Impact of Genotype-Phenotype Interactions on Cardiovascular Function in Paediatric Loeys-Dietz Syndrome.

Background: The relationship between genotype and phenotypical vascular and cardiac properties in paediatric Loeys-Dietz syndrome (LDS) patients are not well characterized. This study explores the phenotypical differences in aortic properties and cardiac structural and functional parameters between paediatric LDS patients with TGFBR1 and TGFBR2 mutations. Methods: We included 32 LDS patients with either TGFBR1 (n = 17) or TGFBR2 (n = 15) mutations. Echocardiographic data included aortic dimensions, distensibility, strain, and stiffness at the level of the annulus, sinuses of Valsalva, sinotubular junction, ascending aorta, and descending aorta. Parameters for left ventricular size and function were also recorded. Results: Demographics were similar between the groups. Patients with TGFBR2 were more likely to have undergone aortic surgery (47% vs 12%, P = 0.057) and use angiotensin receptor blockers (93% vs 47%, P = 0.015). Aortic z scores were significantly larger in the TGFBR2 group at the level of the aortic valve annulus (P = 0.007), sinuses of Valsalva (P = 0.001), sinotubular junction (P = 0.001), and ascending aorta (P = 0.054). Patients with TGFBR2 also had significantly lower aortic distensibility and strain coupled with higher stiffness index at the level of the annulus, sinotubular junction, and ascending aorta. Parameters for the descending aorta, cardiac morphology, and cardiac function were similar between the groups. Conclusions: Paediatric LDS patients with TGFBR2 present with more severe cardiovascular phenotypes than patients with TGFBR1 with larger aortic dimensions and increased aortic stiffness. Our findings suggest that genotypes should be taken into consideration in the clinical management of paediatric LDS patients.

Contexte: Les liens entre le génotype des enfants atteints du syndrome de Loeys-Dietz (SLD) et les particularités phénotypiques vasculaires et cardiaques n'ont pas encore été bien caractérisés. La présente étude vise à explorer les différences phénotypiques entre les propriétés de l'aorte et les paramètres cardiaques structuraux et fonctionnels des enfants atteints du SLD qui présentent une mutation du gène TGFBR1 et ceux qui présentent une mutation du gène TGFBR2. Méthodologie: Nous avons inclus dans notre analyse 32 patients atteints du SLD présentant une mutation de TGFBR1 (n = 17) ou de TGFBR2 (n = 15). Les données échocardiographiques colligées incluaient les dimensions de l'aorte, sa distensibilité, sa déformation (strain) et sa rigidité au niveau de l'anneau aortique, des sinus de Valsalva, de la jonction sinotubulaire, de l'aorte ascendante et de l'aorte descendante. Les paramètres ayant trait à la taille et à la fonction du ventricule gauche ont également été consignés. Résultats: Les caractéristiques démographiques étaient comparables dans les deux groupes. Les patients présentant une mutation du gène TGFBR2 étaient plus susceptibles d'avoir subi une intervention chirurgicale de l'aorte (47 % vs 12 %, p = 0,057) et de prendre un antagoniste des récepteurs de l'angiotensine (93 % vs 47 %, p = 0,015). Les scores z aortiques étaient significativement plus élevés chez les patients présentant une mutation de TGFBR2 pour les dimensions de l'anneau de la valve aortique (p = 0,007), des sinus of Valsalva (p = 0,001), de la jonction sinotubulaire (p = 0,001) et de l'aorte ascendante (p = 0,054). Les patients avec une mutation de TGFBR2 présentaient aussi une élasticité et une déformation aortiques significativement plus faibles ainsi qu'une rigidité accrue au niveau de l'anneau aortique, de la jonction sinotubulaire et de l'aorte ascendante. Les paramètres de l'aorte descendante, les caractéristiques morphologiques cardiaques et la fonction cardiaque étaient comparables pour les deux groupes. Conclusions: Chez les enfants atteints du SLD, une mutation du gène TGFBR2 se traduisait par des phénotypes plus défavorables que dans le cas d'une mutation du gène TGFBR1 et se caractérisait par des dimensions et une rigidité aortiques accrues. Nos observations indiquent qu'il convient de prendre le génotype des patients en considération lors de la prise en charge clinique des enfants atteints du SLD.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

Noninvasive Assessment of Myocardial Work in Children.

The noninvasive assessment of ventricular function is an ongoing challenge with new tools and measurements always being considered and tested. The noninvasive assessment of myocardial work via the pressure-strain relationship is one of the newer tools proposed to evaluate ventricular systolic function. However, prior to using any new tool, one should understand its properties, utility, and limitations. In this commentary we focus on the noninvasive assessment of myocardial work via the pressure-strain relationship from a pediatric point of view. We address the current knowledge, limitations, and propose future directions to better understand this tool.

Challenges in clinical identification of right ventricular dysfunction in preterm infants with persistent pulmonary hypertension of the newborn.

BACKGROUND: Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. METHODS: Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. RESULTS: Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41±7 vs. 47±9 mmHg, p = 0.02) and higher shock index (4.02±0.80 vs. 3.44±0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32-0.77). CONCLUSIONS: The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants.

Novel Techniques in Imaging Congenital Heart Disease: JACC Scientific Statement.

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow at well-resourced centers. Studies to evaluate the clinical value and cost-effectiveness of these techniques are needed. For techniques that enhance the value of care for congenital heart disease patients, resources will need to be allocated for education and training to promote widespread implementation.

Modeling the Relationship Between Diastolic Phenotype and Outcomes in Pediatric Hypertrophic Cardiomyopathy.

BACKGROUND: Pediatric hypertrophic cardiomyopathy (HCM) is associated with adverse events. The contribution of diastolic dysfunction to adverse events is poorly understood. The aim of this study was to explore the association between diastolic phenotype and outcomes in pediatric patients with HCM. METHODS: Children <18 years of age with diagnosed with HCM were included. Diastolic function parameters were measured from the first echocardiogram at the time of diagnosis, including Doppler flow velocities, tissue Doppler velocities, and left atrial volume and function. Using principal-component analysis, key features in echocardiographic parameters were identified. The principal components were regressed to freedom from major adverse cardiac events (MACE), defined as implantable cardioverter-defibrillator insertion, myectomy, aborted sudden cardiac death, transplantation, need for mechanical circulatory support, and death. RESULTS: Variables that estimate left ventricular filling pressures were highly collinear and associated with MACE (hazard ratio, 0.86; 95% CI, 0.75-1.00), though this was no longer significant after controlling for left ventricular thickness and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with outcomes in the covariate-adjusted model (hazard ratio, 0.69; 95% CI, 0.5-0.94). The covariate-adjusted model had an Akaike information criterion of 213, an adjusted R2 value of 0.78, and a concordance index of 0.82 for association with MACE. CONCLUSION: Echocardiographic parameters of diastolic dysfunction were associated with MACE in this population study, in combination with the severity of left ventricular hypertrophy and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with adverse events. Additional study of diastolic function parameters adjusted for patient size could facilitate the prediction of adverse events in pediatric patients with HCM.

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.

Mechanical atrioventricular valve replacement in patients with single ventricle palliation.

OBJECTIVES: Atrioventricular valve (AVV) replacements in patients with single-ventricle circulations pose significant surgical risks and are associated with high morbidity and mortality. METHODS: From 1997 to 2021, 16 consecutive patients with functionally single-ventricle physiology underwent mechanical AVV replacement. Primary outcome was transplant-free survival. Secondary outcomes included major postoperative morbidity. RESULTS: The median age of AVV replacement was 2 years old (interquartile range 0.6-3.8 years). All AVV replacements were performed with a St. Jude Medical mechanical valve, median 24 mm (range, 19-31mm). Extracorporeal membrane oxygenation (ECMO) was required in 4 patients. Operative mortality was 38% (6/16). There were 2 late deaths and 3 transplants. Transplant-free survival was 50% at 1 year, 37.5% at 5 years, and 22% at 10 years. Transplant-free survival was higher for patients with preserved ventricular function (P = 0.01). Difference in transplant-free survival at 1 year was 75% vs 25%, at 5 years was 62.5% vs 12.5% and at 10 years was 57% vs 0%. Three (19%) patients had complete heart block requiring permanent pacemaker insertion. 6 of 13 patients (46%) patients reached Fontan completion (3 patients operated at/after Fontan). Significant bleeding events occurred in 8 patients (50%) with 3 patients suffering major cerebrovascular accidents. There were 6 events of valve thrombosis in 5 patients, resulting in 2 deaths and 2 heart transplants. CONCLUSIONS: Mechanical valve replacement carries significant morbidity and mortality risk. While it successfully salvages about half of patients with preserved ventricular function, careful consideration of alternative options should be made before embarking upon mechanical valve replacement.

Flow Dynamics in Children With Bicuspid Aortic Valve: A Blood Speckle Tracking Study.

OBJECTIVE: Bicuspid aortic valve (BAV) is associated with progressive aortic dilation. Although the etiology is complex, altered flow dynamics is thought to play an important role. Blood speckle tracking (BST) allows for visualization and quantification of complex flow, which could be useful in identifying patients at risk of root dilation and could aid in surgical planning. The aims of this study were to assess and quantify flow in the aortic root and left ventricle using BST in children with bicuspid aortic valves. METHODS AND RESULTS: A total of 38 children <10 y of age were included (24 controls, 14 with BAV). Flow dynamics were examined using BST in the aortic root and left ventricle. Children with BAV had altered systolic flow patterns in the aortic root and higher aortic root average vorticity (25.9 [23.4-29.2] Hz vs. 17.8 [9.0-26.2] Hz, p < 0.05), vector complexity (0.17 [0.14-0.31] vs. 0.05 [0.02-0.13], p < 0.01) and rate of energy loss (7.9 [4.9-12.1] mW/m vs. 2.7 [1.2-7.4] mW/m, p = 0.01). Left ventricular average diastolic vorticity (20.9 ± 5.8 Hz vs. 11.4 ± 5.2 Hz, p < 0.01), kinetic energy (0.11 ± 0.05 J/m vs. 0.04 ± 0.02 J/m, p < 0.01), vector complexity (0.38 ± 0.1 vs. 0.23 ± 0.1, p < 0.01) and rate of energy loss (11.1 ± 4.8 mW/m vs. 2.7 ± 1.9 mW/m, p < 0.01) were higher in children with BAV. CONCLUSION: Children with BAV exhibit altered flow dynamics in the aortic root and left ventricle in the absence of significant aortic root dilation. This may represent a substrate and potential predictor for future dilation and diastolic dysfunction.

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.

Electromechanical Dyssynchrony Is Associated With Right Ventricular Remodeling and Dysfunction Independently of Pulmonary Regurgitation Late After Tetralogy of Fallot Repair.

BACKGROUND: The aim of this study was to investigate the relationship among right ventricular (RV) dilatation, dysfunction, and electromechanical dyssynchrony (EMD) in patients with repaired tetralogy of Fallot (rTOF). METHODS: Data from a prospective rTOF registry of subjects with moderate or greater pulmonary regurgitation (PR) and contemporary imaging were analyzed. Electrocardiograms and echocardiograms were analyzed for EMD (prolonged QRS duration [QRSd], echocardiographic septal flash, and mechanical delay) and mechanical dispersion. The relationship among these, RV measurements on cardiac magnetic resonance, exercise capacity, and incident arrhythmia or death was analyzed with adjustment for PR. RESULTS: In total, 271 patients with rTOF (42% women; median age, 32 years; interquartile range [IQR], 23-34 years) were included. Patients had moderate to severe PR (median PR fraction, 38%; IQR, 30%-47%), moderate to severe RV enlargement (median RV end-diastolic volume index, 161 mL/m2; IQR, 138-186 mL/m2) and mild RV systolic dysfunction (median RV ejection fraction [RVEF], 44%; IQR, 38%-48%). Eleven patients (4%) experienced ventricular arrhythmia or death. Presence of EMD was associated with larger RV size (RV end-diastolic volume index and RV end-systolic volume index, P = .006 and P < .001, respectively) and lower RVEF (P < .001). A sharp inflection in the relation among QRSd, RV size, and RVEF was observed when QRSd exceeded 150 msec (3.1% decrease in RVEF for every 20-msec increase in QRSd between 160 and 200 msec). Similar inflection points were observed for the mechanical delay between the RV basal-lateral and midseptal segments. The mechanical delay was higher in patients with vs without incident atrial arrhythmia (371 vs 276 msec, P = .014). CONCLUSIONS: In adults with rTOF, EMD is independently associated with larger RV size, lower RVEF, and incident atrial arrhythmias.

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.

Longitudinal Changes in Ventricular Mechanics in Adolescents After the Fontan Operation.

BACKGROUND: Ventricular dysfunction is a significant clinical challenge in the long-term follow-up of patients with single-ventricle (SV) physiology. Ventricular function and myocardial mechanics can be studied using speckle-tracking echocardiography, which provides information on myocardial deformation. Limited information is available on serial changes in SV myocardial mechanics after the Fontan operation. The aim of this study was to describe serial changes in myocardial mechanics in children after the Fontan operation and the relationship of these changes with myocardial fibrosis markers as obtained by cardiac magnetic resonance and exercise performance parameters. METHODS: The authors hypothesized that ventricular mechanics decline in patients with SVs over time and are associated with increased myocardial fibrosis and reduced exercise performance. A single-center retrospective cohort study including adolescents after the Fontan operation was conducted. Ventricular strain and torsion were assessed using speckle-tracking echocardiography. Cardiac magnetic resonance and cardiopulmonary exercise testing data closest to the latest echocardiographic examinations were performed. The most recent follow-up echocardiographic and cardiac magnetic resonance data were compared with those from sex- and age-matched control subjects and with individual patients' early post-Fontan data. RESULTS: Fifty patients with SVs (31 left ventricle, 13 right ventricle [RV], and six codominant) were included. Median time at follow-up echocardiography from the time of Fontan was 12.8 years (interquartile range [IQR], 10.6 to 16.6 years). Compared with early post-Fontan echocardiography, follow-up assessment showed reduced global longitudinal strain (-17.5% [IQR, -14.5% to -19.5%] vs -19.8% [IQR, -16.0% to -21.7%], P = .01], circumferential strain (-15.7% [IQR, -11.4% to -18.7%] vs -18.9% [IQR, -15.2% to -25.0%], P = .009), and torsion (1.28°/cm [IQR, 0.51°/cm to 1.74°/cm] vs 1.72°/cm [IQR, 0.92°/cm to 2.34°/cm], P = .02), with decreased apical rotation but no significant change in basal rotation. Single RVs had lower torsion compared with single left ventricles (1.04°/cm [IQR, 0.12°/cm to 2.20°/cm] vs 1.25°/cm [IQR, 0.25°/cm to 2.51°/cm], P = .01). T1 values were higher in patients with SV compared with control subjects (1,009 ± 36 vs 958 ± 40 msec, P = .004) and in those with single RVs compared with single left ventricles (1,023 ± 19 vs 1,006 ± 17 msec, P = .02). T1 was correlated with circumferential strain (r = 0.59, P = .04) and inversely correlated with O2 saturation (r = -0.67, P < .001) and torsion (r = -0.71, P = .02). Peak oxygen consumption was correlated with torsion (r = 0.52, P = .001) and untwist rates (r = 0.23, P = .03). CONCLUSIONS: After the Fontan procedures, there is a progressive decrease in myocardial deformation parameters. The progressive decrease in SV torsion is related to a decrease in apical rotation, which is more pronounced in single RVs. Decreased torsion is associated with increased markers of myocardial fibrosis and lower maximal exercise capacity. Torsional mechanics may be an important parameter to monitor after Fontan palliation, but further prognostic information is required.

Growth of targeted neonatal echocardiography in Chinese neonatal intensive care units: gaps in practice and training.

To evaluate clinical practice, neonatologists' attitudes, and the extent of training and accreditation regarding targeted neonatal echocardiography (TnEcho) among Chinese neonatologists. A web-based questionnaire was emailed to 331 neonatologists across China who completed training in subspecialty neonatology. The survey covered various aspects of TnEcho, including the characteristics of clinical practice, attitudes towards its usefulness, and perceived barriers to implementation and training methods. Survey response rate was 68.0% (225/331). Seventy-nine (35.1%) respondents stated that TnEcho was utilized in their NICUs. Most respondents reported the use of echocardiography to evaluate hemodynamic significance of the patent ductus arteriosus (PDA, 94.9%). The eyeballing technique was most used to evaluate left (82.3%) and right (77.2%) ventricular function. Most respondents (87.3-96.2%) positively valued the role of TnEcho in providing timely and longitudinal hemodynamic information to guide cardiovascular care. Access to TnEcho was more likely in centers with on-site pediatric cardiology service (p = .003), larger bed capacity (p = .004), or level IV status (p = .003). Lack of experienced practitioners with echocardiography expertise (88.9%) and accredited training programs (85.8%) was perceived to be the major barrier to implementation. Of concern, most practitioners with TnEcho skills received training in an informal manner through workshops (60.8%) or self-directed learning (54.4%). Conclusions: The use of TnEcho for longitudinal evaluation of infants with hemodynamic instability is growing within Chinese NICUs. There is an urgent need to develop standardized training programs and accreditation for TnEcho which are adapted to the Chinese context.

Longitudinal Assessment of Cerebral Blood Volume Variation in Human Neonates Using Ultrafast Power Doppler and Diverging Waves.

Longitudinal assessment of brain perfusion is a critical parameter for neurodevelopmental outcome of neonates undergoing cardiopulmonary bypass procedure. In this study, we aim to measure the variations of cerebral blood volume (CBV) in human neonates during cardiac surgery, using Ultrafast Power Doppler and freehand scanning. To be clinically relevant, this method must satisfy three criteria: being able to image a wide field of view in the brain, show significant longitudinal CBV variations, and present reproducible results. To address the first point, we performed for the first time transfontanellar Ultrafast Power Doppler using a hand-held phased-array transducer with diverging waves. This increased the field of view more than threefold compared to previous studies using linear transducers and plane waves. We were able to image vessels in the cortical areas as well as the deep grey matter and temporal lobes. Second, we measured the longitudinal variations of CBV on human neonates undergoing cardiopulmonary bypass. When compared to a pre-operative baseline acquisition, the CBV exhibited significant variation during bypass: on average, + 20±3 % in the mid-sagittal full sector ( [Formula: see text]), - 11±3 % in the cortical regions ( [Formula: see text]) and - 10±4 % in the basal ganglia ( [Formula: see text]). Third, a trained operator performing identical scans was able to reproduce CBV estimates with a variability of 4% to 7.5% depending on the regions considered. We also investigated whether vessel segmentation could further improve reproducibility, but found that it actually introduced greater variability in the results. Overall, this study demonstrates the clinical translation of ultrafast power Doppler with diverging-waves and freehand scanning.

Impact of cardiopulmonary bypass on cerebrovascular autoregulation assessed by ultrafast ultrasound imaging.

Newborns with congenital heart disease undergoing cardiac surgery are at risk of neurodevelopmental impairment with limited understanding of the impact of intra-operative cardiopulmonary bypass (CPB), deep hypothermia and selective cerebral perfusion on the brain. We hypothesized that a novel ultrasound technique, ultrafast power Doppler (UPD), can assess variations of cerebral blood volume (CBV) in neonates undergoing cardiac surgery requiring CPB. UPD was performed before, during and after surgery in newborns with hypoplastic left heart syndrome undergoing a Norwood operation. We found that global CBV was not significantly different between patients and controls (P = 0.98) and between pre- and post-surgery (P = 0.62). UPD was able to monitor changes in CBV throughout surgery, revealing regional differences in CBV during hypothermia during which CBV correlated with CPB flow rate (R2  = 0.52, P = 0.021). Brain injury on post-operative magnetic resonance imaging was observed in patients with higher maximum variation in CBV. Our findings suggest that UPD can quantify global and regional brain perfusion variation during neonatal cardiac surgery with this first intra-operative application demonstrating an association between CBV and CPB flow rate, suggesting loss of autoregulation. Therefore, the measurement of CBV by UPD could enable optimization of cerebral perfusion during cardiac surgery in neonates. KEY POINTS: The impact of cardiopulmonary bypass (CPB) on the neonatal brain undergoing cardiac surgery is poorly understood. Ultrafast power Doppler (UPD) quantifies cerebral blood volume (CBV), a surrogate of brain perfusion. CBV varies throughout CPB surgery and is associated with variation of the bypass pump flow rate during deep hypothermia. Association between CBV and bypass pump flow rate suggests loss of cerebrovascular autoregulatory processes. Quantitative monitoring of cerebral perfusion by UPD could provide a direct parameter to optimize CPB flow rate.