despite our best efforts, full fill occurred frequently, and thus we converted to a systemic centrifugal pump. CONCLUSIONS: Our method of TAH support can be tailored to provide effective support of carefully selected young children with single or biventricular physiology. In our opinion, for pulsatile pumps, oversizing the pump and using valved inflow conduits may be important adjuncts to achieve effective support.

Safety and Efficacy of Vasopressin After Fontan Completion: A Randomized Pilot Study.

BACKGROUND: Arginine vasopressin is a nonapeptide hormone with effects on intracellular water transport and arterial tone that is used in distributive shock and following cardiopulmonary bypass. We sought to evaluate the safety and efficacy of vasopressin infusion on hemodynamics and fluid balance in the early postoperative period after Fontan completion. METHODS: We conducted a randomized, double-blinded, placebo-controlled study of vasopressin infusion for 24 hours after cardiopulmonary bypass for Fontan completion. Patient characteristics, hospital outcomes, and measures of hemodynamic parameters, urine output, chest tube drainage, fluid balance, laboratory data, and plasma arginine vasopressin concentrations were collected at baseline and for 48 postoperative hours. Data were analyzed using mixed-effect regressions. RESULTS: Twenty patients were randomized, 10 to vasopressin and 10 to placebo. Transpulmonary gradient (6.4 ± 0.5 vs 8.3 ± 0.5 mm Hg, P = .011) and chest tube drainage (23 ± 20 vs 40 ± 20 mL/kg, P = .028) for 48 hours after surgery were significantly lower in the vasopressin arm compared to placebo. Arginine vasopressin concentrations were elevated above baseline after surgery until 4 hours post cardiac intensive care unit admission in both arms, and higher in the vasopressin arm during postoperative infusion. No differences in sodium concentration, liver function, or renal function were noted between groups. CONCLUSIONS: Vasopressin infusion after Fontan completion appears safe and was associated with reduced transpulmonary gradient and chest tube drainage in the early postoperative period. A larger multiinstitutional study may show further outcome benefit.

Anatomic Repair of Corrected Transposition of the Great Arteries: The Double Switch.

The long-term outcome of patients with corrected transposition of the great arteries and associated lesions after physiologic repair is uncertain. Anatomic correction, utilizing the morphologic left ventricle as a systemic pumping chamber and the mitral valve as the systemic atrioventricular valve, is considered the preferred method, especially for patients with either tricuspid valve regurgitation, with Ebstein's malformation of the tricuspid valve, or with right ventricular dysfunction. The double switch employs both an atrial switch and arterial switch to "correct" the atrioventricular and ventriculoarterial discordance. Associated lesions are also repaired. The best outcomes with double switch are achieved with patients in the first few years of life even if reconditioning of morphologic left ventricle is required. However, the long-term function of the conduction system, the aortic valve, and the ventricles is variable and requires close surveillance.