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AIMS: We investigated left ventricular (LV) remodeling, mechanics, systolic and diastolic function, combined with clinical characteristics and heart-failure treatment in association to death or heart-transplant (DoT) in pediatric idiopathic, genetic or familial dilated cardiomyopathy (DCM), using interpretable machine-learning. METHODS AND RESULTS: Echocardiographic and clinical data from pediatric DCM and healthy controls were retrospectively analyzed. Machine-learning included whole cardiac-cycle regional longitudinal strain, aortic, mitral and pulmonary vein Doppler velocity traces, age and body surface area. We used unsupervised multiple kernel learning for data dimensionality reduction, positioning patients based on complex conglomerate information similarity. Subsequently, k-means identified groups with similar phenotypes. The proportion experiencing DoT was evaluated. Pheno-grouping identified 5 clinically distinct groups that were associated with differing proportions of DoT. All healthy controls clustered in groups 1 to 2, while all, but one, DCM subjects, clustered in groups 3 to 5; internally validating the algorithm. Cluster-5 comprised the oldest, most medicated patients, with combined systolic and diastolic heart-failure and highest proportion of DoT. Cluster4 included the youngest patients characterized by severe LV remodeling and systolic dysfunction, but mild diastolic dysfunction and the second-highest proportion of DoT. Cluster-3 comprised young patients with moderate remodeling and systolic dysfunction, preserved apical strain, pronounced diastolic dysfunction and lowest proportion of DoT. CONCLUSIONS: Interpretable machine-learning, using full cardiac-cycle systolic and diastolic data, mechanics and clinical parameters, can potentially identify pediatric DCM patients at high-risk for DoT, and delineate mechanisms associated with risk. This may facilitate more precise prognostication and treatment of pediatric DCM. Patricia Garcia-Canadilla has received funding from the postdoctoral fellowships program Beatriu de Pinos (2018-BP-00201), funded by the Secretary of Universities and Research (Goverment of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Skłodowska-Curie grant agreement Nº 801370. Pablo Miki Martí-Castellote has received funding from the predoctoral fellowships program FI-SDUR (2020-FISDU-00169) from AGAUR.

Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored.We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle.Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses.PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p 0.05).Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

Treatment of tubular hypoplasia of the aortic arch (THAA) associated with aortic coarctation (CoA) remains controversial. We aimed to evaluate growth of unrepaired hypoplastic proximal aortic arches (PAAs) after surgical repair for CoA.Preoperative and follow-up echocardiographic images of 139 patients who underwent CoA repairs from 2005 to 2012 were reviewed. THAA was defined as PAA z-score-3 and non-THAA group z-score ≥-3. Reintervention rates due to aortic obstruction were assessed using competing risk models and diameters of the aorta were compared with Mann-Whitney U tests.Fifty patients (36%) had THAA and 89 (64%) had non-THAA. The survival rate was 94% at 10 years. The overall reintervention rate at 10 years was 9% in the THAA group and 16% in the non-THAA group (P = .54). The catheter reintervention rate at ten years was 2% in the THAA group and 16% in the non-THAA group (P = .031). The surgical reintervention rate at ten years was 7% in the THAA group and 0% in the non-THAA group (P = .016). All 4 patients who required surgical reintervention were in the THAA group and 3 patients with PAA obstruction had preoperative PAA z-scores -3.6, -4.2, and -4.3. Follow-up echocardiograms showed PAA catch-up growth in the THAA group compared with the non-THAA group (preoperative z-score of -3.6 vs -2.3, and at 7 years of -1.1 vs -1.2; P .001).Unrepaired PAA hypoplasia grows after CoA repair. Reintervention rates were comparable between groups but those with THAA had higher surgical reintervention rates.

The potential benefit of heart rate reduction (HRR), independent of β-blockade, on right ventricular (RV) function in pulmonary hypertension (PH) remains undecided. We studied HRR effects on RV fib...

Right ventricular (RV) pressure loading leads to RV and left ventricular (LV) dysfunction through RV hypertrophy, dilatation and fibrosis. Relief of RV pressure load improves RV function. However, the impact and mechanisms on biventricular reverse-remodelling and function are only partially characterized. We evaluated the impact of RV pressure overload relief on biventricular remodelling and function in a rabbit model of reversible pulmonary artery banding (PAB). Rabbits were randomized to three groups: (1) Sham-operated controls (n = 7); (2) PAB (NDef, n = 7); (3) PAB followed by band deflation (Def, n = 5). Sham and NDef animals were sacrificed at 6 weeks after PAB surgery. Def animals underwent PAB deflation at 6 weeks and sacrifice at 9 weeks. Biventricular geometry, function, haemodynamics, hypertrophy and fibrosis were compared between groups using echocardiography, magnetic resonance imaging, high-fidelity pressure-tipped catheters and histology. RV pressure loading caused RV dilatation, systolic dysfunction, myocyte hypertrophy and LV compression which improved after PAB deflation. RV end-diastolic pressure (RVEDP) decreased after PAB deflation, although remaining elevated vs. Sham. LV end-diastolic pressure (LVEDP) was unchanged following PAB deflation. RV and LV collagen volumes in the NDef and Def group were increased vs. Sham, whereas RV and LV collagen volumes were similar between NDef and Def groups. RV myocyte hypertrophy (r = 0.75, P 0.001) but not collagen volume was related to RVEDP. LV myocyte hypertrophy (r = 0.58, P = 0.016) and collagen volume (r = 0.56, P = 0.031) correlated with LVEDP. In conclusion, relief of RV pressure overload improves RV and LV geometry, hypertrophy and function independent of fibrosis. The long-term implications of persistent fibrosis and increased biventricular filling pressures, even after pressure load relief, need further study. KEY POINTS: Right ventricular (RV) pressure loading in a pulmonary artery banding rabbit model is associated with RV dilatation, left ventricular (LV) compression; biventricular myocyte hypertrophy, fibrosis and dysfunction. The mechanisms and impact of RV pressure load relief on biventricular remodelling and function has not been extensively studied. Relief of RV pressure overload improves biventricular geometry in conjunction with improved RV myocyte hypertrophy and function independent of reduced fibrosis. These findings raise questions as to the importance of fibrosis as a therapeutic target.

Pediatric hypertrophic cardiomyopathy (HCM) is the most common form of cardiomyopathy in children and a leading cause of sudden cardiac death. Yet, the association between genotype variation, phenotype expression, and adverse events in pediatric HCM has not been fully elucidated. Although the literature on this topic is evolving in adult HCM, the evidence in children is lacking. Solidifying our understanding of this relationship could improve risk stratification as well as improve our comprehension of the underlying pathophysiological characteristics of pediatric HCM. In this state‐of‐the‐art review, we examine the current literature on genetic variations in HCM and their association with outcomes in children, discuss the current approaches to identifying cardiovascular phenotypes in pediatric HCM, and explore possible avenues that could improve sudden cardiac death risk assessment.

Ultrasound techniques currently used in echocardiography are limited by conventional frame rates. Ultrafast ultrasound imaging is able to capture images at frame rates up to 100 times faster compared with conventional imaging. Specific applications of this technology have been developed and tested for clinical use in pediatric and adult cardiac imaging. These include ultrafast Doppler or vector flow imaging, shear wave imaging, electromechanical wave imaging, and backscatter tensor imaging. The principles of these applications are explained in this manuscript with illustrations on how these methods could be applied in clinical practice. Ultrafast ultrasound has great clinical potential in the assessment of cardiac function, in noninvasive hemodynamic analysis, while providing novel techniques for imaging coronary perfusion and evaluating rhythm disorders.

This is the first study to assess right ventricular myocardial performance using the systolic-to-diastolic duration ratio derived from 2D strain. Seventy-six children with repaired Tetralogy of Fallot were evaluated. Echocardiographic data were correlated with cardiac magnetic resonance and peak oxygen consumption during exercise. The results show the right ventricular myocardial systolic-to-diastolic duration ratio incorporates systolic and diastolic performance, electromechanical dyssynchrony, and postsystolic shortening and is associated with exercise capacity in repaired Tetralogy of Fallot.

Background Information on genetic etiology of pediatric hypertrophic cardiomyopathy (HCM) rarely aids in risk stratification and prediction of disease onset. Little data exist on the association between genetic modifiers and phenotypic expression of myocardial performance, hampering an individual precision medicine approach. Methods Single-nucleotide polymorphism genotyping for six previously established disease risk alleles in the hypoxia-inducible factor-1α-vascular endothelial growth factor pathway was performed in a pediatric cohort with HCM. Findings were correlated with echocardiographic parameters of systolic and diastolic myocardial deformation measured by two-dimensional (2-D) speckle-tracking strain. Results Twenty-five children (6.1 ± 4.5 years; 69% male) with phenotypic and genotypic (60%) HCM were included. Out of six risk alleles tested, one, VEGF1 963GG, showed an association with reduced regional systolic and diastolic left ventricular (LV) myocardial deformation. Moreover, LV average and segmental systolic and diastolic strain and strain rate were significantly reduced, as assessed by the standardized difference, in patients harboring the risk allele. Conclusions This is the first study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial function, with the VEGF1 963GG allele associated with reduced LV systolic and diastolic myocardial performance. While studies are needed to link this information to adverse clinical outcomes, this knowledge may help in risk stratification and patient management in HCM. Impact Risk allele in the VEGF gene impacts on LV myocardial deformation phenotype in children with HCM.LV 2-D strain is significantly reduced in patients with risk allele compared to non-risk allele patients within HCM patient groups.Describes that deficiencies in LV myocardial performance in children with HCM are associated with a previously identified risk allele in the angiogenic transcription factor VEGF.First study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial deformation measured by 2-D strain in children with HCM.

Right ventricle (RV) pressure loading can lead to RV fibrosis and dysfunction. We previously found increased RV, septal hinge-point and left ventricle (LV) fibrosis in experimental RV pressure loading. However, the relation of RV wall stress to biventricular fibrosis and dysfunction is incompletely defined. Rabbits underwent progressive pulmonary artery banding (PAB) over 3 wk with hemodynamics, echocardiography, and myocardial samples obtained at a terminal experiment at 6 wk. An additional group received PAB and treatment with an endothelin receptor antagonist. The endocardial and epicardial borders of short-axis echo images were traced and analyzed with invasive pressures to yield regional end-diastolic (ED) and end-systolic (ES) wall stress. To increase clinical translation, computer model-derived wall stress was compared with Laplace wall stress. The relation of wall stress with fibrosis (picrosirius red staining) and ventricular function was analyzed. ED wall stress in all regions and RV and LV free-wall ES wall stress were increased in PAB rabbits versus sham animals. Laplace wall stress correlated well with computational models. In PAB, fibrosis was highest in the RV free wall, then septal hinge regions, and lowest in the septum and LV free wall. Fibrosis was moderately related to ED ( r = 0.47, P = 0.0011), but not ES wall stress. RV ED wall stress was strongly related to echo indexes of function (strain rate: r = 0.71, P = 0.048; E′, r = −0.75, P = 0.0077; tricuspid annular plane systolic excursion: r = 0.85, P = 0.0038) and RV fractional area change ( r = 0.77, P = 0.027). ED, more than ES, wall stress is related moderately to fibrosis and strongly to function in experimental RV pressure loading, especially at the septal hinge-point regions, where fibrosis is prominent. This suggests that wall stress partially links RV pressure loading, fibrosis, and dysfunction and may be useful to follow clinically. NEW & NOTEWORTHY Biventricular fibrosis and dysfunction impact outcomes in RV pressure loading, but their relation to wall stress is poorly defined. Using a pulmonary artery band rabbit model, we entered echocardiography and catheter data into a computer model to yield regional end-diastolic (EDWS) and end-systolic (ESWS) wall stress. EDWS, more than ESWS, correlated with fibrosis and dysfunction, especially at the fibrosis-intense septal hinge-point regions. Thus, wall stress may be clinically useful in linking RV pressure loading to regional fibrosis and dysfunction.

Objectives: Fetal right ventricular (RV) function assessment is challenging due to the RV geometry and limitations of in utero assessment. Postnatally, 2D echocardiographic RV fractional area change (FAC) is used to assess RV global systolic function by calculating the percentage of change in RV area from systole to diastole. Reports on FAC are scarce in prenatal life, and nomograms throughout pregnancy are not available. Our aims were (1) to study prenatal RV FAC feasibility and reproducibility and (2) to construct nomograms for RV FAC and end-diastolic (ED) and end-systolic (ES) RV areas from 18 to 41 weeks of gestation. Methods: Prospective cohort study including 602 low-risk singleton pregnancies undergoing a fetal echocardiography from 18 to 41 weeks of gestation. RV ED and ES areas were measured following standard recommendations for ventricular dimensions and establishing strict landmarks to identify the different phases of the cardiac cycle. RV FAC was calculated as: ([ED area – ES area]/ED area) × 100. RV FAC intra- and inter-observer reproducibility was evaluated in 45 fetuses by calculating the intraclass correlation coefficient (ICC). Parametric regressions were tested to model each parameter against gestational age (GA) and estimated fetal weight (EFW). Results: RV areas and FAC were successfully obtained in ∼99% of fetuses with acceptable reproducibility throughout gestation (RV ED area inter-observer ICC [95% CI] 0.96 [0.93–0.98], RV ES area 0.97 [0.94–0.98], and FAC 0.69 [0.44–0.83]). Nomograms were constructed for RV ED and ES areas and FAC. RV areas showed a quadratic and logarithmic increase with GA and EFW, respectively. In contrast, RV FAC showed a slight quadratic decrease throughout gestation (mean RV FAC ranged from 36% at 18 weeks of gestation [10–90th centiles: 25–47%, respectively] to 29% at 41 weeks [10–90th centiles: 18–40%, respectively]). The best models for RV areas and FAC were a second-degree polynomial. Conclusions: RV FAC is a feasible and reproducible parameter to assess RV global systolic function in fetal life. We provide reference ranges adjusted by GA and EFW that can be used as normal references for the assessment of RV function in prenatal conditions.

BACKGROUND: Chronic elevation of left heart filling pressure causes pulmonary vascular remodeling, pulmonary hypertension, and right heart dysfunction. Although diastolic dysfunction is relatively common in patients with coarctation of aorta (COA), there are limited data about the prevalence and prognostic implications of pulmonary hypertension and right heart dysfunction in this population. The purpose of the study was to assess right heart function and hemodynamics in patients with COA, and to determine the relationship between right heart indices and cardiovascular events defined as heart failure hospitalization, heart transplant or cardiovascular death. METHODS: Right heart structure, function and hemodynamics were assessed with these indices: right atrial (RA) volume, RA pressure, RA reservoir strain, right ventricular (RV) global longitudinal strain, RV end-diastolic area, RV systolic pressure, and tricuspid regurgitation severity. Right heart hemodynamic score (RHHS), range 0–5, was generated based on the correlation between the right heart indices and cardiovascular events, using half of the cohort (derivation cohort, n=411), and then tested on the validation cohort (n=410). The goodness of fit and discrimination power was compared using c-statistics and risk score. RESULTS: The median follow-up in the derivation cohort was 8.2 (4.0–11.1) years, and 59 (14%) patients had cardiovascular events during this period. RHSS was independently associated with cardiovascular events (hazard ratio 1.64, 95% CI: 1.38–2.17) for every unit increase in RHHS) after adjustment for clinical and echocardiographic indices (c-statistic 0.718, 95% CI: 0.682–0.746). The RHHS was also independently associated with cardiovascular events in the validation cohort (c-statistic 0.711, 95% CI: 0.679–0.741). The c-statistic difference (0.007, 95% CI: 0.014–0.022) and risk score (0.86, 95% CI: 0.54–1.17) suggest a good model fit. CONCLUSIONS: The current study underscores the prognostic importance of right heart dysfunction in patients with COA and suggests that right heart indices should be used for risks stratification in this population.

Background: Ventricular torsion is important in assessment of the systolic and diastolic function especially in single ventricle (SV) but is poorly studied. Objective: We aimed to a) examine serial changes in SV torsion, and b) examine its association with CMR data and exercise performance. Methods: We retrospectively studied SV patients after Fontan completion. Speckle-tracking echocardiography was used to evaluate serial changes in ventricular mechanics; strain, torsion, and untwist. CMR volumetric data and cardiopulmonary exercise data closest to echocardiograms were obtained. The most recent follow up echocardiographic and CMR data were compared to data before Fontan. Results: 45 SV patients (27 LV, 12 RV, and 6 co dominant) were studied. Demographics, echocardiographic, CMR, and exercise data are shown in table 1. Mean time at follow up echo from time of Fontan was 12.8 (10.6-16.6) years. Follow up echocardiograms showed reduced global longitudinal strain [-17.5(-6.5 to-19.5) vs -19.8 (-12 to -23%), p=0.01], circumferential strain [-15.7 (-8.4 to - 20.7) vs [-18.9 (-11.2 to -25.0), p=0.009], reduced torsion [5.5°/cm (-6.1 to 17.8) vs 8.1°/cm (-9.7 to18.5) vs, p=0.03], decreased apical rotation [6.5°/cm (-11.3 to 18.1) vs 5.1°/cm (-21.2 to 19.7), p=0.02] with no significant change in basal rotation compared to the echo at time of Fontan. Single RV had lower net torsion compared to single LV [2.7°/cm (-2.5.1 to 13.1) vs 6.1°/cm (-6.3 to 19.5) vs, p=0.03]. Mean interval between echocardiograms and exercise testing and CMR were 3.5±2.2 and 5.6±1.8 months respectively. Torsion and untwist rates correlated with peak oxygen consumption (r=0.64, -0.41, p=0.01, 0.04 respectively) but did not correlate with ventricular volumes or ejection fractions. Conclusion: In long term follow up post Fontan, SV torsion is decreased due to decreased apical rotation, worse in single RV, and is associated with decreased exercise capacity.

Introduction: Diagnosing diastolic dysfunction (DD) non-invasively in children is challenging as no validated pediatric diagnostic algorithm is available. The aim of this study is to use machine learning (ML) to identify a model that integrates echocardiographic measurements to predict invasive hemodynamic markers of DD in children. Methods: We enrolled children with Kawasaki disease, heart transplant, aortic stenosis, and coarctation of the aorta undergoing left heart catheterization. We obtained simultaneous invasive and echo DD measurements. We applied random forest (RF) algorithms to develop separate models for each cath marker (time constant of isovolumic relaxation (Tau), LVEDP, and -dP/dt max) and used demographics, diagnosis, and echo features as inputs. Model approximation was done using a regression tree with the top ranked features of each RF model to improve model interpretability (Figure 1). Spearman correlations were also assessed. Results: 59 children were included. Spearman correlations were low. However, the RF models' adjusted R 2 values in predicting Tau, LVEDP, and -dP/dt max are 0.62, 0.51, and 0.83, respectively. A representative ML-generated tree for LVEDP is shown in Figure 2. The most important features were propagation velocity (Vp) for Tau; E/Vp ratio for LVEDP; and systolic global longitudinal strain rate for -dP/dt max. Model approximation showed that a Vp < 42 cm/s predicted a Tau > 39 ms, and an E/Vp > 2.4 predicted an LVEDP > 13 mmHg. Conclusions: Predicting invasively measured diastolic parameters with echo data may be improved using ML algorithms. Model approximation may help better interpret the complex interactions in ML models.

Background— Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class might be similarly efficacious in the treatment and prevention of right heart failure has not been unexplored.Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional and molecular responses to pressure overload of the right ventricle.Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (1.5mg/kg/day) or vehicle by oral gavage. After six weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses.Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content and alteration in calcium handling protein expression (all pSignificance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

Diagnosing left ventricular diastolic dysfunction (DD) noninvasively in children is difficult as no validated pediatric diagnostic algorithm is available. The aim of this study is to explore the use of machine learning to develop a model that uses echocardiographic measurements to explain patterns in invasively measured markers of DD in children.Children at risk for developing DD were enrolled, including patients with Kawasaki disease, heart transplantation, aortic stenosis, and coarctation of the aorta when undergoing clinical left heart catheterization. Simultaneous invasive pressure measurements were made using a high-fidelity catheter (time constant of isovolumic relaxation [Tau, τ], left ventricular end-diastolic pressure, and maximum negative rate of pressure change) and echocardiographic DD measurements. Spearman correlations were performed for each echocardiographic feature with invasive markers to understand pairwise relationships. Separate random forest (RF) models were implemented to assess all echocardiographic features, key demographic data, and clinical diagnosis in predicting invasive markers. A backward stepwise regression model was simultaneously implemented as a comparative conventional reference model. The relative importance of all parameters was ranked in terms of accuracy reduction. Model approximation was then performed using a regression tree with the top-ranked features of each RF model to improve model interpretability. Regression coefficients of the linear models were presented.Fifty-nine children were included. Spearman correlations were generally low. The RF models' performance measures were noninferior to those of the linear model. However, the linear model's regression coefficients were unintuitive. The highest ranked important features for the RF models were propagation velocity for Tau, E/propagation velocity ratio for left ventricular end-diastolic pressure, and systolic global longitudinal strain rate for maximum negative rate of pressure change.Estimating individual components of DD can potentially improve the noninvasive assessment of pediatric DD. Although pairwise correlations measured were weak and linear regression coefficients unintuitive, approximated machine learning models aided in understanding how echocardiographic and invasive parameters of DD are related. This machine learning approach could help in further development of pediatric-specific diagnostic algorithms.

Background Right ventricular (RV) dilation from pulmonary valve regurgitation (PR) is common after intervention(s) for pulmonary stenosis (PS) or atresia and intact ventricular septum (PA/IVS). It is not well established whether PR and RV dilation have similar effects on RV function and exercise capacity in these patients compared to patients after repair of tetralogy of Fallot (rToF). The aims of this study were to compare exercise tolerance, RV function and myocardial mechanics in non-ToF versus rToF children with significantly increased and comparable RV volumes. Methods Thirty PS or PA/IVS children after intervention(s) with significant PR and RV dilation (non-ToF group) were retrospectively matched for RV end-diastolic volume index (RVEDVi) and age with 30 rToF patients. Clinical characteristics, RV function by echocardiography and CMR, ECG and exercise capacity were compared between groups. Results The groups were well matched for RVEDVi and age. Global RV function (RVEF: 48.7 ± 6.4% vs. 48.5 ± 7.2%, P = .81) and exercise capacity (% predicted peak VO2:82.5 ± 17.7% vs. 75.6 ± 20.4%, P = .27) were similarly reduced between groups. RVEDVi correlated inversely with RVEF in both groups (non-ToF:r = −0.39, P = .04, rToF:r = −0.40, P = .03). QRS duration was wider in rToF patients, and in both groups inversely correlated with RVEF (non-ToF:r = −0.77, P Conclusions Global RV function and exercise capacity are similarly reduced in non-ToF and rToF patients with severely dilated RV, after matching by RVEDVi, suggesting a comparable impact of RV dilation on RV global function. The significance of reduced RV longitudinal function and worse dyssynchrony in rToF patients require further exploration.

Left ventricular (LV) mechanics in patients with different single morphologic LV subtypes, including tricuspid atresia, double-inlet left ventricle, and pulmonary atresia with intact ventricular septum, remain poorly studied. Given that histologic studies indicate differences in LV myocardial fiber orientation, we hypothesized that this may result in altered LV mechanics. The aim of this study was to evaluate the influence of LV morphology on LV mechanics.Fifty-two children with single left ventricles after Fontan operation and age-matched control subjects were prospectively enrolled. Using two-dimensional speckle-tracking echocardiography, longitudinal strain was measured in the four-, three-, and two-chamber long-axis planes, and circumferential strain was measured at the basal, mid, and apical short-axis planes. Apical and basal rotation were measured, and twist and torsion were calculated. We compared strain and rotational mechanics in cases versus control subjects and among LV subtypes.Compared with control subjects, subjects with single left ventricles had similar LV end-diastolic dimensions but significantly decreased ejection fractions. The single left ventricle cohort had normal global longitudinal strain (P = .20) but lower basal mean circumferential strain (P .0001). Single left ventricle subjects had higher apical rotation (P = .0001) but decreased basal rotation (P = .0007); there was no difference in twist but increased torsion (P = .001). LV subtypes had different four-chamber (P = .01), two-chamber (P = .006), and global longitudinal strain (P = .01), lowest in the pulmonary atresia with intact ventricular septum subtype.Longitudinal LV strain was preserved in children with single left ventricles after Fontan. A pattern of reduced basal circumferential strain and rotation with an increase in apical rotation and torsion in the single left ventricle cohort may be related to differences in myofiber orientation, increased fibrosis, and the impact of altered loading conditions throughout palliation. Decreased longitudinal strain in the pulmonary atresia with intact ventricular septum group may also reflect detrimental interventricular interactions.

BACKGROUND: In normal left ventricles, clockwise basal rotation and counterclockwise apical rotation result in systolic torsion. Torsion is important for contractile efficiency and may be especially important in single-ventricle (SV) physiology. However, little is known about torsion in patients with SVs. The aim of this study was to measure torsion in SVs and to determine its relationship with other measures of ventricular function. The hypothesis was that torsion would be decreased in all SVs, most significantly in single right ventricles, and that it would correlate with other measures of ventricular function. METHODS: A prospective cross-sectional study was performed in 61 patients with SVs undergoing pre- or post-Fontan cardiac catheterization and 30 matched control subjects. Echocardiography, catheterization, and cardiac magnetic resonance imaging were performed under the same anesthetic. Torsion and strain were measured using speckle-tracking echocardiography. Intracardiac pressures, pulmonary vascular resistance, and cardiac magnetic resonance imaging-derived ventricular volume and ejection fraction were measured. RESULTS: Thirty-five patients were left ventricular dominant, 15 were right ventricular dominant, 10 were codominant, and one had indeterminate morphology. Thirty-seven patients were pre-Fontan and 24 were post-Fontan. Patients with SVs had similar overall torsion as control subjects (median, 1.7°/cm vs 1.65°/cm; P = NS); however, they had decreased or reversed basal rotation (-0.32°/cm vs -0.93°/cm, P < .0001) and increased apical rotation (1.45°/cm vs 1.06°/cm, P = .0065). There were no differences on the basis of ventricular dominance or palliative stage. Torsion did not significantly correlate with other echocardiographic, catheter-based, or cardiac magnetic resonance imaging measures of cardiac function. CONCLUSIONS: Single left and right ventricles exhibit preserved torsion, mainly because of preserved or increased apical rotation. Possible mechanisms of torsion in single right ventricles include myofiber remodeling and altered ventricular-ventricular interactions. Understanding myocardial deformation in SVs will improve the ability to interpret ventricular function in this precarious population.

Pulmonary regurgitation (PR) after repair of tetralogy of Fallot (rTOF) is associated with progressive right (RV) and left (LV) ventricular dysfunction and fibrosis. However, angiotensin II receptor blockade therapy has shown mixed and often disappointing results. The aim of this study was to serially assess changes in biventricular remodeling, dysfunction, and interactions in a rat model of isolated severe PR and to study the effects of angiotensin II receptor blockade. PR was induced in Sprague-Dawley rats by leaflet laceration. Shams (

Echocardiography plays a key role in the diagnosis and management of adult patients with congenital heart disease and is considered the first-line diagnostic technique. Apart from traditional cross-sectional imaging, three-dimensional echocardiography and strain and strain rate imaging were introduced for specific indications and for better describing anatomical details and functional consequences of the different congenital lesions. For specific indications, additional imaging may be required including cardiac magnetic resonance imaging and computational tomography. Especially in adult congenital heart disease, echocardiographic imaging may be limited by poor acoustic windows and additional evaluation using other imaging modalities may be required. Additionally, MRI and CT imaging have proven to be extremely valuable for evaluation of right ventricular size and function and for describing extracardiac anatomy (pulmonary arteries, pulmonary veins, and aorta).

ispartof: EXPERIMENTAL PHYSIOLOGY vol:106 issue:4 pages:797-800 ispartof: location:England status: published

Cardiac fibrosis is a common finding that is associated with the progression of heart failure (HF) and impacts all chambers of the heart. Despite intense research, the treatment of HF has primarily focused upon strategies to prevent cardiomyocyte remodeling, and there are no targeted antifibrotic strategies available to reverse cardiac fibrosis. Cardiac fibrosis is defined as an accumulation of extracellular matrix (ECM) proteins which stiffen the myocardium resulting in the deterioration cardiac function. This occurs in response to a wide range of mechanical and biochemical signals. Integrins are transmembrane cell adhesion receptors, that integrate signaling between cardiac fibroblasts and cardiomyocytes with the ECM by the communication of mechanical stress signals. Integrins play an important role in the development of pathological ECM deposition. This review will discuss the role of integrins in mechano-transduced cardiac fibrosis in response to disease throughout the myocardium. This review will also demonstrate the important role of integrins as both initiators of the fibrotic response, and modulators of fibrosis through their effect on cardiac fibroblast physiology across the various heart chambers.

The function and mechanics of the left and right ventricles are closely intertwined. In normal physiology, the left ventricle (LV) substantially contributes to right ventricular (RV) pressure development and output. Thus, it can be expected that when LV function is impaired, RV function will be impacted. In normal physiology, the RV has a much lesser effect on the LV. However, the pressure-loaded, volume-loaded, or dyssynchronous RV can profoundly impact LV systolic and diastolic function. These interactions have important clinical implications and the presence of RV dysfunction in “left-heart” disease impacts outcomes. Likewise, concomitant LV dysfunction in “right-heart” disease worsens prognosis. Thus RV-LV interactions are important to understand. Moreover, leveraging of these interactions can be used to treat various diseases.

OBJECTIVES: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time-related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed-wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions. METHODS: This study included a low-risk prospective cohort of singleton pregnancies and a high-risk population of fetuses with severe twin-twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed-wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra- and interobserver reproducibility of FTF and ETF measurements in low-risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low-risk population. Z-scores of FTF and ETF in the high-risk fetuses were calculated and analyzed. RESULTS: In total, 602 low-risk singleton pregnancies and 54 high-risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low-risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831-0.905) and interobserver reproducibility was good (ICC, 0.801-0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low-risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low-risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles. CONCLUSIONS: Measurement of FTF and ETF using pulsed-wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Right ventricular (RV) failure is a commonly encountered problem in patients with congenital heart disease but can also be a consequence of left ventricular disease, primary pulmonary hypertension, or RV-specific cardiomyopathies. Improved survival of the aforementioned pathologies has led to increasing numbers of patients suffering from RV dysfunction, making it a key contributor to morbidity and mortality in this population. Currently available therapies for heart failure were developed for the left ventricle (LV), and there is clear evidence that LV-specific strategies are insufficient or inadequate for the RV. New therapeutic strategies are needed to address this growing clinical problem, and stem cells show significant promise. However, to properly evaluate the prospects of a potential stem cell-based therapy for RV failure, one needs to understand the unique pathophysiology of RV dysfunction and carefully consider available data from animal models and human clinical trials. In this review, we provide a comprehensive overview of the molecular mechanisms involved in RV failure such as hypertrophy, fibrosis, inflammation, changes in energy metabolism, calcium handling, decreasing RV contractility, and apoptosis. We also summarize the available preclinical and clinical experience with RV-specific stem cell therapies, covering the broad spectrum of stem cell sources used to date. We describe two different scientific rationales for stem cell transplantation, one of which seeks to add contractile units to the failing myocardium, while the other aims to augment endogenous repair mechanisms and/or attenuate harmful remodeling. We emphasize the limitations and challenges of regenerative strategies, but also highlight the characteristics of the failing RV myocardium that make it a promising target for stem cell therapy.