Single Ventricle Heart Defects Research Articles

Days alive and out of hospital for children born with single-ventricle heart disease.

This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality. This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital. In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157-319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = -37.55, p = 0.01), presence of a dominant right ventricle (b = -31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = -37.65, p <0.05), index hybrid Norwood operation (b = -138.73, p < 0.01), or index heart transplant (b = -158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital. Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Risk Factors and Outcomes of Children with Congenital Heart Disease on Extracorporeal Membrane Oxygenation-A Ten-Year Single-Center Report.

For children born with congenital heart defects (CHDs), extracorporeal life support may be necessary. This retrospective single-center study aimed to investigate the outcomes of children with CHDs on extracorporeal membrane oxygenation (ECMO), focusing on various risk factors. Among the 88 patients, 36 (41%) had a single-ventricle heart defect, while 52 (59%) had a biventricular defect. In total, 25 (28%) survived, with 7 (8%) in the first group and 18 (20%) in the latter. A p-value of 0.19 indicated no significant difference in survival rates. Children with biventricular hearts had shorter ECMO durations but longer stays in the intensive care unit. The overall rate of complications on ECMO was higher in children with a single ventricle (odds ratio [OR] 1.57, 95% confidence interval [CI] 0.67-3.7); bleeding was the most common complication in both groups. The occurrence of a second ECMO run was more frequent in patients with a single ventricle (22% vs. 9.6%). ECMO can be effective for children with congenital heart defects, including single-ventricle patients. Bleeding remains a serious complication associated with worse outcomes. Patients requiring a second ECMO run within 30 days have lower survival rates.

Abstract 10776: A Supervised Classification Model Detects Fontan Patients Based on Clinical Notes With Higher Accuracy Than ICD Codes

Introduction: The Fontan operation palliates single ventricle heart defects. As native anatomy varies, Fontan cases cannot always be identified by ICD9 or 10CM codes. Hypothesis: We sought to train and evaluate a supervised machine learning (ML) system to identify Fontan cases based on unstructured clinical notes in a large database. Methods: 160 adult Fontan patients from validated clinical data at a single tertiary referral center with available text notes were studied. The imbalanced data set had more non-Fontan cases than Fontan patients; thus we created multiple datasets with different positive : negative case ratios ranging from 1:2 to 1:10. We used stratified 80-20 training-testing splits of data. Vectorized representations of text notes were used as features. We trained a Support Vector Machine (SVM) model, mostly used for text classification, to identify Fontan cases from notes. For each dataset, we performed random 80-20 data splitting 10 times and reported average F 1 score (harmonic mean of recall/sensitivity &amp; precision/positive predictive value) over the positive class. Results: The model achieved a mean F 1 score of 0.95 for the positive class on the data split with 1:2 positive-negative ratio. Increasing data imbalance from 1:2 to 1:10 did not substantially impact performance. The mean F 1 score over all data splits was 0.94, and SD 0.01. We also computed precision, recall, and F 1 score of ICD codes to identify Fontan patients. Performance comparisons between ICD codes only and Natural Language Processing (NLP)/ML are in Table 1. Conclusions: A supervised classification model more effectively detects Fontan patients based on clinical notes with higher accuracy than ICD codes. The model is robust and insensitive to data imbalance. Findings suggest our model may work effectively in real-world data. Since the sensitivity of ICD codes is high but PPV is low, it may be beneficial to apply ICD codes as a filter prior to applying NLP/ML to improve performance.

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Virtual Reality Cardiac Surgical Planning Software (CorFix) for Designing Patient-Specific Vascular Grafts: Development and Pilot Usability Study.

BackgroundPatients with single ventricle heart defects receive 3 stages of operations culminating in the Fontan procedure. During the Fontan procedure, a vascular graft is sutured between the inferior vena cava and pulmonary artery to divert deoxygenated blood flow to the lungs via passive flow. Customizing the graft configuration can maximize the long-term benefits. However, planning patient-specific procedures has several challenges, including the ability for physicians to customize grafts and evaluate their hemodynamic performance.ObjectiveThe aim of this study was to develop a virtual reality (VR) Fontan graft modeling and evaluation software for physicians. A user study was performed to achieve 2 additional goals: (1) to evaluate the software when used by medical doctors and engineers, and (2) to explore the impact of viewing hemodynamic simulation results in numerical and graphical formats.MethodsA total of 5 medical professionals including 4 physicians (1 fourth-year resident, 1 third-year cardiac fellow, 1 pediatric intensivist, and 1 pediatric cardiac surgeon) and 1 biomedical engineer voluntarily participated in the study. The study was pre-scripted to minimize the variability of the interactions between the experimenter and the participants. All participants were trained to use the VR gear and our software, CorFix. Each participant designed 1 bifurcated and 1 tube-shaped Fontan graft for a single patient. A hemodynamic performance evaluation was then completed, allowing the participants to further modify their tube-shaped design. The design time and hemodynamic performance for each graft design were recorded. At the end of the study, all participants were provided surveys to evaluate the usability and learnability of the software and rate the intensity of VR sickness.ResultsThe average times for creating 1 bifurcated and 1 tube-shaped graft after a single 10-minute training session were 13.40 and 5.49 minutes, respectively, with 3 out 5 bifurcated and 1 out of 5 tube-shaped graft designs being in the benchmark range of hepatic flow distribution. Reviewing hemodynamic performance results and modifying the tube-shaped design took an average time of 2.92 minutes. Participants who modified their tube-shaped graft designs were able to improve the nonphysiologic wall shear stress (WSS) percentage by 7.02%. All tube-shaped graft designs improved the WSS percentage compared to the native surgical case of the patient. None of the designs met the benchmark indexed power loss.ConclusionsVR graft design software can quickly be taught to physicians with no engineering background or VR experience. Improving the CorFix system could improve performance of the users in customizing and optimizing grafts for patients. With graphical visualization, physicians were able to improve WSS percentage of a tube-shaped graft, lowering the chance of thrombosis. Bifurcated graft designs showed potential strength in better flow split to the lungs, reducing the risk for pulmonary arteriovenous malformations.

Probing single ventricle heart defects with patient-derived induced pluripotent stem cells and emerging technologies.

Single ventricle heart defects (SVHDs) are a severe type of congenital heart disease with poorly understood pathogenic mechanisms. New research using patient-specific induced pluripotent stem cells (iPSCs) as a cellular model is beginning to uncover genetic and cellular etiologies of SVHDs. Hypoplastic left heart syndrome (HLHS) is a type of SVHD that is characterized by an underdeveloped left ventricle and other malformations in the left side of the heart. Hypoplastic right heart syndrome (HRHS), the second type of SVHD, is characterized by an underdeveloped right heart, including malformed tricuspid and pulmonary valves. Despite a noticeable lack of research on SVHD, emerging technologies offer a promising future to further probe the genetic and cellular mechanisms of these diseases. Pediatric cardiovascular research is at the dawn of a new era in terms of what can be discovered with patient-specific iPSCs in conjunction with other technologies (e.g., organoids, single-cell genomics, CRISPR/Cas9 genome editing). In this review, we present recent approaches and findings utilizing patient-specific iPSCs to identify cellular mechanisms responsible for improper cardiac organogenesis in HLHS and HRHS.

Semi-Automatic Planning and Three-Dimensional Electrospinning of Patient-Specific Grafts for Fontan Surgery.

This paper proposes a semi-automatic Fontan surgery planning method for designing and manufacturing hemodynamically optimized patient-specific grafts. Fontan surgery is a palliative procedure for patients with a single ventricle heart defect by creating a new path using a vascular graft for the deoxygenated blood to be directed to the lungs, bypassing the heart. However, designing patient-specific grafts with optimized hemodynamic performance is a complex task due to the variety of patient-specific anatomies, confined surgical planning space, and the requirement of simultaneously considering multiple design criteria for vascular graft optimization. To address these challenges, we used parameterized Fontan pathways to explore patient-specific vascular graft design spaces and search for optimal solutions by formulating a nonlinear constrained optimization problem, which minimizes indexed power loss (iPL) of the Fontan model by constraining hepatic flow distribution (HFD), percentage of abnormal wall shear stress (%WSS) and geometric interference between Fontan pathways and the heart models (InDep) within clinically acceptable thresholds. Gaussian process regression was employed to build surrogate models of the hemodynamic parameters as well as InDep and [Formula: see text] (conduit model smoothness indicator) for optimization by pattern search. We tested the proposed method on two patient-specific models (n=2). The results showed the automatically optimized (AutoOpt) Fontan models hemodynamically outperformed or at least are comparable to manually optimized Fontan models with significantly reduced surgical planning time (15 hours versus over 2 weeks). We also demonstrated feasibility of manufacturing the AutoOpt Fontan conduits by using electrospun nanofibers.

Two-scale haemodynamic modelling for patients with Fontan circulation

Abstract Palliation of congenital single ventricle heart defects suggests multi-stage surgical interventions that divert blood flow from the inferior and superior vena cava directly to the right and left pulmonary arteries, skipping the right ventricle. Such system with cavopulmonary anastomoses and single left ventricle is called Fontan circulation, and the region of reconnection is called the total cavopulmonary connection (TCPC). Computational blood flow models allow clinicians to predict the results of the Fontan operation, to choose an optimal configuration of TCPC and thus to reduce negative postoperative consequences. We propose a two-scale (1D3D) haemodynamic model of systemic circulation for a patient who has underwent Fontan surgical operation. We use CT and 4D flow MRI data to personalize the model. The model is tuned to patient’s data and is able to represent measured time-averaged flow rates at the inlets and outlets of TCPC, as well as pressure in TCPC for the patient in horizontal position.We demonstrate that changing to quiescent standing position leads to other patterns of blood flow in regional (TCPC) and global haemodynamics. This confirms clinical data on exercise intolerance of Fontan patients.

Transition to Ductal Stenting for Single Ventricle Patients Led to Improved Survival: An Institutional Case Series.

The use of systemic-to-pulmonary shunts (SPS) in neonates with single ventricle heart defects and ductal-dependent pulmonary blood flow (ddPBF) was historically associated with high morbidity and mortality at our center. As a result, we transitioned to the preferential use of ductus arteriosus stents (DS) when feasible. This report describes our initial results with this strategy. A single-center study of single ventricle patients that received DS or SPS from 2015 to 2019 was performed to assess whether DS was associated with decreased in-hospital morbidity and increased survival to stage II palliation. A total of 34 patients were included (DS = 11; SPS = 23). Underlying cardiac anomalies were similar between groups and included pulmonary atresia, unbalanced atrioventricular septal defect, and tricuspid atresia. Procedure success was similar between groups (82% vs 83%). Two DS patients were converted to SPS, due to ductal vasospasm or pulmonary artery obstruction, and four SPS patients required surgical shunt revision. In DS patients, postprocedure mechanical ventilation duration was shorter (one vs three days, P = .009) and fewer required postprocedure extracorporeal membrane oxygenation (9% vs 39%, P = .11). A higher proportion of DS patients survived to stage II palliation (100% vs 64%, P = .035), and the probability of one-year survival was higher in DS patients (100% vs 61%, P = .02). At our center, patients with single ventricle heart defects and ddPBF that received DS experienced reduced in-hospital morbidity and increased survival to stage II palliation compared to SPS.

Fluid-Structure Interaction Simulation of an Intra-Atrial Fontan Connection.

Simple SummaryA fluid-structure interaction (FSI) simulation of an intra-atrial Fontan connection was performed. Power loss and pressure drop results fluctuated less during the FSI simulation than during the simulation run with rigid walls, but there were no observable differences in time-averaged pressure drop, connection power loss or hepatic flow distribution. These results suggested that employing a rigid wall is a reasonable assumption when evaluating time-averaged hemodynamic quantities of the Fontan connection under resting breath-held flow conditions.Total cavopulmonary connection (TCPC) hemodynamics has been hypothesized to be associated with long-term complications in single ventricle heart defect patients. Rigid wall assumption has been commonly used when evaluating TCPC hemodynamics using computational fluid dynamics (CFD) simulation. Previous study has evaluated impact of wall compliance on extra-cardiac TCPC hemodynamics using fluid-structure interaction (FSI) simulation. However, the impact of ignoring wall compliance on the presumably more compliant intra-atrial TCPC hemodynamics is not fully understood. To narrow this knowledge gap, this study aims to investigate impact of wall compliance on an intra-atrial TCPC hemodynamics. A patient-specific model of an intra-atrial TCPC is simulated with an FSI model. Patient-specific 3D TCPC anatomies were reconstructed from transverse cardiovascular magnetic resonance images. Patient-specific vessel flow rate from phase-contrast magnetic resonance imaging (MRI) at the Fontan pathway and the superior vena cava under resting condition were prescribed at the inlets. From the FSI simulation, the degree of wall deformation was compared with in vivo wall deformation from phase-contrast MRI data as validation of the FSI model. Then, TCPC flow structure, power loss and hepatic flow distribution (HFD) were compared between rigid wall and FSI simulation. There were differences in instantaneous pressure drop, power loss and HFD between rigid wall and FSI simulations, but no difference in the time-averaged quantities. The findings of this study support the use of a rigid wall assumption on evaluation of time-averaged intra-atrial TCPC hemodynamic metric under resting breath-held condition.

Abstract 13342: Increasing Use of the Right Ventricle to Pulmonary Artery Shunt for Stage 1 Palliation: A Report From the National Pediatric Cardiology Quality Improvement Collaborative

Introduction: Stage 1 palliation (S1P) of single ventricle heart defects with aortic hypoplasia consists of either the Norwood operation with a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS), or a hybrid procedure. Changes in national trends over time and factors influencing surgical approach remain unclear. Hypothesis: There has been an increase in national use of the RVPAS for S1P. Methods: Data from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase 1 (6/2008-8/2016) and phase 2 (8/2016-9/2019) databases were used. S1P type was evaluated by year of operation. Factors influencing the choice of MBTS versus RVPAS, as well as length of stay after S1P and mortality prior to Stage 2 palliation (S2P) between shunt types, were evaluated. Sites were stratified by the number of patients in the database per year as small (&lt;5), medium (&lt;10) and large (≥10) centers. Results: The combined database included 3335 eligible patients; 1,028 (30.8%) with MBTS, 1,989 (59.7%) with RVPAS, and 318 (9.5%) with hybrid procedure. Overall, of 62 centers, 14.6% of S1P were at small centers (n=26), 40.6% at medium centers (n=24), and 44.7% at large centers (n=12). There was an increase in RVPAS use over time (p=0.02). In multivariable analysis, increasing hospital volume (OR 1.2 [95% CI 1.1-1.4], p=0.003) and absence of other organ system anomalies (OR 1.5 [95% CI 1.0-2.2], p=0.049) were associated with MBTS use over RVPAS. Median length of stay after S1P with MBTS was longer than with RVPAS (31 [95% CI 20-49] vs 29 [95% CI 19-47] days, p=0.054) and mortality was higher prior to S2P (12.3% vs 9.6%, p=0.03). Conclusions: Use of RVPAS with S1P has increased over time with a decrease in MBTS use and unchanged hybrid frequency. MBTS is used more commonly in centers with higher volume and in patients without other anomalies but is associated with longer post-op hospitalization and lower transplant-free survival to stage 2 palliation.

PEMODELAN MATEMATIKA ALIRAN DARAH PADA PEMBULUH DARAH ARTERI DAN VENA PADA KELAINAN JANTUNG SINGLE VENTRICLE

Single ventricle is a heart defect in which one of the ventricle does not developed and bother the blood flow. One of the solutions is fontan surgery. The result of Fontan surgery allows the blood flowing in veins that initially lead to the heart change into the arteries. Because of these changes, there are possibility of swelling and velocity change of blood flowing. This research constructed a mathematical model of blood flowing velocity in arteries and veins due to a single ventricle heart defect that was formed from the momentum and mass equation, which was influenced by the diameter of venous vessel and blood viscosity. The analysis of the blood flow velocity in arteries and veins due to single ventricle heart defect was simulated by MATLAB and FLUENT software. The factors observed were the effect of venous diameter and blood viscosity on the velocity of blood flow in the veins. The result indicated that the greater diameter of the vein, the smaller the flow velocity in the vein. The greater blood viscosity resulted the smaller flow velocity in arteries and veins.

Standardization of the Perioperative Management for Neonates Undergoing the Norwood Operation for Hypoplastic Left Heart Syndrome and Related Heart Defects.

In-hospital complications after the Norwood operation for single ventricle heart defects account for the majority of morbidity and mortality. Inpatient care variation occurs within and across centers. This multidisciplinary quality improvement project standardized perioperative management in a large referral center. Quality improvement project. High volume cardiac center, tertiary care children's hospital. Neonates undergoing Norwood operation. The quality improvement team developed and implemented a clinical guideline (preoperative admission to 48 hr after surgery). The composite process metric, Guideline Adherence Score, contained 13 recommendations in the guideline that reflected consistent care for all patients. One-hundred two consecutive neonates who underwent Norwood operation (January 1, 2013, to July 12, 2016) before guideline implementation were compared with 50 consecutive neonates after guideline implementation (July 13, 2016, to May 4, 2018). No preguideline operations met the goal Guideline Adherence Score. In the first 6 months after guideline implementation, 10 of 12 operations achieved goal Guideline Adherence Score and continued through implementation, reaching 100% for the last 10 operations. Statistical process control analysis demonstrated less variability and decreased hours of postoperative mechanical ventilation and cardiac ICU length of stay during implementation. There were no statistically significant differences in major hospital complications or in 30-day mortality. A higher percentage of patients were extubated by postoperative day 2 after guideline implementation (67% [30/47] vs 41% [41/99], respectively; p = 0.01). Of these patients, reintubation within 72 hours of extubation significantly decreased after guideline implementation (0% [0/30] vs 17% [7/41] patients, respectively; p = 0.02). This initiative successfully implemented a standardized perioperative care guideline for neonates undergoing the Norwood operation at a large center. Positive statistical process control centerline shifts in Guideline Adherence Score, length of postoperative mechanical ventilation, and cardiac ICU length of stay were demonstrated. A higher percentage were successfully extubated by postoperative day 2. Establishment of standard processes can lead to best practices to decrease major adverse events.

Parasitic twin with major cardiac defect: a case report

Parasitic twins are an extremely rare form of asymmetrical conjoined monochorial monoamniotic twins where one of them has a mostly intact body that is able to survive and which is referred to as ‘autosite’, while the counterpart, referred to as ‘parasite’, is only rudimentarily developed being physically attached to and nourished by the other twin. Our case is a baby boy with Single Ventricle Heart defect with a thoraco-abdominal mass (epigastric heteropagus twin) attached to the anterior abdominal wall near the umbilicus with minimal visceral sharing. The twins had two external genitalia both in host and parasite micturating separately. After high risk surgery the parasite could be separated completely from the host and postoperative recovery was uneventful.

Global, regional, and national burden of congenital heart disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

SummaryBackgroundPrevious congenital heart disease estimates came from few data sources, were geographically narrow, and did not evaluate congenital heart disease throughout the life course. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, this study aimed to provide comprehensive estimates of congenital heart disease mortality, prevalence, and disability by age for 195 countries and territories from 1990 to 2017.MethodsMortality estimates were generated for aggregate congenital heart disease and non-fatal estimates for five subcategories (single ventricle and single ventricle pathway congenital heart anomalies; severe congenital heart anomalies excluding single ventricle heart defects; critical malformations of great vessels, congenital valvular heart disease, and patent ductus arteriosus; ventricular septal defect and atrial septal defect; and other congenital heart anomalies), for 1990 through to 2017. All available global data were systematically analysed to generate congenital heart disease mortality estimates (using Cause of Death Ensemble modelling) and prevalence estimates (DisMod-MR 2·1). Systematic literature reviews of all types of congenital anomalies to capture information on prevalence, associated mortality, and long-term health outcomes on congenital heart disease informed subsequent disability estimates.FindingsCongenital heart disease caused 261 247 deaths (95% uncertainty interval 216 567–308 159) globally in 2017, a 34·5% decline from 1990, with 180 624 deaths (146 825–214 178) being among infants (aged <1 years). Congenital heart disease mortality rates declined with increasing Socio-demographic Index (SDI); most deaths occurred in countries in the low and low-middle SDI quintiles. The prevalence rates of congenital heart disease at birth changed little temporally or by SDI, resulting in 11 998 283 (10 958 658–13 123 888) people living with congenital heart disease globally, an 18·7% increase from 1990 to 2017, and causing a total of 589 479 (287 200–973 359) years lived with disability.InterpretationCongenital heart disease is a large, rapidly emerging global problem in child health. Without the ability to substantially alter the prevalence of congenital heart disease, interventions and resources must be used to improve survival and quality of life. Our findings highlight the large global inequities in congenital heart disease and can serve as a starting point for policy changes to improve screening, treatment, and data collection.FundingBill & Melinda Gates Foundation.

Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes

Single ventricle heart defects (SVDs) are congenital disorders that result in a variety of complications, including increased ventricular mechanical strain and mixing of oxygenated and deoxygenated blood, leading to heart failure without surgical intervention. Corrective surgery for SVDs are traditionally handled by the Fontan procedure, requiring a vascular conduit for completion. Although effective, current conduits are limited by their inability to aid in pumping blood into the pulmonary circulation. In this report, we propose an innovative and versatile design strategy for a tissue engineered pulsatile conduit (TEPC) to aid circulation through the pulmonary system by producing contractile force. Several design strategies were tested for production of a functional TEPC. Ultimately, we found that porcine extracellular matrix (ECM)-based engineered heart tissue (EHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary cardiac fibroblasts (HCF) wrapped around decellularized human umbilical artery (HUA) made an efficacious basal TEPC. Importantly, the TEPCs showed effective electrical and mechanical function. Initial pressure readings from our TEPC in vitro (0.68 mmHg) displayed efficient electrical conductivity enabling them to follow electrical pacing up to a 2 Hz frequency. This work represents a proof of principle study for our current TEPC design strategy. Refinement and optimization of this promising TEPC design will lay the groundwork for testing the construct's therapeutic potential in the future. Together this work represents a progressive step toward developing an improved treatment for SVD patients. Statement of significanceSingle Ventricle Cardiac defects (SVD) are a form of congenital disorder with a morbid prognosis without surgical intervention. These patients are treated through the Fontan procedure which requires vascular conduits to complete. Fontan conduits have been traditionally made from stable or biodegradable materials with no pumping activity. Here, we propose a tissue engineered pulsatile conduit (TEPC) for use in Fontan circulation to alleviate excess strain in SVD patients. In contrast to previous strategies for making a pulsatile Fontan conduit, we employ a modular design strategy that allows for the optimization of each component individually to make a standalone tissue. This work sets the foundation for an in vitro, trainable human induced pluripotent stem cell based TEPC.

In This Issue

HomeCirculation ResearchVol. 122, No. 7In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published30 Mar 2018https://doi.org/10.1161/RES.0000000000000206Circulation Research. 2018;122:903Lack of Cardiac Remuscularization by ESCs in Primates (p 958)Human stem cell–derived cardiovascular progenitors do not remuscularize the infarcted hearts of nonhuman primates, say Zhu et al.Download figureDownload PowerPointHuman pluripotent stem cells (hPSCs) are under investigation for their potential to serve as regenerative treatments after myocardial infarction (MI). Indeed, several studies indicate that hPSC-derived cardiovascular progenitors (hPSC-CVPCs) improve recovery from MI in model organisms. Nevertheless, the mechanisms by which human cells promote myocardial recovery after infarction remain unclear. Such mechanisms can be tested by transplanting human cells in nonhuman primates, but such xenotransplant studies are limited by immune rejection of the cells, which prevents their long-term engraftment. Now, Zhu and colleagues have tested the effectiveness of 2 immunosuppression regimens—cyclosporine alone and cyclosporine plus methylprednisolone and basiliximab—for their ability to improve hPSC-CVPC engraftment in 32 cynomolgus monkeys after MI. Compared with the single-drug treatment, the team found that the combination regimen increased cell retention, reduced apoptosis, and improved heart function after 1 month. By 140 days, however, no cells remained in the hearts of animals in either treatment group. Direct remuscularization by the cells can, therefore, be excluded as the mechanism of functional improvement, say the authors.C3aR/C5aR in Tregs Regulates Hypertension (p 970)Lack of the complement receptors C3aR and C5aR protect mice against hypertension, report Chen et al.Download figureDownload PowerPointHypertension is a leading risk factor for coronary artery disease, stroke, and heart failure. To study the condition in mice, researchers experimentally induce hypertension with either angiotensin II or a combination of deoxycorticosterone acetate and salt. Such induced hypertension has been shown to depend on the presence of T-effector cells. Immunosuppressive T-regulatory cells (Tregs), by contrast, are protective against high-blood pressure. Secreted immune proteins of the complement system—C3a and C5a—have been shown to downregulate Tregs, leading Chen and colleagues to predict that absence of the C3a and C5a receptors would protect against hypertension. They found that treatment with Ang II failed to induce hypertension in mice with a double knockout of the C3a and C5a receptors. Furthermore, adoptive transfer of Tregs lacking the receptors to wild-type mice provided greater protection against Ang II–induced hypertension than that conferred by wild-type Tregs. Importantly, the authors found that humans with hypertension have increased expression of the C5a receptor on their Tregs, suggesting the findings of the study may be of relevance to future drug development.Outcomes After Cell Therapy in Single Ventricles (p 994)Sano et al report improved outcomes for patients with single ventricle heart defects after cardiac stem cell treatment.Download figureDownload PowerPointChildren born with single ventricle hearts have a high risk of heart failure and premature death. The treatment for such congenital heart defects is either a heart transplant or a series of 3 reconstructive surgeries, called staged palliation, during infancy and childhood. In adults with heart failure, stem cell therapies to enhance myocardial function have shown some promise, but whether such therapy could enhance recovery and heart function in single-ventricle patients after surgery is largely unknown. Sano and colleagues compared 41 patients enrolled in either the TICAP or PERSEUS trials—in which patients received intracoronary infusions of autologous cardiosphere-derived cells (CDCs) shortly after stage 2 or 3 surgeries—with 60 patients who underwent staged palliation only. The authors found that at 2 years of follow up, patients who received CDCs had improved ventricular function as well as fewer late failures and adverse events compared with controls. Improved survival rates were also observed in a subset of patients suffering heart failure with reduced ejection fraction. Together, these results serve as a foundation for longer-term follow-up studies and larger-scale trials. Previous Back to top Next FiguresReferencesRelatedDetails March 30, 2018Vol 122, Issue 7 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000206 Originally publishedMarch 30, 2018 PDF download Advertisement

Launching a New Strategy for Multidisciplinary Management of Single-Ventricle Heart Defects

Children born with single-ventricle heart defects, particularly hypoplastic left heart syndrome, have a lifetime high risk of mortality and comorbidities. They have complex medical challenges in addition to their cardiac needs, including growth and feeding complications and neurodevelopmental issues. These concerns require a coordinated effort among specialties to help patients maximize their potential. Additionally, because many complex heart defects are diagnosed prenatally, coordination of care between the pre- and postnatal care teams is imperative. Nursing leadership improves program coordination and efficiency. The purpose of this article is to describe the development and implementation of our hospital's synchronized, multidisciplinary team to support children with single-ventricle heart defects and their families. (Critical Care Nurse. 2018;38[1]:60-71).

Early insight of 4D flow imaging in patients with congenital heart disease

Cardiac magnetic resonance has become common in the management of congenital heart disease because of its ability to visualize structures that remain obscure by echocardiography without ionizing radiation. The 4D flow is an MRI method that simultaneously processes the quantification of blood flow, the quantification of ventricular volumes and function, the visualization of intracardiac and extracardiac structures and blood flow. The objectives of this study are to assess the feasibility of 4D flow routinely in children and young adults, to compare 4D flow with 2D phase-contrast MRI for quantification of aortic and pulmonary flow and to evaluate the advantage of 4D flow-based volumetric flow analysis compared to 2D phase contrast MRI. Two-dimensional phase-contrast MRI of the aortic root, main pulmonary artery, right and left ventricles and atrias and 4D flow with volumetric coverage of the aorta and pulmonary arteries were performed in 14 patients, 2 (12 and 14 years old) and 12 adults (mean age: 24.1 ± 7.3 years). This CMR concerned various diseases: repaired tetralogy of Fallot ( n = 10), aortic coarctation ( n = 1), single ventricle heart defect ( n = 1) and ventricular communicating shunt (2). Four-dimensional volumetric assessments of ventricles, pulmonary flow and aortic flow were performed and compared to 2D phase-contrast. Four dimensional flow analyses included calculation of net flow and regurgitant fraction with 4D flow analysis. Excellent correlations were found between 2D phase-contrast MRI and 4D flow for stroke volumes, aortic and pulmonary flows. Four-dimensional flow provided both anatomic visualization and comprehensive functional analysis showing stenosis, aneurysm and complex turbulent flows. In each of these circumstances, CMR has been achieved and has been found to be contributory for complete visualization and adequate evaluation.

Longitudinal Myocardial Deformation Does Not Predict Single Ventricle Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging in Children with a Total Cavopulmonary Connection

Survival of children with single ventricle heart defects after the total cavopulmonary connection (TCPC) has improved, but impaired cardiac function remains a major cause of morbidity and mortality. Cardiac magnetic resonance imaging (cMRI) is the gold standard in assessing single ventricle volume and function, but high costs and limited availability hamper its routine use. A cheaper and more available alternative is echocardiography. Myocardial function can be studied in more detail using speckle tracking echocardiography (STE). The purpose of the study was to describe the association between myocardial deformation assessed by speckle tracking echocardiography (STE) and single ventricle function assessed by cMRI and to evaluate differences in myocardial deformation in children with single left and single right ventricular morphology. Cross-sectional, multicenter study in 77 children after TCPC was conducted. STE segmental and global longitudinal peak strain and systolic strain rate (SR) of the dominant ventricle were measured. Impaired SV function by cMRI was defined as ejection fraction (EF) < 45%. Mean age was 11.8 (range 9.7–14.3) years. Pearson R for cMRI EF versus global longitudinal strain and SR was − 0.25 (p = 0.06) and − 0.03 (p = 0.82), respectively. Global single ventricle longitudinal strain and SR was similar in patients after TCPC with single left and single right ventricular morphology (− 19.0 ± 3.1% vs 19.2 ± 3.2%, p = 0.94). STE myocardial deformation parameters do not correlate with single ventricle ejection fraction assessed by cMRI.