Ectopia cordis coexisting with hypoplastic left heart structures.

Herein we present the fatal case of premature baby with coincidence of extreme form of ectopia cordis and hypoplastic left heart structures.

Hybrid stage 1 Norwood combined with reverse Blalock-Taussig shunt and sutureless repair of total anomalous pulmonary venous connections.

The patient is a 35-week-old, 2.6-kg neonate who was diagnosed prenatally with hypoplastic left heart syndrome and a supracardiac variant of total anomalous pulmonary venous connection. We present the technique of stage 1 hybrid palliation combined with repair of total anomalous pulmonary venous connection. Due to the risk of retrograde aortic arch obstruction from the ductal stents, a reverse Blalock-Taussig shunt was performed as well.

The impact of specialty training and physician attitudes on fetal cardiac counseling.

OBJECTIVE: Fetal cardiac anomalies are the most commonly diagnosed structural anomalies. In these cases, Maternal-Fetal Medicine (MFM) specialists are tasked with counseling patients on a spectrum of diagnoses as well as their prognostic implications. A recent study of pediatric cardiologists demonstrated that personal beliefs regarding termination impact the counseling provided to patients. Our objective was to study whether the personal beliefs of MFMs impact counseling of patients with severe fetal cardiac anomalies and to compare these providers to their cardiology counterparts. METHODS: We conducted an anonymous cross-sectional survey of MFMs in New England that assessed personal beliefs and counseling practices when diagnosing hypoplastic left heart syndrome (HLHS). We subsequently compared these providers to the previously surveyed cardiologists. RESULTS: A total of 34 respondents representing a broad spectrum of age and experience across several states in New England were analyzed. When presented with the statement "some life is always better than no life at all," 79% (n = 27) of respondents disagreed and all respondents (n = 34) offered termination, palliative care, and treatment options when counseling patients with HLHS. Additionally, while 74% (n = 25) of providers would personally support a decision to terminate a pregnancy with HLHS, 94% (n = 32) would professionally support the decision to pursue termination.MFMs and cardiologists differed in their responses to "some life is better than no life" and the belief that termination should be offered, though differences did not reach statistical significance. However, with respect to the providers' personal and professional support of the decision to terminate the pregnancy, the groups of respondents varied significantly in their level of support, both professionally and personally with fewer cardiologists supporting this decision. CONCLUSION: When diagnosing a severe and potentially fatal congenital cardiac anomaly, counseling by MFMs was largely unaffected by personal beliefs regarding termination of pregnancy. While this is consistent with previously published data on counseling practices among pediatric cardiology specialists, some important differences between the specialties were seen.

Common atrial reservoir strain during the interstage period is a predictor of poor outcomes prior to Fontan completion in hypoplastic left heart syndrome.

BACKGROUND: The atrium augments ventricular function, but the significance of atrial function in hypoplastic left heart syndrome (HLHS) has not been well evaluated. OBJECTIVE: We investigated the association of atrial reservoir strain (common atrial strain [CAS]) to death or need for transplantation in patients with HLHS. METHODS: In this retrospective single-center study, echocardiograms from three timepoints (pre-stage 1 palliation [S1P], 4-8 weeks post-S1P, and pre-Glenn) were analyzed in infants with classic HLHS. Patients were separated based on transplant-free survival to Fontan (survivors) versus death or heart transplant prior to Fontan (composite outcome). Echocardiographic parameters evaluated included CAS, right ventricle (RV) global longitudinal strain (RVGLS), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE). An equal variance t-test, regression, and receiver operating characteristic (ROC) analyses were performed. RESULTS: A total of 45 HLHS patients (25 survivors, 20 patients meeting endpoint) were included in this study. There were no significant differences in any of the functional parameters during the pre-stage 1 or post-stage 1 timepoints. Pre-Glenn CAS and RVGLS were significantly worse in those meeting composite endpoint compared to survivors. CAS was significantly correlated to RVGLS during the pre-S1P and pre-Glenn timepoints. A pre-Glenn CAS < 19.5 had an area under the curve of  .78 and a 75% sensitivity and 83% specificity for death or need for transplantation. CONCLUSION: Pre-Glenn CAS is significantly lower in patients with mortality or need for the transplantation prior to Fontan completion and may carry prognostic significance in patients with HLHS.

Hybrid palliation to promote growth of left ventricle and left ventricular outflow tract.

OBJECTIVES: In patients with borderline left hearts or a severe left ventricular outflow tract obstruction, hybrid palliation can be used to stabilize the patient and postpone biventricular repair (BVR). In this study, we analysed growth of left-sided structures and outcomes of these patients. METHODS: We conducted a retrospective cohort study including patients who received hybrid palliation between January 2010 and September 2023. Echo measurements were collected at hybrid palliation, BVR and last follow-up. Growth of left ventricular structures were analysed. RESULTS: In 38 patients, hybrid palliation was used to promote growth of left ventricular structures. In total, 15 patients received a Ross-Konno/Yasui procedure, while 23 patients received conventional BVR. In patients with a conventional BVR, a significant increase was found in left ventricular volume indexed by body surface area, Z-score of aortic valve and left ventricular outflow tract between hybrid palliation and BVR. Mitral valve Z-score did not increase significantly. After BVR until follow-up, only increase of the aortic valve Z-scores and left ventricular volume indexed by body surface area was found significant. Of all included patients (n = 38), additional surgical procedures were necessary in 8 patients during the interstage period and 15 patients after BVR. Additional catheter interventions were needed in 14 patients in the interstage period and 15 after BVR. Six patients died, with no mortality in the conventional BVR group. CONCLUSIONS: Hybrid palliation as part of a staged BVR is a safe and effective initial step and promotes the growth of left ventricular structures in patients with small left-sided heart structures. Close follow-up is mandatory because extra catheter or surgical interventions are frequently needed.

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.

Contemporary management of borderline left ventricle.

Borderline left ventricle cases present considerable difficulties in determining the most effective surgical approaches. The evolution of approaches in the field has shifted from classical systemic pulmonary shunts to orthodox univentricular palliation and has subsequently seen the emergence of biventricular repair concepts. The concept of biventricular repair for borderline left heart conditions has developed through studies that aim to establish predictive scoring systems for identifying appropriate candidates. Despite continuous efforts, a definitive scoring system for guiding this decision is still difficult to find. There is a growing trend to provide neonatal patients with borderline ventricles with options other than univentricular palliation. Several centres have developed personalized strategies, including hybrid and staged ventricular recruitment approaches. These strategies provide sufficient time for personalized decision-making, taking into account the individual circumstances of each patient. This article presents an overview of the changing approaches to borderline left ventricular cases. It discusses the use of predictive scoring systems and emphasizes the advancements in staged strategies that improve the likelihood of successful biventricular repairs.

Clinical Presentation and Therapy of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart defect characterized by several abnormalities that result in a significantly underdeveloped left ventricle and severe hypoplasia of the ascending aorta, often leading to retrograde perfusion. These abnormalities include aortic valve atresia or severe stenosis, accompanied by a severely hypoplastic aortic valve annulus (Fig. 59.1). Mitral valve atresia, hypoplasia, and/or stenosis with a hypoplastic valve annulus with or without a ventricular septal defect can also contribute to the development of HLHS. Endocardial fibroelastosis and sinusoids may be present as well. The interatrial septum can either be closed or the foramen ovale severely stenotic. Other malformations, such as anomalous pulmonary venous drainage or variations of the systemic veins, may coexist. It is also common to observe a coarctation of the aorta in these cases.

Human Genetics of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital cardiovascular malformation characterized by hypoplasia of the left ventricle, aorta, and other structures on the left side of the heart. The pathologic definition includes atresia or stenosis of both the aortic and mitral valves. Despite considerable progress in clinical and surgical management of HLHS, mortality and morbidity remain concerns. One barrier to progress in HLHS management is poor understanding of its cause. Several lines of evidence point to genetic origins of HLHS. First, some HLHS cases have been associated with cytogenetic abnormalities (e.g., Turner syndrome). Second, studies of family clustering of HLHS and related cardiovascular malformations have determined HLHS is heritable. Third, genomic regions that encode genes influencing the inheritance of HLHS have been identified. Taken together, these diverse studies provide strong evidence for genetic origins of HLHS and related cardiac phenotypes. However, using simple Mendelian inheritance models, identification of single genetic variants that "cause" HLHS has remained elusive, and in most cases, the genetic cause remains unknown. These results suggest that HLHS inheritance is complex rather than simple. The implication of this conclusion is that researchers must move beyond the expectation that a single disease-causing variant can be found. Utilization of complex models to analyze high-throughput genetic data requires careful consideration of study design.

Outcomes of heart transplantation in children with previously palliated hypoplastic left heart syndrome.

OBJECTIVES: Paediatric heart transplantation in children who fail multistage palliation for hypoplastic left heart syndrome is associated with challenges related to immune, clinical or anatomic risk factors. We review current outcomes and risk factors for survival following heart transplantation in this challenging patient population. METHODS: The United Network for Organ Sharing transplantation database was merged with Paediatric Health Information System database to identify children who received heart transplantation following prior palliation for hypoplastic left heart syndrome. Multivariable Cox analysis of outcomes and factors affecting survival was performed. RESULTS: Our cohort included 849 children between 2009 and 2021. The median age was 1044 days (interquartile range 108-3535), and the median weight was 13 kg (interquartile range 7-26). Overall survival at 10 years following heart transplantation was 71%, with most of the death being perioperative. On multivariable analysis, risk factors for survival included Black race (hazard ratio = 1.630, P = 0.0253), blood type other than B (hazard ratio = 2.564, P = 0.0052) and male donor gender (hazard ratio = 1.367, P = 0.0483). Recipient age, the use of ventricular assist device or extracorporeal membrane oxygenation were not significantly associated with survival. Twenty-four patients underwent retransplantation, and 10-year freedom from retransplantation was 98%. Rejection before hospital discharge and within 1 year from transplantation was 20% and 24%, respectively, with infants having lower rejection rates. CONCLUSIONS: Compared with existing literature, the number of children with prior hypoplastic left heart syndrome palliation who receive heart transplantation has increased in the current era. Survival following transplantation in this patient population is acceptable. Most of the death is perioperative. Efforts to properly support these patients before transplantation might decrease early mortality and improve overall survival.

Atrial septal interventions during and after hybrid stage I palliation of hypoplastic left heart syndrome.

BACKGROUND: Hybrid stage I palliation (HS1P) is an alternative approach for initial palliation in hypoplastic left heart syndrome (HLHS) patients. Unlike surgical stage I palliation where atrial septectomy is routinely performed, atrial septal intervention (ASI) during HS1P is variable. In this study, we described our experience with ASI in single ventricle (SV) patients who underwent HS1P and identified factors associated with need for ASI after HS1P. METHODS: Data were retrospectively collected for all HLHS patients who underwent HS1P at our center over the past 12 years. We evaluated ASIs performed during the HS1P (intra-HS1P ASI) and ASIs performed during the period from HS1P to the subsequent surgical stage, either interval Norwood stage I or comprehensive stage II (post-HS1P ASI). Patient factors and procedural data were compared to identify factors associated with undergoing post-HS1P ASI and the impact of ASI on patient outcomes was evaluated. RESULTS: Of 50 SV patients included, 23 (46%) underwent intra-HS1P ASI and 26 (52%) underwent post-HS1P ASI. Need for post-HS1P ASI was lower among patients who had an intra-HS1P ASI as compared to those who did not (30% vs. 70%; p = 0.005). There were no significant differences in short or Midterm outcomes between patients who underwent intra-HS1P ASI or post-HS1P ASI and their counterparts. CONCLUSIONS: ASI is common both during and after HS1P but is generally well tolerated and type of ASI does not significantly impact overall patient outcomes. Our findings suggest that the current approach of individualizing management of ASI in the HS1P population is effective and safe.

Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with underdevelopment of left-sided heart structures. While previously uniformly fatal, surgical advances now provide highly effective palliation that allows most HLHS patients to survive their critical CHD. Nevertheless, there remains high morbidity and mortality with high risk of heart failure. As hemodynamic compromise from restricted aortic blood flow has been suggested to underlie the poor LV growth, this suggests the possibility of prenatal fetal intervention to recover LV growth. As such interventions have yielded ambiguous results, the optimization of therapy will require more mechanistic insights into the developmental etiology for HLHS. Clinical studies have shown high heritability for HLHS, with an oligogenic etiology indicated in conjunction with genetic heterogeneity. This is corroborated with the recent recovery of mutant mice with HLHS. With availability-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from HLHS mice and patients, new insights have emerged into the cellular and molecular etiology for the LV hypoplasia in HLHS. Cell proliferation defects were observed in conjunction with metaphase arrest and the disturbance of Hippo-YAP signaling. The left-sided restriction of the ventricular hypoplasia may result from epigenetic perturbation of pathways regulating left-right patterning. These findings suggest new avenues for fetal interventions with therapies using existing drugs that target the Hippo-YAP pathway and/or modulate epigenetic regulation.

Geospatial Distribution of Prenatally and Postnatally Diagnosed Congenital Heart Disease: Implications for Equitable Care from a Fetal Heart Society Research Collaborative Study.

OBJECTIVE: To characterize patterns in the geospatial distribution of pre- and postnatally diagnosed congenital heart disease (CHD) across 6 surgical centers. STUDY DESIGN: A retrospective, multicenter case series from the Fetal Heart Society identified patients at 6 centers from 2012 through 2016 with prenatally (PrND) or postnatally (PoND) diagnosed hypoplastic left heart syndrome (HLHS) or d-transposition of the great arteries (TGA). Geospatial analysis for clustering was done by the average nearest neighbor (ANN) tool or optimized hot spot tool, depending on spatial unit and data type. Both point location and county case rate per 10 000 live births were assessed for geographic clustering or dispersion. RESULTS: Of the 453 CHD cases, 26% were PoND (n = 117), and 74% were PrND (n = 336). PrND cases, in all but one center, displayed significant geographic clustering by the ANN. Conversely, PoND cases tended toward geographic dispersion. Dispersion of PoND HLHS occurred in 2 centers (ANN = 1.59, P < .001; and 1.47, P = .016), and PoND TGA occurred in 2 centers (ANN = 1.22, P < .05; and ANN = 1.73, P < .001). Hot spot analysis of all CHD cases (TGA and HLHS combined) revealed clustering near areas of high population density and the tertiary surgical center. Hot spot analysis of county-level case rate, accounting for population density, found variable clustering patterns. CONCLUSION: Geographic dispersion among postnatally detected CHD highlights the need for a wider reach of prenatal cardiac diagnosis tailored to the specific needs of a community. Geospatial analysis can support centers in improving the equitable delivery of prenatal care.

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.

OBJECTIVES: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. METHOD: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. RESULTS: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. CONCLUSION: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

Reprint of: How He Did It - The James S. Tweddell Approach to Single Ventricle Palliation in Patients With Hypoplastic Left Heart Syndrome.

This article will detail Dr. James Tweddell's operative technique and considerations for 26 all three stages of SVP in patients with HLHS. This will include the Norwood Procedure with 27 Right-Ventricle-to-Pulmonary-Artery Conduit (Sano Modification), Bidirectional Glenn 28 (Superior Cavopulmonary Connection), and Extracardiac, Fenestrated Fontan Completion (Total 29 Cavopulmonary Connection). These techniques are the culmination of over 20 years of experience 30 and represent the final techniques he employed at both Children's Hospital of Wisconsin and 31 Cincinnati Children's Hospital Medical Center.

Fetal aortic valvuloplasty as the first step in a complex therapeutic strategy.

BACKGROUND: Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis. OBJECTIVE: to report our experience on FAV as the first step in a complex therapeutic strategy. METHOD: Series of patients with FAV over an 18-year period. RESULTS: 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28 days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28 days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up. CONCLUSION: FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28 days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy.

Short-Term Outcomes, Functional Status, and Risk Factors for Requiring Extracorporeal Life Support After Norwood Operation: A Single-Center Retrospective Study.

Patients requiring extracorporeal life support (ECLS) post-Norwood operation constitute an extremely high-risk group. We retrospectively described short-term outcomes, functional status, and assessed risk factors for requiring ECLS post-Norwood operation between January 2010 and December 2020 in a high-volume center. During the study period, 269 patients underwent a Norwood procedure of which 65 (24%) required ECLS. Of the 65 patients, 27 (41.5%) survived to hospital discharge. Mean functional status scale (FSS) score at discharge increased from 6.0 on admission to 8.48 (p < 0.0001). This change was primary in feeding (p < 0.0001) and respiratory domains (p = 0.017). Seven survivors (26%) developed new morbidity, and two (7%) developed unfavorable functional outcomes. In the regression analysis, we showed that patients with moderate-severe univentricular dysfunction on pre-Norwood transthoracic echocardiogram (odds ratio [OR] = 6.97), modified Blalock Taussig Thomas (m-BTT) shunt as source of pulmonary blood flow (OR = 2.65), moderate-severe atrioventricular valve regurgitation on transesophageal echocardiogram (OR = 8.50), longer cardiopulmonary bypass time (OR = 1.16), longer circulatory arrest time (OR = 1.20), and delayed sternal closure (OR = 3.86), had higher odds of requiring ECLS (p < 0.05). Careful identification of these risk factors is imperative to improve the care of this high-risk cohort and improve overall outcomes.

Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

OBJECTIVES: The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. METHODS: Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. RESULTS: The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. CONCLUSIONS: Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.