Comprehensive Approach to the Management of Patients with HLHS: Analysis of 100 Consecutive Neonates.

BACKGROUND: We report our comprehensive approach to patients with hypoplastic left heart syndrome (HLHS) and describe our outcomes in 100 consecutive neonates. METHODS: One-hundred consecutive neonates (2015-2023) were stratified into 3 pathways: Pathway(1): 77/100=77% were standard-risk and underwent initial Norwood (Stage 1). Pathway(2): 10/100=10% were high-risk with noncardiac risk factors and underwent initial Hybrid Stage 1. Pathway(3): 13/100=13% were high-risk with cardiac risk factors: 10 underwent initial Hybrid Stage 1 + ventricular assist device insertion (HYBRID+VAD), while 3 underwent primary transplantation. RESULTS: One-year mortality=9/100=9%. Pathway(1): Operative Mortality for initial Norwood (Stage 1)=2/77=2.6%. Of 75 survivors of Norwood (Stage 1): 72 underwent successful Glenn, 2 underwent successful biventricular repair, and 1 underwent successful cardiac transplantation. Pathway(2): Operative Mortality for initial Hybrid Stage 1 without VAD=1/10=10%. Of 9 survivors of Hybrid (Stage 1): 4 underwent successful cardiac transplantation, 2 died while awaiting cardiac transplantation, 3 underwent Comprehensive Stage 2 (with 1 death), and 1 underwent successful biventricular repair. Pathway(3): Of 10 HYBRID+VAD: 7/10=70% underwent successful cardiac transplantation and are alive today and 3/10=30% died on VAD while awaiting transplantation. Median VAD support time=134 days (range=56-226). (Two of three patients who were bridged-to-transplant with prostaglandin underwent successful transplantation and one died while awaiting transplantation.) CONCLUSIONS: A comprehensive approach to the management of patients with HLHS is associated with Operative Mortality after Norwood of 2/77=2.6% and an overall one-year mortality of 9/100=9%. 10/100 patients=10% were stabilized with HYBRID+VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged wait times.

Elevated Aortic Stiffness after Pediatric Heart Transplantation.

In adults, arterial stiffness has been linked to the development of target end-organ damage, thought to be related to abnormal transmission of pulse pressure. Increased arterial stiffness and endothelial dysfunction have been hypothesized to contribute to the development of microvascular dysfunction and coronary allograft vasculopathy (CAV), an important comorbidity after heart transplantation. However, little data exists regarding arterial stiffness in pediatric heart transplantation and its influence on development of coronary allograft vasculopathy is not well understood. We sought to assess aortic stiffness and distensibility in pediatric post-heart transplant patients. A prospective, observational study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in patients aged < 21 years was conducted. Descending and ascending aorta M-modes were obtained from the subcostal long axis view, and the parasternal long axis view 3-5mm above the sinotubular junction, respectively. Two independent reviewers averaged measurements over 2-3 cardiac cycles, and Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) were calculated using previously validated methods. We recruited 39 heart transplant (HT) patients and 47 healthy controls. Median end diastolic dimension of the ascending aorta (donor tissue) was significantly larger in the transplant group than the control group (1.92 cm vs. 1.74 cm, p = 0.01). Ascending aortic distensibility in post-transplant patients was significantly lower than in the control group (4.87 vs. 10.53, p < 0.001). Ascending aortic stiffness index was higher in the transplant patients compared to the controls (4.63 vs. 2.21, p < 0.001). There is evidence of altered ascending aortic distensibility and stiffness parameters in post-heart transplant patients. Further studies are required to assess its influence on complications like development of coronary artery vasculopathy.

A Comprehensive Approach to the Management of Patients With HLHS and Related Malformations: An Analysis of 83 Patients (2015-2021).

Background: Some patients with hypoplastic left heart syndrome (HLHS) and HLHS-related malformations with ductal-dependent systemic circulation are extremely high-risk for Norwood palliation. We report our comprehensive approach to the management of these patients designed to maximize survival and optimize the utilization of donor hearts. Methods: We reviewed our entire current single center experience with 83 neonates and infants with HLHS and HLHS-related malformations (2015-2021). Standard-risk patients (n = 62) underwent initial Norwood (Stage 1) palliation. High-risk patients with risk factors other than major cardiac risk factors (n = 9) underwent initial Hybrid Stage 1 palliation, consisting of application of bilateral pulmonary bands, stent placement in the patent arterial duct, and atrial septectomy if needed. High-risk patients with major cardiac risk factors (n = 9) were bridged to transplantation with initial combined Hybrid Stage 1 palliation and pulsatile ventricular assist device (VAD) insertion (HYBRID + VAD). Three patients were bridged to transplantation with prostaglandin. Results: Overall survival at 1 year = 90.4% (75/83). Operative Mortality for standard-risk patients undergoing initial Norwood (Stage 1) Operation was 2/62 (3.2%). Of 60 survivors: 57 underwent Glenn, 2 underwent biventricular repair, and 1 underwent cardiac transplantation. Operative Mortality for high-risk patients with risk factors other than major cardiac risk factors undergoing initial Hybrid Stage 1 palliation without VAD was 0/9: 4 underwent transplantation, 1 awaits transplantation, 3 underwent Comprehensive Stage 2 (with 1 death), and 1 underwent biventricular repair. Of 9 HYBRID + VAD patients, 6 (67%) underwent successful cardiac transplantation and are alive today and 3 (33%) died while awaiting transplantation on VAD. Median length of VAD support was 134 days (mean = 134, range = 56-226). Conclusion: A comprehensive approach to the management of patients with HLHS or HLHS-related malformations is associated with Operative Mortality after Norwood of 2/62 = 3.2% and a one-year survival of 75/83 = 90.4%. A subset of 9/83 patients (11%) were stabilized with HYBRID + VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged wait times.

Optimized Computed Tomography Angiography Protocol for the Evaluation of Thrombus in Patients with Fontan Anatomy.

The Fontan procedure is the final stage in the palliative surgical approach to patients with single-ventricle physiology. These patients have an increased risk for thromboembolic disease in the Fontan circuit, which can be evaluated by chest computed tomography angiography (CTA) in acute settings. However, false-positive results are common secondary to unusual streaming patterns in the Fontan circuit. A biphasic CTA protocol was evaluated for the capability to clearly identify structures of the Fontan circuit that are critical for the evaluation of thromboembolic disease. The study was a retrospective chart review of Fontan patients with a chest CTA scan obtained between 2011 and 2017. Two pediatric cardiologists with additional training in cardiac CT imaging independently reviewed each CTA and awarded one point for each of 5 Fontan circuit structures clearly identified resulting in a score range of 0-5. A score of 0-2 considered not capable, 3-4 partially capable, and 5 capable to clearly identify critical structures of the Fontan circuit. During the study period, 46 CTA scans were performed on 21 patients. Of the CTA scans using a biphasic protocol, 62.5% (10/16) were considered capable to clearly identify all 5 critical structures of the Fontan circuit vs 27% (8/30) of the CTA scans using a monophasic protocol (p = 0.027). Overall our results suggest that the single-site biphasic CTA protocol has greater diagnostic capability to detect the presence of Fontan thromboembolic disease when compared to the more traditional monophasic CTA protocol. Future prospective studies are needed to confirm these findings.

Impact of 3D Printouts in Optimizing Surgical Results for Complex Congenital Heart Disease.

Planning corrective and palliative surgery for patients who have complex congenital heart disease often relies on the assessment of cardiac anatomy using two-dimensional noninvasive cardiac imaging modalities (echocardiography, cardiac magnetic resonance imaging, and computed tomography scan). Advances in cardiac noninvasive imaging now include the use of three-dimensional (3D) reconstruction tools that produce 3D images and 3D printouts. There is scant evidence available in the literature as to what effect the availability of 3D printouts of complex congenital heart defects has on surgical outcomes. Surgical outcomes of study subjects with a 3D cardiac printout available and their paired control subject without a 3D cardiac printout available were compared. We found a trend toward shorter surgical times in the study group who had the benefit of 3D models, but no statistical significance was found for bypass time, cross-clamp time, total time, length of stay, or respiratory support. These preliminary results support the proposal that 3D modeling be made readily available to congenital cardiac surgery teams, for use in patients with the most complex congenital heart disease.

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature.

OBJECTIVES: To assess efficacy, safety, outcomes, and intrauterine complications following maternal hyperoxygenation (MH) therapy in fetuses with congenital heart disease (CHD). METHODS: A systematic review was performed following an electronic search of databases. Articles were published before January 1, 2017, in an English-language and non-English-language journals (with English translations), and included human fetuses and expectant mothers with a fetal diagnosis of CHD who received MH. RESULTS: Ninety-six articles were identified; 72 were excluded and 24 full-text articles were reviewed. Only 9 articles met inclusion criteria and were analyzed. A total of 270 fetuses underwent MH therapy: 169 had CHD, and 101 had normal heart anatomies. Seven studies used fetal echocardiography, while 2 studies used cardiac magnetic resonance imaging (CMR). The mean gestational age at therapy was 33.4 weeks (26-38 weeks). Majority of MH protocols used 100% FiO2 with non-rebreather face mask at 8 L of flow, achieving 60%-70% FiO2 , or maternal PaO2 goal of 250 mm Hg. No significant adverse events were reported. Four studies reported increased size of the hypoplastic cardiac structures after MH. Three studies utilized acute MH to risk stratify hypoplastic left heart syndrome fetuses. Two studies assessed acute MH in the setting of CMR. CONCLUSION: The current evidence for MH therapy suggests an increase in pulmonary blood flow, and venous return, ductal flow, and heart dimensions in fetuses. MH has potential as a diagnostic and therapeutic tool in fetuses with CHD. Further randomized controlled trials are needed to ascertain whether MH therapy provides improved outcomes on fetuses with certain types of CHD.

Effect of Aerobic versus Resistance Exercise on Pulse Wave Velocity, Intima Media Thickness and Left Ventricular Mass in Obese Adolescents.

A cardiovascular comorbidity in obese adolescents is increased aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and left ventricular mass (LVM). We investigated in obese adolescents 1) the risk factors associated with aPWV, cIMT and LVM, and 2) the effects of aerobic (AE) versus resistance (RE) exercise alone (without calorie restriction) on aPWV, cIMT, LVM index (LVMI) and cardiometabolic risk factors. Eighty-one obese adolescents (12-18 yrs, BMI ≥95th percentile) were randomized to 3 months of AE (n = 30), RE (n = 27) or a control group (n = 24). Outcome measures included aPWV, cIMT, LVMI, body composition, cardiorespiratory fitness (CRF), blood pressure (BP) and lipids. At baseline, the strongest correlates of aPWV were body weight (r = .31) and diastolic BP (r = .28); of cIMT were body weight (r=0.26) and CRF (r=-0.25); and of LVMI was CRF (r=0.32) after adjusting for sex and race (p < .05 for all). Despite significant reductions in total fat and improvements in CRF in the AE and RE groups, aPWV, cIMT, LVMI, BP, lipids and body weight did not change as compared with controls (p > .05 for all). Interventions of longer duration or together with weight loss may be required to improve these early biomarkers of CVD in obese adolescents.

Pocket echocardiography system for detection of patent ductus arteriosus in neonates.

BACKGROUND: Neonates are commonly referred for a cardiology consult and an echocardiogram to rule out patent ductus arteriosus (PDA). OBJECTIVES: Evaluate the usefulness of current pocket echocardiography system (PES) in PDA detection compared to traditional full-featured echo system (FFES). HYPOTHESIS: The determination of the presence of a PDA in neonates can be done using PES. METHODS: Fifty newborns with orders for echo evaluation were included in this study. A 5-minute PES scan was performed first. Then a full echo study was performed on a traditional FFES. Images were evaluated by three pediatric cardiologists blinded to the patients and the FFES results. RESULTS: The overall accuracy of reviewers rating PES versus FFES to rule in PDA had low false-positive rates 9.5% (95% CI: 1.2-30%), 11.8% (95% CI: 1.5-36%), 11.1% (95% CI: 1.4-35%) and the false-negative rate to rule out PDA was 0% (95% CI: 0-18%), 5.5% (95% CI: 0.14-27%), 0% (95% CI: 0-26%) for each reviewer 1, 2, and 3, respectively. Upon further analysis, PES scan was shown not to be accurate on infants with body weight below 1000 g with encouraging results for infants above 1000 g and those >37 weeks gestational age. CONCLUSIONS: Our results suggest that the current PES could potentially be used in larger and near-term infants but has less than acceptable performance in low birth weight and premature infants in determining who should undergo a FFES study for persistent PDA diagnosis. Improvements in the technology along with developing limited training protocols for noncardiology personnel should make it possible for PES scan to be used as a screening tool and as an extension of physical examination especially in limited resource settings.

Protocol for relative hydrodynamic assessment of tri-leaflet polymer valves.

Limitations of currently available prosthetic valves, xenografts, and homografts have prompted a recent resurgence of developments in the area of tri-leaflet polymer valve prostheses. However, identification of a protocol for initial assessment of polymer valve hydrodynamic functionality is paramount during the early stages of the design process. Traditional in vitro pulse duplicator systems are not configured to accommodate flexible tri-leaflet materials; in addition, assessment of polymer valve functionality needs to be made in a relative context to native and prosthetic heart valves under identical test conditions so that variability in measurements from different instruments can be avoided. Accordingly, we conducted hydrodynamic assessment of i) native (n = 4, mean diameter, D = 20 mm), ii) bi-leaflet mechanical (n= 2, D = 23 mm) and iii) polymer valves (n = 5, D = 22 mm) via the use of a commercially available pulse duplicator system (ViVitro Labs Inc, Victoria, BC) that was modified to accommodate tri-leaflet valve geometries. Tri-leaflet silicone valves developed at the University of Florida comprised the polymer valve group. A mixture in the ratio of 35:65 glycerin to water was used to mimic blood physical properties. Instantaneous flow rate was measured at the interface of the left ventricle and aortic units while pressure was recorded at the ventricular and aortic positions. Bi-leaflet and native valve data from the literature was used to validate flow and pressure readings. The following hydrodynamic metrics were reported: forward flow pressure drop, aortic root mean square forward flow rate, aortic closing, leakage and regurgitant volume, transaortic closing, leakage, and total energy losses. Representative results indicated that hydrodynamic metrics from the three valve groups could be successfully obtained by incorporating a custom-built assembly into a commercially available pulse duplicator system and subsequently, objectively compared to provide insights on functional aspects of polymer valve design.

Pulsatile venous waveform quality affects the conduit performance in functional and "failing" Fontan circulations.

OBJECTIVE: To investigate the effect of pulsatility of venous flow waveform in the inferior and superior caval vessels on the performance of functional and "failing" Fontan patients based on two primary performance measures - the conduit power loss and the distribution of inferior caval flow (hepatic factors) to the lungs. METHODS: Doppler angiography flows were acquired from two typical extra-cardiac conduit "failing" Fontan patients, aged 13 and 25 years, with ventricle dysfunction. Using computational fluid dynamics, haemodynamic efficiencies of "failing", functional, and in vitro-generated mechanically assisted venous flow waveforms were evaluated inside an idealised total cavopulmonary connection with a caval offset. To investigate the effect of venous pulsatility alone, cardiac output was normalised to 3 litres per minute in all cases. To quantify the pulsatile behaviour of venous flows, two new performance indices were suggested. RESULTS: Variations in the pulsatile content of venous waveforms altered the conduit efficiency notably. High-frequency and low-amplitude oscillations lowered the pulsatile component of the power losses in "failing" Fontan flow waveforms. Owing to the offset geometry, hepatic flow distribution depended strongly on the ratio of time-dependent caval flows and the pulsatility content rather than mixing at the junction. "Failing" Fontan flow waveforms exhibited less balanced hepatic flow distribution to lungs. CONCLUSIONS: The haemodynamic efficiency of single-ventricle circulation depends strongly on the pulsatility of venous flow waveforms. The proposed performance indices can be calculated easily in the clinical setting in efforts to better quantify the energy efficiency of Fontan venous waveforms in pulsatile settings.

Adult definitions for dyssynchrony are inappropriate for pediatric patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising approach to improve cardiac function in children in heart failure with cardiomyopathy. Cardiac timing measures in pediatrics are typically based on age and heart rate. However, pediatric CRT studies to date have used adult based timing cutoff values. We investigated the applicability of using these adult standards in pediatric patients with normal hearts. METHODS: We studied 88 outpatients referred for cardiac evaluation who had a normal cardiac evaluation. Subjects had 12 lead EKG and normal echocardiogram. Patients with known heart disease or abnormal rhythms were excluded. 2D echo and Doppler including color tissue Doppler imaging (TDI, Vivid 7 GE Ultrasound, Norway) were obtained. TDI was performed on three standard apical views (four chamber, two chamber, and long axis). Longitudinal dyssynchrony was determined from (1) Yu index--standard deviation of differences in timing of peak TDI velocity of all 12 basal and mid LV wall segments, adult cutoff >32 ms and (2) opposing wall difference (OWD) in timing of peak TDI velocity of 12 LV wall segments, adult cutoff >65 ms. Radial dyssynchrony was determined from differences in timing of peak radial strain between anterior-septal and posterior LV segments from speckle tracking of 2D LV views, adult cutoff >130 ms. RESULTS: Median age was 11.5 years; median heart rate was 74.5. Longitudinal dyssynchrony was present in 40% of normals based on Yu index, and in 43% based on OWD. No child had Radial dyssynchrony. CONCLUSIONS: This pilot study of children with normal hearts suggests that current adult CRT dyssynchrony cutoff values are inappropriate in the pediatric population.

Optimization of inflow waveform phase-difference for minimized total cavopulmonary power loss.

The Fontan operation is a palliative surgical procedure performed on children, born with congenital heart defects that have yielded only a single functioning ventricle. The total cavo-pulmonary connection (TCPC) is a common variant of the Fontan procedure, where the superior vena cava (SVC) and inferior vena cava (IVC) are routed directly into the pulmonary arteries (PA). Due to the limited pumping energy available, optimized hemodynamics, in turn, minimized power loss, inside the TCPC pathway is required for the best optimal surgical outcomes. To complement ongoing efforts to optimize the anatomical geometric design of the surgical Fontan templates, here, we focused on the characterization of power loss changes due to the temporal variations in between SVC and IVC flow waveforms. An experimentally validated pulsatile computational fluid dynamics solver is used to quantify the effect of phase-shift between SVC and IVC inflow waveforms and amplitudes on internal energy dissipation. The unsteady hemodynamics of two standard idealized TCPC geometries are presented, incorporating patient-specific real-time PC-MRI flow waveforms of "functional" Fontan patients. The effects of respiration and pulsatility on the internal energy dissipation of the TCPC pathway are analyzed. Optimization of phase-shift between caval flows is shown to lead to lower energy dissipation up to 30% in these idealized models. For physiological patient-specific caval waveforms, the power loss is reduced significantly (up to 11%) by the optimization of all three major harmonics at the same mean pathway flow (3 L/min). Thus, the hemodynamic efficiency of single ventricle circuits is influenced strongly by the caval flow waveform quality, which is regulated through respiratory dependent physiological pathways. The proposed patient-specific waveform optimization protocol may potentially inspire new therapeutic applications to aid postoperative hemodynamics and improve the well being of the Fontan patients.

Pulsatile in vitro simulation of the pediatric univentricular circulation for evaluation of cardiopulmonary assist scenarios.

The characteristic depressed hemodynamic state and gradually declining circulatory function in Fontan patients necessitates alternative postoperative management strategies incorporating a system level approach. In this study, the single-ventricle Fontan circulation is modeled by constructing a practical in vitro bench-top pulsatile pediatric flow loop which demonstrates the ability to simulate a wide range of clinical scenarios. The aim of this study is to illustrate the utility of a novel single-ventricle flow loop to study mechanical cardiac assist to Fontan circulation to aid postoperative management and clinical decision-making of single ventricle patients. Two different pediatric ventricular assist devices, Medos and Pediaflow Gen-0, are anastomosed in two nontraditional configurations: systemic venous booster (SVB) and pulmonary arterial booster (PAB). Optimum ventricle assist device strategy is analyzed under normal and pathological (pulmonary hypertension) conditions. Our findings indicate that the Medos ventricular assist device in SVB configuration provided the highest increase in pulmonary (46%) and systemic (90%) venous flow under normal conditions, whereas for the hypertensive condition, highest pulmonary (28%) and systemic (55%) venous flow augmentation were observed for the Pediaflow ventricular assist device inserted as a PAB. We conclude that mechanical cardiac assist in the Fontan circulation effectively results in flow augmentation and introduces various control modalities that can facilitate patient management. Assisted circulation therapies targeting single-ventricle circuits should consider disease state specific physiology and hemodynamics on the optimal configuration decisions.

Minimal sedation second dose strategy with intranasal midazolam in an outpatient pediatric echocardiographic setting.

BACKGROUND: Anxiety and movement in children during transthoracic echocardiography (TTE) can compromise study quality and reliability. Minimal sedation is often required. Intranasal midazolam (INM), used in various procedures, is an excellent sedative. Optimal INM dosing strategies for uncooperative children undergoing TTE are largely unknown, including second-dose INM strategies, introduced to maximize the potential for successful sedation and minimize risk. The purpose of this retrospective review was to evaluate the effectiveness of a second-dose INM minimal sedation strategy recently adopted at the Children's Hospital of Pittsburgh. METHODS: The strategy incorporates a second dose of INM if needed (10-15 minutes after the first dose) to obtain the desired level of anxiolysis. The effectiveness of this strategy was assessed in 100 consecutive patients (age range, 1-59 months). RESULTS: There were no reported complications, minimal untoward side reactions, and no delays in discharge. Eighty patients attained satisfactory minimal sedation levels. CONCLUSION: A second-dose INM strategy was effective in achieving satisfactory minimal sedation in children undergoing TTE. The results of this study also suggest that only a small proportion of patients would benefit from a one-dose INM strategy.