Achieving an Optimal Outcome After Stage 1 Palliation for Hypoplastic Left Heart Syndrome and Variants: Frequency, Associated Factors, and Subsequent Outcomes.

BACKGROUND: We sought to measure frequency of achieving an optimal outcome after stage 1 palliation (S1P) for hypoplastic left heart syndrome and variants, determine factors associated with optimal outcomes, and compare outcomes after stage 2 palliation (S2P) using the National Pediatric Cardiology Quality Improvement Collaborative database (2008-2016). METHODS AND RESULTS: This is a retrospective cohort study with optimal outcome defined a priori as meeting all of the following: (1) discharge after S1P in <19 days (top quartile), (2) no red flag or major event readmissions before S2P, and (3) performing S2P between 90 and 240 days of age. Optimal outcome was achieved in 256 of 2182 patients (11.7%). Frequency varied among centers from 0% to 25%. Factors independently associated with an optimal outcome after S1P were higher gestational age (odds ratio [OR], 1.1 per week [95% CI, 1.0-1.2]; P=0.02); absence of a genetic syndrome (OR, 2.5 [95% CI, 1.2-5]; P=0.02); not requiring a post-S1P catheterization (OR, 2.7 [95% CI, 1.5-4.8]; P=0.01), intervention (OR, 1.5 [95% CI, 1.1-2]; P=0.006), or a procedure (OR, 4.5 [95% CI, 2.8-7.1]; P<0.001) before discharge; and not having a post-S1P complication (OR, 2.7 [95% CI, 1.9-3.7]; P<0.001). Those with an optimal outcome after S1P had improved S2P outcomes including shorter length of stay, less ventilator days, shorter bypass time, and fewer postoperative complications. CONCLUSIONS: Identifying patients at lowest risk for poor outcomes during the home interstage period could shift necessary resources to those at higher risk, alter S2P postoperative expectations, and improve quality of life for families at lower risk.

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

Defining Expectations for Infants With Hypoplastic Left Heart Syndrome Who Survive Initial Surgical Palliation.

BACKGROUND: Overall one-year non-mortality outcomes for surgically palliated hypoplastic left heart syndrome (HLHS) patients remain understudied. Using the metric Days Alive and Outside of Hospital (DAOH), the present study sought to characterize expectations for surgically palliated patients' first year of life. METHODS: The Pediatric Health Information System database was used to identify by ICD-10 code all HLHS patients who underwent surgical palliation (Norwood/hybrid and/or heart transplantation [HTx]) during their index neonatal admission and were successfully discharged alive (n = 2227) and for whom one-year DAOH could be calculated. DAOH quartiles were used to group patients for analysis. RESULTS: Median one-year DAOH was 304 (interquartile range [IQR] 250-327), including a median index admission length of stay of 43 days (IQR 28-77). Patients required a median 2 (IQR 1-3) readmissions, each spanning 9 days (IQR 4-20). One-year readmission mortality or hospice discharge occurred in 6% of patients. Patients with lower-quartile DAOH had a median DAOH of 187 (IQR 124-226), whereas upper-quartile DAOH patients had a median DAOH of 335 (IQR 331-340) (P < .001). Readmission mortality/hospice-discharge rates were 14% and 1%, respectively (P < .01). On multivariable analysis, factors independently associated with lower-quartile DAOH included interstage hospitalization (odds ratio [OR] 44.78 [95% confidence interval [CI] 25.1-80.2]), index-admission HTx (8.73 [4.66-16.3]), preterm birth (1.97 [1.34-2.90]), chromosomal abnormality (1.85 [1.26-2.73]), age >7 days at surgery (1.50 [1.14-1.99]), and non-white race/ethnicity (1.33 [1.01-1.75]). CONCLUSIONS: In the current era, surgically palliated HLHS infants spend approximately 10 months alive and outside of the hospital, although outcomes are highly variable. Knowledge of the factors associated with lower DAOH can inform expectations and guide management decisions.

Altered white matter connectivity in children with congenital heart disease with single ventricle physiology.

Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6-11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Increasing Use of the Right Ventricle-to-Pulmonary Artery Shunt for Stage 1 Palliation.

BACKGROUND: Stage 1 palliation of hypoplastic left heart syndrome entails use of the Norwood operation with a modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt, or the hybrid procedure. Use trends and factors influencing palliation selection remain unclear. We aimed to evaluate these questions and to compare outcomes between types of stage 1 palliation. METHODS: The National Pediatric Cardiology Quality Improvement Collaborative phase 1 (June 2008-August 2016) and phase 2 (August 2016-September 2019) databases were used. Procedure type was assessed by operation year. Baseline characteristics and annual hospital volume were evaluated. Postsurgical admission duration and outcomes were compared. RESULTS: A total of 3497 patients were included, 30.8% with modified Blalock-Taussig shunt, 59.7% with right ventricle-to-pulmonary artery shunt, and 9.5% with hybrid. Use of the right ventricle-to-pulmonary artery shunt increased over time (P = .02). This increase was similar among all hospital volumes. Higher hospital volume (odds ratio [OR], 1.2; 95% CI, 1.1-1.4; P = .003), male sex (OR, 1.3; 95% CI, 1.1-1.6; P = .01), and isolated cardiac disease (OR, 1.33; 95% CI, 1.01-1.55; P = .05) were associated with relatively higher likelihoods of a modified Blalock-Taussig shunt. Mortality/transplant rates before stage 2 palliation were higher with the modified Blalock-Taussig shunt than with the right ventricle-to-pulmonary artery shunt (12.3% vs 9.6%, P = .03). CONCLUSIONS: In stage 1 palliation, use of right ventricle-to-pulmonary artery shunts has increased over time, use of modified Blalock-Taussig shunts has decreased, and use of hybrids was unchanged. The modified Blalock-Taussig shunt has a higher likelihood of use in higher-volume centers, males, and less complex patients but is associated with longer hospitalizations and lower transplant-free survival to stage 2 palliation.

Palliated Hypoplastic Left Heart Syndrome Patients Experience Superior Waitlist and Comparable Post-Heart Transplant Survival to Non-Single Ventricle Congenital Heart Disease Patients.

Congenital heart disease (CHD) is a well-established risk factor for inferior waitlist and post-heart transplant survival in children. Differences in outcomes between CHD subgroups are understudied. The present study compared outcomes for palliated hypoplastic left heart syndrome (HLHS) patients to other non-single ventricle CHD (non-SVCHD) and non-CHD patients. United Network for Organ Sharing was used to identify children (age < 18) listed for heart transplant in the United States between 2016 and 2021. CHD sub-diagnoses were only available for United Network for Organ Sharing status 1a after 2015, thereby defining the cohort. Waitlist outcomes were studied using competing-risk time-to-event analysis for transplantation, mortality/decompensation, and alive-on-waitlist. Multivariable Cox proportional hazards regression analyses were used to identify factors associated with inferior post-transplant survival. Patients included: palliated-HLHS (n = 477), non-SVCHD (n = 686), and non-CHD (n = 1261). At listing, Palliated-HLHS patients were older than non-SVCHD (median 2-year [IQR 0-8] vs median 0-year [0-3], respectively) and younger than non-CHD (median 7-year [0-14]) (P < 0.001 vs both), and were more likely to be white (P < 0.01 vs both). Upon time-to-event analysis, rates of waitlist mortality/decompensation rates were greater among non-SVCHD than palliated-HLHS. Post-transplant survival was comparable between palliated-HLHS and non-SVCHD (P = 0.920) but worse compared to non-CHD (P < 0.001). Both palliated-HLHS (HR 2.40 [95% CI 1.68-3.42]) and non-SVSCHD (2.04 [1.39-2.99]) were independently associated with post-transplant mortality. Palliated-HLHS patients with heart failure experience significantly worse post-transplant outcomes than non-CHD but, compared to other CHD patients, experience superior waitlist and comparable post-transplant survival. While a high-risk cohort, HLHS patients can achieve gratifying waitlist and post-transplant survival.

Optimizing Neurodevelopmental Outcomes in Neonates With Congenital Heart Disease.

Neurodevelopmental impairment is a common and important long-term morbidity among infants with congenital heart disease (CHD). More than half of those with complex CHD will demonstrate some form of neurodevelopmental, neurocognitive, and/or psychosocial dysfunction requiring specialized care and impacting long-term quality of life. Preventing brain injury and treating long-term neurologic sequelae in this high-risk clinical population is imperative for improving neurodevelopmental and psychosocial outcomes. Thus, cardiac neurodevelopmental care is now at the forefront of clinical and research efforts. Initial research primarily focused on neurocritical care and operative strategies to mitigate brain injury. As the field has evolved, investigations have shifted to understanding the prenatal, genetic, and environmental contributions to impaired neurodevelopment. This article summarizes the recent literature detailing the brain abnormalities affecting neurodevelopment in children with CHD, the impact of genetics on neurodevelopmental outcomes, and the best practices for neonatal neurocritical care, focusing on developmental care and parental support as new areas of importance. A framework is also provided for the infrastructure and resources needed to support CHD families across the continuum of care settings.

Pattern of head circumference growth following bidirectional Glenn in infants with single ventricle heart disease.

BACKGROUND: Infants with single ventricle congenital heart disease demonstrate increasing head growth after bidirectional Glenn; however, the expected growth trajectory has not been well described. AIMS: 1) We will describe the pattern of head circumference growth in the first year after bidirectional Glenn. 2) We will determine if head growth correlates with motor developmental outcomes approximately 12 months after bidirectional Glenn. METHODS: Sixty-nine single ventricle patients underwent bidirectional Glenn between 2010 and 2016. Patients with structural brain abnormalities, grade III-IV intra-ventricular haemorrhage, significant stroke, or obstructive hydrocephalus were excluded. Head circumference and body weight measurements from clinical encounters were evaluated. Motor development was measured with Psychomotor Developmental Index of the Bayley Scales of Infant Development, Third Edition. Generalised estimating equations assessed change in head circumference z-scores from baseline (time of bidirectional Glenn) to 12 months post-surgery. RESULTS: Mean age at bidirectional Glenn was 4.7 (2.3) months and mean head circumference z-score based on population-normed data was -1.13 (95% CI -1.63, -0.63). Head circumference z-score increased to 0.35 (95% CI -0.20, 0.90) (p < 0.0001) 12 months post-surgery. Accelerated head growth, defined as an increase in z-score of >1 from baseline to 12 months post-surgery, was present in 46/69 (66.7%) patients. There was no difference in motor Psychomotor Developmental Index scores between patients with and without accelerated head growth. CONCLUSION: Single ventricle patients demonstrated a significant increase in head circumference after bidirectional Glenn until 10-12 months post-surgery, at which time growth stabilised. Accelerated head growth did not predict sub-sequent motor developmental outcomes.

Norwood Procedure With Left Ventricle Exclusion in Complex Single Ventricle Patients: A Novel Technique.

BACKGROUND: Hypoplastic left heart disease and its variants complicated by severe semilunar and atrioventricular valve insufficiency are associated with a high mortality risk in utero and postnatally. Through the description of three cases, this report outlines the evolution of a successful strategy of morphological left ventricle isolation (ie, "left-sided Starnes") in caring for this rare cohort of patients with hypoplastic left heart syndrome (HLHS). METHODS: This study includes three patients: two patients prenatally diagnosed and one transferred from an outside hospital. All patients presented with complex univentricular heart disease with a nonfunctional left ventricle and severe left-sided atrioventricular and/or semilunar valve insufficiency. RESULTS: Two patients were delivered with an operating room on standby due to the possibility of emergent surgery being necessary; however, all patients were able to be medically stabilized after birth. Patient 1 underwent successful left ventricle exclusion with a fenestrated polytetrafluoroethylene (PTFE) patch, despite severe mitral valve regurgitation. Patient 2 reinforced the efficacy of PTFE patch occlusion in addition to having aortic valve closure with a small washing jet. Patient 3's clinical course was successfully predicted based on the previous patients and outlined for the family prenatally. All patients are currently growing well at home, awaiting Fontan with marked improvement in cardiac function. CONCLUSION: This rare cohort of patients with HLHS having severe left-sided atrioventricular and/or semilunar valve insufficiency appear to survive to birth and can be medically stabilized prior to semiurgent intervention. The Norwood procedure with left ventricle exclusion appears to be a successful strategy for these unique patients.

The Impact of Concomitant Left Ventricular Non-compaction with Congenital Heart Disease on Perioperative Outcomes.

Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent trabeculations and inter-trabecular recesses which may occur in association with congenital heart disease (CHD). To date, few studies have been performed to assess whether the concomitant diagnosis of LVNC affects the outcomes of CHD surgery. A retrospective review of patients with LVNC with CHD (LVNC-CHD), 0-5 years of age, was conducted. Patients with CHD without LVNC (CHD-only) and 0-5 years of age with similar diagnosis distribution were selected for comparison. Perioperative data, including CHD diagnosis, operative course, and postoperative complications were collected and compared between groups. LVNC-CHD was diagnosed in 26 children. Of the 26 with LVNC-CHD, 20 underwent surgery and these patients were compared with 276 CHD-only controls. Median total length of stay in the hospital was 12.5 days (IQR 5.5-63 days) in LVNC-CHD compared to 5 days (IQR 3-10 days) in CHD-only (p < 0.005). Postoperative death, cardiac arrest, or need for ECMO or transplantation occurred in 6/20 (30 %) of the LVNC-CHD patients compared to 3/276 (1 %) of the CHD-only group (p < 0.0001). LVNC-CHD patients had significantly longer hospital length of stay and higher perioperative complications compared to CHD-only patients without myocardial abnormalities. Pediatric cardiac care teams should be cognizant of the possibility of the increased perioperative risk associated with concomitant LVNC. Future prospective studies are warranted.

Diagnosis of congenital heart disease in an era of universal prenatal ultrasound screening in southwest Ohio.

OBJECTIVES: Diagnostic ultrasound is widespread in obstetric practice, yet many babies with major congenital heart disease remain undiagnosed. Factors affecting prenatal diagnosis of major congenital heart disease are not well understood. This study aims to document prenatal detection rates for major congenital heart disease in the Greater Cincinnati area, and identify factors associated with lack of prenatal diagnosis. METHODS: All living infants diagnosed with major congenital heart disease by 4 months of age at our centre were prospectively identified. Prenatal care data were obtained by parent interview. Neonatal records were reviewed for postnatal data. Obstetricians were contacted for diagnostic ultrasound data. RESULTS: A total of 100 infants met the inclusion criteria. In all, 95 infants were analysed, of whom 94 were offered diagnostic ultrasound. In all, 41 had a prenatal diagnosis of major congenital heart disease. The rate of prenatal detection varied by cardiac lesion, with aortic arch abnormalities, semilunar valve abnormalities, and venous anomalies going undetected in this sample. Among subjects without prenatal detection, the highest proportion consisted of those having Level 1 diagnostic ultrasound only (66%). Prenatal detection was not significantly influenced by maternal race, education level, income, or insurance type. CONCLUSIONS: Despite nearly universal diagnostic ultrasound, detection rates of major congenital heart disease remain low in southwest Ohio. An educational outreach programme including outflow tract sweeps for community-level obstetrical personnel may improve detection rates.