A comprehensive study on machine learning models combining with oversampling for bronchopulmonary dysplasia-associated pulmonary hypertension in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) remains a devastating clinical complication seriously affecting the therapeutic outcome of preterm infants. Hence, early prevention and timely diagnosis prior to pathological change is the key to reducing morbidity and improving prognosis. Our primary objective is to utilize machine learning techniques to build predictive models that could accurately identify BPD infants at risk of developing PH. METHODS: The data utilized in this study were collected from neonatology departments of four tertiary-level hospitals in China. To address the issue of imbalanced data, oversampling algorithms synthetic minority over-sampling technique (SMOTE) was applied to improve the model. RESULTS: Seven hundred sixty one clinical records were collected in our study. Following data pre-processing and feature selection, 5 of the 46 features were used to build models, including duration of invasive respiratory support (day), the severity of BPD, ventilator-associated pneumonia, pulmonary hemorrhage, and early-onset PH. Four machine learning models were applied to predictive learning, and after comprehensive selection a model was ultimately selected. The model achieved 93.8% sensitivity, 85.0% accuracy, and 0.933 AUC. A score of the logistic regression formula greater than 0 was identified as a warning sign of BPD-PH. CONCLUSIONS: We comprehensively compared different machine learning models and ultimately obtained a good prognosis model which was sufficient to support pediatric clinicians to make early diagnosis and formulate a better treatment plan for pediatric patients with BPD-PH.

Moderate Aortic Valve Stenosis Is Associated With Increased Mortality Rate and Lifetime Loss: Systematic Review and Meta-Analysis of Reconstructed Time-to-Event Data of 409 680 Patients.

BACKGROUND: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). METHODS AND RESULTS: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P<0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P<0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P<0.001; and 1.9 years, P<0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. CONCLUSIONS: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. METHODS: PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. RESULTS: PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LIMITATIONS: The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. CONCLUSION: Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.

Abnormal Cardiac Magnetic Resonance-Derived Ascending Aortic Area Strain Demonstrates Altered Ventriculo-Vascular Function in Marfan Syndrome.

PURPOSE: There remains a need for improved imaging markers for risk stratification and treatment guidance in Marfan syndrome (MFS). After aortic root replacement (ARR), vascular remodeling and progressive aneurysm formation can occur due to alterations in up- and downstream wall biomechanics and hemodynamics. We aim to compare the ventriculo-vascular properties of patients with MFS with controls, and investigate the correlation between ascending aortic area strain and descending aortic area strain (DAAS) with other clinical variables. PATIENTS AND METHODS: Nineteen patients with MFS (47% males), including 6 with ARR were studied. In 26 studies, aortic area strain was measured using cross-sectional cardiac magnetic resonance images at the ascending and proximal descending aortic levels. Left atrial, left ventricular longitudinal, and left ventricle circumferential strain (left atrial longitudinal strain, left ventricular longitudinal strain, and left ventricular circumferential strain, respectively) were measured using cardiac magnetic resonance-feature tracking. RESULTS: Compared with healthy controls, patients with MFS had significantly impaired left ventricular longitudinal strain and left ventricular circumferential strain (-15.8 ± 4.7 vs -19.7 ± 4.8, P = 0.005, and -17.7 ± 4.0 vs -27.0 ± 4.1, P < 0.001). Left atrial longitudinal strain was comparable between patients with MFS and controls. AAAS was significantly reduced (19.0 [11.9, 23.7] vs 46.1 ± 11.3, P < 0.001), whereas DAAS was not significantly decreased. AAAS and DAAS were negatively correlated with age, whereas no significant associations were identified with left ventricle function indices. No significant differences were observed between the ventriculo-vascular properties of patients with MFS who underwent ARR and those who did not. CONCLUSION: Patients with MFS demonstrated impaired ventricular and vascular function compared with healthy controls. Further investigations are warranted to determine clinical utility of aortic stiffness indices for predicting primary and repeat aortic events.

Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF stress trial.

BACKGROUND: With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests. METHODS: The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e' > 8) who underwent simultaneous rest and exercise-stress echocardiography and right heart catheterisation (RHC). HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15 mmHg stress: ≥25 mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e'). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH). RESULTS: The final study population included 68 patients (HFpEF n = 34 and NCD n = 34) of which 23 reached the clinical endpoint, 1 patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p < 0.001) compared to patients with a score ≤ 4. LA compliance at rest outperformed E/e' (AUC 0.78 vs 0.87, p = 0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p = 0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p < 0.001) irrespective of concomitant atrial fibrillation. CONCLUSIONS: LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.

Impact of epicardial adipose tissue on cardiac function and morphology in patients with diastolic dysfunction.

AIMS: This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. METHODS AND RESULTS: Sixty-eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e' ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short-axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA-PEFF and H2FPEFF scores as well as N-terminal prohormone of brain natriuretic peptide levels (all P < 0.048). They were diagnosed with manifest heart failure with preserved ejection fraction (HFpEF) more frequently (low EAT: 37% vs. high EAT: 64%; P = 0.029) and had signs of adverse remodelling indicated by higher T1 times (P < 0.001). No differences in biventricular volumetry and left ventricular mass (all P > 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. CONCLUSIONS: Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.

Neonates and Infants with Left Heart Obstruction and Borderline Left Ventricle Undergoing Biventricular Repair: What Do We Know about Long-Term Outcomes? A Critical Review.

BACKGROUND: The decision to perform biventricular repair (BVR) in neonates and infants presenting with either single or multiple left ventricle outflow obstructions (LVOTOs) and a borderline left ventricle (BLV) is subject to extensive discussion, and limited information is known regarding the long-term outcomes. As a result, the objective of this study is to critically assess and summarize the available data regarding the prognosis of neonates and infants with LVOTO and BLV who underwent BVR. METHODS: In February 2023, we conducted a review study with three different medical search engines (the National Library of Medicine, Science Direct, and Cochrane Library) for Medical Subject Headings and free text terms including "congenital heart disease", "outcome", and "borderline left ventricle". The search was refined by adding keywords for "Shone's complex", "complex LVOT obstruction", "hypoplastic left heart syndrome/complex", and "critical aortic stenosis". RESULTS: Out of a total of 51 studies, 15 studies were included in the final analysis. The authors utilized heterogeneous definitions to characterize BLV, resulting in considerable variation in inclusion criteria among studies. Three distinct categories of studies were identified, encompassing those specifically designed to evaluate BLV, those focused on Shone's complex, and finally those on aortic stenosis. Despite the challenges associated with comparing data originating from slightly different cardiac defects and from different eras, our results indicate a favorable survival rate and clinical outcome following BVR. However, the incidence of reintervention remains high, and concerns persist regarding residual pulmonary hypertension, which has been inadequately investigated. CONCLUSIONS: The available data concerning neonates and infants with LVOTO and BLV who undergo BVR are inadequate and fragmented. Consequently, large-scale studies are necessary to fully ascertain the long-term outcome of these complex defects.

Mortality and Heart Transplantation After Hybrid Palliation of Hypoplastic Left Heart Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) who are considered at increased risk for death following Norwood/Sano surgery often undergo hybrid palliation (HP) as initial surgery. We aimed to compile the HP experience in HLHS and its variants and assess the rates of, and risk factors for, death and heart transplantation. METHODS: CINAHL, CINAHL PLUS, PubMed/MEDLINE, and SCOPUS were systematically searched for HP outcome studies of death or heart transplantation in HLHS between 1998 and 2022. Pooled incidence was estimated, and potential risk factors were identified using random-effects meta-analysis and reconstructed time-to-event data from Kaplan-Meier curves. RESULTS: Thirty-three publications were included in our review. Overall, of 1,162 patients 417 died and 57 underwent heart transplantation, resulting in a combined outcome of 40.7%, (474/1,162). There was a trend toward decreasing mortality risk across the stages of palliation. Pooled mortality between HP and comprehensive stage 2 palliation was 25%, after stage 2 up to Fontan palliation was 16%, and 6% post-Fontan. The incidence of death or heart transplantation was higher in high-risk patients-43% died and 10% received heart transplantation. CONCLUSION: Our systematic review and meta-analysis found high rates of death or heart transplantation in HP of HLHS patients between HP and Fontan surgeries. All patients should be closely followed during the initial interstage period, which is associated with the highest hazard. Prospective studies on appropriate patient selection, indications, and / or alternatives, as well as refining HP strategies for managing newborns with HLHS are needed to improve outcomes.

Assessment of the cardiac output at rest and during exercise stress using real-time cardiovascular magnetic resonance imaging in HFpEF-patients.

This methodological study aimed to validate the cardiac output (CO) measured by exercise-stress real-time phase-contrast cardiovascular magnetic resonance imaging (CMR) in patients with heart failure and preserved ejection fraction (HFpEF). 68 patients with dyspnea on exertion (NYHA ≥ II) and echocardiographic signs of diastolic dysfunction underwent rest and exercise stress right heart catheterization (RHC) and CMR within 24 h. Patients were diagnosed as overt HFpEF (pulmonary capillary wedge pressure (PCWP) ≥ 15mmHg at rest), masked HFpEF (PCWP ≥ 25mmHg during exercise stress but < 15mmHg at rest) and non-cardiac dyspnea. CO was calculated using RHC as the reference standard, and in CMR by the volumetric stroke volume, conventional phase-contrast and rest and stress real-time phase-contrast imaging. At rest, the CMR based CO showed good agreement with RHC with an ICC of 0.772 for conventional phase-contrast, and 0.872 for real-time phase-contrast measurements. During exercise stress, the agreement of real-time CMR and RHC was good with an ICC of 0.805. Real-time measurements underestimated the CO at rest (Bias:0.71 L/min) and during exercise stress (Bias:1.4 L/min). Patients with overt HFpEF had a significantly lower cardiac index compared to patients with masked HFpEF and with non-cardiac dyspnea during exercise stress, but not at rest. Real-time phase-contrast CO can be assessed with good agreement with the invasive reference standard at rest and during exercise stress. While moderate underestimation of the CO needs to be considered with non-invasive testing, the CO using real-time CMR provides useful clinical information and could help to avoid unnecessary invasive procedures in HFpEF patients.

Anxiety and Depression in Adults With Congenital Heart Disease.

BACKGROUND: A comprehensive understanding of adult congenital heart disease outcomes must include psychological functioning. Our multisite study offered the opportunity to explore depression and anxiety symptoms within a global sample. OBJECTIVES: In this substudy of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults With Congenital Heart Disease-International Study), the authors we investigated the prevalence of elevated depression and anxiety symptoms, explored associated sociodemographic and medical factors, and examined how quality of life (QOL) and health status (HS) differ according to the degree of psychological symptoms. METHODS: Participants completed the Hospital Anxiety and Depression Scale, which includes subscales for symptoms of anxiety (HADS-A) and depression (HADS-D). Subscale scores of 8 or higher indicate clinically elevated symptoms and can be further categorized as mild, moderate, or severe. Participants also completed analogue scales on a scale of 0 to 100 for QOL and HS. Analysis of variance was performed to investigate whether QOL and HS differed by symptom category. RESULTS: Of 3,815 participants from 15 countries (age 34.8 ± 12.9 years; 52.7% female), 1,148 (30.1%) had elevated symptoms in one or both subscales: elevated HADS-A only (18.3%), elevated HADS-D only (2.9%), or elevations on both subscales (8.9%). Percentages varied among countries. Both QOL and HS decreased in accordance with increasing HADS-A and HADS-D symptom categories (P < 0.001). CONCLUSIONS: In this global sample of adults with congenital heart disease, almost one-third reported elevated symptoms of depression and/or anxiety, which in turn were associated with lower QOL and HS. We strongly advocate for the implementation of strategies to recognize and manage psychological distress in clinical settings. (Patient-Reported Outcomes in Adults With Congenital Heart Disease [APPROACH-IS]; NCT02150603).

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Semi-automated quantification of tricuspid valve dynamics and structure in tetralogy of Fallot and hypoplastic left heart syndrome using three-dimensional echocardiography.

Anomalies of the tricuspid valve (TV) are associated with worsened prognosis in congenital heart disease (CHD). Here, we present a descriptive study examining changes in TV morphology in two CHD conditions-repaired tetralogy of Fallot (rTOF) and hypoplastic left heart syndrome (HLSH), using three-dimensional echocardiography. Full volume acquisitions of the TV and right ventricle (RV) were performed from an RV-focused apical view using ECG gating over 2-5 consecutive cardiac cycles using 3D echocardiography, from which TV annulus and leaflet parameters were quantified. A total of 40 rTOF patients (age 14 ± 9.8 years), 40 HLHS patients (age1.0 ± 1.5 years) and 80 age and gender matched controls were included. Among leaflet parameters, antero-posterior and posterior-septal TV coaptation heights were smaller in rTOF (p < 0.001) vs. control. Conversely, only the short-axis TV height was different in HLHS vs. controls (HLHS 1.6 ± 0.4 cm vs. control 1.4 ± 0.3 cm). TV leaflet parameters tended to be larger in HLHS, while leaflet coaptation distances were similar between groups. We demonstrate that 3D echocardiography for assessment of the TV is feasible in rTOF and HLHS patients and identifies unique differences in TV morphology. Future studies should clarify the clinical significance of TV morphology in these patient populations.

Echocardiographic Parameters for Risk Prediction in Borderline Right Ventricle: Review with Special Emphasis on Pulmonary Atresia with Intact Ventricular Septum and Critical Pulmonary Stenosis.

The aim of the present review is to highlight the strengths and limitations of echocardiographic parameters and scores employed to predict favorable outcome in complex congenital heart diseases (CHDs) with borderline right ventricle (RV), with a focus on pulmonary atresia with intact ventricular septum and critical pulmonary stenosis (PAIVS/CPS). A systematic search in the National Library of Medicine using Medical Subject Headings and free-text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords "PAIVS/CPS", Ebstein's anomaly, and unbalanced atrioventricular septal defect with left dominance. A total of 22 studies were selected for final analysis; 12 of them were focused on parameters to predict biventricular repair (BVR)/pulmonary blood flow augmentation in PAIVS/CPS. All of these studies presented numerical (the limited sample size) and methodological limitations (retrospective design, poor definition of inclusion/exclusion criteria, variability in the definition of outcomes, differences in adopted surgical and interventional strategies). There was heterogeneity in the echocardiographic parameters employed and cut-off values proposed, with difficultly in establishing which one should be recommended. Easy scores such as TV/MV (tricuspid/mitral valve) and RV/LV (right/left ventricle) ratios were proven to have a good prognostic accuracy; however, the data were very limited (only two studies with <40 subjects). In larger studies, RV end-diastolic area and a higher degree of tricuspid regurgitation were also proven as accurate predictors of successful BVR. These measures, however, may be either operator and/or load/pressure dependent. TV Z-scores have been proposed by several authors, but old and heterogenous nomograms sources have been employed, thus producing discordant results. In summary, we provide a review of the currently available echocardiographic parameters for risk prediction in CHDs with a diminutive RV that may serve as a guide for use in clinical practice.

Data Quality Degradation on Prediction Models Generated From Continuous Activity and Heart Rate Monitoring: Exploratory Analysis Using Simulation.

BACKGROUND: Limited data accuracy is often cited as a reason for caution in the integration of physiological data obtained from consumer-oriented wearable devices in care management pathways. The effect of decreasing accuracy on predictive models generated from these data has not been previously investigated. OBJECTIVE: The aim of this study is to simulate the effect of data degradation on the reliability of prediction models generated from those data and thus determine the extent to which lower device accuracy might or might not limit their use in clinical settings. METHODS: Using the Multilevel Monitoring of Activity and Sleep in Healthy People data set, which includes continuous free-living step count and heart rate data from 21 healthy volunteers, we trained a random forest model to predict cardiac competence. Model performance in 75 perturbed data sets with increasing missingness, noisiness, bias, and a combination of all 3 perturbations was compared to model performance for the unperturbed data set. RESULTS: The unperturbed data set achieved a mean root mean square error (RMSE) of 0.079 (SD 0.001) in predicting cardiac competence index. For all types of perturbations, RMSE remained stable up to 20%-30% perturbation. Above this level, RMSE started increasing and reached the point at which the model was no longer predictive at 80% for noise, 50% for missingness, and 35% for the combination of all perturbations. Introducing systematic bias in the underlying data had no effect on RMSE. CONCLUSIONS: In this proof-of-concept study, the performance of predictive models for cardiac competence generated from continuously acquired physiological data was relatively stable with declining quality of the source data. As such, lower accuracy of consumer-oriented wearable devices might not be an absolute contraindication for their use in clinical prediction models.

Characterization of Aortic Flow Patterns by High-Frame-Rate Blood Speckle Tracking Echocardiography in Children.

Background Blood speckle tracking echocardiography allows for direct quantification of interventricular and aortic flow profiles, principally in children. Here, we sought to demonstrate the feasibility and reproducibility of blood speckle tracking echocardiography in the aortas of healthy children. Methods and Results One hundred healthy White children evaluated for the screening of congenital heart disease were prospectively enrolled. Echocardiographic examinations were performed using a Vivid E 95 ultrasound system, with blood speckle tracking from a focused and zoomed view of the aortic root and the ascending aorta. Vortex position, height (mm), width (mm), sphericity index, and area (cm2) were measured and indexed by body surface area. Median (interquartile range) age was 8.2 (5.6-11.0) years, median (interquartile range) weight was 28 (19-35) kg, and median (interquartile range) body surface area was 1.01 (0.79-1.16) m2. Vortices were visualized in only a single phase of the cardiac cycle in 25 subjects-14 (56.0%) were evident in early diastole and 11 (44.0%) in late systole. Vortices visualized in diastole had a mean area of 0.27±0.1 cm2/m2, while those in systole had a mean area of 0.34±0.12 cm2/m2. In a subset of 20 patients, inter- and intraobserver coefficient of variation and intraclass correlation coefficients were determined and showed good reproducibility. Conclusions We demonstrate feasibility and reproducibility of blood speckle tracking and identified vortical flow patterns in the aortic root and ascending aorta in healthy children. These data may serve as a baseline for evaluating aortic flow patterns in children with congenital and acquired heart disease.

Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data.

BACKGROUND: Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices. RESULTS: Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into "highest score" and "lowest score", and "best response to elamipretide" and "worst response to elamipretide". Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60-93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%). CONCLUSIONS: In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.

Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial.

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418.