Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize RV myocyte contractile depression in HFrEF-PH, identify those components reflected by clinical RV indices, and uncover underlying biophysical mechanisms. METHODS: Resting, calcium-, and load-dependent mechanics were prospectively studied in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 patients with HFrEF-PH undergoing cardiac transplantation and 9 organ donor controls. RESULTS: Unsupervised machine learning using myocyte mechanical data with the highest variance yielded 2 HFrEF-PH subgroups that in turn mapped to patients with decompensated or compensated clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in decompensated clinical RV function, whereas surprisingly, many other major myocyte contractile measures including peak power and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick filament defects, myofibrillar structure was assessed by x-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in decompensated clinical RV function, but not compensated clinical RV function, as compared with controls. This corresponded to reduced myosin ATP turnover in decompensated clinical RV function myocytes, indicating less myosin in a crossbridge-ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Last, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human heart failure. CONCLUSIONS: Although there are many RV myocyte contractile deficits in HFrEF-PH, commonly used clinical indices only detect reduced isometric calcium-stimulated force, which is related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.

Poor Cardiac Output Reserve in Pulmonary Arterial Hypertension is Associated With Right Ventricular Stiffness and Impaired Interventricular Dependence.

BACKGROUND: Pulmonary arterial hypertension is characterized by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (p-V) loop analysis to characterize the impact of RV diastology on poor flow augmentation during exercise in PAH. METHODS: RV p-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance, Eed) and ventricular interdependence (left ventricular transmural pressure, LVTMP) were compared at matched exercise stages. RESULTS: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 ml·m-2, p=0.0001), with higher associated exercise afterload (Ea 1.76 versus 0.90 mmHg·mL-1, p<0.0001), RV stiffness (Eed 0.68 versus 0.26 mmHg·mL-1, p=0.003), and right-sided pressures (RA 14 versus 8 mmHg, p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg, p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. CONCLUSIONS: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness, and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiologic PAH differences unapparent at rest.

Modification of a Transvalvular Microaxial Flow Pump for Instantaneous Determination of Native Cardiac Output and Volume.

BACKGROUND: The current Impella cardiopulmonary (CP) pump, used for mechanical circulatory support in patients with cardiogenic shock (CS), cannot assess native cardiac output (CO) and left ventricular (LV) volumes. These data are valuable in facilitating device management and weaning. Admittance technology allows for accurate assessment of cardiac chamber volumes. OBJECTIVES: This study tested the ability to engineer admittance electrodes onto an existing Impella CP pump to assess total and native CO as well as LV chamber volumes in an instantaneous manner. METHODS: Impella CP pumps were fitted with 4 admittance electrodes and were placed in the LVs of adult swine (n = 9) that were subjected to 3 different hemodynamic conditions, including Impella CP speed adjustments, administration of escalating doses of dobutamine and microsphere injections into the left main artery to result in cardiac injury. CO, according to admittance electrodes, was calculated from LV volumes and heart rate. In addition, CO was calculated in each instance via thermodilution, continuous CO measurement, the Fick principle, and aortic velocity-time integral by means of echocardiography. RESULTS: Modified Impella CP pumps were placed in swine LVs successfully. CO, as determined by admittance electrodes, was similar by trend to other methods of CO assessment. It was corrected for pump speed to calculate native CO, and calculated LV chamber volumes trended as expected in each experimental protocol. CONCLUSIONS: We report, for the first time, that an Impella CP pump can be fitted with admittance electrodes and used to determine total and native CO in various hemodynamic situations. CONDENSED ABSTRACT: Transvalvular mechanical circulatory support devices such as the Impella CP do not have the ability to provide real-time information on native cardiac output (CO) and left ventricular (LV) volumes. This information is critical in device management and in weaning in patients with cardiogenic shock. We demonstrate, for the first time, that Impella CP pumps coupled with admittance electrodes are able to determine native CO and LV chamber volumes in multiple hemodynamic situations such as Impella pump speed adjustments, escalating dobutamine administration and cardiac injury from microsphere injection.

Echocardiographic scores for biventricular repair risk prediction of congenital heart disease with borderline left ventricle: a review.

The aim of this review is to highlight the strengths and limitations of major echocardiographic biventricular repair (BVR) prediction models for borderline left ventricle (LV) in complex congenital heart disease (CHD). A systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords for critical aortic stenosis (AS), borderline LV, complex left ventricular outflow tract (LVOT) obstruction, hypoplastic left heart syndrome/complex (HLHS/HLHC), and unbalanced atrio-ventricular septal defects (uAVSD). Fifteen studies were selected for the final analysis. We outlined what echocardiographic scores for different types of complex CHD with diminutive LV are available. Scores for CHD with LVOT obstruction including critical AS, HLHS/HLHC, and aortic arch hypoplasia have been validated and implemented by several studies. Scores for uAVSD with right ventricle (RV) dominance have also been established and implemented, the first being the atrioventricular valve index (AVVI). In addition to AVII, both LV/RV inflow angle and LV inflow index have all been validated for the prediction of BVR. We conclude with a discussion of limitations in the development and validation of each of these scores, including retrospective design during score development, heterogeneity in echocardiographic parameters evaluated, variability in the definition of outcomes, differences in adopted surgical and Interventional strategies, and institutional differences. Furthermore, scores developed in the past two decades may have little clinical relevance now. In summary, we provide a review of echocardiographic scores for BVR in complex CHD with a diminutive LV that may serve as a guide for use in modern clinical practice.

PDE1 Inhibition Modulates Cav1.2 Channel to Stimulate Cardiomyocyte Contraction.

[Figure: see text].

Myofibril orientation as a metric for characterizing heart disease.

Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in the orientation of individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight has predominantly been because of a paucity of methods for objective and quantitative analysis. Here, we introduce a novel, less-biased approach to quantify myofibrillar and myofilament orientation in cardiac muscle under near-physiological conditions and demonstrate its superiority as compared with conventional histological assessments. Using small-angle x-ray diffraction, we first investigated changes in myofibrillar orientation at increasing sarcomere lengths in permeabilized, relaxed, wild-type mouse myocardium from the left ventricle by assessing the angular spread of the 1,0 equatorial reflection (angle σ). At a sarcomere length of 1.9 µm, the angle σ was 0.23 ± 0.01 rad, decreased to 0.19 ± 0.01 rad at a sarcomere length of 2.1 µm, and further decreased to 0.15 ± 0.01 rad at a sarcomere length of 2.3 µm (p < 0.0001). Angle σ was significantly larger in R403Q, a MYH7 hypertrophic cardiomyopathy model, porcine myocardium (0.24 ± 0.01 rad) compared with wild-type myocardium (0.14 ± 0.005 rad; p < 0.0001), as well as in human heart failure tissue (0.19 ± 0.006 rad) when compared with nonfailing samples (0.17 ± 0.007 rad; p = 0.01). These data indicate that diseased myocardium suffers from greater myofibrillar disorientation compared with healthy controls. Finally, we showed that conventional, histology-based analysis of disarray can be subject to user bias and/or sampling error and lead to false positives. Our method for directly assessing myofibrillar orientation avoids the artifacts introduced by conventional histological approaches that assess myocyte orientation and only indirectly evaluate myofibrillar orientation, and provides a precise and objective metric for phenotypically characterizing myocardium. The ability to obtain excellent x-ray diffraction patterns from frozen human myocardium provides a new tool for investigating structural anomalies associated with cardiac diseases.

Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

BACKGROUND: The ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) is a validated index of right ventricular-pulmonary arterial (RV-PA) coupling with prognostic value. We determined the predictive value of TAPSE/PASP ratio and adverse clinical outcomes in hospitalized patients with COVID-19. METHODS: Two hundred and twenty-nine consecutive hospitalized racially/ethnically diverse adults (≥18 years of age) admitted with COVID-19 between March and June 2020 with clinically indicated transthoracic echocardiograms (TTE) that included adequate tricuspid regurgitation (TR) velocities for calculation of PASP were studied. The exposure of interest was impaired RV-PA coupling as assessed by TAPSE/PASP ratio. The primary outcome was in-hospital mortality. Secondary endpoints comprised of ICU admission, incident acute respiratory distress syndrome (ARDS), and systolic heart failure. RESULTS: One hundred and seventy-six patients had both technically adequate TAPSE measurements and measurable TR velocities for analysis. After adjustment for age, sex, BMI, race/ethnicity, diabetes mellitus, and smoking status, log(TAPSE/PASP) had a significantly inverse association with ICU admission (p = 0.015) and death (p = 0.038). ROC analysis showed the optimal cutoff for TAPSE/PASP for death was 0.51 mm mmHg-1 (AUC = 0.68). Unsupervised machine learning identified two groups of echocardiographic function. Of all echocardiographic measures included, TAPSE/PASP ratio was the most significant in predicting in-hospital mortality, further supporting its significance in this cohort. CONCLUSION: Impaired RV-PA coupling, assessed noninvasively via the TAPSE/PASP ratio, was predictive of need for ICU level care and in-hospital mortality in hospitalized patients with COVID-19 suggesting utility of TAPSE/PASP in identification of poor clinical outcomes in this population both by traditional statistical and unsupervised machine learning based methods.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

EMD-57033 Augments the Contractility in Porcine Myocardium by Promoting the Activation of Myosin in Thick Filaments.

Sufficient cardiac contractility is necessary to ensure the sufficient cardiac output to provide an adequate end-organ perfusion. Inadequate cardiac output and the diminished perfusion of vital organs from depressed myocardium contractility is a hallmark end-stage of heart failure. There are no available therapeutics that directly target contractile proteins to improve the myocardium contractility and reduce mortality. The purpose of this study is to present a proof of concept to aid in the development of muscle activators (myotropes) for augmenting the contractility in clinical heart failure. Here we use a combination of cardiomyocyte mechanics, the biochemical quantification of the ATP turnover, and small angle X-ray diffraction on a permeabilized porcine myocardium to study the mechanisms of EMD-57033 (EMD) for activating myosin. We show that EMD increases the contractility in a porcine myocardium at submaximal and systolic calcium concentrations. Biochemical assays show that EMD decreases the proportion of myosin heads in the energy sparing super-relaxed (SRX) state under relaxing conditions, which are less likely to interact with actin during contraction. Structural assays show that EMD moves the myosin heads in relaxed muscles from a structurally ordered state close to the thick filament backbone, to a disordered state closer to the actin filament, while simultaneously inducing structural changes in the troponin complex on the actin filament. The dual effects of EMD on activating myosin heads and the troponin complex provides a proof of concept for the use of small molecule muscle activators for augmenting the contractility in heart failure.

Extracellular vesicle interplay in cardiovascular pathophysiology.

Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles released from cells that mediate intercellular communications and play a pivotal role in various physiological and pathological processes. Subtypes of EVs may include plasma membrane ectosomes or microvesicles and endosomal origin exosomes, although functional distinctions remain unclear. EVs carry cargo proteins, nucleic acids (RNA and DNA), lipids, and metabolites. By presenting or transferring this cargo to recipient cells, EVs can trigger cellular responses. We summarize contemporary understanding of EV biogenesis, composition, and function, with an emphasis on the role of EVs in the cardiovascular system. In addition, we outline the functional relevance of EVs in cardiovascular pathophysiology, further highlighting their potential for diagnostic and therapeutic applications.

A statistical comparison of reproducibility in current pediatric two-dimensional echocardiographic nomograms.

BACKGROUND: The aim of this study is to compare new pediatric nomograms for clinical parameters from 2D echocardiography. METHODS: 2D pediatric echocardiographic parameters from four recent nomograms were used for statistical analysis. To assess the accuracy of the predictive models from each study, namely multivariate, linear, and nonlinear regression, mean values and 5th and 95th percentiles (µ ± 1.65σ) were calculated. A Z-score calculator was created. RESULTS: Mean values and 5th and 95th percentiles have been provided for a range of BSA (0.15-2.20 m2) for each nomogram assessed in this study. Moreover, plots of Z-scores over the same range of BSA have been generated to assess trends among different studies. For most measurements from the two most recent nomograms, namely Lopez et al. and Cantinotti et al., differences were within a Z-score of 0.5 (Z-score range: 0.001-1.26). Measurements from Sluysmans and Colan and Pettersen et al. were observed to diverge from Lopez et al. at the upper extremities of BSA. Differences among various nomograms emerged at lower extremes of BSA. CONCLUSIONS: The two most recent echocardiographic nomograms were observed to have the most statistically similar ranges of normality. Significant deviations in ranges of normality were observed at extremes of BSA. IMPACT: Echocardiographic nomograms for pediatric age are discordant. Comparison of current pediatric echocardiographic nomograms. A Z-score calculator was created. Clinical relevance of differences among nomograms is highlighted.

Progression of left ventricular diastolic function in the neonate and early childhood from transmitral color M-mode filling analysis.

BACKGROUND: We implemented sophisticated color M-mode analysis to assess age-dependent progression of left ventricular (LV) diastolic function. METHODS: Normal infants were prospectively enrolled for serial echocardiograms at 1 week, 1 month, 6 months, 1 year, and 2 years. From color M-mode scans, propagation velocity (VP), strength of filling (VS), and intraventricular pressure difference (IVPD) in 3 segments along apex-to-mitral valve scan line were measured. RESULTS: Age-wise comparisons of diastolic filling from 121 echocardiograms in 31 infants showed VP (cm/s), VS (cm2/s), and E-wave IVPD (mmHg) at 1 week to be 66.2 ± 11.9, 75.3 ± 19.9, and 1.5 ± 0.4, respectively, while VP, VS, and E-wave IVPD at 1 month were 80.3 ± 14.4, 101.2 ± 28.3, and 2.42 ± 1.1, respectively. There were significant differences in VP and segmental IVPD between first week and first month (p < 0.005) and IVPD between the age groups (p < 0.001). CONCLUSIONS: Comprehensive analysis of transmitral color M-mode data is feasible in infants, enabling calculation of pressure drop between the LV base and apex and strength of propagation from two distinct slopes. Profound changes very early followed by relatively constant filling mechanics in later infancy indicate significant LV maturation occurring during the first month of life. IMPACT: We implemented sophisticated analytic methods for color M-mode echocardiography in infants to assess age- and dimension-dependent changes in left ventricular diastolic function. Comprehensive characterization of transmitral color M-mode flow was feasible, enabling calculation of pressure drop between left ventricular base and apex and strength of propagation. Left ventricular diastolic filling function has predictable maturational progression, with significant differences in the intraventricular pressure between infants from birth to 2 years. This study forms the basis for future studies to examine alteration of early diastolic filling in congenital heart disease.

Ultrasound Theranostics in Adult and Pediatric Cardiovascular Research.

Theranostics, the practice of systematically integrating diagnostics with treatment, has evolved as a field of medicine. In the context of ultrasound based theranostics, both traditional microbubbles and inorganic nanoparticles have emerged as technologies of clinical interest. Ultrasound induced microbubble cavitation has demonstrated efficacy in a variety of applications, including thrombolysis, tumor ablation, targeted microvascular flow enhancement, and targeted drug and gene delivery. This commentary summarizes the mechanisms and applications of ultrasound-based theranostics in cardiovascular medicine, including its impact in pediatric cardiology. It also provides an overview of ongoing clinical trials for theranostics in cardiovascular medicine.

Impaired myocardial deformation and ventricular vascular coupling in obese adolescents with dysglycemia.

BACKGROUND: It is unknown that dysglycemia in obese adolescents has effects on myocardial deformation that are more pronounced when compared to obesity alone. We hypothesized that obesity associated abnormal glucose tolerance (dysglycemia) would have adverse effects on two-dimensional speckle tracking echocardiography derived longitudinal, radial and circumferential strain (LS, RS, CS) compared to age and gender lean controls. We also examined if changes in deformation would be reflected in abnormal ventricular vascular coupling indices (VVI). METHODS: In a prospective cross-sectional design 39 obese adolescents (15.9 ± 1.7 years; 101.5 ± 39 kg; female - 58%) were compared to age and gender matched lean controls (15.7 ± 1.8 yrs, 60 ± 12.8 kg). Based on results from an oral glucose tolerance test (OGTT), obese adolescents were categorized as obese normoglycemic (ONG, n = 25) or obese dysglycemic (ODG, n = 14). Left ventricular (LV) global and average LS, CS, RS and strain rate were measured. LV ejection fraction and mass index were measured and VVI approximated as ratio of arterial elasticity (Ea) and end-systolic elastance (Ees). RESULTS: Adolescents with ODG had significantly (P = 0.005) impaired global LS (- 20.98% ± 2.8%) compared to controls (- 23.01% ± 2.3%). A similar (P = 0.0027) reduction was observed in average LS for adolescents with ODG (18.87% ± 2.5%) compared to controls (20.49% ± 2%). Global CS was also decreased (P = 0.03) in ODG (- 23.95%) compared to ONG (- 25.80). A similar trend was observed in average CS after multivariate regression for BMI and blood pressure. CS correlated with HbA1c in both groups (P = 0.05). VVI had a negative correlation with both LS (r = - 0.4, P = 0.025) and CS rate (r = - 0.36, P = 0.04). CONCLUSIONS: Myocardial strain and strain rate were significantly altered in obese adolescents. Unfavorable subclinical reductions in global and average CS were more pronounced in adolescents with dysglycemia compared to obese adolescents with normoglycemia and controls. These data indicate progressive worsening of subendocardial function across the spectrum of glucose tolerance. Strain rate was predictive of VVI in obese adolescents, suggesting strain rate may be a sensitive marker for cardiac remodeling in abnormal glucose homeostasis states.

A mathematical model of tissue axial and radial diffusion in the microvasculature for intravascular microscopy and phosphorescence quenching data.

This study aims to extend earlier Krogh Cylinder Models of an oxygen profile by considering axial diffusion and analytically solving Fick's Law Partial Differential Equation with novel boundary conditions via the separation of variables. We next prospectively collected a total of 20 animals, which were randomly assigned to receive either fresh or two-week-old stored red blood cell (RBC) transfusions and PQM oxygen data were measured acutely (90 min) or chronically (24 h). Transfusion effects were evaluated in vivo using intravital microscopy of the dorsal skinfold window chamber in Golden Syrian Hamsters. Hamsters were initially hemorrhaged by 50% of total blood volume and resuscitated 1-h post hemorrhage. PQM data were subsequently collected and fit the derived 2D Krogh cylinder model. Systemic hemodynamics (mean arterial pressure, heart rate) were similar in both pre and post-transfusion with either stored or fresh cells. Transfusion with stored cells was found to impair axial and radial oxygen gradients as quantified by our model and consistent with previous studies. Specifically, we observed a statistically significant decrease in the arteriolar tissue radial oxygen gradient after transfusion with stored RBCs at 24 h compared with fresh RBCs (0.33 ± 0.17 mmHg µ m-1 vs, 0.14 ± 0.12 mmHg µ m-1; p = 0.0280). We also observed a deficit in the arteriolar tissue oxygen gradient (0.03 ± 0.01 mmHg µ m-1 fresh vs. 0.018 ± 0.007 mmHg µ m-1 stored; p = 0.0185). We successfully derived and validated an analytical 2D Krogh cylinder model in an animal model of microhemodynamic oxygen diffusion aberration secondary to storage lesions.

Deep learning for automatic volumetric segmentation of left ventricular myocardium and ischaemic scar from multi-slice late gadolinium enhancement cardiovascular magnetic resonance.

AIMS: This study details application of deep learning for automatic volumetric segmentation of left ventricular (LV) myocardium and scar and automated quantification of myocardial ischaemic scar burden from late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR). METHODS AND RESULTS: We included 501 images and manual segmentations of short-axis LGE-CMR from over 20 multinational sites, from which 377 studies were used for training and 124 studies from unique participants for internal validation. A third test set of 52 images was used for external evaluation. Three models, U-Net, Cascaded U-Net, and U-Net++, were trained with a novel adaptive weighted categorical cross-entropy loss function. Model performance was evaluated using concordance correlation coefficients (CCCs) for LV mass and per cent myocardial scar burden. Cascaded U-Net was found to be the best model for the quantification of LV mass and scar percentage. The model exhibited a mean difference of -5 ± 23 g for LV mass, -0.4 ± 11.2 g for scar mass, and -0.8 ± 7% for per cent scar. CCC were 0.87, 0.77, and 0.78 for LV mass, scar mass, and per cent scar burden, respectively, in the internal validation set and 0.75, 0.71, and 0.69, respectively, in the external test set. For segmental scar mass, CCC was 0.74 for apical scar, 0.91 for mid-ventricular scar, and 0.73 for basal scar, demonstrating moderate to strong agreement. CONCLUSION: We successfully trained a convolutional neural network for volumetric segmentation and analysis of LV scar burden from LGE-CMR images in a large, multinational cohort of participants with ischaemic scar.

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.