RARE DISEASE
Hypoplastic right heart syndrome
Hypoplastic right heart syndrome
Hypoplastic right heart syndrome
Drug discovery
0
drugs
With orphan designations
Overview
Hypoplastic Right Heart Syndrome (HRHS) is a rare congenital heart defect characterized by underdevelopment of right-sided cardiac structures (tricuspid valve, right ventricle, pulmonary valve, and pulmonary artery), leading to diminished pulmonary blood flow, right-to-left atrial shunting, and cyanosis [1][6][12]. Associated with atrial septal defects, it manifests neonatally with hypoxia, dyspnea, and heart failure. Management involves staged surgical palliation (Norwood/Glenn/Fontan procedures) or heart transplantation to redirect blood flow [2][6][16].
Burden
Therapies
Neonatal palliation via prostaglandin E1 to maintain ductal patency [3][16].
Three-stage surgical approach: systemic-to-pulmonary shunt (Norwood/Blalock-Taussig), bidirectional Glenn shunt (4–12 months), and Fontan procedure (≥18 months) [2][6][16].
Heart transplantation for refractory cases, requiring lifelong immunosuppression [9][16].
Categories: rare cardiac malformations, rare developmental anomalies during embryogenesis
Research Papers
138 drug discovery papers about Hypoplastic right heart syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
138 drug discovery papers about Hypoplastic right heart syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-03-01 | 659: INHALED EPOPROSTENOL FOR REFRACTORY HYPOXEMIA IN AN ADULT FONTAN PATIENT WITH HLHS: A CASE REPORT
Introduction: Hypoplastic left heart syndrome (HLHS) is a rare congenital cardiac defect in which systemic circulation is dependent on right ventricular output. The Fontan procedure creates a pathway for blood to circulate directly into the lung, which ultimately results in persistent shunt physiology. The complex hemodynamic physiology that arises is especially challenging in critically ill patients, where adequate oxygenation is of utmost importance. Inhaled pulmonary vasodilators such as epoprostenol (EPO) can selectively reduce pulmonary vascular resistance (PVR), improve ventilation-perfusion matching, and optimize systemic oxygen delivery. Description: 32-year-old male with HLHS status post-Fontan presented with progressive dyspnea following a week of nausea and vomiting. He transitioned from an oxymizer to high-flow nasal cannula (40 L/min, FiO2 1.0), then to BiPAP (12/5, FiO2 1.0), but remained hypoxic. ABG on BiPAP showed PaO2 50 mmHg. He was intubated for worsening respiratory failure, but oxygenation declined with PEEP of 8 cm H2O (PaO2 54 mmHg on FiO2 0.8, SpO2 92.5%), likely due to impaired pulmonary blood flow from elevated intrathoracic pressure. Inhaled epoprostenol was initiated, resulting in marked improvement in oxygenation. The patient was weaned to HFNC with epoprostenol, then transitioned as low as HFNC 30L/.45 FIO2 and transferred to a congenital heart center for further management. Discussion: In Fontan patients, positive pressure ventilation can worsen oxygenation by impeding passive pulmonary blood flow and increasing right-to-left shunting. Inhaled epoprostenol improves V/Q matching by reducing PVR and enhancing pulmonary flow without systemic vasodilation. This case demonstrates the utility of epoprostenol as a rescue strategy for refractory hypoxemia in adults with complex congenital heart disease. Recognition of unique physiologic interactions in this population is crucial for individualized management in the ICU.
2025-12-01 | Volume Loading May Compromise Left Ventricular Filling in Patients with a Borderline Hypoplastic Left Ventricle.
Given the high prevalence of end-organ damage in the long term after the Fontan procedure, patients presenting with borderline hypoplastic left ventricle (LV) are increasingly directed towards biventricular circulation. We present the case of a patient with borderline LV who developed severe pulmonary hypertension shortly after biventricular repair. We initially thought it was purely caused by a hypoplastic LV; however, it was partly induced by a delayed/prolonged right ventricular (RV) contraction that compressed the interventricular septum and impaired left ventricular filling, which was exacerbated by volume loading during cardiac catheterization. Although the coexisting right bundle branch block (RBBB) might have contributed to the delayed RV contraction, volume depletion through aggressive diuresis shortened the RV contraction interval, resulting in improvement of interventricular crosstalk and the alleviation of symptoms related to pulmonary congestion, regardless of the presence of complete RBBB. Subsequently, our patient achieved favorable LV growth after 2 years of observation. While volume loading has been considered as an option to promote the growth of the hypoplastic LV, aggressive fluid management may offer an alternative for allowing sufficient time to achieve adequate ventricular growth in cases of non-compliant LV properties.
2025-05-19 | Aneurysm of the fetal right ventricular free wall progressing to hypoplastic right heart syndrome: prenatal diagnosis, maternal digoxin therapy, and successful surgical intervention-a case report.
Congenital right ventricular aneurysm (CVA) and diverticulum (CVD) are rare heart diseases that can be diagnosed prenatally. Data on the natural progression of ventricular aneurysms or diverticula identified during fetal life remains scarce, with insights primarily derived from a limited number of case reports and case series. This case report aims to highlight the diagnosis, management, and outcomes of a rare right ventricular free wall aneurysm progressing to hypoplastic right heart syndrome (HRHS), utilizing advanced fetal imaging and prenatal therapy. These findings provide valuable perspective on the underlying cause, diagnostic approaches, and treatment strategy for rare cardiac anomaly. The aneurysm of the right ventricular free wall was diagnosed 13 weeks of gestation during prenatal ultrasound of the fetus in the first trimester. At the time of diagnosis, severe tricuspid valve stenosis with severe tricuspid regurgitation, critical pulmonary stenosis, pericardial effusion, ascites, and secondary flow reversal in the ductus venosus was found. Genetic testing using microarray-based comparative genomic hybridization (aCGH) on amniotic fluid samples showed no genomic imbalance. Digoxin treatment was initiated at 13 weeks of gestation, starting with a loading dose of 1,200 micrograms, followed by a maintenance dose of 375 micrograms daily, to address signs of fetal heart failure. The fetalHQ® software was utilized to assess the size and contractility of both the right and left ventricles, focusing on global and segmental strain measurements. The gradual reduction in right ventricular cardiac output led to the progression of HRHS with pulmonary atresia. At 39 weeks of gestation, a female newborn weighing 2,480 g was delivered in good condition, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Prostaglandin E1 treatment was initiated postnatally to maintain ductal patency. Postnatal echocardiography and angio-computed tomography (CT) confirmed the prenatal diagnosis, revealing a right ventricle-to-right coronary artery (RCA) fistula and interruption of RCA perfusion continuity. The newborn underwent successful first-stage palliation with a Blalock-Taussig shunt to establish systemic-pulmonary circulation. Follow-up during the interstage period showed the child remained in good clinical condition, with no significant complications reported. CVAs are rare but significant anomalies with potential for severe hemodynamic consequences. Multidisciplinary approaches integrating advanced imaging techniques, prenatal counseling, and tailored postnatal management are essential for optimizing outcomes.
2024-11-12 | Abstract 4140558: Circulating plasma proteins in the Fontan circulation predict mitochondrial oxidative stress
Background: Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation constitute the largest group of children hospitalized with circulation failure, experiencing an in-hospital mortality rate of 20-50%. We investigated the mechanisms leading to circulation failure so as to identify novel therapeutic targets. Methods: Blood was collected from patients with HLHS s/p Fontan and controls with normal cardiac anatomy and function (N=6/group). Plasma microvesicles (MV) were isolated, and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change >1.5 or < -1.5, p<0.05, were evaluated using DAVID and Ingenuity pathway analysis. We assessed the association of most highly dysregulated proteins with NYHA class (clinical indicator of heart failure), right ventricular fractional area change (RV FAC) (echocardiographic indicator of RV systolic function), oxygen saturation and hemoglobin using Pearson correlation. Results: Age of Fontan patients vs. controls was 16.14±23 vs. 15.78±2; 40% were male in both groups. 80% of Fontan patients were in NYHA class II/III, 20% in NYHA class IV; 60% had Fontan-associated liver disease. Increasing expression of the following proteins was associated with worsening NYHA class: complement system (C1QA, r=0.91; C7, r=0.53; FCN3, r=0.52), membrane transporters (SLC2A1, r=0.82; SLC4A1, r=0.76), mitochondrial reactive oxygen species (mROS) generation (HSPD1, r=0.81; ATP5F1A, r=0.75) and cytoskeletal proteins (ANK1, r=0.63; ACTN1, r=0.76). Increasing expression of proteins involved in mROS generation were also associated with worsening RV FAC. Decreasing expression of the following proteins was associated with worsening NYHA class and RV FAC: B-cell lymphopoiesis (DOCK10; r=-0.80), adhesion (ADAM10, r=-0.72; CD151, r=-0.69), and coagulation (SERPINF2, r=-0.55). Higher expression of proteins involved in mitochondrial ROS generation and lower expression of proteins involved in lymphopoiesis and adhesion were associated with lower oxygen saturation and higher hemoglobin(Figure). Conclusion: Circulating plasma proteins in the Fontan circulation predict complement activation, mROS, cytoskeletal changes and decreased cell-cell adhesion. This circulating proteomic profile is associated with worsening heart failure and cyanosis providing mechanistic insight into heart failure progression and highlights novel therapeutic targets.
2024-06-28 | Outcomes of Children With Hypoplastic Left Heart Syndrome and Heart Failure on Medical Therapy.
Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.
cell therapies
2026-03-14 | Outcomes of Heart Transplantation in Single-Ventricle Physiology: A Retrospective Single-Center Experience with Emphasis on Surgical Complexity.
Background: Patients with single-ventricle physiology represent a high-risk group for heart transplantation. Due to complex anatomical and physiological challenges, including multiple prior sternotomies, pulmonary artery abnormalities, and systemic consequences of altered circulation, they represent both a surgical and a clinical challenge. We aimed to analyze perioperative challenges, as well as early and long-term complications, in this specific group of patients. Methods: We performed a retrospective data analysis of a high-volume heart transplant center, focusing on patients with single-ventricle physiology who were scheduled for heart transplantation due to end-stage heart failure. We retrospectively analyzed the period from the beginning of the transplant program in November 1985 to the end of November 2024. Results: Among 1553 transplanted patients (adults and children), 29 were transplanted due to congenital heart disease (congenital valvular disease not included). In this group, nine patients were transplanted due to end-stage heart failure in the course of single-ventricle physiology. Age at transplantation ranged from 7 to 31 years (median, 17 years), and body weight ranged from 15 to 69 kg (median, 47.9 kg). All nine patients referred for heart transplantation presented with single-ventricle physiology. Their underlying congenital heart defects were heterogeneous and included hypoplastic left heart syndrome (HLHS), double-outlet left ventricle (DOLV), transposition of the great arteries (TGA) with associated ventricular septal defects (VSDs), atrial septal defects (ASDs), valvular abnormalities such as tricuspid and or pulmonary valve atresia or stenosis, systemic or atrioventricular valve regurgitation, and vascular abnormalities, including right-sided aortic arch, aortic coarctation, and pulmonary artery hypoplasia, stenosis, or occlusion, as well as associated pulmonary vascular abnormalities such as left pulmonary artery stenosis and MAPCAs. All patients had previously undergone staged palliative procedures, including Norwood, Hemi-Fontan, Fontan, bidirectional Glenn, modified Blalock-Taussig shunts, Bjork-Fontan, or pulmonary artery banding, often with repeated interventions such as balloon angioplasty, stent placement, or MAPCA closure. Extracardiac comorbidities were common and included coagulopathies, protein-losing enteropathy, hepatic dysfunction, and chronic venous insufficiency. Preoperative functional status was markedly impaired in all patients (NYHA III-IV, INTERMACS 3-4), with severely reduced exercise capacity and thrombotic events in several individuals. Perioperative transplant surgical strategies included femoral cannulation in four cases and standard aortic and caval cannulation in five cases. Pulmonary artery reconstruction was required in all patients. Extended donor pulmonary arteries were applied in eight cases, while a bifurcated Dacron prosthesis was utilized in one patient. Perioperative mortality was 33%, with three deaths attributed to bleeding and hemodynamic instability, while overall mortality was 44% including one late death unrelated to transplantation. Protein-losing enteropathy, although persistent in the immediate postoperative period, resolved in all surviving patients, underscoring the transformative impact of transplantation. Conclusions: These findings emphasize the importance of individualized surgical planning, extended donor pulmonary artery harvesting, and careful preoperative coordination. Heart transplantation remains a viable and life-extending option for selected single-ventricle patients, despite the significant technical and clinical challenges involved.
2025-10-14 | Engineered heart tissues formed with cardiac progenitors and differentiated cardiomyocytes exhibit similar physiologic properties at differentiation-matched timepoints.
Congenital heart diseases, including single ventricle heart defects such as hypoplastic left and right heart syndromes, remain a leading cause of neonatal death and long-term morbidity. Regenerative medicine approaches hold great therapeutic promise for treating single ventricle disease, specifically through the use of human pluripotent stem cell-derived cardiomyocytes (iPSC-CM) to generate pulsatile conduits capable of growing and developing over time within the recipient. However, current strategies for rapidly fabricating large-scale engineered heart muscle to create such conduits face limitations, including the shear stress generated during most bioprinting processes along with harsh enzymatic treatments required for initial singularization of cells prior to bioprinting, which together can compromise cell viability and downstream tissue function. Here, we explored the use of derived cardiovascular progenitors (iPSC-CVP) as an alternative to fully differentiated cardiomyocytes as a potential cell source for future biomanufacturing efforts. We demonstrate that iPSC-CVP can be used to form functional engineered heart tissues with similar electrophysiological properties to tissues formed from fully differentiated iPSC-CM, while also being more amenable to enzymatic dissociation and mechanical manipulation. Our results suggest that iPSC-CVP may be an ideal cell population for future efforts in biofabrication of contractile structures such as engineered heart muscle and pulsatile conduits.
2024-06-05 | Staged repair of borderline hypoplastic heart disease with early biventricular conversion.
In select patients with borderline ventricular hypoplasia, we adopted a strategy of initial single-ventricle palliation followed by staged or direct biventricular conversion by 2 years of age. Between 2018 and 2023, 14 newborns with borderline hypoplastic heart disease deemed high risk for primary biventricular repair underwent palliative procedures as a neonate/infant, followed by staged or direct biventricular conversion. Of the 14 patients, 6 had borderline left ventricles and 8 had borderline right ventricles. Index neonatal operations were performed in 12 patients and included the Norwood operation (n = 5), pulmonary artery band (n = 3), ductal stent (n = 3), and hybrid Norwood (n = 1). Five patients underwent direct biventricular conversion, and the remaining 9 patients underwent staged ventricular recruitment operations at a mean age of 6 months (range, 3-11 months). Ventricular recruitment operations included atrial septation with or without ventricular rehabilitation, atrioventricular valve repair, or outflow tract operations. At a mean duration of 8 months (range, 4-10 months) after ventricular recruitment, there was a significant increase in chamber volume, aortic valve, and mitral valve size in patients with borderline left ventricles, and a normalization of the right ventricle:left ventricle end-diastolic volume ratio in patients with borderline right ventricles. To date, 13 of 14 patients have undergone successful biventricular conversion at a mean age of 16 months (range, 4-31 months). In select newborns with borderline hypoplastic heart disease, single-ventricle palliation followed by staged or direct biventricular conversion may increase infant survival while allowing for early attainment of a biventricular circulation.
2023-11-07 | Abstract 12344: Effect of Valved versus Non-Valved Conduits in Norwood Procedure on Ventricular Size and Function in Stage I Palliation for Hypoplastic Left Heart Syndrome
Background: Mortality in the interstage period remains high in hypoplastic left heart syndrome (HLHS) after introduction of the right ventricle (RV) to pulmonary artery conduit to the Norwood procedure. Prior studies have not shown long term survival benefit with conduits, possibly due to regurgitation and volume load, which may cause decreased RV function. Valved conduits (VC) were introduced more recently to address these limitations. Hypothesis: The goal of the study was to assess differences in RV size and function during the interstage period between patients undergoing Norwood procedure with valved versus non-valved conduits (NVC). We hypothesized that patients with VC would have smaller increases in RV size and improved function compared to those with NVC. Methods: Twenty-five consecutive neonates with HLHS who underwent Norwood procedure with VC were compared to 25 consecutive neonates who underwent Norwood with NVC from 2013 and 2022. Primary outcomes were RV size measured by end diastolic area (EDA) on 4-chamber images and function measured by RV fractional area change and global longitudinal strain. Results: Most patients with VC (96%) did not develop more than mild conduit regurgitation. There was no difference in EDA increase one month post op between groups, but there was a significantly smaller increase in EDA pre-Glenn compared to baseline in the VC group (Table 1). Functional measures were not significantly different during follow up. There was no difference in interstage cardiac events or mortality. Conclusions: Patients with VC at time of Norwood had smaller increases in ventricular size compared to those with NVC, but there were no differences in functional parameters during follow up. It is possible decreased volume load will have a beneficial long term effect on the immature myocardium of infants with HLHS. Larger studies are needed to further examine the hemodynamic benefits of VC in the interstage period and throughout the stages of palliation.
2021-01-12 | [Fetal cardiac intervention and perioperative management of fetus with hypoplastic right heart syndrome].
Objective: To summarize the experience of perioperative management strategy of fetal pulmonary valvuloplasty (FPV) for hypoplastic right heart syndrome (HRHS). Methods: In the retrospective study of perioperative data, 13 fetuses of HRHS were treated with FPV in Qingdao Women and Children's Hospital from July 2018 to June 2019. Results: (1) The evaluation indexes of the right ventricle in 13 fetuses before FPV: the mean ratio of tricuspid/mitral annulus, right/left ventricular length, pulmonary/aortic annulus, and tricuspid inflow time/cardiac cycle were 0.81±0.04, 0.56±0.14, 0.69±0.06, and 0.35±0.03, respectively. (2) All pregnant mothers underwent general anesthesia. The basic fetal heart rate was (156±12) beats per minutes before FPV, and 9 fetuses showed bradycardia during the operation, and recovered to normal after drug resuscitation. On the first day after FPV, two cases had bradycardia and pregnancy was terminated. The fluctuation of systolic blood pressure of pregnant mother was less than 20%, and there was no significant difference between preoperative and intraoperative pulse pressure [(36.0±5.6) vs (35.8±6.9) mmHg (1 mmHg=0.133 kPa); t=8.102, P=0.951]. (3) All cases of HRHS fetus successfully underwent FPV. The average gestational age was (27.3±0.8) weeks. The average operation time was (23.2±1.0) minutes. The ratio of tricuspid to mitral annulus (t=-2.513, P=0.022) and the ratio of right to left ventricular length (t=-3.373, P=0.003) were significantly improved at 6 weeks postoperatively. Ten fetuses were delivered, and there was no death after early intervention. (4) Of 13 pregnant women, 3 cases were nausea and vomiting on the day of FPV operation, the treatment of the symptoms was improved by tropisetron; one case had tolerable abdominal pain and improved without special treatment. Pregnant women had no major complications such as cardiac failure, abortion and death. (5) Chromosome karyotype analysis and microarray analysis of amniotic fluid was retained during the operation. No typical chromosome abnormality or other abnormal genetic diagnosis was found. Conclusions: FPV colud be used as an effective intervention measure to promote the development of right ventricle in HRHS fetuses. The scientific management of multidisciplinary professional technical team in perioperative period is particularly important to ensure the success of FPV and the safety of pregnant women and fetuses. 目的： 探讨右心发育不良综合征（HRHS）胎儿的心脏介入治疗及围手术期管理。 方法： 收集2018年7月至2019年6月青岛市妇女儿童医院行胎儿肺动脉瓣成形术（FPV）介入治疗的13例HRHS胎儿的围手术期临床资料进行回顾性分析，探讨FPV的术前评估、麻醉、手术治疗及结果、围手术期并发症以及HRHS胎儿的遗传学筛查结果。 结果： （1）术前评估：13例HRHS胎儿的右心室相关指标，三尖瓣瓣环直径/二尖瓣瓣环直径比值、右心室长径/左心室长径比值、肺动脉瓣瓣环直径/主动脉瓣瓣环直径比值、三尖瓣流入时间/心动周期比值分别为0.81±0.04、0.56±0.14、0.69±0.06、0.35±0.03，与FPV的适应证（上述指标分别为≤0.83、≤0.64、≤0.75、<0.36）符合，可行FPV。（2）麻醉：采用舒芬太尼、丙泊酚联合七氟醚的静脉-吸入复合全身麻醉，13例HRHS胎儿的术前基线胎心率为（156±12）次/min，术中9例胎儿出现心动过缓，均予心内注射药物复苏治疗后恢复正常；孕妇术前血压与术中比较，收缩压［分别为（114.7±3.9）、（99.7±6.0） mmHg（1 mmHg=0.133 kPa）］和舒张压［分别为（78.7±5.6）、（63.8±3.2） mmHg］均显著下降（P<0.01），但术前脉压差与术中脉压差［分别为（36.0±5.6）、（35.8±6.9） mmHg］比较无显著差异（t=8.102，P=0.951）。（3）手术治疗及结果：13例HRHS胎儿行FPV时的孕周为（27.3±0.8）周，均顺利完成FPV，手术时间为（23.2±1.0） min。10例继续妊娠的HRHS胎儿，术后6周评估右心室相关指标，三尖瓣瓣环直径/二尖瓣瓣环直径比值（t=-2.513，P=0.022）、右心室长径/左心室长径比值（t=-3.373，P=0.003）分别与术前比较，差异均有统计学意义。10例继续妊娠的HRHS胎儿均顺利分娩，出生后经早期干预后均存活。（4）围手术期并发症：13例孕妇中，FPV术后当日，3例出现恶心、呕吐，对症给予托烷司琼治疗后好转；1例出现腹痛，可耐受，未予特殊处理自行好转。13例孕妇围手术期无心力衰竭、流产、死亡等严重并发症。13例HRHS胎儿中，2例FPV术后当日出现严重的持续性心动过缓，1例术后随访过程中出现依赖右心室的冠状动脉循环，均选择终止妊娠。（5）遗传学筛查：13例HRHS胎儿均行染色体核型分析及染色体微阵列分析，未见典型的染色体异常及其他遗传学异常。 结论： FPV可作为HRHS胎儿的有效干预措施，可促进胎儿右心室的发育。多学科专业技术团队围手术期科学管理对确保手术成功及孕妇、胎儿的安全尤为重要。.
gene therapies
2025-08-11 | Hypoplastic right heart with heterotaxy has worse five-year transplant-free survival than the hypoplastic left heart syndrome: a thirteen-year single-centre experience.
Outcomes of single ventricle heart defects may be influenced by the morphological type of the hypoplastic ventricle. Recent multi-centre studies have targeted on outcomes of hypoplastic left heart syndrome with limited focus on outcomes of hypoplastic right heart syndrome. We aimed at studying the clinical outcomes of hypoplastic right heart syndrome in the recent era. We performed a retrospective analysis of all hypoplastic right heart syndrome patients (n = 153) born between January 2010 and January 2023. Five-year transplant-free survival was compared with hypoplastic left heart syndrome patients without heterotaxy (n = 144) born during the same time. Double-inlet left ventricle was the most common anatomic hypoplastic right heart syndrome subtype (n = 39, 25%). Twenty-six (17%) patients with hypoplastic right heart had associated heterotaxy. Five-year transplant-free survival was high for most groups (double inlet left ventricle: 100%, pulmonary atresia: 94%, Ebstein's anomaly: 92%, tricuspid atresia: 90% respectively). The heterotaxy group had worse early outcomes with 3 deaths and 3 heart transplants, before Fontan completion. Heterotaxy was a significant risk factor for death/transplant prior to Fontan completion in hypoplastic right heart syndrome patients (p = 0.03). Patients with hypoplastic right heart syndrome with heterotaxy had significantly worse 5-year transplant-free survival (71%) when compared to hypoplastic right heart syndrome without heterotaxy (95%) and hypoplastic left heart syndrome without heterotaxy (75%), p < 0.001. Hypoplastic right heart syndrome patients have excellent clinical outcomes and better early childhood survival than hypoplastic left heart syndrome in the current era, except when associated with heterotaxy. The survival advantage conferred by a single left ventricle appears to be negated by heterotaxy syndrome and should be strongly considered during caregiver counselling and medical decision-making.
2025-02-13 | A Cardiocraniofacial Syndrome Associated With a Novel Missense Variant in GATA6: A Fetal Case Report.
Hypoplastic right heart syndrome (HRHS) is an uncommon congenital cardiac defect, characterized by variable underdevelopment of the right-sided heart structures. We report on a case of HRHS in a 25-week female fetus. Prenatal karyotype was normal. Autopsy performed following pregnancy termination demonstrated characteristic craniofacial dysmorphism and complex congenital heart disease encompassing severe hypoplasia of the right ventricle, main pulmonary artery and tricuspid valve, ostium secundum atrial septal defect, and ductus arteriosus agenesis. Macroscopic and histologic examinations of the brain and organs were unremarkable. Post-mortem array CGH didn't detect any unbalanced chromosomal abnormalities. Exome and Sanger sequencing revealed a novel de novo heterozygous missense variant in GATA6 (NM_005257.6:c.1385A>G) which is located in the hotspot exon 4 encoding the highly conserved C-terminal zinc finger domain. This report ascertains that GATA6 haploinsufficiency may cause a cardiocraniofacial syndrome consisting of distinctive craniofacial dysmorphism and HRHS.
2023-11-15 | Dichorionic Diamniotic Twin Pairs with Complex Congenital Heart Disease.
Complex congenital heart disease (CHD) in each of dichorionic diamniotic (DiDi) twin pairs is extremely rare and has not been well characterized. Four DiDi twin pairs were included in this multi-institutional case series. The congenital cardiac abnormalities noted included tetralogy of Fallot (ToF) with pulmonary atresia and collaterals (n = 1), ToF with absent pulmonary valve (n = 1), ToF (n = 2), discontinuous right pulmonary artery (RPA) (n = 1), tricuspid atresia (TA) with normally related great arteries and pulmonary valve stenosis or atresia (n = 2) and coarctation of aorta (CoA) with bicuspid aortic valve (BAV) and borderline left-sided structures (n = 1). Genetic testing was obtained on seven of the eight twins but did not reveal any causal abnormality. A comprehensive review of literature yielded another 8 DiDi twin pairs with complex CHD. The CHD noted in these twin pairs included ToF (n = 2), CoA (n = 4), corrected transposition of great arteries (ccTGA) (n = 2), truncus arteriosus (n = 2), complete common atrioventricular canal (CCAVC) (n = 2), hypoplastic left heart syndrome (HLHS) (n = 2), Shone's complex (n = 1), and hypoplastic right heart syndrome (HRHS) (n = 1). Limited genetic testing was obtained on 4 of these twins and revealed trisomy 21 in a twin pair. Conotruncal abnormalities (42%), CoA (21%), and abnormalities of the right ventricle, the right ventricular outflow tract and pulmonary arteries (17%) are more prevalent in DiDi twins with complex CHD. Clustering of these abnormalities suggests a possible genetic basis; however, genetic testing was obtained on eleven of the twins, and except for trisomy 21 in a twin pair both of whom had CCAVC, did not reveal any causal abnormality. A major direct genetic contribution is therefore unlikely and like other CHD, the underlying etiopathological basis is likely multifactorial.
small molecules
2026-03-01 | 659: INHALED EPOPROSTENOL FOR REFRACTORY HYPOXEMIA IN AN ADULT FONTAN PATIENT WITH HLHS: A CASE REPORT
Introduction: Hypoplastic left heart syndrome (HLHS) is a rare congenital cardiac defect in which systemic circulation is dependent on right ventricular output. The Fontan procedure creates a pathway for blood to circulate directly into the lung, which ultimately results in persistent shunt physiology. The complex hemodynamic physiology that arises is especially challenging in critically ill patients, where adequate oxygenation is of utmost importance. Inhaled pulmonary vasodilators such as epoprostenol (EPO) can selectively reduce pulmonary vascular resistance (PVR), improve ventilation-perfusion matching, and optimize systemic oxygen delivery. Description: 32-year-old male with HLHS status post-Fontan presented with progressive dyspnea following a week of nausea and vomiting. He transitioned from an oxymizer to high-flow nasal cannula (40 L/min, FiO2 1.0), then to BiPAP (12/5, FiO2 1.0), but remained hypoxic. ABG on BiPAP showed PaO2 50 mmHg. He was intubated for worsening respiratory failure, but oxygenation declined with PEEP of 8 cm H2O (PaO2 54 mmHg on FiO2 0.8, SpO2 92.5%), likely due to impaired pulmonary blood flow from elevated intrathoracic pressure. Inhaled epoprostenol was initiated, resulting in marked improvement in oxygenation. The patient was weaned to HFNC with epoprostenol, then transitioned as low as HFNC 30L/.45 FIO2 and transferred to a congenital heart center for further management. Discussion: In Fontan patients, positive pressure ventilation can worsen oxygenation by impeding passive pulmonary blood flow and increasing right-to-left shunting. Inhaled epoprostenol improves V/Q matching by reducing PVR and enhancing pulmonary flow without systemic vasodilation. This case demonstrates the utility of epoprostenol as a rescue strategy for refractory hypoxemia in adults with complex congenital heart disease. Recognition of unique physiologic interactions in this population is crucial for individualized management in the ICU.
2025-12-01 | Volume Loading May Compromise Left Ventricular Filling in Patients with a Borderline Hypoplastic Left Ventricle.
Given the high prevalence of end-organ damage in the long term after the Fontan procedure, patients presenting with borderline hypoplastic left ventricle (LV) are increasingly directed towards biventricular circulation. We present the case of a patient with borderline LV who developed severe pulmonary hypertension shortly after biventricular repair. We initially thought it was purely caused by a hypoplastic LV; however, it was partly induced by a delayed/prolonged right ventricular (RV) contraction that compressed the interventricular septum and impaired left ventricular filling, which was exacerbated by volume loading during cardiac catheterization. Although the coexisting right bundle branch block (RBBB) might have contributed to the delayed RV contraction, volume depletion through aggressive diuresis shortened the RV contraction interval, resulting in improvement of interventricular crosstalk and the alleviation of symptoms related to pulmonary congestion, regardless of the presence of complete RBBB. Subsequently, our patient achieved favorable LV growth after 2 years of observation. While volume loading has been considered as an option to promote the growth of the hypoplastic LV, aggressive fluid management may offer an alternative for allowing sufficient time to achieve adequate ventricular growth in cases of non-compliant LV properties.
2025-05-19 | Aneurysm of the fetal right ventricular free wall progressing to hypoplastic right heart syndrome: prenatal diagnosis, maternal digoxin therapy, and successful surgical intervention-a case report.
Congenital right ventricular aneurysm (CVA) and diverticulum (CVD) are rare heart diseases that can be diagnosed prenatally. Data on the natural progression of ventricular aneurysms or diverticula identified during fetal life remains scarce, with insights primarily derived from a limited number of case reports and case series. This case report aims to highlight the diagnosis, management, and outcomes of a rare right ventricular free wall aneurysm progressing to hypoplastic right heart syndrome (HRHS), utilizing advanced fetal imaging and prenatal therapy. These findings provide valuable perspective on the underlying cause, diagnostic approaches, and treatment strategy for rare cardiac anomaly. The aneurysm of the right ventricular free wall was diagnosed 13 weeks of gestation during prenatal ultrasound of the fetus in the first trimester. At the time of diagnosis, severe tricuspid valve stenosis with severe tricuspid regurgitation, critical pulmonary stenosis, pericardial effusion, ascites, and secondary flow reversal in the ductus venosus was found. Genetic testing using microarray-based comparative genomic hybridization (aCGH) on amniotic fluid samples showed no genomic imbalance. Digoxin treatment was initiated at 13 weeks of gestation, starting with a loading dose of 1,200 micrograms, followed by a maintenance dose of 375 micrograms daily, to address signs of fetal heart failure. The fetalHQ® software was utilized to assess the size and contractility of both the right and left ventricles, focusing on global and segmental strain measurements. The gradual reduction in right ventricular cardiac output led to the progression of HRHS with pulmonary atresia. At 39 weeks of gestation, a female newborn weighing 2,480 g was delivered in good condition, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Prostaglandin E1 treatment was initiated postnatally to maintain ductal patency. Postnatal echocardiography and angio-computed tomography (CT) confirmed the prenatal diagnosis, revealing a right ventricle-to-right coronary artery (RCA) fistula and interruption of RCA perfusion continuity. The newborn underwent successful first-stage palliation with a Blalock-Taussig shunt to establish systemic-pulmonary circulation. Follow-up during the interstage period showed the child remained in good clinical condition, with no significant complications reported. CVAs are rare but significant anomalies with potential for severe hemodynamic consequences. Multidisciplinary approaches integrating advanced imaging techniques, prenatal counseling, and tailored postnatal management are essential for optimizing outcomes.
2024-11-12 | Abstract 4140558: Circulating plasma proteins in the Fontan circulation predict mitochondrial oxidative stress
Background: Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation constitute the largest group of children hospitalized with circulation failure, experiencing an in-hospital mortality rate of 20-50%. We investigated the mechanisms leading to circulation failure so as to identify novel therapeutic targets. Methods: Blood was collected from patients with HLHS s/p Fontan and controls with normal cardiac anatomy and function (N=6/group). Plasma microvesicles (MV) were isolated, and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change >1.5 or < -1.5, p<0.05, were evaluated using DAVID and Ingenuity pathway analysis. We assessed the association of most highly dysregulated proteins with NYHA class (clinical indicator of heart failure), right ventricular fractional area change (RV FAC) (echocardiographic indicator of RV systolic function), oxygen saturation and hemoglobin using Pearson correlation. Results: Age of Fontan patients vs. controls was 16.14±23 vs. 15.78±2; 40% were male in both groups. 80% of Fontan patients were in NYHA class II/III, 20% in NYHA class IV; 60% had Fontan-associated liver disease. Increasing expression of the following proteins was associated with worsening NYHA class: complement system (C1QA, r=0.91; C7, r=0.53; FCN3, r=0.52), membrane transporters (SLC2A1, r=0.82; SLC4A1, r=0.76), mitochondrial reactive oxygen species (mROS) generation (HSPD1, r=0.81; ATP5F1A, r=0.75) and cytoskeletal proteins (ANK1, r=0.63; ACTN1, r=0.76). Increasing expression of proteins involved in mROS generation were also associated with worsening RV FAC. Decreasing expression of the following proteins was associated with worsening NYHA class and RV FAC: B-cell lymphopoiesis (DOCK10; r=-0.80), adhesion (ADAM10, r=-0.72; CD151, r=-0.69), and coagulation (SERPINF2, r=-0.55). Higher expression of proteins involved in mitochondrial ROS generation and lower expression of proteins involved in lymphopoiesis and adhesion were associated with lower oxygen saturation and higher hemoglobin(Figure). Conclusion: Circulating plasma proteins in the Fontan circulation predict complement activation, mROS, cytoskeletal changes and decreased cell-cell adhesion. This circulating proteomic profile is associated with worsening heart failure and cyanosis providing mechanistic insight into heart failure progression and highlights novel therapeutic targets.
2024-06-28 | Outcomes of Children With Hypoplastic Left Heart Syndrome and Heart Failure on Medical Therapy.
Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.
cell therapies
2026-03-14 | Outcomes of Heart Transplantation in Single-Ventricle Physiology: A Retrospective Single-Center Experience with Emphasis on Surgical Complexity.
Background: Patients with single-ventricle physiology represent a high-risk group for heart transplantation. Due to complex anatomical and physiological challenges, including multiple prior sternotomies, pulmonary artery abnormalities, and systemic consequences of altered circulation, they represent both a surgical and a clinical challenge. We aimed to analyze perioperative challenges, as well as early and long-term complications, in this specific group of patients. Methods: We performed a retrospective data analysis of a high-volume heart transplant center, focusing on patients with single-ventricle physiology who were scheduled for heart transplantation due to end-stage heart failure. We retrospectively analyzed the period from the beginning of the transplant program in November 1985 to the end of November 2024. Results: Among 1553 transplanted patients (adults and children), 29 were transplanted due to congenital heart disease (congenital valvular disease not included). In this group, nine patients were transplanted due to end-stage heart failure in the course of single-ventricle physiology. Age at transplantation ranged from 7 to 31 years (median, 17 years), and body weight ranged from 15 to 69 kg (median, 47.9 kg). All nine patients referred for heart transplantation presented with single-ventricle physiology. Their underlying congenital heart defects were heterogeneous and included hypoplastic left heart syndrome (HLHS), double-outlet left ventricle (DOLV), transposition of the great arteries (TGA) with associated ventricular septal defects (VSDs), atrial septal defects (ASDs), valvular abnormalities such as tricuspid and or pulmonary valve atresia or stenosis, systemic or atrioventricular valve regurgitation, and vascular abnormalities, including right-sided aortic arch, aortic coarctation, and pulmonary artery hypoplasia, stenosis, or occlusion, as well as associated pulmonary vascular abnormalities such as left pulmonary artery stenosis and MAPCAs. All patients had previously undergone staged palliative procedures, including Norwood, Hemi-Fontan, Fontan, bidirectional Glenn, modified Blalock-Taussig shunts, Bjork-Fontan, or pulmonary artery banding, often with repeated interventions such as balloon angioplasty, stent placement, or MAPCA closure. Extracardiac comorbidities were common and included coagulopathies, protein-losing enteropathy, hepatic dysfunction, and chronic venous insufficiency. Preoperative functional status was markedly impaired in all patients (NYHA III-IV, INTERMACS 3-4), with severely reduced exercise capacity and thrombotic events in several individuals. Perioperative transplant surgical strategies included femoral cannulation in four cases and standard aortic and caval cannulation in five cases. Pulmonary artery reconstruction was required in all patients. Extended donor pulmonary arteries were applied in eight cases, while a bifurcated Dacron prosthesis was utilized in one patient. Perioperative mortality was 33%, with three deaths attributed to bleeding and hemodynamic instability, while overall mortality was 44% including one late death unrelated to transplantation. Protein-losing enteropathy, although persistent in the immediate postoperative period, resolved in all surviving patients, underscoring the transformative impact of transplantation. Conclusions: These findings emphasize the importance of individualized surgical planning, extended donor pulmonary artery harvesting, and careful preoperative coordination. Heart transplantation remains a viable and life-extending option for selected single-ventricle patients, despite the significant technical and clinical challenges involved.
2025-10-14 | Engineered heart tissues formed with cardiac progenitors and differentiated cardiomyocytes exhibit similar physiologic properties at differentiation-matched timepoints.
Congenital heart diseases, including single ventricle heart defects such as hypoplastic left and right heart syndromes, remain a leading cause of neonatal death and long-term morbidity. Regenerative medicine approaches hold great therapeutic promise for treating single ventricle disease, specifically through the use of human pluripotent stem cell-derived cardiomyocytes (iPSC-CM) to generate pulsatile conduits capable of growing and developing over time within the recipient. However, current strategies for rapidly fabricating large-scale engineered heart muscle to create such conduits face limitations, including the shear stress generated during most bioprinting processes along with harsh enzymatic treatments required for initial singularization of cells prior to bioprinting, which together can compromise cell viability and downstream tissue function. Here, we explored the use of derived cardiovascular progenitors (iPSC-CVP) as an alternative to fully differentiated cardiomyocytes as a potential cell source for future biomanufacturing efforts. We demonstrate that iPSC-CVP can be used to form functional engineered heart tissues with similar electrophysiological properties to tissues formed from fully differentiated iPSC-CM, while also being more amenable to enzymatic dissociation and mechanical manipulation. Our results suggest that iPSC-CVP may be an ideal cell population for future efforts in biofabrication of contractile structures such as engineered heart muscle and pulsatile conduits.
2024-06-05 | Staged repair of borderline hypoplastic heart disease with early biventricular conversion.
In select patients with borderline ventricular hypoplasia, we adopted a strategy of initial single-ventricle palliation followed by staged or direct biventricular conversion by 2 years of age. Between 2018 and 2023, 14 newborns with borderline hypoplastic heart disease deemed high risk for primary biventricular repair underwent palliative procedures as a neonate/infant, followed by staged or direct biventricular conversion. Of the 14 patients, 6 had borderline left ventricles and 8 had borderline right ventricles. Index neonatal operations were performed in 12 patients and included the Norwood operation (n = 5), pulmonary artery band (n = 3), ductal stent (n = 3), and hybrid Norwood (n = 1). Five patients underwent direct biventricular conversion, and the remaining 9 patients underwent staged ventricular recruitment operations at a mean age of 6 months (range, 3-11 months). Ventricular recruitment operations included atrial septation with or without ventricular rehabilitation, atrioventricular valve repair, or outflow tract operations. At a mean duration of 8 months (range, 4-10 months) after ventricular recruitment, there was a significant increase in chamber volume, aortic valve, and mitral valve size in patients with borderline left ventricles, and a normalization of the right ventricle:left ventricle end-diastolic volume ratio in patients with borderline right ventricles. To date, 13 of 14 patients have undergone successful biventricular conversion at a mean age of 16 months (range, 4-31 months). In select newborns with borderline hypoplastic heart disease, single-ventricle palliation followed by staged or direct biventricular conversion may increase infant survival while allowing for early attainment of a biventricular circulation.
2023-11-07 | Abstract 12344: Effect of Valved versus Non-Valved Conduits in Norwood Procedure on Ventricular Size and Function in Stage I Palliation for Hypoplastic Left Heart Syndrome
Background: Mortality in the interstage period remains high in hypoplastic left heart syndrome (HLHS) after introduction of the right ventricle (RV) to pulmonary artery conduit to the Norwood procedure. Prior studies have not shown long term survival benefit with conduits, possibly due to regurgitation and volume load, which may cause decreased RV function. Valved conduits (VC) were introduced more recently to address these limitations. Hypothesis: The goal of the study was to assess differences in RV size and function during the interstage period between patients undergoing Norwood procedure with valved versus non-valved conduits (NVC). We hypothesized that patients with VC would have smaller increases in RV size and improved function compared to those with NVC. Methods: Twenty-five consecutive neonates with HLHS who underwent Norwood procedure with VC were compared to 25 consecutive neonates who underwent Norwood with NVC from 2013 and 2022. Primary outcomes were RV size measured by end diastolic area (EDA) on 4-chamber images and function measured by RV fractional area change and global longitudinal strain. Results: Most patients with VC (96%) did not develop more than mild conduit regurgitation. There was no difference in EDA increase one month post op between groups, but there was a significantly smaller increase in EDA pre-Glenn compared to baseline in the VC group (Table 1). Functional measures were not significantly different during follow up. There was no difference in interstage cardiac events or mortality. Conclusions: Patients with VC at time of Norwood had smaller increases in ventricular size compared to those with NVC, but there were no differences in functional parameters during follow up. It is possible decreased volume load will have a beneficial long term effect on the immature myocardium of infants with HLHS. Larger studies are needed to further examine the hemodynamic benefits of VC in the interstage period and throughout the stages of palliation.
2021-01-12 | [Fetal cardiac intervention and perioperative management of fetus with hypoplastic right heart syndrome].
Objective: To summarize the experience of perioperative management strategy of fetal pulmonary valvuloplasty (FPV) for hypoplastic right heart syndrome (HRHS). Methods: In the retrospective study of perioperative data, 13 fetuses of HRHS were treated with FPV in Qingdao Women and Children's Hospital from July 2018 to June 2019. Results: (1) The evaluation indexes of the right ventricle in 13 fetuses before FPV: the mean ratio of tricuspid/mitral annulus, right/left ventricular length, pulmonary/aortic annulus, and tricuspid inflow time/cardiac cycle were 0.81±0.04, 0.56±0.14, 0.69±0.06, and 0.35±0.03, respectively. (2) All pregnant mothers underwent general anesthesia. The basic fetal heart rate was (156±12) beats per minutes before FPV, and 9 fetuses showed bradycardia during the operation, and recovered to normal after drug resuscitation. On the first day after FPV, two cases had bradycardia and pregnancy was terminated. The fluctuation of systolic blood pressure of pregnant mother was less than 20%, and there was no significant difference between preoperative and intraoperative pulse pressure [(36.0±5.6) vs (35.8±6.9) mmHg (1 mmHg=0.133 kPa); t=8.102, P=0.951]. (3) All cases of HRHS fetus successfully underwent FPV. The average gestational age was (27.3±0.8) weeks. The average operation time was (23.2±1.0) minutes. The ratio of tricuspid to mitral annulus (t=-2.513, P=0.022) and the ratio of right to left ventricular length (t=-3.373, P=0.003) were significantly improved at 6 weeks postoperatively. Ten fetuses were delivered, and there was no death after early intervention. (4) Of 13 pregnant women, 3 cases were nausea and vomiting on the day of FPV operation, the treatment of the symptoms was improved by tropisetron; one case had tolerable abdominal pain and improved without special treatment. Pregnant women had no major complications such as cardiac failure, abortion and death. (5) Chromosome karyotype analysis and microarray analysis of amniotic fluid was retained during the operation. No typical chromosome abnormality or other abnormal genetic diagnosis was found. Conclusions: FPV colud be used as an effective intervention measure to promote the development of right ventricle in HRHS fetuses. The scientific management of multidisciplinary professional technical team in perioperative period is particularly important to ensure the success of FPV and the safety of pregnant women and fetuses. 目的： 探讨右心发育不良综合征（HRHS）胎儿的心脏介入治疗及围手术期管理。 方法： 收集2018年7月至2019年6月青岛市妇女儿童医院行胎儿肺动脉瓣成形术（FPV）介入治疗的13例HRHS胎儿的围手术期临床资料进行回顾性分析，探讨FPV的术前评估、麻醉、手术治疗及结果、围手术期并发症以及HRHS胎儿的遗传学筛查结果。 结果： （1）术前评估：13例HRHS胎儿的右心室相关指标，三尖瓣瓣环直径/二尖瓣瓣环直径比值、右心室长径/左心室长径比值、肺动脉瓣瓣环直径/主动脉瓣瓣环直径比值、三尖瓣流入时间/心动周期比值分别为0.81±0.04、0.56±0.14、0.69±0.06、0.35±0.03，与FPV的适应证（上述指标分别为≤0.83、≤0.64、≤0.75、<0.36）符合，可行FPV。（2）麻醉：采用舒芬太尼、丙泊酚联合七氟醚的静脉-吸入复合全身麻醉，13例HRHS胎儿的术前基线胎心率为（156±12）次/min，术中9例胎儿出现心动过缓，均予心内注射药物复苏治疗后恢复正常；孕妇术前血压与术中比较，收缩压［分别为（114.7±3.9）、（99.7±6.0） mmHg（1 mmHg=0.133 kPa）］和舒张压［分别为（78.7±5.6）、（63.8±3.2） mmHg］均显著下降（P<0.01），但术前脉压差与术中脉压差［分别为（36.0±5.6）、（35.8±6.9） mmHg］比较无显著差异（t=8.102，P=0.951）。（3）手术治疗及结果：13例HRHS胎儿行FPV时的孕周为（27.3±0.8）周，均顺利完成FPV，手术时间为（23.2±1.0） min。10例继续妊娠的HRHS胎儿，术后6周评估右心室相关指标，三尖瓣瓣环直径/二尖瓣瓣环直径比值（t=-2.513，P=0.022）、右心室长径/左心室长径比值（t=-3.373，P=0.003）分别与术前比较，差异均有统计学意义。10例继续妊娠的HRHS胎儿均顺利分娩，出生后经早期干预后均存活。（4）围手术期并发症：13例孕妇中，FPV术后当日，3例出现恶心、呕吐，对症给予托烷司琼治疗后好转；1例出现腹痛，可耐受，未予特殊处理自行好转。13例孕妇围手术期无心力衰竭、流产、死亡等严重并发症。13例HRHS胎儿中，2例FPV术后当日出现严重的持续性心动过缓，1例术后随访过程中出现依赖右心室的冠状动脉循环，均选择终止妊娠。（5）遗传学筛查：13例HRHS胎儿均行染色体核型分析及染色体微阵列分析，未见典型的染色体异常及其他遗传学异常。 结论： FPV可作为HRHS胎儿的有效干预措施，可促进胎儿右心室的发育。多学科专业技术团队围手术期科学管理对确保手术成功及孕妇、胎儿的安全尤为重要。.
gene therapies
2025-08-11 | Hypoplastic right heart with heterotaxy has worse five-year transplant-free survival than the hypoplastic left heart syndrome: a thirteen-year single-centre experience.
Outcomes of single ventricle heart defects may be influenced by the morphological type of the hypoplastic ventricle. Recent multi-centre studies have targeted on outcomes of hypoplastic left heart syndrome with limited focus on outcomes of hypoplastic right heart syndrome. We aimed at studying the clinical outcomes of hypoplastic right heart syndrome in the recent era. We performed a retrospective analysis of all hypoplastic right heart syndrome patients (n = 153) born between January 2010 and January 2023. Five-year transplant-free survival was compared with hypoplastic left heart syndrome patients without heterotaxy (n = 144) born during the same time. Double-inlet left ventricle was the most common anatomic hypoplastic right heart syndrome subtype (n = 39, 25%). Twenty-six (17%) patients with hypoplastic right heart had associated heterotaxy. Five-year transplant-free survival was high for most groups (double inlet left ventricle: 100%, pulmonary atresia: 94%, Ebstein's anomaly: 92%, tricuspid atresia: 90% respectively). The heterotaxy group had worse early outcomes with 3 deaths and 3 heart transplants, before Fontan completion. Heterotaxy was a significant risk factor for death/transplant prior to Fontan completion in hypoplastic right heart syndrome patients (p = 0.03). Patients with hypoplastic right heart syndrome with heterotaxy had significantly worse 5-year transplant-free survival (71%) when compared to hypoplastic right heart syndrome without heterotaxy (95%) and hypoplastic left heart syndrome without heterotaxy (75%), p < 0.001. Hypoplastic right heart syndrome patients have excellent clinical outcomes and better early childhood survival than hypoplastic left heart syndrome in the current era, except when associated with heterotaxy. The survival advantage conferred by a single left ventricle appears to be negated by heterotaxy syndrome and should be strongly considered during caregiver counselling and medical decision-making.
2025-02-13 | A Cardiocraniofacial Syndrome Associated With a Novel Missense Variant in GATA6: A Fetal Case Report.
Hypoplastic right heart syndrome (HRHS) is an uncommon congenital cardiac defect, characterized by variable underdevelopment of the right-sided heart structures. We report on a case of HRHS in a 25-week female fetus. Prenatal karyotype was normal. Autopsy performed following pregnancy termination demonstrated characteristic craniofacial dysmorphism and complex congenital heart disease encompassing severe hypoplasia of the right ventricle, main pulmonary artery and tricuspid valve, ostium secundum atrial septal defect, and ductus arteriosus agenesis. Macroscopic and histologic examinations of the brain and organs were unremarkable. Post-mortem array CGH didn't detect any unbalanced chromosomal abnormalities. Exome and Sanger sequencing revealed a novel de novo heterozygous missense variant in GATA6 (NM_005257.6:c.1385A>G) which is located in the hotspot exon 4 encoding the highly conserved C-terminal zinc finger domain. This report ascertains that GATA6 haploinsufficiency may cause a cardiocraniofacial syndrome consisting of distinctive craniofacial dysmorphism and HRHS.
2023-11-15 | Dichorionic Diamniotic Twin Pairs with Complex Congenital Heart Disease.
Complex congenital heart disease (CHD) in each of dichorionic diamniotic (DiDi) twin pairs is extremely rare and has not been well characterized. Four DiDi twin pairs were included in this multi-institutional case series. The congenital cardiac abnormalities noted included tetralogy of Fallot (ToF) with pulmonary atresia and collaterals (n = 1), ToF with absent pulmonary valve (n = 1), ToF (n = 2), discontinuous right pulmonary artery (RPA) (n = 1), tricuspid atresia (TA) with normally related great arteries and pulmonary valve stenosis or atresia (n = 2) and coarctation of aorta (CoA) with bicuspid aortic valve (BAV) and borderline left-sided structures (n = 1). Genetic testing was obtained on seven of the eight twins but did not reveal any causal abnormality. A comprehensive review of literature yielded another 8 DiDi twin pairs with complex CHD. The CHD noted in these twin pairs included ToF (n = 2), CoA (n = 4), corrected transposition of great arteries (ccTGA) (n = 2), truncus arteriosus (n = 2), complete common atrioventricular canal (CCAVC) (n = 2), hypoplastic left heart syndrome (HLHS) (n = 2), Shone's complex (n = 1), and hypoplastic right heart syndrome (HRHS) (n = 1). Limited genetic testing was obtained on 4 of these twins and revealed trisomy 21 in a twin pair. Conotruncal abnormalities (42%), CoA (21%), and abnormalities of the right ventricle, the right ventricular outflow tract and pulmonary arteries (17%) are more prevalent in DiDi twins with complex CHD. Clustering of these abnormalities suggests a possible genetic basis; however, genetic testing was obtained on eleven of the twins, and except for trisomy 21 in a twin pair both of whom had CCAVC, did not reveal any causal abnormality. A major direct genetic contribution is therefore unlikely and like other CHD, the underlying etiopathological basis is likely multifactorial.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.