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

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

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

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

Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome.

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

Clinical Presentation and Therapy of Hypoplastic Left Heart Syndrome.

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

Myocardial biomechanical effects of fetal aortic valvuloplasty.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV.

Cardiovascular magnetic resonance reference values of right ventricular volumetric variables in patients with hypoplastic left heart syndrome.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has established itself as the gold standard for serial assessment of systemic right ventricular (RV) performance but due to the lack of standardized RV reference values for hypoplastic left heart syndrome (HLHS) patients, the interpretation of RV volumetric data in HLHS remains difficult. Therefore, this study aimed to close this gap by providing CMR reference values for the systemic RV in HLHS patients. METHODS: CMR scans of 160 children, adolescents, and young adults (age range 2.2-25.2 years, 106 males) with HLHS were retrospectively evaluated. All patients were studied following total cavopulmonary connection. Short-axis stacks were used to measure RV end-diastolic and end-systolic volumes (RVEDV, RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), and RV end-diastolic myocardial mass (RVEDMM). Univariable and multiple linear regression analyses were performed to assess associations between RV parameters and demographic and anthropometric characteristics. Following the results of the regression analysis, reference graphs and tables were created with the Lambda-Mu-Sigma method. RESULTS: Multiple linear regression analysis showed strong associations between body height and RVEDV, RVESV as well as RVSV. Age was highly associated with RVEDMM. Therefore, percentile curves and tables were created with respect to body height (RVEDV, RVESV, RVSV) and age (RVEDMM). The influence of demographic and anthropometric parameters on RVEF was mild, thus no percentile curves and tables for RVEF are provided. CONCLUSION: We were able to define CMR reference values for RV volumetric variables for HLHS patients. These data might be useful for the assessment and interpretation of CMR scans in these patients and for research in this field.

Prognostic Value of RV Function Analysis During the Interstage Period in Patients with Hypoplastic Left Heart Syndrome.

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4-8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > -15.6 (AUC 0.79), RVFWS > -18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period.

Hypoplastic Left Heart Syndrome with Mitral Stenosis and Aortic Atresia-Echocardiographic Findings and Early Outcomes.

BACKGROUND: Mitral stenosis/aortic atresia (MS/AA) has been reported as a high-risk variant of hypoplastic left heart syndrome (HLHS), potentially related to ventriculocoronary connections (VCCs) or endocardial fibroelastosis (EFE) and myocardial hypoperfusion. We aimed to identify echocardiographic and clinical factors associated with early death or transplant in this group. METHODS: Patients with HLHS MS/AA treated at our center between 2000 and 2020 were included. Pre-stage I palliation echocardiograms were reviewed. Certain imaging factors, such as determination of VCC, EFE, and measurement of tricuspid annular plane systolic excursion were measured from retrospective review of preoperative images; others were derived from clinical reports. Groups were compared according to primary outcome of death or transplant prior to stage II palliation. RESULTS: Of 141 patients included, 39 (27.7%) experienced a primary outcome. Ventriculocoronary connections were identified in 103 (73.0%) patients and EFE in 95 (67.4%) patients. Among imaging variables, smaller ascending aorta size (median, 2.2 [interquartile range (IQR) 1.7-2.8] vs 2.6 [2.2-3.4] mm, P = .01) was associated with primary outcome. There was similar frequency of VCC (74.4% vs 72.5%, P = .83), EFE (59.0% vs 72.5%, P = .19), moderate or greater tricuspid regurgitation (5.1% vs 5.9%, P = 1.00), and similar right ventricular systolic function (indexed tricuspid annular plane systolic excursion 32.5 ± 7.3 vs 31.4 ± 7.2 mm/m2, P = .47) in the primary outcome group compared to other patients. Clinical factors associated with primary outcome included lower birth weight (mean, 2.8 ± SD 0.8 vs 3.3 ± 0.5 kg, P = .0003), gestational age <37 weeks (31.6% vs 4.9%, P < .0001), longer cardiopulmonary bypass time (median, 112 [IQR, 93-162] vs 82 [71-119] minutes, P = .001), longer intensive care unit length of stay (median, 19 [IQR, 10-30] vs 10 [7-15] days, P = .001), and extracorporeal membrane oxygenation following stage I palliation (43.6% vs 8.8%, P < .0001). Presence of VCCs and EFE was not associated with death or transplant after controlling for birth weight and era of stage I palliation. CONCLUSIONS: In one of the largest reported single-center cohorts of HLHS MS/AA, there were few pre-stage I palliation imaging characteristics associated with primary outcome. Imaging findings evaluated in this study, including the presence of VCC and/or EFE as determined using highly sensitive echocardiogram criteria, should not preclude intervention, although impact on long-term outcomes requires further evaluation.

Surgical Modulation of Pulmonary Artery Shear Stress: A Patient-Specific CFD Analysis of the Norwood Procedure.

PURPOSR: This study created 3D CFD models of the Norwood procedure for hypoplastic left heart syndrome (HLHS) using standard angiography and echocardiogram data to investigate the impact of shunt characteristics on pulmonary artery (PA) hemodynamics. Leveraging routine clinical data offers advantages such as availability and cost-effectiveness without subjecting patients to additional invasive procedures. METHODS: Patient-specific geometries of the intrathoracic arteries of two Norwood patients were generated from biplane cineangiograms. "Virtual surgery" was then performed to simulate the hemodynamics of alternative PA shunt configurations, including shunt type (modified Blalock-Thomas-Taussig shunt (mBTTS) vs. right ventricle-to-pulmonary artery shunt (RVPAS)), shunt diameter, and pulmonary artery anastomosis angle. Left-right pulmonary flow differential, Qp/Qs, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were evaluated. RESULTS: There was strong agreement between clinically measured data and CFD model output throughout the patient-specific models. Geometries with a RVPAS tended toward more balanced left-right pulmonary flow, lower Qp/Qs, and greater TAWSS and OSI than models with a mBTTS. For both shunt types, larger shunts resulted in a higher Qp/Qs and higher TAWSS, with minimal effect on OSI. Low TAWSS areas correlated with regions of low flow and changing the PA-shunt anastomosis angle to face toward low TAWSS regions increased TAWSS. CONCLUSION: Excellent correlation between clinically measured and CFD model data shows that 3D CFD models of HLHS Norwood can be developed using standard angiography and echocardiographic data. The CFD analysis also revealed consistent changes in PA TAWSS, flow differential, and OSI as a function of shunt characteristics.

Two-dimensional speckle tracking echocardiography in fetuses with critical aortic stenosis before and after fetal aortic valvuloplasty.

BACKGROUND: Critical aortic stenosis (AS) in fetuses may progress to hypoplastic left heart syndrome (HLHS) with need for postnatal single ventricular (SV) palliation. Fetal aortic valvuloplasty (FAV) is performed to achieve postnatal biventricular (BV) circulation. However, the impact of FAV on fetal myocardial function is difficult to measure. Prediction of postnatal circulatory status and, therefore, counseling is challenging. METHODS: Retrospective study of fetuses with critical AS who underwent FAV. Global Longitudinal Peak Systolic Strain (GLPSS) of the left ventricle (LV) and right ventricle (RV) were retrospectively analyzed before and after intervention. Fisher's Exact Test and Mann-Whitney-U Test were used for univariant statistical analysis. RESULTS: 23 fetuses with critical AS were included. After intervention fetuses demonstrated more negative LV-GLPSS mean values post- vs. pre-intervention (- 5.36% vs. - 1.57%; p < 0.05). RV-GLPSS was decreased in all fetuses, there was no peri-interventional change. 20 fetuses were born alive. Postnatally, 10 had BV and 10 SV circulation. Improved post-interventional LV-GLPSS strain values correlated with BV outcome (p < 0.05). Pre-interventional continuous LV-GLPSS values correlated with postnatal SV vs. BV outcome (p < 0.05). CONCLUSION: In some fetuses, LV myocardial function assessed by speckle tracking echocardiography (STE) improves after FAV. Improved post-interventional LV-GLPSS correlates with biventricular postnatal outcome. Furthermore, pre-interventional LV- and RV-GLPSS correlate with postnatal outcome. Further studies are needed to asses, if pre-interventional STE parameters might predict which fetuses will benefit from FAV with postnatal BV circulation.

Mitral valve orifice area predicts outcome after biventricular repair in patients with hypoplastic left ventricles.

BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

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

OBJECTIVE: This study used cardiac magnetic resonance imaging to evaluate flow characteristics and ventricular hemodynamics for children with single right (hypoplastic left heart syndrome) and single left (hypoplastic right heart syndrome) systemic ventricle anatomy after Fontan palliation compared with normal biventricular controls. METHODS: Twenty children with single ventricle anatomy (hypoplastic left heart syndrome, n = 10; hypoplastic right heart syndrome, n = 10) underwent standardized 4-dimensional flow cardiac magnetic resonance and were compared with age-matched controls (n = 10). End-diastolic volume was partitioned into 4 defined components of variable kinetic energy (direct flow, retained inflow, delayed ejection, and residual volume) and compared between groups. Further, volumetric and functional parameters as defined by cardiac magnetic resonance were evaluated. RESULTS: Children with hypoplastic left heart syndrome had significantly increased indexed end-diastolic and end-systolic volumes compared with both hypoplastic right heart syndrome and control groups. Flow component analysis demonstrated diastolic inefficiency in both hypoplastic left heart syndrome and hypoplastic right heart syndrome groups compared with controls as defined by decreased direct flow and increased residual volumes. Decreased direct flow correlated with decreased ejection fraction and increased end-diastolic and end-systolic volume indices. Increased residual volume correlated with decreased ejection fraction and increased end-systolic volume index. CONCLUSIONS: Fontan-palliated patients with single ventricle physiology (hypoplastic left heart syndrome and hypoplastic right heart syndrome) demonstrate altered and inefficient flow patterns in the systemic ventricle as defined by 4-dimensional flow cardiac magnetic resonance compared with normal biventricular controls. Decreased direct flow and increased residual volume indicate that diastolic ventricular dysfunction is prevalent after Fontan palliation. This study provides a foundation for future predictive modeling and cardiac magnetic resonance flow diagnostic studies in this high-risk patient population.

Myocardial Perfusion in Hypoplastic Left Heart Syndrome.

BACKGROUND: The status of the systemic right ventricular coronary microcirculation in hypoplastic left heart syndrome (HLHS) is largely unknown. It is presumed that the systemic right ventricle's coronary microcirculation exhibits unique pathophysiological characteristics of HLHS in Fontan circulation. The present study sought to quantify myocardial blood flow by cardiac magnetic resonance imaging and evaluate the determinants of microvascular coronary dysfunction and myocardial ischemia in HLHS. METHODS: One hundred nineteen HLHS patients (median age, 4.80 years) and 34 healthy volunteers (median age, 5.50 years) underwent follow-up cardiac magnetic resonance imaging ≈1.8 years after total cavopulmonary connection. Right ventricle volumes and function, myocardial perfusion, diffuse fibrosis, and late gadolinium enhancement were assessed in 4 anatomic HLHS subtypes. Myocardial blood flow (MBF) was quantified at rest and during adenosine-induced hyperemia. Coronary conductance was estimated from MBF at rest and catheter-based measurements of mean aortic pressure (n=99). RESULTS: Hyperemic MBF in the systemic ventricle was lower in HLHS compared with controls (1.89±0.57 versus 2.70±0.84 mL/g per min; P<0.001), while MBF at rest normalized by the rate-pressure product, was similar (1.25±0.36 versus 1.19±0.33; P=0.446). Independent risk factors for a reduced hyperemic MBF were an HLHS subtype with mitral stenosis and aortic atresia (P=0.017), late gadolinium enhancement (P=0.042), right ventricular diastolic dysfunction (P=0.005), and increasing age at total cavopulmonary connection (P=0.022). The coronary conductance correlated negatively with systemic blood oxygen saturation (r, -0.29; P=0.02). The frequency of late gadolinium enhancement increased with age at total cavopulmonary connection (P=0.014). CONCLUSIONS: The coronary microcirculation of the systemic ventricle in young HLHS patients shows significant differences compared with controls. These hypothesis-generating findings on HLHS-specific risk factors for microvascular dysfunction suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.

The Perinatal Transition and Early Neonatal Period in Hypoplastic Left Heart Syndrome Is Associated With Reduced Systemic and Cerebral Perfusion.

BACKGROUND: The impact of the striking perinatal circulatory changes on blood flow distribution have not to date been well examined in hypoplastic left heart syndrome (HLHS). This study aimed to document perinatal redistribution of cardiac output in HLHS compared with healthy control subjects, to further understand the impact of the perinatal transition on cerebral and systemic blood flow. METHODS: Prospectively recruited HLHS case subjects (n = 31) and healthy control subjects (n = 19) underwent serial echocardiography from late fetal stages to 96 hours after birth. Combined cardiac output (CCO), systemic, pulmonary, cerebrovascular, and splanchnic flow data were compared between neonates with HLHS and control subjects, and the impact of vasoactive support and positive pressure ventilation in HLHS patients was examined. RESULTS: In late gestation, CCO was similar between HLHS and control subjects, whereas middle cerebral artery (MCA) pulsatility index (PI) in HLHS was consistent with low cerebral vascular resistance. In the 96 hours after birth, CCO and pulmonary blood flow progressively increased in HLHS compared with control subjects (P < 0.001), and CCO was further increased in neonates with HLHS receiving vasoactive support (P = 0.01). Neonates with HLHS had reduced systemic and 6-24-hour superior vena cava (SVC) flow compared with control subjects (P < 0.001). Low systemic flow was further suggested by increased MCA and celiac artery PI at 6-48 hours in neonates with HLHS (P < 0.001). Systemic and SVC flow did not differ between those with and without vasoactive support. CONCLUSIONS: We provide quantitative echocardiographic evidence associating impaired cerebral and systemic blood flow with perinatal hemodynamic changes in the preoperative neonate with HLHS.

Longitudinal Assessment of Right Ventricular Function in Hypoplastic Left Heart Syndrome.

Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan-Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71 ± 4.4%, 69 ± 4.5% and 66 ± 4.7% at 1, 2 and 5 years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7 ± 9.3% to 31.1 ± 8.3% (p < 0.001). Similarly, tricuspid valve annular systolic excursion (TAPSE) Z-score declined from -2.9 ± 1.3 to -9.7 ± 1.3 (p < 0.001) with a decrement at every stage of evaluation. In comparison to patients with post-Norwood RV FAC >35% and TAPSE Z-score > -5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p < 0.0001). In patients with HLHS undergoing staged palliation, decrement in RV function manifests longitudinally. Post-Norwood RV FAC and TAPSE Z-score appear to be early markers of poor outcome in this population.

High-degree Norwood neoaortic tapering is associated with abnormal flow conduction and elevated flow-mediated energy loss.

OBJECTIVE: The Norwood neoaortic arch biomechanical properties are abnormal due to reduced vessel wall compliance and abnormal geometry. Others have previously described neoaortic geometric distortion by the degree of diameter reduction (tapering) and associated this with mismatched ventricular-neoaortic coupling, abnormal flow hemodynamic parameters, and worse patient outcome. Our purposes were to investigate the influence of neoaortic tapering (ie, diameter reduction) on flow-mediated viscous energy loss (EL') in post-Norwood palliated hypoplastic left heart syndrome patients, and correlate flow-geometry with single ventricle power generation. METHODS: Twenty-six palliated hypoplastic left heart syndrome patients underwent comprehensive cardiac evaluation with 4-dimensional-flow magnetic resonance imaging. Patients were grouped into high- (group H, n = 13) and low- (group L, n = 13) degree neoaortic tapering using the median cutoff value of neoaortic diameter variance. EL' was calculated along standardized segments using 4-dimensional-flow magnetic resonance imaging. Flow-mediated power loss as a percentage of total power generated by the single ventricle was determined. RESULTS: Group H had a higher prevalence of abnormal recirculating flow in the neoaorta and elevated neoaortic EL' in the ascending aorta (1.0 vs 0.6 mW; P = .004). Group H EL' was increased across the entire thoracic aorta (2.6 vs 1.3 mW; P = .002) and accounted for 0.7% of generated ventricular power versus 0.3% in group L (P = .024). EL' directly correlated with the degree of ascending aortic dilation (R = 0.49; P = .012). CONCLUSIONS: Patients with high degree neoaortic tapering have more perturbed flow through the neoaorta and increased EL'. Flow-mediated energy loss due to abnormal flow represents irreversibly wasted power generated by the single right ventricle. In patients with high-degree neoaortic tapering, EL' was more than 2-fold greater than low-degree tapering patients. These data suggest that oversizing the Norwood neoaortic reconstruction should be avoided and that patients with distorted neoaortic geometry may warrant increased surveillance for single-ventricle deterioration.

Fluid mechanics of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome.

Left atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model.