Single Heart Research Articles

Paraganglioma and phaeochromocytoma in adult Fontan patients.

The purpose of this study was to address the gap in knowledge in the incidence, presentation and imaging features of PPGL in Fontan patients. It has been hypothesised in the literature that Fontan circulation patients have an increased incidence of these tumours. This study is the largest cohort of adult Fontan patients in North America. The Fontan procedure is a palliative procedure for single ventricle congenital heart disease where the systemic venous return is directed into the pulmonary circulation. Fontan patients are at increased risk of developing several extracardiac complications including phaeochromocytoma and paraganglioma (PPGL). This retrospective single-centre study includes all adult patients who were treated between 1 September 2015 and 1 September 2022 in a tertiary referral centre for adult congenital heart disease. Imaging and electronic medical records were retrospectively searched for the presence of PPGL. Five hundred and forty-seven Fontan patients were included in the study. Three patients had PPGL with an incidence of 0.5%. Two patients were diagnosed with paraganglioma and one with phaeochromocytoma. All patients were female. Median age of Fontan procedure was 1.8 years (range: 1.75-27 years). Median age of PPGL diagnosis was 19 years (range: 12-39 years). Median time from Fontan operation to diagnosis of PPGL was 12 years (range: 10.3-17.2 years). Fontan patients are at increased risk of PPGL. Clinically, the diagnosis of PPGL is challenging as symptoms and serum markers can be confounding in this population; however, the imaging features of PPGL remain typical making the role of the radiologist crucial.

Abstract 4120856: Abdominal Aortic Blood Flow and Interstage Growth and Neurodevelopment in Patients with Single Ventricle Heart Disease

Background: Achieving normal somatic growth and neurodevelopmental (ND) milestones is a common challenge for children with single ventricle heart disease (SV) prior to stage 2 palliation (S2P). This study aimed to characterize the potential association with poor splanchnic and cerebral circulations. Methods: This retrospective single centre study included SV patients born February 1, 2012, to May 30, 2022 who underwent MRI evaluation and S2P <12 months of age. Blood flow indices, including descending aorta flow (DAoNet), were measured by phase-contrast MRI. Primary outcomes were weight-for-age Z score (WFAZ) at S2P, and 18-month ND outcomes measured by Bayley Scales of Infant and Toddler Development 3rd Ed. Spearman’s correlation was used to model associations; statistical significance was considered for p<0.05. Results: A total of 144 patients were included: 61% (n=88) male, 12% (n=17) with genetic anomalies/syndrome, median (interquartile range) gestational age was 38.7 (38, 39.6) weeks, birth weight of 3.2 (2.8-3.6) kg, and birth WFAZ -0.23 (-1.1-0.6). Stage-1 palliation (n=130) was completed at 6 (3-23) days, 34% (n=49) for hypoplastic left heart syndrome, and S2P at 6.1 (5.3-7.1) months with a WFAZ of -1.4 (-2.3- (-0.5)). S2P WFAZ did not correlate with DAoNet (Figure 1), systemic cardiac output, or other blood flow indices. Lower S2P WFAZ was associated with lower birth WFAZ, and perioperative gastrointestinal complications. Lower 18-month motor development score was associated with lower birth WFAZ, native high pulmonary blood flow physiology, and indices of increase pulmonary blood flow: superior vena cava flow (b=8.8; [95% CI: 0.7 to17], p=0.03) and pulmonary venous to systemic blood flow (Qp:Qs) (b=-7, [95% CI: -11.1 to -2.9], p=0.001). Other ND domains were associated with lower birth WFAZ, not blood flow indices. Conclusion: In SV patients, DAoNet did not correlate with growth at S2P. Modifiable factors studied were not associated with somatic growth. DAoNet, superior vena cava flow, and Qp:Qs were associated with 18-months motor development, which may indicate long-term risks of high pulmonary blood flow. Studies are needed to delineate the pathophysiology by which these findings are mediated.

Abstract 4135497: Model-informed dosing recommendations for digoxin in interstage single ventricle heart disease

Digoxin is commonly used in infants with single ventricle heart disease (SVD) and may decrease mortality in the interstage period. While labeled for the treatment of heart failure in infants, dosing recommendations do not account for alterations in drug disposition in SVD. We aimed to characterize digoxin pharmacokinetics (PK) in interstage infants with SVD. Infants <3 months with SVD who received enteral digoxin per standard of care after stage 1 and prior to stage 2 palliation were included in this prospective, multicenter, open-label PK study. Preterm infants and those with creatinine >2mg/dL or on extracorporeal support at enrollment were excluded. PK samples were prospectively collected and digoxin plasma concentrations quantitated by HPLC/MS/MS assay validated per FDA guidance. Population PK analysis was performed in NONMEM. Effects of covariates on PK parameters were evaluated. Dosing simulations were conducted in a virtual cohort of infants with SVD that optimized dosing to achieve trough concentrations of 0.5-2 ng/mL, the label-endorsed reference range for heart failure. Across 10 sites, 50 infants contributed 207 PK samples. Table 1 shows cohort characteristics. A 2-compartment model with transit compartment absorption and linear elimination best described the data. Renal function and weight were significant covariates. Infants with SVD had lower apparent clearance than previously reported in infants without SVD. Current labeled dosing resulted in simulated exposures above the reference range ( Figure 1 ). A new dosing regimen for infants with SVD is proposed. Digoxin PK is altered in infants with SVD. Dosing should account for renal function, age, and weight.

Abstract 4134460: Application of Principal Component Analysis to Heterogenous Fontan Registry Data to Identify Independent Contributing Factors to Decline

Introduction: Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that may ultimately require heart transplant. Goal: Our study goal was to determine if principal component analysis (PCA), which determines unique directions of data variance, applied to data collected from a pediatric Fontan cohort can predict functional decline (N=140). Methods: Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO 2max ), lymphatic biomarkers, and blood biomarkers were collected over 9 years at a single site as part of a prospectively applied clinical care pathway; in that time, 16 events occurred that are considered here in a composite adverse outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Results: Our main findings suggest that the 6 th PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by albumin, alkaline phosphatase, total protein, BUN and BNP max and is a superior measure of proportional hazard compared to EF; it displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and blood biomarkers (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Conclusion: Our findings support the hypothesis that a broad, prospectively collected, multiorgan system model analyzed by way of unsupervised machine learning methods will improve prognosis of adverse outcomes in a Fontan cohort.

Abstract 4135951: Single Nuclei RNA Sequencing Reveals Distinct Cellular Composition of Pericoronary Adipose Tissue

Introduction: Adipose tissue is a metabolically active organ with local paracrine interactions on adjacent tissues. Pericoronary adipose tissue (PcAT) is an emerging cardiovascular disease (CVD) risk factor and likely has paracrine effects on coronary vasculature that may promote coronary artery disease (CAD) development. PcAT may be functionally and clinically distinct from epicardial adipose tissue (EAT) given its proximity to the coronary artery adventitia. The cellular composition of PcAT and EAT and whether they have unique inflammatory cell signatures and functional expression at a single cell level has not been explored. Hypothesis: PcAT will have diverse cellular composition with heightened inflammatory cell content compared to EAT. Methods: Visual dissection of paired EAT not adjacent to an epicardial coronary artery and PcAT in direct apposition to an epicardial artery (left anterior descending artery) was performed from a single human heart immediately after explant (prior to heart transplantation). Nuclei were isolated using the Chromium Nuclei Isolation Kit (10x Genomics) with RNAse inhibitor. Cells were counted with a Cellometer K2 and Chromium Next GEM Single Cell libraries were prepared, followed by reverse transcription, PCR and NovaSeq 6000 platform sequencing. Raw sequence reads from single nuclei RNA-seq (snRNA-seq) were processed and after QC filtering, cells were clustered using Seurat. Clusters were annotated using singleR. Results: In PcAT and EAT, >7000 cells were successfully extracted with 73755 and 48750 mean snRNA-seq reads per cell, respectively. snRNA-seq cellular composition analysis delineated a heightened inflammatory milieu and distinct cellular composition of human PcAT vs. EAT. A UMAP (Uniform Manifold Approximation and Projection) plot displays higher inflammatory cell infiltrate with a neutrophil predominance and lesser adipocyte composition in PcAT compared with EAT ( Figure 1) . Conclusions: We have generated snRNA-seq data from human PcAT and shown distinct cellular composition compared to EAT. Given the proximity of PcAT to coronary vasculature, these results are supportive of paracrine inflammatory effects and highlight adipose tissue biology in cardiovascular disease. Understanding this biology may identify novel therapeutic targets for CVD.

Abstract 4145857: The effect of homebase exercise training on single ventricle heart (SVH) function, exercise performance, body composition and quality of Life in children and adolescents living with a Fontan circulation

Objectives: Fontan patients have impaired exercise capacity. Exercise training has been shown to improve exercise performance. We aim to determine the effect of exercise training on SVH function, and its correlation with exercise capacity, body composition and self-reported QOL. Methods: 31 paediatric Fontan patients were prospectively recruited to complete 3x30 minute homebased HIIT sessions per week for 20 weeks. Baseline physical activity levels, including structured sports participation, daily step-counts and active-zone-minutes (AZM) were recorded by accelerometer (Fitbit inspire3). Patients were considered active if they met 2 of the 3 criteria: 1/Structured sports training ≥ 2 per week (moderate-vigorous intensity >30 minutes) 2/Daily steps ≥ 10k 3/AZM ≥60 minutes per day Bio-impedance-analysis, cardiopulmonary exercise tests, echocardiography including deformation imaging and PedQL questionnaires were performed at baseline and upon completion. Results: 28 participants completed the programme. 86% had good compliance (completed >45/60 sessions). 17 male (60.7%), mean age 14.3±2.03 years, 14 LV-dominant, 14 non-LV dominant (9RV, 5BiV). No serious adverse events reported. The exercise duration improved from 7.56±2.6 to 9.16±2.5 minutes, p<0.001 and peak workload from 110±43.6 to 129±45.8 watts, p<0.001. Indexed oxygen consumption (VO 2 /kg peak) improved from 30.9±7.1 to 32.2±7ml/min/kg, p=0.003 and oxygen pulse, O 2 pulse peak from 9.1±2.6 to 9.7±3 mL/beat, p<0.001. Submaximal analysis showed normal %predicted VO2 (>40%) and improvement of O 2 pulse, p=0.024. LV systolic function showed improved MAPSE from 1.65±0.2 to 1.86±0.2, p=0.017, and improved apical rotation from 2.3±3.8 to 5.9±3.1, p=0.043. RV systolic function showed improved TAPSE of 1.4±0.2 to 1.6±0.3, p=0.032 and FAC of 44±5.6% to 49±10.5%, p=0.170. Self-reported QOL scores were higher in Fontan children who were physically active at baseline, with a downward trend noted when poor compliance was evident (Child’s QOL V3.0 91.21±0.7 to 86.1±5.2, p=0.018 (Table 2). Although no significant change in body composition, a higher appendicular skeletal muscle mass, SMMa% and lower body fat% were noted pre and post exercise training in the active Fontan group (Table 3), Conclusions: We observed significant improvements in both the submaximal and peak exercise performance in paediatric Exercise training associated with improvement of single ventricle longitudinal systolic function and ventricular mechanics.

Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease.

Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years. This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; P=0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; P=0.036) at 8 years. By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.

The Single Ventricle of the Heart in Combination with Transposition of the Main Vessels in the Practice of a Doctor: A Clinical Case

The most vulnerable period in terms of the formation of congenital malformations of organs is 3-4 weeks of pregnancy. It is during this period that the formation of the interventricular septum occurs. Exposure to teratogenic factors on the fetus or genetic mutations at the initial stages of embryogenesis can lead to the development of a single ventricle of the heart, which is considered a severe congenital malformation. The article describes a clinical case of a single heart ventricle in a 19-year-old patient complicated by cardiorenal syndrome.

Preexisting Heart Disease Spectrum and In‐Hospital Outcomes for Patients With Acute Ischemic Stroke

Background Although many studies have examined the influence of individual preexisting heart conditions on stroke outcomes, the combined effects of these conditions remain understudied. Methods The data supporting this study's findings are available from the corresponding author upon reasonable request. Data on patients with acute ischemic stroke from the Third China National Stroke Registry were analyzed. Preexisting heart disease spectrum was defined based on the combination pattern of coronary heart disease, atrial fibrillation, and heart failure. In‐hospital stroke outcomes included moderate or severe stroke at admission (the National Institutes of Health Stroke Scale score ≥16), ambulation by day 2, and in‐hospital death. Results Among the 14 019 analyzed patients, 1856 (13.2%) had preexisting heart diseases, of which the most common single heart disease was coronary heart disease (1313 [70.7%]), and the most common combination was coronary heart disease and atrial fibrillation (116 [6.3%]). Patients with preexisting heart diseases had higherprevalence of moderate or severe stroke at admission (4.7% versus 1.9%; adjusted odds ratio [aOR], 2.25 [95% CI, 1.73–2.93]), in‐hospital mortality (0.5% versus 0.2%; aOR, 2.41 [95% CI, 1.11–5.25]), and a lower rate of ambulation by day 2 (73.9% versus 78.6%; aOR, 0.84 [95% CI, 0.75–0.95]). Atrial fibrillation alone (moderate or severe stroke: aOR, 4.82 [95% CI, 3.29–7.06]; in‐hospital mortality: aOR, 4.76 [95% CI, 1.58–14.36]; ambulation by day 2: aOR, 0.58 [95% CI, 0.46–0.72]) or in combination with coronary heart disease and heart failure (moderate or severe stroke: aOR, 11.47 [95% CI, 3.66–35.89]; ambulation by day 2: aOR, 0.41 [95% CI, 0.16–1.05]) had the strongest association with unfavorable outcomes. Conclusion Preexisting heart diseases, particularly atrial fibrillation combined with other heart diseases, are associated with unfavorable in‐hospital stroke outcomes.

Insulin Resistance after Fontan Palliation.

Patients with a single ventricle heart who had Fontan palliation (S/P Fontan) are at increased risk for acquired morbidity. Insulin resistance (IR) is a predictor of cardiac morbidity and mortality. A single-center, cross-sectional study using S/P Fontan and controls was designed to assess IR S/P Fontan. Group comparisons were made in IR via the Quantitative Insulin Index (QUICKI) and the natural log-transformed homeostasis model assessment, ln (HOMA-IR), without/with adjusting for age. A total of 89 patients (59 Fontan and 30 controls) were included. Fontan patients showed a significant decrease in QUICKI (0.34 ± 0.03 vs 0.37 ± 0.02) and an elevation of ln (HOMA-IR) (0.82 ± 0.62 vs 0.24 ± 0.44) compared to controls (both p < 0.0001); this remained significant even adjusting for age. With older age, there was a significant, progressive decrease in QUICKI (p = 0.01) and an increase in ln (HOMA-IR) (p = 0.02) S/P Fontan. Analysis excluding Fontan patients with obesity still showed a significant reduction of QUICKI and an elevation of ln (HOMA-IR) in Fontan patients compared to controls when adjusting for age (both p < 0.05). Using QUICKI, IR was present in 41 (69.5%) Fontan patients vs. 3 (10%) controls (p < 0.0001) and using HOMA-IR, IR was present in 32 (54.2%) vs 5 (16.7%) controls (p = 0.001). Fontan patients had significantly more IR compared to controls and the prevalence of IR increases with age. Since IR is known to correlate with long-term morbidity and mortality and can be ameliorated by therapies, we believe it is critical that IR be identified as early as possible in Fontan patients.

Trisomy 21 and Congenital Heart Disease: Impact on Health and Functional Outcomes From Birth Through Adolescence: AScientific Statement From the American Heart Association.

Due to improvements in recognition and management of their multisystem disease, the long-term survival of infants, children, and adolescents with trisomy 21 and congenital heart disease now matches children with congenital heart disease and no genetic condition in many scenarios. Although this improved survival is a triumph, individuals with trisomy 21 and congenital heart disease have unique and complex care needs in the domains of physical, developmental, and psychosocial health, which affect functional status and quality of life. Pulmonary hypertension and single ventricle heart disease are 2 known cardiovascular conditions that reduce life expectancy in individuals with trisomy 21. Multisystem involvement with respiratory, endocrine, gastrointestinal, hematological, neurological, and sensory systems can interact with cardiovascular health concerns to amplify adverse effects. Neurodevelopmental, psychological, and functional challenges can also affect quality of life. A highly coordinated interdisciplinary care team model, or medical home, can help address these complex and interactive conditions from infancy through the transition to adult care settings. The purpose of this Scientific Statement is to identify ongoing cardiovascular and multisystem, developmental, and psychosocial health concerns for children with trisomy 21 and congenital heart disease from birth through adolescence and to provide a framework for monitoring and management to optimize quality of life and functional status.

Suppression of B-type natriuretic peptide gene expression in cardiomyocytes under anoxic conditions

Several cell biology studies have focused on the effects of hypoxic environments on cardiomyocytes. However, the effect of anoxic conditions on cardiomyocytes remains largely unexplored. In the present study, we investigated the direct effects of anoxia on B-type natriuretic peptide (BNP) gene expression in cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were exposed to anoxia using an airtight chamber saturated with 95% N2/5% CO2. BNP mRNA levels in NRCM were substantially reduced after more than 8hours of anoxia exposure, whereas after reoxygenation, BNP gene expression levels recovered in a time-dependent manner and significantly increased after 24hours of reoxygenation. BNP mRNA levels suppressed under anoxic conditions were significantly increased by aldosterone-induced activation of sodium-proton exchanger 1 (NHE1), which was cancelled by an NHE1 inhibitor, suggesting that anoxia reduces BNP gene expression, at least in part, in an NHE1-dependent manner. In summary, we found that BNP gene expression in cardiomyocytes decreases under anoxic conditions, in contrast to previous research findings that BNP expression increases under hypoxic conditions. These findings reveal a new insight that, within a single heart tissue in various cardiovascular diseases, such as myocardial infarction, the biological responses of cardiomyocytes are fundamentally different in regions of anoxia and hypoxia.

Resuscitation arterial waveform quantification and outcomes in pediatric bidirectional Glenn and Fontan patients.

Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

Association of Lipoprotein(a) With Severe Degenerative Aortic Valve Stenosis

BackgroundLipoprotein(a) (Lp[a]) is associated with the development of aortic valve calcification. ObjectivesThe aim of this study was to evaluate the association between the serum level of Lp(a) and the development of severe degenerative aortic stenosis (AS) and subsequent aortic valve replacement (AVR). MethodsA total of 44,742 patients with Lp(a) measurements and echocardiography at baseline evaluation between 2000 and 2020 were included from a single tertiary heart center. The primary outcome was the development of severe degenerative AS, defined as a transaortic maximal velocity of ≥4.0 m/s. ResultsDuring a median follow-up period of 6.8 years (Q1-Q3: 2.3-12.4 years), severe degenerative AS was diagnosed in 472 patients (1.1%), and subsequent AVR was performed in 387 patients (0.9%). Lp(a) levels were associated with risk for severe degenerative AS, with levels of 30 to 50, 50 to 100, and >100 mg/dL demonstrating adjusted HRs of 1.02 (95% CI: 0.78-1.34; P = 0.88), 1.18 (95% CI: 0.91-1.53; P = 0.22), and 1.96 (95% CI: 1.31-2.94; P = 0.001) compared to <30 mg/dL. Similarly, the risk for AVR due to severe degenerative AS was significantly associated with higher levels of Lp(a) (>100 mg/dL) (adjusted HR: 2.05; 95% CI: 1.31-3.19; P = 0.002). Such associations were not observed in the development of severe bicuspid (P = 0.63) or rheumatic (P = 0.96) AS. ConclusionsLp(a) levels >100 mg/dL were significantly associated with risk for severe degenerative AS and subsequent AVR, regardless of the baseline severity of AS. Such associations were not observed in other etiologies of severe AS.

Practice variation using the hybrid stage I procedure in congenital heart disease: Results from a national survey

ObjectivesHybrid stage I palliation has been used in many clinical scenarios including initial palliation in single ventricle heart disease, a bridge to biventricular repair, a bridge to transplant, and as a destination therapy. There is considerable hybrid stage I palliation practice variation, which we aimed to better understand in this study. MethodsSurvey-based assessment of practice variation related to hybrid stage I palliation was sent to congenital heart centers across the United States and Canada. ResultsOf the 106 centers surveyed, responses were received from 54 centers (50.9%). Of respondents, 45 centers perform hybrid stage I palliation. Centers most commonly (97.7%) perform hybrid stage I palliation on “high-risk” patients with single ventricle heart disease. Regarding the technical aspects of hybrid stage I palliation, most centers (95.3%) accomplish restrictive pulmonary blood flow using pulmonary artery bands and primarily use changes in oxygen saturation (34.1%) to identify appropriate restriction. Ductal stents are most often used (67.4%) to maintain ductal patency. Only 10 centers (23.3%) routinely enlarge the atrial septal defect. Indications for atrial septal defect intervention varied widely. Most centers (71.9%) discharge patients home to follow with a formal “interstage” program. ConclusionsThere is significant variation in practice patterns for hybrid stage I palliation indications, technical aspects, and postoperative care. Therefore, generalizability of single-center studies on outcomes after hybrid stage I palliation is limited. Future multicenter studies are needed to best delineate which patients benefit most from hybrid stage I palliation and to further define optimal approaches to caring for these patients.

Anaesthetic considerations in congenital single ventricle cyanotic heart disease patients undergoing non – cardiac surgery

Congenital heart disease (CHD) is one of the most prevalent congenital disorders, with an incidence rate of 9.1 per 1000 live births. Lesions featuring single ventricle physiology make up about 20% of these cases. This condition involves an abnormal parallel circulation, leading to complications such as ventricular dysfunction, chronic hypoxia, polycythaemia, and infective endocarditis, which collectively increase mortality risk. Patients with a single functioning ventricle have limited tolerance for changes in preload, afterload, myocardial depression, and fluctuations in pulmonary and systemic vascular resistance. Factors like reduced tidal volume, atelectasis, interstitial lung water, and hypoxic pulmonary vasoconstriction contribute to a balanced circulation, but these factors can be significantly altered during induction and intubation. Here, we report the successful management of a male child with single ventricle physiology who underwent an emergency burr hole procedure and tapping of a brain abscess under general anesthesia.

Quantitative plasma proteomic analysis in children after superior cavopulmonary anastomosis with pulmonary arteriovenous malformations.

Approximately 1000 children are born every year in the United States with one effective cardiac pumping chamber, or single ventricle heart disease. One of the early causes of mortality in this population is pulmonary arteriovenous malformations (PAVMs), which allow blood to bypass gas exchange in the lungs. PAVMs most frequently occur in children after superior cavopulmonary anastomosis (SCPA), a procedure that redirects venous blood from the upper body to the lungs. Because plasma proteins are in part responsible for directing angiogenesis, we hypothesized that differential protein concentrations would be observed in superior caval blood among children after SCPA according to PAVM status. We performed quantitative plasma proteomics from 11 children with PAVMs and in seven children without PAVMs; an additional 11 children with Fontan circulation were included as a reference. Among children with SCPA, there were no significant differences in the plasma proteomes for those with and without PAVMs. When comparing children with Fontan circulation to those with SCPA and PAVMs, 18 proteins exhibited differential expression (10 downregulated and eight upregulated) in superior caval plasma. These results suggest that factors other than, or in addition to, plasma proteins may be responsible for single ventricle patients' susceptibility to PAVMs after SCPA. IMPACT: What is the key message of your article? We did not identify significant differences in plasma proteins when comparing those children with and without pulmonary arteriovenous malformations (PAVMs) after superior cavopulmonary anastomosis (SCPA). What does it add to the existing literature? The etiology of PAVMs in this population is likely due to factors other than, or in addition to, differences in plasma proteins. What is the impact? Further studies are needed to identify causes of PAVMs among children after SCPA.

Early Circulating Biomarkers of Language Development in Single Ventricle Heart Disease

This cohort study assesses proteins measured in infancy and neurodevelopmental outcomes in single ventricle heart disease.

Abstract We029: Common and Divergent Cellular Etiologies Underlying Hypoplastic Left Heart Syndrome and Hypoplastic Right Heart Syndrome

Single ventricle heart defects are the most severe forms of congenital heart defects and are classified based on the affected ventricles: hypoplastic left heart syndrome (HLHS) and hypoplastic right heart syndrome (HRHS). Cellular etiologies underlying differential left and right ventricular hypoplasia are unknown and remain intractable without an experimental model to probe common and divergent cellular etiologies between HLHS and HRHS. In this study, we leveraged patient-specific induced pluripotent stem cells (iPSCs) and single-cell transcriptomics to interrogate distinct etiologies of HLHS and HRHS. Both HLHS and HRHS iPSC-derived cardiomyocytes (iPSC-CMs) exhibit a reduced proliferation capacity compared to sex-matched family controls under both static and cyclic stretch conditions. Biological pathways related to cell cycle progression, DNA replication, and cell proliferation are downregulated in both HLHS and HRHS iPSC-CMs, suggesting an intrinsic cardiac proliferation deficiency. Single-cell transcriptomics indicate that differentiation of cardiac mesoderm towards second heart field (SHF) progenitors are compromised in both HLHS and HRHS. However, differentiation of epicardial progenitors is enhanced at the expense of SHF progenitors in HLHS, whereas first heart field (FHF) progenitors are prevalent in HRHS. Trajectory inference analysis uncovers distinct cell lineage determination pathways in FHF and SHF progenitors between HLHS and HRHS. Moreover, HLHS iPSC-CMs exhibit reduced mitochondrial activities whereas HRHS iPSC-CMs show enhanced mitochondrial respiration and ATP production compared to controls. In sum, these common and divergent cellular etiologies of HLHS and HRHS may underlie ventricular hypoplasia in the left side and right side of the heart.

Abstract We050: Elevated Cell-Free RNA in Maternal Circulation during Single Ventricle Heart Defect Pregnancies Dysregulate Human Cardiomyocyte Proliferation

Congenital single-ventricle heart defects (SVHDs) are life-threatening conditions in newborns, where one of the heart's ventricular chambers is severely underdeveloped. While medical advancements have improved survival rates, many SVHD patients still suffer lifelong cardiac complications and comorbidities. Clinical diagnosis of fetal SVHD occurs at around 20 weeks of gestation through echocardiogram. In this study, we aimed to identify novel maternal blood biomarkers that could signal SVHD development in fetuses. The study's premise is based on the limited regenerative capacity of adult human cardiomyocytes, like those in pregnant mothers, compared to the extensive proliferation seen in fetal cardiomyocytes that form the functional heart. We hypothesized small signaling molecules secreted by proliferating fetal cardiomyocytes enter the maternal circulatory system and could indicate abnormal ventricular growth in SVHD-affected fetuses. Both clinical and in vitro approaches were employed to identify potential cell-free miRNAs released by the developing fetal heart into maternal circulation. Blood plasma samples from pregnant women carrying healthy and SVHD-affected fetuses were screened for differentially expressed cell-free miRNAs and were compared with those from the supernatants of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) grown from healthy and SVHD donors. This comparative approach led to the identification of an miRNA panel (miR-487b, miR-433, mi-134, and miR-889) that were elevated in pregnant women carrying SVHD-affected fetuses and in proliferating iPSC-CMs from SVHD patients compared to healthy controls (p.adj&lt;0.05). From this panel, forced-expression of miR-487b and mir-134 modulated the proliferation profiles of human cardiomyocytes in vitro . Results from this study establish these circulating cell-free miRNAs in maternal blood as potential non-invasive biomarkers for predicting abnormal fetal cardiac development leading to SVHDs. These findings could potentially revolutionize SVHD screening as an alternative diagnostic tool to echocardiogram.