Mortality and Heart Transplantation After Hybrid Palliation of Hypoplastic Left Heart Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) who are considered at increased risk for death following Norwood/Sano surgery often undergo hybrid palliation (HP) as initial surgery. We aimed to compile the HP experience in HLHS and its variants and assess the rates of, and risk factors for, death and heart transplantation. METHODS: CINAHL, CINAHL PLUS, PubMed/MEDLINE, and SCOPUS were systematically searched for HP outcome studies of death or heart transplantation in HLHS between 1998 and 2022. Pooled incidence was estimated, and potential risk factors were identified using random-effects meta-analysis and reconstructed time-to-event data from Kaplan-Meier curves. RESULTS: Thirty-three publications were included in our review. Overall, of 1,162 patients 417 died and 57 underwent heart transplantation, resulting in a combined outcome of 40.7%, (474/1,162). There was a trend toward decreasing mortality risk across the stages of palliation. Pooled mortality between HP and comprehensive stage 2 palliation was 25%, after stage 2 up to Fontan palliation was 16%, and 6% post-Fontan. The incidence of death or heart transplantation was higher in high-risk patients-43% died and 10% received heart transplantation. CONCLUSION: Our systematic review and meta-analysis found high rates of death or heart transplantation in HP of HLHS patients between HP and Fontan surgeries. All patients should be closely followed during the initial interstage period, which is associated with the highest hazard. Prospective studies on appropriate patient selection, indications, and / or alternatives, as well as refining HP strategies for managing newborns with HLHS are needed to improve outcomes.

Infants less than or equal to 2.5 kg have increased mortality and worse motor neurodevelopmental outcomes at 2 years of age after Norwood-Sano palliation.

Objectives: In infants with single-ventricle congenital heart disease, prematurity and low weight at the time of the Norwood operation are risk factors for mortality. Reports assessing outcomes (including neurodevelopment) post Norwood palliation in infants ≤2.5 kg are limited. Methods: All infants who underwent a Norwood-Sano procedure between 2004 and 2019 were identified. Infants ≤2.5 kg at the time of the operation (cases) were matched 3:1 with infants >3.0 kg (comparisons) for year of surgery and cardiac diagnosis. Demographic and perioperative characteristics, survival, and functional and neurodevelopmental outcomes were compared. Results: Twenty-seven cases (mean ± standard deviation: weight 2.2 ± 0.3 kg and age 15.6 ± 14.1 days at surgery) and 81 comparisons (3.5 ± 0.4 kg and age 10.9 ± 7.9 days at surgery) were identified. Post-Norwood, cases had a longer time to lactate ≤2 mmol/L (33.1 ± 27.5 vs 17.9 ± 12.2 hours, P < .001), longer duration of ventilation (30.5 ± 24.5 vs 18.6 ± 17.5 days, P = .005), greater need for dialysis (48.1% vs 19.8%, P = .007), and greater need for extracorporeal membrane oxygenation support (29.6% vs 12.3%, P = .004). Cases had significantly greater postoperative (in-hospital) (25.9% vs 1.2%, P < .001) and 2-year (59.2% vs 11.1%, P < .001) mortality. Neurodevelopmental assessment showed the following for cases versus comparisons, respectively: cognitive delay (18.2% vs 7.9%, P = .272), language delay (18.2% vs 11.1%, P = .505), and motor delay (27.3% vs 14.3%, P = .013). Conclusions: Infants ≤2.5 kg at Norwood-Sano palliation have significantly increased postoperative morbidity and mortality up to 2-year follow-up. Neurodevelopmental motor outcomes were worse in these infants. Additional studies are warranted to assess the outcome of alternative medical and interventional treatment plans in this patient population.

Neurodevelopmental Outcomes of Infants after Neonatal Surgical Intervention for Tetralogy of Fallot or Pulmonary Atresia.

OBJECTIVE: To determine the 2-year neurodevelopmental outcomes for survivors of neonatal cardiac surgery for the most common right ventricular outflow tract obstructive lesions: tetralogy of Fallot and pulmonary atresia with a ventricular septal defect. STUDY DESIGN: A single-center consecutive cohort of 77 children underwent neonatal surgery for tetralogy of Fallot or pulmonary atresia with a ventricular septal defect at ≤6 weeks of age between 2006 and 2017. The patients underwent a multidisciplinary neurodevelopmental assessment at 18-24 months of age. Survivor outcomes were compared by univariable and multivariable analyses. RESULTS: The 2-year mortality was 7.8% (6/77) with a postoperative in-hospital mortality of 3.9% (3/77). Freedom from reintervention by cardiac catheterization or surgical intervention at 2 years was 36%. Functional and neurodevelopmental assessment for 69 of 71 survivors was completed at a mean age of 22.6 ± 4.0 months using the Bayley Scales of Infant and Toddler Development III. The mean neurodevelopmental outcome scores were 83.4 ± 16.5 for cognitive skills, 82.2 ± 18.7 for language skills, and 81.4 ± 18.1 for motor skills. Cognitive, language, and motor delay, defined as a score of <70, was identified in 25%, 25%, and 23% of patients, respectively. Multivariable analyses for factors associated with worse neurodevelopmental outcomes identified chromosomal anomalies (P < .001) and postoperative complications (P < .03). CONCLUSIONS: Cyanotic tetralogy of Fallot and pulmonary atresia with ventricular septal defect requiring neonatal repair showed similar 2-year neurodevelopmental outcomes below normative values and a high prevalence of cognitive, language and motor delays.

Percutaneous Treatment of Ascending Aortic Obstruction in a Young Child After Orthotopic Heart Transplantation.

We report a case of a 14-month-old child with ascending aortic obstruction (AAO) post cardiac transplantation, who underwent successful percutaneous ascending aortic stent angioplasty. Congenital or acquired AAO is typically treated with surgical augmentation. The experience with percutaneous techniques is limited and often avoided due to challenges with equipment stability and proximity to coronary arteries and aortic valve leaflets. This case highlights that a percutaneous approach to relief of AAO is a feasible alternative even in small children utilizing a newer pre-mounted stent.

A North American, single-center experience implanting fenestrated atrial devices and atrial flow regulators into a heterogeneous group of pediatric pulmonary hypertension patients.

Introduction: The clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation. Materials and Methods: We performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada. Results: Fourteen patients (eight female) with a median age of 4.6 (range 0.3-17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs. Conclusion: This work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.

Practice Patterns in the Management of Pressure Restrictive Perimembranous Ventricular Septal Defects: A Multinational Survey.

Indications for the closure of pressure restrictive perimembranous ventricular septal defects (pmVSD) are not well established in the pediatric population. We sought to assess practice variability among pediatric cardiologists in the United States (US), Canada, Australia, and New Zealand. A survey ascertaining practice patterns, including case vignettes with incremental progression of disease severity, was designed and administered through representative professional cardiac organizations and email listservs in the designated countries. Among the 299 respondents, 209 (70.0%) were from the US, 65 (21.7%) were from Canada and 25 (8.3%) were from Australia and New Zealand. Indications for pressure restrictive pmVSD closure included the presence of left ventricular (LV) dilation for 81.6% (244/299) (defined as z-score ≥ 2 for 59.0% (144/244) and ≥ 3 for 40.2% (98/244)) and significant pulmonary-systemic flow ratio (QP:QS) for 71.2% (213/299) [defined as ≥ 1.5:1 for 36.2% (77/213) and ≥ 2 for 62% (132/213)]. US pediatric cardiologists elected to close restrictive pmVSD at lower LV z-score and QP:QS ratio cut-offs (p-value 0.0002 and 0.013, respectively). In a case vignette, 63.6% (173/272) chose to intervene if there was right coronary cusp prolapse with stable mild aortic regurgitation. Of the remaining cardiologists, 93% (92/99) intervened if the aortic regurgitation was progressive (from trivial to mild). Commonly identified indications with variable thresholds for closure of pressure restrictive pmVSDs included the presence or progression of LV dilation, significant volume loading, and aortic valve prolapse with regurgitation. US pediatric cardiologists may have a lower threshold for pmVSD closure.

Occult Diastolic Dysfunction and Adverse Clinical Outcomes in Adolescents and Young Adults With Fontan Circulation.

Background In Fontan circulation, diastolic dysfunction portends a worse clinical outcome but may be concealed during routine assessment. Invasive evaluation with rapid volume expansion (RVE) can identify patients with occult diastolic dysfunction (ODD). We sought to evaluate the association between ODD and adverse clinical outcomes at medium-term follow-up. Methods and Results We conducted a single-center observational study of patients with Fontan circulation who underwent clinical catheterization with RVE from 2012 to 2017. ODD was defined as post-RVE end-diastolic pressure ≥15 mm Hg. A composite adverse clinical outcome included mortality, cardiac transplant, ventricular assist device, plastic bronchitis, protein-losing enteropathy, arrhythmia, stroke/thrombus, or cardiac-related hospital admission. Proportional hazards regression was used to compare the ODD-positive and ODD-negative groups for risk of the composite adverse clinical outcome. Eighty-nine patients with Fontan circulation (47% female patients) were included at a median age of 14 years. ODD was identified in 31%. Fontan duration was longer in the ODD group (P=0.001). The composite adverse clinical outcome occurred more frequently in the ODD group (52 versus 26%, P=0.03) during a median follow-up duration of 2.9 years after catheterization. ODD (hazard ratio [HR], 2.68 [95% CI, 1.28-5.66]; P=0.02) and Fontan duration (HR, 1.07 [95% CI, 1.02-1.12]; P=0.003) were associated with the composite adverse clinical outcome. When stratified by Fontan duration, ODD remained significantly associated with the hazard of adverse clinical outcomes in patients with a Fontan duration ≥10 years (HR, 2.57 [95% CI, 1.03-6.57]; P=0.04). Conclusions Cardiac catheterization with rapid volume expansion reveals a significant incidence of ODD, which relates to Fontan duration. ODD is associated with an increased hazard of adverse clinical outcomes during medium-term follow-up, especially in patients with longer Fontan duration. ODD may portend a worse prognosis in Fontan circulation.

Angiotensin-converting enzyme inhibition and pre-superior cavopulmonary connection haemodynamics in infants with single-ventricle physiology.

INTRODUCTION: Preliminary animal and human data suggest that angiotensin-converting enzyme inhibition has a role in pulmonary vascular remodelling. We sought to assess the effect of ACEi versus placebo on pulmonary artery pressure and transpulmonary gradient amongst infants undergoing single-ventricle palliation. MATERIALS AND METHODS: Using the publicly available Pediatric Heart Network Infant Single-Ventricle trial dataset, we compared mean PA pressure at pre-superior cavopulmonary connection catheterisation (primary outcome), transpulmonary gradient, pulmonary-to-systemic flow ratio, and post-SCPC oxygen saturation (secondary outcomes) in infants receiving enalapril versus placebo. RESULTS: A total of 179 infants underwent pre-SCPC catheterisation, of which 85 (47%) received enalapril. There was no difference between the enalapril and placebo group in the primary and the secondary outcomes. Mean PA pressure in the enalapril group was 13.1 ± 2.9 compared to 13.7 ± 3.4 mmHg in the placebo group. The transpulmonary gradient was 6.7 ± 2.5 versus 6.9 ± 3.2 mmHg in the enalapril and placebo groups, respectively. The pulmonary-to-systemic flow ratio was 1.1 ± 0.5 in the enalapril group versus 1.0 ± 0.5 in the placebo group and the post-SCPC saturation was 83.1 ± 5.0% in the enalapril group versus 82.2 ± 5.3% in the placebo group. In the pre-specified subgroup analyses comparing enalapril and placebo according to ventricular morphology and shunt type, there was no difference in the primary and secondary outcomes. CONCLUSION: ACEi did not impact mean pulmonary artery pressure or transpulmonary gradient amongst infants with single-ventricle physiology prior to SCPC palliation.

Myocardial fibrosis, diastolic dysfunction and elevated liver stiffness in the Fontan circulation.

INTRODUCTION: Single ventricle diastolic dysfunction and hepatic fibrosis are frequently observed in patients with a Fontan circulation. The relationship between adverse haemodynamics and end-organ fibrosis has not been investigated in adolescents and young adults with Fontan circulation. METHODS: Prospective observational study of Fontan patients who had a cardiac catheterisation. Cardiac MRI with T1 mapping was obtained to measure extracellular volume (ECV), a marker of myocardial fibrosis. Hepatic magnetic resonance elastography was performed to assess liver shear stiffness. Serum biomarkers of fibrosis including matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were measured. Very high ECV was defined as >30% and elevated serum biomarkers as >75th percentile for each biomarker. RESULTS: 25 Fontan patients (52% female) with mean age of 16.3±6.8 years were included. Mean ECV was 28%±5%. There was a significant correlation between ECV and systemic ventricular end-diastolic pressure (r=0.42, p=0.03) and between ECV and liver stiffness (r=0.45, p=0.05). Patients with elevated ECV demonstrated elevations in MMPs and TIMPs. Similarly, patients with elevated MMPs and TIMPs had greater liver stiffness compared with patients with normal levels of these biomarkers. CONCLUSIONS: In Fontan patients, cardiac magnetic resonance evidence of myocardial fibrosis is associated with diastolic dysfunction, increased liver stiffness and elevated circulating biomarkers of fibrosis. These findings suggest the presence of a profibrotic milieu, with end-organ implications, in some patients with Fontan circulation.

Life-threatening airway bleeding after palliation of single ventricle congenital heart disease.

OBJECTIVE: To describe acute and mid-term outcomes following presentation with, and treatment for, life-threatening airway bleeding (hemoptysis) in palliated single ventricle congenital heart disease (SV-CHD). METHODS: Case series of patients with SV-CHD who presented to a large congenital heart centre with hemoptysis between 2004 and 2015. RESULTS: Twenty-one episodes of hemoptysis occurred in 12 patients (58% female, median 10.5 (IQR 7.2, 16.4) years). First hemoptysis episode occurred after Fontan completion (n=8), after superior cavopulmonary anastomosis (SCPA, n=3) and in one shunt-dependent patient. Bronchoscopy was performed in conjunction with catheterisation in 14/21 (67%) initial catheterisations. A specific anatomic source of airway bleeding was identified in 95% of bronchoscopy cases and was uniformly distributed in all lobar segments. Transcatheter intervention with systemic-to-pulmonary collateral artery (SPC) occlusion was performed in 28/30 catheterisations. Apart from increased airway bleeding during interventional bronchoscopy (37%), there were no procedural complications. Median hospital length of stay was 9.0 (3.5, 14.5) days with patients undergoing 1.0 (1.0,2.0) catheterisations per episode of hemoptysis. Two SCPA patients did not survive to discharge. During a median follow-up of 32.5 (12.5, 87.5) months, freedom from mortality was 75%, with all three deaths occurring in the SCPA group by 4 months posthemoptysis. Recurrent hemoptysis occurred in 60% of patients. CONCLUSIONS: Despite the potentially life-threatening nature of hemoptysis in patients with SV-CHD, a policy of bronchoscopic evaluation and transcatheter treatment is safe and may contribute to low mortality at mid-term follow-up in Fontan patients. Hemoptysis in SCPA patients may portend a poor prognosis. Recurrent hemoptysis is common.

Diagnosis of occult diastolic dysfunction late after the Fontan procedure using a rapid volume expansion technique.

OBJECTIVES: Diastolic dysfunction (DD), a key driver of long-term Fontan outcomes, may be concealed during standard haemodynamic evaluation. We sought to identify Fontan patients with occult DD using 'ventricular stress testing' with rapid volume expansion (RVE). METHODS: Cardiac catheterisation with RVE was performed routinely in Fontan patients between 11/2012 and 4/2015. Baseline and post-stress haemodynamic data were compared using t test, Mann-Whitney U test, χ(2) and Fisher's exact tests. A post-stress ventricular end diastolic pressure (EDP) threshold of 15 mm Hg defined occult DD. RESULTS: Forty-six Fontan patients (48% female, median age 14.1 (IQR 9.1 to 21.3) years) were included. The median Fontan duration was 10.8 (IQR 5.1 to 17.8) years and dominant left ventricular morphology was present in 63% of patients. Volume expansion increased mean Fontan pressure (15.2±2.5 vs 12.4±2.2 mm Hg, p<0.001), pulmonary capillary wedge pressure (11.3±2.6 vs 7.9±2 mm Hg, p<0.001) and EDP (12.7±3.3 vs 8.5±2.1 mm Hg, p<0.001). Sixteen patients (35%) had occult DD, demonstrating higher baseline EDP (10.3±1.9 vs 7.6±1.5 mm Hg, p<0.001) and greater increase in EDP (6.3±2.4 vs 3.1±1.4 mm Hg, p<0.001) compared with patients without DD. Higher baseline EDP, lower baseline cardiac index and longer duration of Fontan circulation were associated with higher post-stress EDP. There were no complications related to RVE. CONCLUSIONS: Ventricular stress testing by RVE is feasible, safe and identifies a subgroup of Fontan patients with occult DD. Higher baseline EDP and longer duration of Fontan circulation are associated with worse diastolic function. Future work is necessary to better understand the aetiology, associations and clinical implications of occult DD in Fontan survivors.

Changes in Ventricular Geometry Predict Severity of Right Ventricular Hypertension.

Changes in ventricular geometry are often seen in patients with right ventricular hypertension secondary to pulmonary hypertension (PH). Progressive systolic bowing of the inter-ventricular septum occurs with increasing right ventricular pressure (RVp) and can be quantified with the left ventricular end-systolic eccentricity index (LVEI). Only limited data exist in children to evaluate the relationship between the LVEI and invasive RVp. We sought to assess the correlation between the LVEI and an invasively measured peak systolic RVp to aortic pressure (pAo) ratio. Medical records of patients undergoing echocardiography within 30 days of right and left heart catheterization for evaluation of PH between February 2009 and March 2014 were retrospectively reviewed. Forty-six studies in 29 subjects (median age 3.8 years, 46 % female), with a median time from echocardiogram to catheterization of -1.0 days, were included for analysis. The mean LVEI was 1.6 ± 0.5, and mean RVp/pAo ratio was 0.68 ± 0.26. There was a significant positive correlation (r = 0.76, p < 0.001) between LVEI and RVp/pAo ratio. ROC analysis demonstrated an area under the curve = 0.91 for prediction of RVp/pAo >0.50 by the LVEI. An LVEI >1.48 had a sensitivity of 76 % and specificity of 100 % in predicting RVp/pAo >0.50, while an LVEI >1.24 had a sensitivity of 88 % and specificity of 83 %. Echocardiographically derived LVEI is strongly correlated with invasively determined RVp/pAo ratio. In combination with other noninvasive measures of RVp, LVEI may help minimize the need for invasive patient evaluation.

Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output.

Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17 years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.87 ± 2.67 years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6 h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4 % (32.6 ± 2.1 to 25.2 ± 2.0 %, p < 0.001), rSO2 increased by 5.5 % (63.1 vs 68.6 %, p < 0.001), and serum lactate decreased by 0.9 mmol/l (3.3 vs 2.4 mmol/l, p < 0.001) with no change in HR (149.1 vs 145.6 bpm p = 0.07). Urine output increased 0.66 ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p = 0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions.

Anaphylactic shock after amiodarone infusion resulting in haemodynamic collapse requiring a temporary ventricular assist device.

Acute heart failure related to anaphylactic shock is often reversible and necessitates aggressive support to ensure full recovery. We report the case of a 15-year-old boy who developed severe ventricular dysfunction and haemodynamic instability after administration of amiodarone and required temporary mechanical circulatory support with a left ventricular assist device. He had full recovery of cardiac function and returned to baseline neurologic status. This is the first report of successful left ventricular assist device use for recovery from cardiovascular collapse due to anaphylaxis.

Postoperative assessment of laryngopharyngeal dysfunction in neonates after Norwood operation.

BACKGROUND: The purpose of this study was to evaluate the incidence of vocal cord (VC) and swallowing dysfunction in infants after the Norwood operation and to examine the relationship between laryngopharyngeal dysfunction and postoperative outcomes. METHODS: We conducted a retrospective review of 63 infants who underwent routine postoperative fiberoptic endoscopic evaluation of swallowing function and vocal cords after a Norwood operation at our institution during a recent 6-year period (2003-2009). RESULTS: The overall incidence of VC dysfunction after the Norwood operation was 58.7%. After a modification of the aortic arch dissection technique in 2007, the incidence of VC dysfunction decreased significantly from 79.5% in 2003 through 2006 to 25% in 2007 through 2009 (p<0.001). The incidence of swallowing dysfunction also decreased from 23.1% in 2003 through 2006 to 4.2% in 2007 through 2009 (p=0.07). Swallowing dysfunction was more common in patients with VC dysfunction (21.6%) as compared with patients without VC dysfunction (7.7%; p=0.18). Patients with VC dysfunction were more often discharged home on tube-only feeding regimens compared with infants without VC dysfunction (46% versus 26.9%). In infants with both VC and swallowing dysfunction, 75% were discharged exclusively to have tube feeding. Median hospital length of stay tended to be longer in infants with swallowing dysfunction (31 days) than in infants without swallowing dysfunction (23 days; p=0.16). CONCLUSIONS: Vocal cord and swallowing dysfunction are common in infants after the Norwood operation and may increase the need for tube feeding regimens. Modification of surgical techniques for dissection and mobilization of the aorta can significantly reduce the incidence of these adverse outcomes.