Reversal of right ventricular pressure loading improves biventricular function independent of fibrosis in a rabbit model of pulmonary artery banding.

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.

Retraining an Artificial Intelligence Algorithm to Calculate Left Ventricular Ejection Fraction in Pediatrics.

OBJECTIVES: Identifying patients with low left ventricular ejection fraction (LVEF) and monitoring LVEF responses to treatment are important clinical goals. Can a deep-learning algorithm predict pediatric LVEF within clinically acceptable error? DESIGN: The study authors wanted to fine-tune an adult deep-learning algorithm to calculate LVEF in pediatric patients. A priori, their objective was to refine the algorithm to perform LVEF calculation with a mean absolute error (MAE) ≤5%. SETTING: A quaternary pediatric hospital PARTICIPANTS: A convenience sample (n = 321) of echocardiograms from newborns to 18 years old with normal cardiac anatomy or hemodynamically insignificant anomalies. Echocardiograms were chosen from a group of healthy controls with known normal LVEF (n = 267) and a dilated cardiomyopathy patient group with reduced LVEF (n = 54). INTERVENTIONS: The artificial intelligence model EchoNet-Dynamic was tested on this data set and then retrained, tested, and further validated to improve LVEF calculation. The gold standard value was LVEF calculated by clinical experts. MEASUREMENTS AND MAIN RESULTS: In a random subset of subjects (n = 40) not analyzed prior to selection of the final model, EchoNet-Dynamic calculated LVEF with a MAE of 8.39%, R2 = 0.47 without, and MAE 4.47%, R2 = 0.87 with fine-tuning. Bland-Altman analysis suggested that the model slightly underestimates LVEF (bias = -2.42%). The 95% limits of agreement between actual and calculated values were -12.32% to 7.47%. CONCLUSIONS: The fine-tuned model calculates LVEF in a range of pediatric patients within clinically acceptable error. Potential advantages include reducing operator error in LVEF calculation and supporting independent LVEF assessment by inexperienced users.

Increased Arterial Stiffness Adversely Affects Left Ventricular Mechanics in Patients With Pediatric Takayasu Arteritis From a Toronto Cohort.

BACKGROUND/OBJECTIVE: Takayasu arteritis (TA) is characterized by extensive aortic, large and midsize arterial wall inflammation. The aim of this study was to assess the morphological and elastic properties of the aorta and large arteries and the impact on left ventricular (LV) mechanics in children with TA. METHODS: Seven pediatric TA patients (6 female patients, 13.8 ± 3.2 years) were assessed with magnetic resonance imaging, vascular ultrasound, applanation tonometry, and echocardiography from February 2015 until July 2017 and compared with 7 age- and sex-matched controls. Takayasu arteritis disease activity was assessed clinically by the Pediatric Vasculitis Activity Score (PVAS). RESULTS: Pediatric TA patients showed increased carotid-to-radial artery pulse wave velocity (8.1 ± 1.8 vs. 6.4 ± 0.6 m/s, p = 0.03) and increased carotid-to-femoral artery pulse wave velocity (8.3 ± 1.9 vs. 5.1 ± 0.8 m/s, p < 0.01) when compared with controls. Patients demonstrated increased LV mass index (74.3 ± 18.8 vs. 56.3 ± 10.9 g/m, p = 0.04), altered myocardial deformation with increased basal rotation (-9.8 ± 4.5 vs. -4.0 ± 2.0 degrees, p = 0.01) and torsion (19.9 ± 8.1 vs. 9.1 ± 3.1 degrees, p = 0.01), and impaired LV diastolic function with decreased mitral valve E/A ratio (1.45 ± 0.17 vs. 2.40 ± 0.84, p = 0.01), increased mitral valve E/E' ratio (6.8 ± 1.4 vs. 4.9 ± 0.7, p < 0.01), and increased pulmonary vein A-wave velocity (26.7 ± 5.7 vs. 16.8 ± 3.3 cm/s, p = 0.03). Carotid-to-radial artery pulse wave velocity was associated with systolic (R = 0.94, p < 0.01), diastolic (R = 0.85, p = 0.02), and mean blood pressure (R = 0.91, p < 0.01), as well as disease activity by PVAS (R = 0.75, p = 0.05). The PVAS was associated with carotid-to-radial artery pulse wave velocity (R = 0.75, p = 0.05), as well as systolic (R = 0.84, p = 0.02), diastolic (R = 0.82, p = 0.03), and mean blood pressure (R = 0.84, p = 0.02). CONCLUSIONS: Increased arterial stiffness is present in pediatric TA patients and associated with increased blood pressure and TA disease activity. Pediatric TA patients demonstrate altered LV mechanics, LV hypertrophy, and impaired diastolic function.

Prevalence of anthracycline-related cardiac dysfunction in long-term survivors of adult-onset lymphoma.

BACKGROUND: Anthracycline-related heart failure is a leading cause of morbidity in survivors of adult-onset lymphoma. There is a paucity of information on screening for late-occurring preclinical disease, which, in turn, has limited guidelines for early detection and intervention. The objectives of this study were to examine the prevalence and risk of cardiac dysfunction, as measured by echocardiography (abnormal left ventricular systolic/diastolic function or strain), in lymphoma survivors who received treatment with anthracyclines and to evaluate the diagnostic yield of blood biomarkers in the asymptomatic setting. METHODS: Lymphoma survivors who underwent hematopoietic cell transplantation (HCT) (n = 78) or received conventional therapy (non-HCT; n = 77) were compared with each other and with a group of matched controls (n = 51); the study was limited to lymphoma survivors who were >5 years from diagnosis. RESULTS: At a median follow-up of 9.4 years after diagnosis, 1 in 5 (20.6 %) lymphoma survivors had cardiac dysfunction; the odds of having cardiac dysfunction were 6.6-fold greater (odds ratio [OR], 6.6; P = .01) among lymphoma survivors compared with matched controls. There was a dose-dependent risk of cardiac dysfunction according to the cumulative anthracycline dose (controls [referent group], 1-249 mg/m2 [OR, 4.7; P = .05], and ≥250 mg/m2 [OR, 7.6; P < .01]), but there was no difference in the prevalence of cardiac dysfunction between conventionally treated and HCT survivors. The diagnostic accuracy of cardiac blood biomarkers in the asymptomatic setting was quite poor. CONCLUSIONS: In these long-term survivors, there was a high rate of cardiac dysfunction that was independent of HCT status. The growing number of lymphoma survivors makes it imperative to identify reliable and cost-effective strategies to decrease the burden of heart failure in this population. Cancer 2018;124:850-7. © 2017 American Cancer Society.

The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes.

The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1) levels of urinary RAAS components and 2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC (P < 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (P < 0.0001, P = 0.0003, P = 0.003, and P = 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (P < 0.0001) and ACE activity (P = 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range.

Relationship between serum inflammatory markers and vascular function in a cohort of adolescents with type 1 diabetes.

OBJECTIVE: The contribution of inflammation to endothelial/vascular dysfunction in early Type I Diabetes (T1D) is not well understood. The objective of this study was to examine the interaction between systemic inflammation and vascular function in adolescent's with and without-T1D. METHODS: 51 subjects from our observational cohort of adolescents with T1D (JDRF-CCTN), and 59 healthy controls (HC) were studied. Serum cytokines-chemokines were quantified using Human 41-Plex Array, and vascular function was measured by Flow Mediated Dilatation (FMD), Pulse Wave Velocity (PWV) and Blood Pressure (BP). Factor Analysis was used to identify pro- and anti-inflammatory cytokine-chemokine factors, which were then correlated with vascular outcomes. RESULTS: Three pro-inflammatory factors were identified in HC and three in TID, and a single anti-inflammatory factor in both groups. In HC there was a positive correlation (r=0.33; p=0.01) between control proinflammatory Factor 1 and systolic BP and a negative correlation between control proinflammatory Factor 3(r=-0.29; p=0.02) and diastolic BP. Control proinflammatory Factor 2 correlated positively with PWV. In TID subjects, no correlations were found between any of the pro-inflammatory factors and the vascular measurements. No correlations were found between the anti-inflammatory factors and BP, FMD and PWV in either HC or T1D. Levels of pro-inflammatory analytes, EGF, GRO, PDGF-BB, PDGF-AA and sCD40L were significantly higher in T1D. CONCLUSIONS: The cytokine-chemokine signature in early T1D, prior to the development of arterial disease, is significantly different from that seen in healthy controls. This may be relevant to pathophysiology, determining risk and identifying target cytokines-chemokines for intervention in T1D.

Early changes in cardiovascular structure and function in adolescents with type 1 diabetes.

BACKGROUND: Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. METHODS AND RESULTS: 199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0-12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e' (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a' (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e' (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (-20.4 ± 2.3 vs. -19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (-19.0 ± 1.9 vs. -19.8 ± 1.5 % p < 0.001) in T1D. CONCLUSIONS: Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.

Fetal growth restriction and cardiovascular outcome in early human infancy: a prospective longitudinal study.

The association between low birth weight and premature cardiovascular disease has led to the "prenatal origin of adult disease-hypothesis". We postulated that fetal growth restriction is associated with cardiovascular changes detectable at birth and in early infancy. Fifty-two appropriately grown fetuses (AGA) and 60 growth-restricted fetuses (FGR) with (n = 20) or without (n = 40) absent or reversed end-diastolic umbilical artery blood flow were prospectively examined by echocardiography before birth, at 1 week and 6 months of life. The impact of growth restriction on postnatal blood pressure, heart rate, cardiovascular dimensions, and function, as well as on vascular morphology of umbilical cord vessels was studied. FGR fetuses displayed significant blood flow redistribution and were delivered earlier with lower birth weights than AGA fetuses. After adjustment for gender, gestational age, and weight at birth, there were no intergroup differences in blood pressure, heart rate, left ventricular morphology, mass, and performance, and in cord vessel morphology. During the first 6 months of life brachioradial pulse wave velocity increased more in FGR fetuses, while other parameters describing vascular stiffness remained comparable between the groups. Fetal growth restriction had no detectable adverse impact on cardiovascular dimensions and function at birth. Cardiovascular findings also remained comparable during the first 6 months of life between the groups except a higher increase in brachioradial pulse wave velocity in the FGR group. Our observations suggest that abnormalities that link reduced intrauterine growth with premature cardiovascular diseases may commence later in childhood, indicating a potential window for screening and prevention.

Relation of right ventricular mechanics to exercise tolerance in children after tetralogy of Fallot repair.

BACKGROUND: Progressive right ventricular (RV) dysfunction and exercise intolerance are common problems after tetralogy of Fallot (TOF) repair. We investigated RV myocardial deformation and dyssynchrony in children after TOF repair and their association with exercise capacity. METHODS: Asymptomatic children after TOF repair were investigated by 2-dimensional speckle tracking echocardiography, magnetic resonance, and metabolic exercise study. Patients with RV outflow obstruction were excluded. Peak RV longitudinal strain and strain rate (SR) and dyssynchrony (RV intraventricular delay) were compared with healthy controls. Associations between RV strain, dyssynchrony, and exercise capacity were analyzed. RESULTS: Thirty-nine (81%) of 48 TOF patients and 40 healthy controls had adequate RV strain imaging. The TOF patients had moderately dilated RVs and normal RV ejection fraction. Right ventricular peak systolic strain (-23.2% ± 5.1% vs -28.5% ± 8.5%, P < .001) and SR (-1.46 ± 0.68 vs -2.1 ± 0.8, P < .001) were reduced in TOF patients compared with controls. Right ventricular intraventricular delay was higher in TOF patients (146.0 ± 159 vs 71.0 ± 92 milliseconds, P = .008). Decreased RV strain and SR were associated with increased RV dyssynchrony (strain parameter estimate [PE] 6.31 [2.30], P = .007; SR [PE] 11.32 [3.84], P = .004). Increased RV-left ventricular delay was associated with prolonged QRS duration (PE 0.13 [0.058], P = .03) and reduced RV ejection fraction (PE -2.95 [1.275], P = .02). Reduced RV peak SR was associated with decreased exercise peak oxygen uptake (PE 0.14 [0.07], P = .04). CONCLUSIONS: After repair of TOF, asymptomatic children have reduced RV deformation in association with RV dyssynchrony and reduced exercise tolerance.

Evolution of the arterial structure and function from infancy to adolescence is related to anthropometric and blood pressure changes.

OBJECTIVE: To develop a normative data set and to study the relationship among arterial structure, different anthropometric measures, blood pressure, and arterial function during healthy childhood using very-high-resolution ultrasound (25-55 MHz). METHODS AND RESULTS: In 135 healthy children between 0 and 18 years of age, we assessed the structure of the carotid arteries, larger peripheral arteries, aorta, and left ventricle with ultrasound. Arterial stiffness was assessed by pulse wave velocity and endothelial function by brachial flow-mediated dilation. Reference curves adjusted for age and body surface area of arterial lumen diameters, intima-media thickness, and adventitia thickness were developed. Arterial walls thicken during childhood predominantly as a result of a progressive increase in intima-media thickness. There were significant associations among lumen diameter (R(2) range, 0.20-0.88 for different arteries; P<0.001), intima-media thickness (R(2) range, 0.47-0.85; P<0.001), left ventricular mass (R(2)=0.90; P<0.001), and adventitia thickness (R(2) range, 0.15-0.22; P<0.001) with sex, age, body surface, and systolic blood pressure. Arterial wall stress was associated with lumen diameter (R(2) range, 0.52-0.83; P<0.001) and intima-media thickness (R(2) range, 0.53-0.88; P<0.001). Limited relationships were found among arterial wall layer thickness, stiffness, and endothelial function. CONCLUSIONS: In healthy children, the evolution of the arterial structure is mainly related to anthropometrics and blood pressure.

Assessment of vascular remodeling after the Fontan procedure using a novel very high resolution ultrasound method: arterial wall thinning and venous thickening in late follow-up.

The Fontan circulation is associated with an increased central venous pressure, decreased ventricular preload, and increased afterload. We postulated that these central hemodynamic abnormalities would have consequences for the structural and functional properties of the peripheral arteries and veins, and performed a cross-sectional study in a tertiary health-care setting. We prospectively examined venous and arterial wall morphology by very high resolution ultrasound (VHRU, 25-55 MHz), and function by conventional vascular ultrasound (flow-mediated dilatation, FMD) and applanation tonometry (pulse wave velocity, PWV) in 28 patients after the Fontan procedure (age 14.8 ± 1.3 years) and 54 age-matched controls. Pig venous samples were studied with VHRU and compared with histology for accuracy. The precision of the venous VHRU method was studied in healthy volunteers. The lumen dimension was reduced in Fontans compared with controls in the common carotid, brachial, radial, and femoral arteries (p < 0.05). The common carotid, brachial, radial, ulnar, femoral, and dorsal tibial artery intima-media thicknesses (IMTs) and the brachial, ulnar, and femoral artery adventitial thicknesses were decreased (p < 0.05 for all), while the cubital and dorsal tibial vein IMTs were increased in Fontans (p < 0.001). FMD, abdominal aortic stiffness, and carotid-femoral PWV were similar, while carotid-radial artery PWV was increased in Fontans (p < 0.01). Venous wall layer assessment with VHRU was accurate and precise. The Fontan circulation is associated with significant arterial and venous remodeling, presumably reflecting abnormalities of central hemodynamics. These novel data may be of clinical importance in the circulatory management as well as the understanding of the early pathogenesis of vasculopathy in patients after the Fontan procedure.

Diastolic myocardial mechanics and their relation to ventricular filling pressures and postoperative course in functionally single ventricles.

Diastolic dysfunction affects clinical outcomes in patients with a functionally single ventricle (FSV). The objective of this work is to study the association of ventricular mechanics and interventricular dependence on diastolic parameters and early post-Fontan outcomes. Sixty-one patients with FSV underwent echocardiography, cardiac catheterization, and magnetic resonance imaging on the same day before or after the Fontan procedure. Echocardiographic diastolic parameters, ventricular mass, and incoordinate wall motion, defined by the number of dyskinetic segments or by the lateral wall delay, were determined and studied for relationships with invasively measured hemodynamics and early postoperative Fontan course. In subjects with a sizable secondary ventricle, incoordinate motion was additionally analyzed at the left- and right-sided ventricular free walls. Resting ventricular end-diastolic pressure (VEDP) was ≤10 mmHg in most subjects. Individual echocardiographic parameters of the diastolic flow and tissue velocities did not correlate with VEDP, other hemodynamics, or post-Fontan clinical course. Incoordinate wall motion in the dominant and in the sizeable secondary ventricle, defined by the lateral wall delay or by the number of dyskinetic segments, was the only echo parameter that correlated, albeit weakly, with VEDP (r = 0.247, P = 0.040), oxygen saturation (r = -0.417, P = 0.001), pulmonary vascular resistance and flow (Qp) (r = -0.303, P = 0.011), Fontan fenestration flow (r = 0.512, P = 0.009), and duration of endotracheal intubation (r = 0.292, P = 0.022). When the nondominant (secondary) ventricle was accounted for in the analysis of incoordinate wall motion, these associations strengthened. The degree of incoordinate ventricular wall motion in diastole was associated with VEDP and postoperative Fontan course in FSV. Analysis of incoordinate wall motion of the dominant and sizeable secondary ventricle may be warranted and should be included in the assessment of the FSV after the Fontan procedure.NEW & NOTEWORTHY Diastolic dysfunction affects outcomes in patients with functionally single ventricles (FSVs) but is difficult to assess. We found that incoordinate wall motion was the only echo parameter that correlated with FSV end-diastolic pressure, oxygen saturation, pulmonary vascular resistance and flow, and duration of endotracheal intubation. Analysis of incoordinate wall motion in the nondominant (secondary) ventricle strengthened these associations. Analyzing incoordinate wall motion should be included in the assessment of the FSV after the Fontan procedure.

Automatic Prediction of Paediatric Cardiac Output From Echocardiograms Using Deep Learning Models.

Background: Cardiac output (CO) perturbations are common and cause significant morbidity and mortality. Accurate CO assessment is crucial for guiding treatment in anaesthesia and critical care, but measurement is difficult, even for experts. Artificial intelligence methods show promise as alternatives for accurate, rapid CO assessment. Methods: We reviewed paediatric echocardiograms with normal CO and a dilated cardiomyopathy patient group with reduced CO. Experts measured the left ventricular outflow tract diameter, velocity time integral, CO, and cardiac index (CI). EchoNet-Dynamic is a deep learning model for estimation of ejection fraction in adults. We modified this model to predict the left ventricular outflow tract diameter and retrained it on paediatric data. We developed a novel deep learning approach for velocity time integral estimation. The combined models enable automatic prediction of CO. We evaluated the models against expert measurements. Primary outcomes were root-mean-squared error, mean absolute error, mean average percentage error, and coefficient of determination (R2). Results: In a test set unused during training, CI was estimated with the root-mean-squared error of 0.389 L/min/m2, mean absolute error of 0.321 L/min/m2, mean average percentage error of 10.8%, and R2 of 0.755. The Bland-Altman analysis showed that the models estimated CI with a bias of +0.14 L/min/m2 and 95% limits of agreement -0.58 to 0.86 L/min/m2. Conclusions: Our model estimated CO with strong correlation to ground truth and a bias of 0.17 L/min, better than many CO measurements in paediatrics. Model pretraining enabled accurate estimation despite a small dataset. Potential uses include supporting clinicians in real-time bedside calculation of CO, identification of low-CO states, and treatment responses.

Contexte: Les perturbations du débit cardiaque sont fréquentes et associées à des taux élevés de morbidité et de mortalité. Une évaluation juste du débit cardiaque est essentielle pour orienter le choix du traitement anesthésique et des soins critiques. Or, il est difficile de mesurer le débit cardiaque, même pour les experts. Les méthodes fondées sur l'intelligence artificielle semblent toutefois prometteuses pour évaluer le débit cardiaque avec exactitude et rapidité. Méthodologie: Nous avons analysé des échocardiogrammes pédiatriques chez des personnes dont le débit cardiaque est normal ainsi que chez des patients qui étaient atteints d'une cardiomyopathie dilatée et dont le débit cardiaque était réduit. Des experts ont mesuré le diamètre de la voie d'éjection ventriculaire gauche, l'intégrale de la vitesse par rapport au temps (IVT), le débit cardiaque et l'index cardiaque. L'outil EchoNet-Dynamic est un modèle d'apprentissage profond qui donne une estimation de la fraction d'éjection chez les adultes. Nous avons modifié ce modèle afin qu'il puisse prédire le diamètre de la voie d'éjection ventriculaire gauche et l'avons entraîné à l'aide de données pédiatriques. Nous avons également mis au point une nouvelle approche d'apprentissage profond pour l'estimation des valeurs d'IVT. La combinaison de ces modèles a permis de prédire de façon automatique le débit cardiaque, et nous avons évalué les résultats obtenus par rapport à ceux des experts. Les principaux critères d'évaluation étaient l'erreur moyenne quadratique (EMQ), l'erreur moyenne absolue (EMA), le pourcentage d'erreur moyen (PEM) ainsi que le coefficient de détermination (R2). Résultats: Dans un ensemble d'essais n'ayant pas été utilisé au cours de l'entraînement du modèle, l'index cardiaque a été estimé avec une EMQ de 0,389 L/min/m2, une EMA de 0,321 L/min/m2, un PEM de 10,8 % et un R2 de 0,755. Selon l'analyse de Bland-Altman, le biais pour les estimations de l'index cardiaque était de + 0,14 L/min/m2, et les limites de concordance à 95 % étaient de ­0,58 à 0,86 L/min/m2. Conclusions: Les estimations générées par le modèle pour le débit cardiaque montraient une forte corrélation avec les valeurs de référence et un biais à 0,17 L/min, ce qui est mieux que bien des mesures du débit cardiaque utilisées en pédiatrie. Malgré un petit ensemble de données, le modèle entraîné a permis de produire une estimation juste. Les utilisations potentielles comprennent l'aide aux cliniciens dans le calcul du débit cardiaque en temps réel et au chevet du patient, le dépistage d'un faible débit cardiaque et l'évaluation de la réponse au traitement.

Impact of Ventricular Geometric Characteristics on Myocardial Stiffness Assessment Using Shear-Wave Velocity in Healthy Children and Young Adults.

BACKGROUND: Diastolic myocardial stiffness (MS) can serve as a key diagnostic parameter for congenital or acquired heart diseases. Using shear modulus and shear-wave velocity (SWV), shear-wave elastography (SWE) is an emerging ultrasound-based technique that can allow noninvasive assessment of MS. However, MS extrinsic parameters such as left ventricular geometric characteristics could affect shear-wave propagation. The aims of this study were to determine a range of normal values of MS using SWE in age groups of healthy children and young adults and to explore the impact of left ventricular geometric characteristics on SWE. METHODS: Sixty healthy volunteers were recruited in the study and divided into 2 groups: neonates (0-1 months old, n = 15) and >1 month old (1 month to 45 years of age, n = 45). SWE was performed using the Verasonics Vantage systems with a phased-array ultrasound probe. The anteroseptal basal segment was assessed in two views. SWE was electrocardiographically triggered during the end-diastolic phase. Conventional echocardiography was performed to assess ventricular function and anatomy. Results are presented as stiffness values along with mean velocity measurements and SDs. Simple and multivariate linear regression analyses were performed. RESULTS: For neonates, mean MS was 1.87 ± 0.79 kPa (range, 0.59-2.91 kPa; mean SWV, 1.37 ± 0.57 m/sec), with high variability and no correlation with age (P = .239). For this age group, no statistically significant correlation was found between MS and any demographic or echocardiographic parameters (P > .05). For the >1 month old group, a mean MS value of 1.67 ± 0.53 kPa was observed (range, 0.6-3 kPa; mean SWV, 1.29 ± 0.49 m/sec) for healthy volunteers. When paired for age, no sex-related difference was observed (P = .55). In univariate linear regression analysis, age (r = 0.83, P < .01), diastolic interventricular septal thickness (r = 0.72, P < .01), and left ventricular end-diastolic diameter (r = 0.67, P < .01) were the parameters with the highest correlation coefficients with MS. In a multiple linear regression analysis incorporating these three parameters as cofounding factors, age was the only statistically significant parameters (r = 0.81, P = .02). CONCLUSION: Diastolic MS increases linearly in children and young adults. Diastolic MS correlates more robustly with age than with myocardial and left ventricular geometric characteristics. However, the geometry affects SWV, implying the need to determine well-established boundaries in future studies for the clinical application of SWE.

Local arterial stiffness measured by ultrafast ultrasound imaging in childhood cancer survivors treated with anthracyclines.

Background: There is conflicting literature regarding the long-term effect of anthracycline treatment on arterial stiffness. This study assessed local arterial stiffness using ultrafast ultrasound imaging (UUI) in anthracycline treated childhood cancer survivors, at rest and during exercise. Methods: 20 childhood cancer survivors (mean age 21.02 ± 9.45 years) treated with anthracyclines (mean cumulative dose 200.7 ± 126.80 mg/m2) and 21 healthy controls (mean age 26.00 ± 8.91 years) were included. Participants completed a demographic survey, fasting bloodwork for cardiovascular biomarkers, and performed a submaximal exercise test on a semi-supine bicycle. Pulse wave velocity (PWV) was measured in the left common carotid artery by direct pulse wave imaging using UUI at rest and submaximal exercise. Both PWV at the systolic foot (PWV-SF) and dicrotic notch (PWV-DN) were measured. Central (carotid-femoral) PWV was obtained by applanation tonometry. Carotid measurements were taken by conventional ultrasound. Measures were compared using two-tailed Students t-test or Chi-squared test, as appropriate. Results: There was no statistically significant difference (p > 0.05) between childhood cancer survivors and healthy controls in demographic parameters (age, sex, weight, height, BMI), blood biomarkers (total cholesterol, triglycerides, LDL-c, HDL-c, hs-CRP, fasting glucose, insulin, Hb A1c), cardiovascular parameters (intima media thickness, systolic and diastolic blood pressure, heart rate, carotid diameters, distensibility) or PWV measured by UUI at rest or at exercise. There was also no difference in the cardiovascular adaptation between rest and exercise in the two groups (p > 0.05). Multivariate analysis revealed age (p = 0.024) and LDL-c (p = 0.019) to be significant correlates of PWV-SF in childhood cancer survivors, in line with previously published data. Conclusion: We did not identify a significant impact of anthracycline treatment in young survivors of childhood cancer on local arterial stiffness in the left common carotid artery as measured by UUI.

Right Ventricular Electromechanical Dyssynchrony and Its Relation to Right Ventricular Remodeling, Dysfunction, and Exercise Capacity in Ebstein Anomaly.

BACKGROUND: Abnormal atrioventricular and intraventricular electrical conduction and dysfunction of the functional right ventricle (fRV) are common in Ebstein anomaly (EA). However, fRV mechanical dyssynchrony and its relation to fRV function are poorly characterized. We evaluated fRV mechanical dyssynchrony in EA patients in relation to fRV remodeling, dysfunction, and exercise intolerance. METHODS: We retrospectively analyzed data from nonoperated EA patients and age-matched controls who underwent echocardiography, cardiovascular magnetic resonance imaging, and cardiopulmonary exercise testing to quantify right ventricular (RV) remodeling, dysfunction, and exercise capacity. The relation of these to fRV dyssynchrony was retrospectively investigated. Right ventricular mechanical dyssynchrony was defined by early fRV septal activation (right-sided septal flash), RV lateral wall prestretch/late contraction, postsystolic shortening, and intra-RV delay using two-dimensional strain echocardiography. The SD of time to peak shortening among the fRV segments was calculated as a parameter of mechanical dispersion. RESULTS: Thirty-five EA patients (10 of whom were <18 years of age) and 35 age-matched controls were studied. Ebstein anomaly patients had worse RV function and increased intra-RV dyssynchrony versus controls. Nineteen of 35 (54%) EA patients had early septal activation with simultaneous stretch and consequent late activation and postsystolic shortening of RV lateral segments. Intra-fRV mechanical delay correlated with fRV end-diastolic volume index (r = 0.43, P < .05) and fRV end-systolic volume index (r = 0.63, P < .001). The fRV ejection fraction was lower in EA with versus without right-sided septal flash (44.9 ± 11.0 vs 54.2 ± 8.2, P = .012). The fRV mechanical dispersion correlated with the percentage of predicted peak VO2 (r = -0.35, P < .05). CONCLUSIONS: In EA, fRV mechanical dyssynchrony is associated with fRV remodeling, dysfunction, and impaired exercise capacity. Mechanical dyssynchrony as a therapeutic target in selected EA patients warrants further study.

Systemic hemodynamic function in humans with type 1 diabetes treated with protein kinase Cß inhibition and renin-angiotensin system blockade: a pilot study.

The protein kinase Cß (PKCß) system has been implicated in the deleterious vascular responses to hyperglycemia and angiotensin II (Ang II) in experimental models of diabetes (DM). Whether these interactions are important in humans is unknown. Flow-mediated vasodilatation (FMD) was measured during clamped euglycemia and hyperglycemia, before and after randomization to PKCß inhibition (ruboxistaurin; RBX, 32 mg daily, n = 13) or a placebo (n = 7) for 8 weeks in renin-angiotensin system (RAS) blockade-treated subjects with type 1 DM. Blood pressure responses to infused Ang II were measured before and after randomization to RBX or a placebo. The RBX and placebo groups displayed similar clinical characteristics. Before RBX, FMD declined in response to hyperglycemia (6.8% ± 2.8% to 4.9% ± 1.8%). This effect was reversed after treatment with RBX (5.6% ± 3.1% to 6.0% ± 1.6% (within-group change, p = 0.009 (ANOVA)). No changes were observed in the placebo group. Infused Ang II was associated with hypertensive responses in the RBX and placebo groups (p < 0.05 (ANOVA)), and RBX did not influence this effect. In conclusion, RBX blunted the effect of hyperglycemia on FMD, suggesting that PKCß may modulate endothelial function in type 1 DM. The lack of effect on Ang II responses suggests that PKCß inhibition may act through non-RAS pathways in humans with DM.

Measurement of effective aortic valve area using three-dimensional echocardiography in children undergoing aortic balloon valvuloplasty for aortic stenosis.

AIMS: Pressure gradient is used for timing of balloon aortic valvuloplasty for aortic stenosis (AS) in children, but does not correlate well with outcome and is limited if ventricular function is poor. In adults, effective orifice area (EOA) is used to assess AS severity, but EOA by continuity equation or 2D echo is unreliable in children. Three-dimensional echocardiography (3DE) may reliably assess EOA but has not been studied in children. We assessed measurement of aortic valve EOA by 3DE in children with AS before and after balloon aortic valvuloplasty and compared results with change in aortic valve gradient. METHODS: 3DE was performed at time of catheterization before and after balloon aortic valvuloplasty. Using 3DE multiplanar review mode, valve annulus diameter, area, and EOA were measured and compared with change in aortic gradient and degree of aortic insufficiency. RESULTS: Twenty-four 3DE studies in 12 children (mean age 4.4 ± 5.0 years) were analyzed. EOA was measurable in all. Catheter peak gradient decreased from 45 ± 10 to 26 ± 17 mmHg (P = 0.0018). 3DE EOA increased after balloon aortic valvuloplasty (0.59 ± 0.52 cm(2) vs 0.80 ± 0.70 cm(2) ; P = 0.03), without change in valve diameter. EOA change correlated with change in peak (r = 0.77; P = 0.005) and mean (r = 0.60; P = 0.03) aortic valve gradient post balloon aortic valvuloplasty. CONCLUSION: 3DE facilitates EOA measurement in pediatric AS and correlates with change in aortic valve gradient after balloon valvuloplasty.

Regional Vascular Changes and Aortic Dilatation in Pediatric Patients With Bicuspid Aortic Valve.

BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital heart disease, often associated with valve dysfunction, coarctation of the aorta, and ascending aorta dilatation. Aortic dilatation might result from abnormal regional hemodynamics or inherent vascular disease. Vascular function in pediatric BAV remains poorly characterized. METHODS: A cross-sectional study was performed to evaluate vascular function in 142 children with BAV aged 7-18 years compared with healthy control children. Echocardiography was performed to assess aortic dimensions, BAV function, and vascular function (aortic arch pulse wave velocity [PWV]), carotid intima media thickness, and aortic stiffness and distensibility). Carotid-femoral and carotid-radial PWV were assessed using tonometry. Vascular function was compared for 4 patient groups stratified according to aortic dilatation and a history of coarctation of the aorta. Multivariate regression analysis was performed to determine predictors of aortic dilatation. RESULTS: Children with BAV had stiffer and less distensible ascending aortas with higher aortic arch PWV compared with control children. Carotid-femoral and carotid-radial PWV were not increased in patients with BAV, and the vascular assessment of the abdominal aorta was unremarkable. Multivariate regression revealed that aortic arch PWV was the only vascular function parameter that was associated with aortic dilatation. CONCLUSIONS: Children with BAV have differences in vascular function that are confined to their proximal aorta, even in normal functioning BAV. The observed differences in vascular function are likely multifactorial, with contributions from abnormal regional flow and a potential localized primary aortopathy.

Machine-learning-based exploration to identify remodeling patterns associated with death or heart-transplant in pediatric-dilated cardiomyopathy.

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. Cluster-4 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.