From Surgical to Total Transcatheter Stage I Palliation: Exploring Evidence and Perspectives.

Neonates with single ventricle physiology and ductal-dependent systemic circulation, such as those with hypoplastic left heart syndrome, undergo palliation in the first days of life. Over the past decades, variations on the traditional Stage 1 palliation, also known as Norwood operation, have emerged. These include the hybrid palliation and the total transcatheter approach. Here, we review the current evidence and data on different Stage 1 approaches, with a focus on their advantages, challenges, and future perspectives. Overall, although controversy remains regarding the superiority or inferiority of one approach to another, outcomes after the Norwood and the hybrid palliation have improved over time. However, both procedures still represent high-risk approaches that entail exposure to sternotomy, surgery, and potential cardiopulmonary bypass. The total transcatheter Stage 1 palliation spares patients the surgical and cardiopulmonary bypass insults and has proven to be an effective strategy to bridge even high-risk infants to a later palliative surgery, complete repair, or transplant. As the most recently proposed approach, data are still limited but promising. Future studies will be needed to better define the advantages, challenges, outcomes, and overall potential of this novel approach.

Short and Mid-term Outcomes of Ductal Graft with Bilateral Pulmonary Banding in Hypoplastic Left Heart Syndrome and Variants.

This study evaluates a novel surgical technique inspired by the hybrid Norwood procedure, which involves ductal graft placement and bilateral pulmonary artery banding. This technique is designed to avoid the high-risk classical Norwood stage 1 operation and to avoid the need for first stage invasive catheter interventions and interstage catheter interventions when ductal stent placement is not feasible in developing countries with limited resources. Between June 2015 and December 2022, 14 patients with hypoplastic left heart syndrome and variants were treated using this procedure at our center. Polytetrafluoroethylene graft was used for ductal graft procedure and polytetrafluoroethylene bands were used for bilateral pulmonary banding. Atrial septectomy was done selectively. Patients with adequate left heart growth underwent biventricular repair and pulmonary debanding. Patients without left heart growth underwent cavopulmonary anastomosis or necessary intermediate surgical revisions. Seven patients out of 14 reached the second stage. Two received biventricular repair, three underwent bidirectional cavopulmonary anastomosis, and two required repeat palliations other than bidirectional cavopulmonary anastomosis. Modifications of the Norwood procedure is an ongoing process due to the complex nature of hypoplastic left heart syndrome and variants. As experience grows, the mortality associated with ductal graft and bilateral pulmonary banding procedure may decrease, making this technique an alternative for centers where classical Norwood operation or hybrid palliation is not possible, especially in developing countries with limited resources. We might predict promising outcomes, especially for patients with hypoplastic left heart complex where biventricular repair is expected.

Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Impact of calorie intake and weight gain after Norwood procedure on the outcome of stage II palliation.

BACKGROUND: This study aimed to assess the impact of caloric intake and weight-for-age-Z-score after the Norwood procedure on the outcome of bidirectional cavopulmonary shunt. METHODS: A total of 153 neonates who underwent the Norwood procedure between 2012 and 2020 were surveyed. Postoperative daily caloric intake and weight-for-age-Z-score up to five months were calculated, and their impact on outcome after bidirectional cavopulmonary shunt was analysed. RESULTS: Median age and weight at the Norwood procedure were 9 days and 3.2 kg, respectively. Modified Blalock-Taussig shunt was used in 95 patients and right ventricle to pulmonary artery conduit in 58. Postoperatively, total caloric intake gradually increased, whereas weight-for-age-Z-score constantly decreased. Early and inter-stage mortality before stage II correlated with low caloric intake. Older age (p = 0.023) at Norwood, lower weight (p < 0.001) at Norwood, and longer intubation (p = 0.004) were correlated with low weight-for-age-Z-score (< -3.0) at 2 months of age. Patients with weight-for-age-Z-score < -3.0 at 2 months of age had lower survival after stage II compared to those with weight-for-age-Z-score of -3.0 or more (85.3 versus 92.9% at 3 years after stage II, p = 0.017). There was no difference between inter-stage weight gain and survival after bidirectional cavopulmonary shunt between the shunt types. CONCLUSION: Weight-for-age-Z-score decreased continuously throughout the first 5 months after the Norwood procedure. Age and weight at Norwood and intubation time were associated with weight gain. Inter-stage low weight gain (Z-score < -3) was a risk for survival after stage II.

Preterm Birth Is Associated With Adverse Cardiac Remodeling and Worse Outcomes in Patients With a Functional Single Right Ventricle.

OBJECTIVE: To assess the effects of preterm birth on cardiac structure and function and transplant-free survival in patients with hypoplastic left heart syndrome and associated anomalies throughout the staged palliation process. STUDY DESIGN: Data from the Single Ventricle Reconstruction trial were used to assess the impact of prematurity on echocardiographic measures at birth, Norwood, Stage II, and 14 months in 549 patients with a single functional right ventricle. Medical history was recorded once a year using medical records or telephone interviews. Cox regression models were applied to analyze transplant-free survival to age 6 years. Causal mediation analysis was performed to estimate the mediating effect of birth weight within this relationship. RESULTS: Of the 549 participants, 64 (11.7%) were born preterm. Preterm-born participants had lower indexed right ventricle end-diastolic volumes at birth but higher volumes than term-born participants by age 14 months. Preterm-born participants had an increased risk of death or heart transplantation from birth to age 6 years, with an almost linear increase in the observed risk as gestational age decreased below 37 weeks. Of the total effect of preterm birth on transplant-free survival, 27.3% (95% CI 2.5-59.0%) was mediated through birth weight. CONCLUSIONS: Preterm birth is associated with adverse right ventricle remodeling and worse transplant-free survival throughout the palliation process, in part independently of low birth weight. Further investigation into this vulnerable group may allow development of strategies that mitigate the impact of prematurity on outcomes in patients with hypoplastic left heart syndrome.

A word of caution: Early failure of Magmaris® bioresorbable stent after pulmonary artery stenting.

Bioresorbable scaffolds (BRS) have been advocated as the fourth revolution in interventional cardiology medical devices with promising technology to improve the treatment of coronary artery disease with an event-free future. We describe the first reported use and early collapse of the Magmaris® Resorbable Magnesium Scaffold (RMS) stent (BIOTRONIK AG, Switzerland) to relieve left pulmonary artery severe stenosis in a newborn after the Norwood procedure. The stent collapse was detected 2 weeks after implantation and urgently treated with a balloon-expandable stent. This complication raises the alarm about the need to keep implanted RMS under scrutiny. The possibility of faster scaffold resorption in small babies or lack of sufficient radial force of RMS to resist acute vessel recoil has led to ineffective relief of branch pulmonary artery stenosis and failure to enable a safe short-term bridge to Stage II palliation.

Fluid Overload and AKI After the Norwood Operation: The Correlation and Characterization of Routine Clinical Markers.

The purpose of this study was to determine the correlation of different methods of assessing fluid overload and determine which metrics are associated with development of acute kidney injury (AKI) in the period immediately following Norwood palliation. This was a retrospective single-center study of Norwood patients from January 2011 through January 2021. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO). Patients were separated into two groups: those with AKI and those without. A logistic regression analysis was conducted with AKI at any point in the study period as the dependent variable and clinical and laboratory data as independent variables. Analysis was conducted as a stepwise regression. The coefficients from the logistic regression were then used to develop a cumulative AKI risk score. Spearman correlations were conducted to analyze the correlation of fluid markers. 116 patients were included, and 49 (42.4%) developed AKI. The duration of open chest, duration of mechanical ventilation, need for dialysis, need for extracorporeal membrane oxygenation, and inpatient mortality were associated with AKI (p ≤ 0.05). Stepwise logistic regression demonstrated the following significant independent associations AKI: age at Norwood in days (p < 0.01), blood urea nitrogen (p < 0.01), central venous pressure (p = 0.04), and renal oxygen extraction ratio (p < 0.01). The area under the receiver operating characteristic curve for the logistic regression was 0.74. The fluid markers had weak R-value. Urea, central venous pressure, and renal oxygen extraction ratio are associated with AKI after the Norwood operation. Common clinical metrics used to assess fluid overload are poorly correlated with each other for postoperative Norwood patients.

Norwood Operation with Right Ventricular-Pulmonary Artery Shunt Versus Comprehensive Stage II After Bilateral Pulmonary Artery Banding Palliation.

As a strategy for the primary Norwood operation, the right ventricular-pulmonary artery shunt is associated with satisfactory early outcome. However, use of this shunt after bilateral pulmonary artery banding remains controversial. This study compared the operative outcomes and late hemodynamics in patients who underwent the Norwood operation, preceded by bilateral pulmonary artery banding, with a right ventricular-pulmonary artery shunt or with bidirectional Glenn anastomosis (comprehensive stage II strategy). We retrospectively reviewed 38 patients who underwent the Norwood operation preceded by bilateral pulmonary artery banding between 2004 and 2017. Of these, 17 underwent the Norwood operation with a right ventricular-pulmonary artery shunt (Group S), whereas 21 underwent the comprehensive stage II strategy (Group G). 5 years after the Norwood operation, 10 (60%) and 17 (81%) patients in Group S and Group G, respectively, underwent the Fontan procedure. Group S showed significantly lower pressure in the superior vena cava after bidirectional Glenn anastomosis than Group G (13 ± 2 mmHg vs. 18 ± 3 mmHg; p < 0.01), but pressures were similar after the Fontan procedure. The right ventricular end-diastolic volume at 1 year post-Fontan procedure was significantly higher in Group S than in Group G (142 ± 41% vs. 91 ± 28%; p < 0.01). In terms of early outcomes, the Norwood operation with a right ventricular-pulmonary artery shunt enabled low pressure in the superior vena cava, but in the long term, this shunt adversely influenced the right ventricular volume.

Pre-Glenn aorto-pulmonary collaterals in single-ventricle patients.

BACKGROUND: In single-ventricle patients undergoing staged-bidirectional Glenn, 36-59% have aorto-pulmonary collateral flow, but risk factors and clinical outcomes are unknown. We hypothesise that shunt type and catheter haemodynamics may predict pre-bidirectional Glenn aorto-pulmonary collateral burden, which may predict death/transplantation, pulmonary artery or aorto-pulmonary collateral intervention. METHODS: Retrospective cohort study of patients undergoing a Norwood procedure for single-ventricle anatomy. Covariates included clinical and haemodynamic characteristics up to/including pre-bidirectional Glenn catheterisation and aorto-pulmonary collateral burden at pre-bidirectional Glenn catheterisation. Multivariable models used to evaluate relationships between risk factors and outcomes. RESULTS: From January 2011 to March 2016, 104 patients underwent Norwood intervention. Male sex (odds ratio 3.36, 95% confidence interval 1.17-11.4), age at pre-bidirectional Glenn assessment (2.12, 1.33-3.39 per month), and pulmonary to systemic flow ratio (1.23, 1.08-1.41 per 0.1 unit) were associated with aorto-pulmonary collateral burden. Aorto-pulmonary collateral burden was not associated with death/transplantation (hazard ratio 1.19, 95% confidence interval 0.37-3.85), pulmonary artery (sub-hazard ratio 1.38, 0.32-2.61), or aorto-pulmonary collateral interventions (sub-hazard ratio 1.11, 0.21-5.76). Longer post-Norwood length of stay was associated with greater risk of death/transplantation (hazard ratio 1.22 per week, 95% confidence interval 1.08-1.38), but lower risk of aorto-pulmonary collateral intervention (sub-hazard ratio 0.86 per week, 95% confidence interval 0.75-0.98). Time to pre-bidirectional Glenn catheterisation was associated with lower risk of pulmonary artery (sub-hazard ratio 0.80 per month, 95% confidence interval 0.65-0.98) and aorto-pulmonary collateral intervention (sub-hazard ratio 0.79, 0.63-0.99). Probability of moderate/severe aorto-pulmonary collateral burden increased with left-to-right shunt (22.5% at <1.0, 57.6% at >1.4) and the age at pre-bidirectional Glenn catheterisation (10.6% at <2 months, 56.9% at >5 months). CONCLUSIONS: Aorto-pulmonary collateral burden is common after Norwood procedure and increases as age at bidirectional Glenn increases. As expected, higher pulmonary to systemic flow ratio is a marker for greater aorto-pulmonary collateral burden pre-bi-directional Glenn; aorto-pulmonary collateral burden does not confer risk of death/transplantation or pulmonary artery intervention.

Milrinone for treatment of elevated lactate in the pre-operative newborn with hypoplastic left heart syndrome.

BACKGROUND: There is a paucity of information reported regarding the use of milrinone in patients with hypoplastic left heart syndrome prior to the Norwood procedure. At our institution, milrinone is initiated in the pre-operative setting when over-circulation and elevated serum lactate levels develop. We aimed to review the responses associated with the administration of milrinone in the pre-operative hypoplastic left heart syndrome patient. Second, we compared patients who received high- versus low-dose milrinone prior to Norwood procedure. METHODS: Single-centre retrospective study of patients diagnosed with hypoplastic left heart syndrome between January 2000 and December 2019 who underwent Norwood procedure. Patient characteristics and outcomes were compared. RESULTS: During the study period, 375 patients were identified; 79 (21%) received milrinone prior to the Norwood procedure with median lactate 2.55 mmol/l, and SpO2 93%. Patients who received milrinone were older at the time of Norwood procedure (6 vs. 5 days) and were more likely to be intubated and sedated. In a subset analysis stratifying patients to low- versus high-dose milrinone, median lactate decreased from time of initiation (2.39 vs 2.75 to 1.6 vs 1.8 mmol/l) at 12 hours post-initiation, respectively. Repeated measures analysis showed a significant decrease in lactate levels by 4 hours following initiation of milrinone, that persisted over time, with no significant difference in mean arterial pressure. CONCLUSIONS: The use of milrinone in the pre-operative over-circulated hypoplastic left heart syndrome patient is well tolerated, is associated with decreased lactate levels, and was not associated with significant hypotension or worsening of excess pulmonary blood flow.

Outcomes After Stage I Norwood Palliation in a Recently Established Program Can Achieve Results Similar to Longer Established Services.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) or similar single ventricle cardiac lesions require a three-stage surgical approach, the first step being the Stage I Norwood procedure. The Queensland Children's Hospital (QCH) in Australia is a tertiary hospital providing the only cardiac surgical service to children in Queensland and northern New South Wales. OBJECTIVE: To review the centre's outcomes of Norwood procedures performed in the last 6 years. MATERIALS AND METHODS: We retrospectively evaluated all infants undergoing the stage I Norwood procedure between January 2015 and August 2021. Mortality, intensive care length of stay, events of cardiac arrest following surgery and duration of mechanical ventilation were calculated and analysed for subgroups depending on type of pulmonary shunt type (right-ventricle-to-pulmonary-artery shunt [RVPAS] vs the modified Blalock-Taussig shunt [MBTS]). RESULTS: Forty-nine (49) patients were included. Overall survival to stage two operation (Glenn) was 90%. Both shunts were used evenly with the RVPA conduit preferred for HLHS and the MBTS largely chosen for hypoplastic left heart variants. In univariable analysis there was no difference in cardiac arrest or mortality rate for the patient with a RVPAS compared to the patient with a MBTS. CONCLUSION: We show that a recently established Norwood program can achieve results that are comparable to those reported by longer established centres, and the international literature.

[Early and long-term results after the Norwood procedure]. / Rannie i otdalennye rezul'taty posle protsedury Norvud.

OBJECTIVE: To assess the early and long-term results after the Norwood procedure and to identify predictors of aortic recoarctation and arterial hypertension. MATERIAL AND METHODS: We have operated on 2789 infants in the department of congenital heart diseases of the Meshalkin National Medical Research Center between January 2015 and December 2018. The current single-center prospective cohort study included 39 (1.4%) patients with hypoplastic left heart syndrome who underwent the Norwood procedure. RESULTS: In-hospital mortality was 15.3% (n=6). An inter-stage mortality was 10.2% (n=4). Recoarctation of the aorta and Sano shunt stenosis in inter-stage period occurred in 8 (24.2%) and 4 patients (12.1%), respectively. Body mass <3 kg was the only risk factor of recoarctation (OR 7.08, 95% CI 1.17; 42.79, p=0.033). We found no risk factors of Sano shunt stenosis. There were no signs of recoarctation and Sano shunt dysfunction in the early postoperative period. Arterial hypertension developed in 14 (48.3%) patients. We found the correlation between systolic blood pressure and ventricular ejection fraction (ß coefficient -0.88, 95% CI -1.33; -0.44, p=0.001). The only risk factor of arterial hypertension was increased stiffness of the aorta. CONCLUSION: The early and inter-stage mortality are still the issues after the Norwood procedure. Postoperative reduced ejection fraction of single ventricle is one of the most common complications that could be related with residual arterial hypertension.

Role of gated cardiac computed tomographic angiography in the evaluation of postsurgical complications after stage I Norwood procedure and its implications on management: a comparative study with two-dimensional echocardiography.

BACKGROUND: The Norwood procedure is the first part of a three-stage surgical palliation for patients with functionally single ventricle anatomy. Complications after the stage I operation are not uncommon. Transthoracic echocardiography (TTE) is traditionally the mainstay for evaluation. OBJECTIVE: The purpose of our study is to compare gated cardiac computed tomographic angiography (CCTA) with TTE when evaluating for postoperative complications after stage I Norwood procedure and to describe management implications. MATERIALS AND METHODS: A retrospective chart review of all patients over a 4-year period who underwent nonelective urgent CCTA for suspected complications related to stage I Norwood procedure was performed. Elective CCTA studies before stage II palliation were excluded. Patient demographics, CCTA and TTE findings, as well as interventions performed, were recorded. RESULTS: Thirty-four patients were included. The mean age at CCTA was 63 days (range: 4-210 days). All patients had a recent TTE with a mean time interval between TTE and CCTA of 2 days. CCTA detected 56 abnormalities in 30 patients, with 23 directly related to postsurgical complications, including shunt-related complications (10/23, 43%), Damus-Kaye-Stansel anastomotic narrowing (2/23, 9%) and neo-aortic arch/branch vessel abnormalities (11/23, 48%). These complications were managed as follows: surgery (9, 39%), catheter-based intervention (7, 30%), medical (4, 17%) and no change in management (3, 13%). TTE did not detect 8/23 (35%) findings found on CCTA, of which 75% were either managed with surgery (4/8, 50%) or catheter-based intervention (2/8, 25%). CONCLUSION: CCTA plays an important role in detecting surgical complications after stage I Norwood procedure and demonstrates additional findings that have direct management implications.

A milestone in congenital cardiac surgery: Four decades of the Norwood procedure.

Hypoplastic left heart syndrome (HLHS) was first described by Lev in 1952, but it was not until 1958 that it received a name from Noonan and Nadas. For the next several decades, the defect was considered untreatable. In 1979, William Norwood and his colleagues from Boston initiated a program to evaluate staged surgical management for infants with HLHS. The Norwood operation has became a milestone in the effective palliation for neonates born with HLHS. Today, the Norwood procedure is the first step of a three-stage heart surgery aimed at creating a new circulatory pathway (i.e., the Fontan pathway).

Standardisation of management after Norwood operation has not improved 1-year outcomes.

INTRODUCTION: Treatment of hypoplastic left heart syndrome varies across institutions. This study examined the impact of introducing a standardised programme. METHODS: This retrospective cohort study evaluated the effects of a comprehensive strategy on 1-year transplant-free survival with preserved ventricular and atrioventricular valve (AVV) function following a Norwood operation. This strategy included standardised operative and perioperative management and dedicated interstage monitoring. The post-implementation cohort (C2) was compared to historic controls (C1). Outcomes were assessed using logistic regression and Kaplan-Meier analysis. RESULTS: The study included 105 patients, 76 in C1 and 29 in C2. Groups had similar baseline characteristics, including percentage with preserved ventricular (96% C1 versus 100% C2, p = 0.28) and AVV function (97% C1 versus 93% C2, p = 0.31). Perioperatively, C2 had higher indexed oxygen delivery (348 ± 67 ml/minute/m2 C1 versus 402 ± 102ml/minute/m2 C2, p = 0.015) and lower renal injury (47% C1 versus 3% C2, p = 0.004). The primary outcome was similar in both groups (49% C1 and 52% C2, p = 0.78), with comparable rates of death and transplantation (36% C1 versus 38% C2, p = 0.89) and ventricular (2% C1 versus 0% C2, p = 0.53) and AVV dysfunction (11% C1 versus 11% C2, p = 0.96) at 1-year. When accounting for cohort and 100-day freedom from hospitalisation, female gender (OR 3.7, p = 0.01) increased and ventricular dysfunction (OR 0.21, p = 0.02) and CPR (OR 0.11, p = 0.002) or ECMO use (OR 0.15, p = 001) decreased the likelihood of 1-year transplant-free survival. CONCLUSIONS: Standardised perioperative management was not associated with improved 1-year transplant-free survival. Post-operative ventricular or AVV dysfunction was the strongest predictor of 1-year mortality.

Incidence and impact of acute kidney injury in patients with hypoplastic left heart syndrome following the hybrid stage 1 palliation.

OBJECTIVE: Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality. METHODS: A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed. RESULTS: The incidence of acute kidney injury is 13.4-20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047). DISCUSSION: The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.

Update on stem cell technologies in congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) continues to be among the most common birth defects, affecting an estimated 40 000 births annually in the United States. The most common complication of CHD is heart failure. With improved medical management and surgical outcomes, survival for complex congenital heart defects has dramatically improved, but consequentially there are more adults with CHD than children with CHD. Due to longer-term sequelae of CHD, surgical and medical treatment previously thought to be curative is now realized at best to be palliative, and there is a considerable burden of CHD-related heart failure. Stem cell therapy as an adjunct to current surgical and medical strategies is being explored in an effort to ameliorate CHD-related heart failure. This review aims to explore the current literature with regard to stem cell therapy for CHD as well as ongoing trials. METHODS: A MEDLINE (Ovid), MEDLINE (Pubmed), and clinicaltrials.gov search were performed using the medical subject headings congenital heart defects combined with hematopoietic stem cells, stem cell transplantation, mesenchymal stem cells (MSC), cell- or tissue-based therapy, or MSC transplantation. Articles must have been published after 2010. RESULTS: Twenty three articles and 9 ongoing trials met all inclusion criteria. CONCLUSIONS: Areas of interest include myocardiocyte regeneration, tissue graft development to minimize reoperations, and methods of stem cell delivery. While several small trials are showing promise, it is too soon to make definitive statements about the future of stem cell therapies in this field.

Transplant-Free Survival and Interventions at 6 Years in the SVR Trial.

BACKGROUND: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. METHODS: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. RESULTS: Transplant-free survival for the RVPAS versus modified Blalock-Taussig shunt groups did not differ at 6 years (64% versus 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS versus modified Blalock-Taussig shunt treatment effect had nonproportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48-0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86-2.17; P=0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33-1.74; P=0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P<0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00-3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures. CONCLUSIONS: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock-Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Evaluating the utility of routine screening catheterisation before interstage discharge of infants with single-ventricle physiology.

INTRODUCTION: Interstage mortality causes are often unknown in infants with shunt-dependent univentricular defects. For 2 years, screening catheterisation was encouraged before neonatal discharge to determine if routine evaluation improved interstage outcomes. METHODS: Retrospective single-centre review of home monitoring programme from December, 2010 to June, 2012. Composite scores were created for physical examination/echocardiography risk factors; catheterisation risk factors; and interstage adverse events. Composite scores were compared between usual care and screening catheterisation groups. The ability of each risk factor composite to predict interstage adverse events, individually and in combination, was assessed with sensitivity, specificity, and receiver operating characteristic curves. RESULTS: There were 27 usual care and 32 screening catheterisation patients. There were no significant differences between groups except rates of catheterisation before discharge (29.6 versus 100%, p < 0.001). Usual care patients who underwent catheterisation for clinical indications had higher intervention rates (37.5 versus 3.1%, p = 0.004). Physical examination/echocardiography risk factor frequency was similar, but usual care patients with catheterisation had a higher catheterisation risk factor frequency. Interstage adverse event frequency was similar (48.2 versus 53.1%, p = 0.7). For interstage adverse event prediction, sensitivity for the physical examination/echocardiography, catheterisation, and either risk factor composites was 53.3, 72, and 80%, respectively; specificity was 59, 60, and 48%. The area under the receiver operating characteristic curve was 0.56, 0.66, and 0.64. CONCLUSION: Screening catheterisation evaluation offered slightly increased sensitivity and specificity, but no difference in interstage adverse event frequency. Given this small advantage versus known risks, screening catheterisations are no longer encouraged.

Dead space fractions in neonates following first-stage palliation for hypoplastic left heart syndrome.

PURPOSE: (1) To characterise changes in dead space fraction during the first 120 post-operative hours in neonates undergoing stage 1 palliation for hypoplastic left heart syndrome, including hybrid procedure; (2) to document whether dead space fraction varied by shunt type (Blalock-Taussig shunt and Sano) and hybrid procedure; and (3) to determine the association between dead space fraction and outcomes. METHODS: Retrospective chart review in neonates undergoing stage 1 palliation for hypoplastic left heart syndrome in a cardiac intensive care unit over a consecutive 30-month period. A linear mixed model was used to determine the differences in dead space over time. Multivariable linear regression and a multivariable linear mixed model were used to assess the association between dead space and outcomes at different time points and over time, respectively. RESULTS: Thirty-four neonates received either a Blalock-Taussig shunt (20.5%), Sano shunt (59%), or hybrid procedure (20.5%). Hospital mortality was 8.8%. Dead space fractions in patients undergoing the hybrid procedure were significantly lower on day 1 (p = 0.01) and day 2 (p = 0.02) and increased over time. A dead space fraction >0.6 on post-operative days 3-5 was significantly associated with decreased duration of mechanical ventilation in all surgical groups (p 0.6 on post-operative days 3-5 was associated with lower duration of mechanical ventilation in all surgical groups. A more comprehensive, prospective assessment of dead space in this delicate patient population would likely be beneficial in improving outcomes.