Hypoplastic left heart syndrome in context

Hypoplastic left heart syndrome (HLHS) and single ventricle (SV) remain a significant cause of cardiac deaths occurring in the first week of life. Their pathogenesis and seasonal frequency are still unknown. Therefore, we attempt to look at the genesis of the HLHS and SV in the context of territorial distribution as well as seasonality. A total of 193 fetuses diagnosed with HLHS and 92 with SV were selected. The frequency was analyzed depending on the year, calendar month, quarter and season (fall-winter vs. spring-summer). The spatial distribution of HLHS and SV in Poland was analyzed. We observed a statistically significant overrepresentation of HLHS formation frequency in March: 27 (14.00%) in comparison to a monthly median of 15 (IQR: 13.75–16.25; p = 0.039), as well as a significantly higher frequency of HLHS in 2007−2009: 65 cases (33.68%) in comparison to the annual mean of 13.79 ± 6.36 (p < 0.001). We noted a higher frequency of SV among parous with the last menstrual period reported in the fall/winter season of 58 vs. 34 in the spring/summer season (p = 0.014). The performed analysis also revealed significant SV overrepresentation in 2008: 11 cases (12.00%) in comparison to the annual mean of 6.57 ± 2.71 (p = 0.016). Every single case of HLHS was observed when the concentration of benzo(a)pyrene and/or PM10 exceeded the acceptable/target level. Our research indicates that both the season and the level of pollution are significant factors affecting the health of parous women and their offspring. The reason why HLHS and SV develop more frequently at certain times of the year remains unclear, therefore research on this topic should be continued, as well as on the effects of PM10 and benzo(a)pyrene exposure.

Outcomes in Hypoplastic Left Heart Syndrome

Comparison of outcome when hypoplastic left heart syndrome and transposition of the great arteries are diagnosed prenatally versus when diagnosis of these two conditions is made only postnatally

Right Ventricular Systolic-to-Diastolic Time Index: Hypoplastic Left Heart Fetuses Differ Significantly from Normal Fetuses

Diastolic inflow is associated with inefficient ventricular flow dynamics in Fontan patients

We sought to evaluate the impact of prenatal diagnosis on morbidity and mortality in single ventricle (SV) lesions. All consecutive patients with pre- or postnatally diagnosed SV physiology admitted to our centre between January 2001 and June 2013 were reviewed. Primary endpoints included survival until 30days after bidirectional cavopulmonary connection (BCPC) without transplant or BCPC takedown. Prenatal diagnosis was performed in 160 of 259 cases (62%). After excluding all cases with termination of pregnancy, intrauterine demise or treated with comfort care, a total of 180 neonates were admitted to our centre for treatment, including 87 with a prenatal and 93 with a postnatal diagnosis. Both groups showed similar distribution regarding diagnosis, dominant ventricle and risk factors such as restrictive foramen or some form of atrial isomerism. A larger proportion of postnatally diagnosed children presented at admission with elevated lactate > 10mmol/l (p = 0.02), a higher dose of prostaglandin (p = 0.0013) and need for mechanical ventilation (p < 0.0001). Critical lesions such as hypoplastic left heart syndrome were an important determinant for morbidity and mortality. Thirty-days survival after BCPC was better in patients with prenatal diagnosis (p = 0.025). Prenatal diagnosis is associated with higher survival in neonates with SV physiology.

Patients with single ventricle physiology (SVP)--specifically, hypoplastic left heart syndrome (HLHS)--frequently need long-term enteral access; however, they are at an extremely high operative risk. Nothing has been published on the physiologic impact on single ventricle function during laparoscopy in this patient population. Therefore, we performed intraoperative transesophageal echocardiography (TEE) to study the physiologic effects of laparoscopic surgery in these patients. After Internal Review Board approval, patients with SVP undergoing laparoscopic gastrostomy were studied with intraoperative TEE, and fractional shortening was determined. Patients were separated into those with HLHS and others with SVP. Data are reported as mean ± standard deviation values. Analysis of variance was used for continuous variables. From August 2011 to February 2013, in total, 11 patients with SVP underwent laparoscopic gastrostomy, including 6 with HLHS. One of the 6 HLHS patients and 1 of the SVP patients underwent concurrent fundoplication. All patients were post-first-stage palliation; two had completed post-second stage. Fractional shortening tended to decrease during insufflation and return to baseline after desufflation. There was no 30-day mortality. Pneumoperitoneum associated with laparoscopic gastrostomy tube placement results in a reversible decrease in fractional shortening in patients with HLHS and SVP. Overall, the children tolerated pneumoperitoneum. TEE allows for real-time assessment of ventricular function and volume and may improve safety during longer procedures.

Hypoplastic left heart syndrome (HLHS) is a deadly congenital heart disease that arises when the left ventricle and outflow tract fail to develop appropriately, inhibiting the adequate perfusion of the rest of the body. Historically, this disease has been treated via a series of surgeries that allows the heart to use a single ventricle. These surgeries are often a palliative measure, and heart transplantation is the only definitive therapy that exists for this condition. It has been hypothesized that stem cell-based regenerative therapies could have a role in promoting cardiac tissue regeneration in HLHS patients who are undergoing palliative surgery. Several clinical trials have demonstrated that introducing pluripotent cells into the heart is safe, feasible, and capable of improving right ventricular ejection fraction (RVEF). However, while these approaches show great promise, there is still room for development. There is a substantial body of pre-clinical work that is focused on generating increasingly large and complex pieces of cardiac tissue in the form of cardiac patches, with the idea that these could be used to rebuild and strengthen the heart in a robust and long-lasting manner. In total, stem cell-based therapies have much to offer when it comes to improving the treatment of HLHS.

Cerebral oxygen saturation before congenital heart surgery

Hypoplastic left heart syndrome (HLHS) is one of the most complex forms of congenital heart disease, characterized by an underdeveloped left ventricle, outflow tract and aorta. Current surgical and medical treatment for this disease remains palliative. As a result of the multi-step surgery, the right ventricle plays the role of the systemic ventricle, which inevitably leads to its failure. There is an urgent need to develop new treatments to ameliorate the right ventricle failure. Stem cell therapy may represent a new approach to single ventricle pathology. Great numbers of small and large animal studies have proven this therapy to be safe and effective in hypoplastic left heart syndrome. Several clinical trials have been designed to investigate the potential of mesenchymal stem cells in univentricular heart physiology. With increasing evidence, understanding of the mechanism of stem cells’ action has shifted from the concept of differentiation into various heart cell types to paracrine activity playing the major role. The secretome of stem cells has been identified as their functional unit. In this review, we present different types of stem cells used in single ventricle diseases in children as well as their preclinical investigations. We also summarize clinical applications of stem cells in children with HLHS.

Dynamic Three-Dimensional Geometry of the Tricuspid Valve Annulus in Hypoplastic Left Heart Syndrome with a Fontan Circulation

Significant surgical and medical advances over the past several decades have resulted in a growing number of infants and children surviving with hypoplastic left heart syndrome (HLHS) and other congenital heart defects associated with a single systemic right ventricle (RV). However, cardiac dysfunction and ultimately heart failure (HF) remain the most common cause of death and indication for transplantation in this population. Moreover, while early recognition and treatment of single ventricle-related complications are essential to improving outcomes, there are no proven therapeutic strategies for single systemic RV HF in the pediatric population. Importantly, prototypical adult HF therapies have been relatively ineffective in mitigating the need for cardiac transplantation in HLHS, likely due to several unique attributes of the failing HLHS myocardium. Here, we discuss the most commonly used medical therapies for the treatment of HF symptoms in HLHS and other single systemic RV patients. Additionally, we provide an overview of potential novel therapies for systemic ventricular failure in the HLHS and related populations based on fundamental science, pre-clinical, clinical, and observational studies in the current literature.

Fetuses with congenital heart disease (CHD) are at increased risk of pregnancy loss compared with the general population. We aimed to assess the incidence, timing and risk factors of pregnancy loss in cases with major fetal CHD, overall and according to cardiac diagnosis. This was a retrospective, population-level cohort study of fetuses and infants diagnosed with major CHD between 1997 and 2018 identified by the Utah Birth Defect Network (UBDN), excluding cases with termination of pregnancy and minor cardiovascular diagnoses (e.g. isolated aortic/pulmonary pathology and isolated septal defects). The incidence and timing of pregnancy loss were recorded, overall and according to CHD diagnosis, with further stratification based on presence of isolated CHD vs additional fetal diagnosis (genetic diagnosis and/or extracardiac malformation). Adjusted risk of pregnancy loss was calculated and risk factors were assessed using multivariable models for the overall cohort and prenatal diagnosis subgroup. Of 9351 UBDN cases with a cardiovascular code, 3251 cases with major CHD were identified, resulting in a study cohort of 3120 following exclusion of cases with pregnancy termination (n = 131). There were 2956 (94.7%) live births and 164 (5.3%) cases of pregnancy loss, which occurred at a median gestational age of 27.3 weeks. Of study cases, 1848 (59.2%) had isolated CHD and 1272 (40.8%) had an additional fetal diagnosis, including 736 (57.9%) with a genetic diagnosis and 536 (42.1%) with an extracardiac malformation. The observed incidence of pregnancy loss was highest in the presence of mitral stenosis (< 13.5%), hypoplastic left heart syndrome (HLHS) (10.7%), double-outlet right ventricle with normally related great vessels or not otherwise specified (10.5%) and Ebstein's anomaly (9.9%). The adjusted risk of pregnancy loss was 5.3% (95% CI, 3.7-7.6%) in the overall CHD population and 1.4% (95% CI, 0.9-2.3%) in cases with isolated CHD (adjusted risk ratio, 9.0 (95% CI, 6.0-13.0) and 2.0 (95% CI, 1.0-6.0), respectively, based on the general population risk of 0.6%). On multivariable analysis, variables associated with pregnancy loss in the overall CHD population included female fetal sex (adjusted odds ratio (aOR), 1.6 (95% CI, 1.1-2.3)), Hispanic ethnicity (aOR, 1.6 (95% CI, 1.0-2.5)), hydrops (aOR, 6.7 (95% CI, 4.3-10.5)) and additional fetal diagnosis (aOR, 6.3 (95% CI, 4.1-10)). On multivariable analysis of the prenatal diagnosis subgroup, years of maternal education (aOR, 1.2 (95% CI, 1.0-1.4)), presence of an additional fetal diagnosis (aOR, 2.7 (95% CI, 1.4-5.6)), atrioventricular valve regurgitation ≥ moderate (aOR, 3.6 (95% CI, 1.3-8.8)) and ventricular dysfunction (aOR, 3.8 (95% CI, 1.2-11.1)) were associated with pregnancy loss. Diagnostic groups associated with pregnancy loss were HLHS and variants (aOR, 3.0 (95% CI, 1.7-5.3)), other single ventricles (aOR, 2.4 (95% CI, 1.1-4.9)) and other (aOR, 0.1 (95% CI, 0-0.97)). Time-to-pregnancy-loss analysis demonstrated a steeper survival curve for cases with an additional fetal diagnosis, indicating a higher rate of pregnancy loss compared to cases with isolated CHD (P < 0.0001). The risk of pregnancy loss is higher in cases with major fetal CHD compared with the general population and varies according to CHD type and presence of additional fetal diagnoses. Improved understanding of the incidence, risk factors and timing of pregnancy loss in CHD cases should inform patient counseling, antenatal surveillance and delivery planning. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A Comparison of Perinatal Circulatory Transition in Critical Right and Left Heart Obstructive Lesions

Introduction: With advances in care, survival into adulthood of single-ventricle (SV) palliation is more frequent. Fertility and family planning in this setting is complex. In the general population, maternal mortality is 0.02%, post-partum hemorrhage (PPH) is 3.1% and pre-eclampsia is 7.5%. There are limited data on outcomes of pregnancies of women with SV physiology. This study reviews deliveries of SV mothers in Texas over the past 14 years. Methods: This is a retrospective review of the Texas Inpatient Discharge Dataset, an administrative dataset containing most hospital discharges. All discharges of females≥15 years old between 1/1/2006-12/31/2019 were reviewed. ICD-9/10 diagnosis codes consistent with Hypoplastic Left Heart Syndrome (HLHS), Double Inlet Ventricle (DIV)/Common Ventricle (CV), and Hypoplastic Right Heart Syndrome (HRHS)/Tricuspid Atresia (TA) were included. Pregnancy-related discharges were identified by ICD-9/10 codes. Descriptive and univariate statistics were utilized. Results: A total of 56 pregnancy-related discharges were identified, with 40 (71.4%) deliveries (Table). One (2.5%) was a twin gestation and 4(10%) had fetal demise. Number of annual deliveries increased from 0 in 2006 to 8 in 2019. Median gestational age was 37[IQR: 33.25-38] weeks, 7 (17.5%) had fetal anomalies and 7(17.5%) had poor fetal growth. Twelve (30%) underwent C-Section. Median length of stay was 3.5[2-5] days, 3(7.5%) mothers had PPH, 2(5%) required ventilator support, and there were no in-hospital mortalities. Conclusions: As the number of patients with SV surviving into adulthood increases, accurate counseling on risks of pregnancy is required. While these data cannot evaluate the outcomes for the delivered baby, they suggest favorable short-term outcomes for mothers with no in-hospital mortalities. Further research is needed to both understand outcomes for the delivered babies as well as potential longer-term sequelae for mothers.