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.

Fetal Cardiology Bioethics: An Innovative New Curriculum for Cardiology Trainees.

Decision-making in fetal cardiology is fraught with ethical issues yet education in bioethics for trainees is limited or nonexistent. In this innovation report, we describe the development of a fetal cardiology bioethics curriculum designed to address this gap. The curriculum was developed to supplement the core curriculum for cardiology fellows and fetal cardiology subspecialty trainees. The series combines didactic and interactive teaching modalities and contains 5 key components: (1) introduction to bioethics and its role in fetal cardiology, (2) counseling and pathways for compassionate terminal care, (3) case vignette-based ethical analysis and discussion cases, (4) fetal counseling considerations for shared decision-making and recommendations, (5) facilitated communications role play. The curriculum was refined using session evaluations from end users. This report describes the innovative curriculum as a starting point for further incorporation and study of bioethical education in pediatric cardiology and fetal training programs.

Long-term outcomes of pulmonary embolism in children and adolescents.

ABSTRACT: Knowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Organization of Pediatric Echocardiography Laboratories: Impact of Sonographers on Clinical, Academic, and Financial Performance.

Echocardiography has evolved the first-line imaging for diagnosis and management of pediatric and congenital heart disease all over the world. While it recognized as essential component of pediatric cardiac care delivery, organization of pediatric echocardiography services is very heterogeneous across the world, mainly related to significant differences in material and human resources in heterogeneous health care systems. In this paper, we focus on the role of pediatric sonographers, defined as expert technicians in pediatric echocardiography. While in some services sonographers are an essential part of the organizational structure, other laboratories operate only with physicians trained in echocardiography. The impact of sonographers on clinical, academic and financial performance will be discussed. Two organizational models (with and without sonographers) will be compared, and the advantages and disadvantages of each model will be evaluated. Different models of care provision are possible and decisions on organizational models need to be adjusted to the demands and available resources.

Effects of Transplacental Dexamethasone Therapy on Fetal Immune-Mediated Complete Heart Block.

INTRODUCTION: Antibody-mediated complete atrioventricular block (CAVB) is considered irreversible. We sought to examine the effects of transplacental steroids on fetal AV conduction. METHODS: Fifty-nine fetuses diagnosed with CAVB at our center from 1996 to 2018 were reviewed. Routine dexamethasone administration to birth was used to limit cardiac inflammatory damage. Restoration of fetal AV conduction was classified as "unexpected" treatment response. RESULTS: CAVB resolved in 5/29 (17%) fetuses first treated ≤24-week gestation with 8 mg/day of dexamethasone, when compared with 0/30 (0%) when treatment was initiated later and/or at a starting dose of 4 mg/day (odds ratio 13.69; 95% confidence interval 0.72-260.13; p = 0.024). Treatment response was also associated with a faster ventricular rate at diagnosis (median [range]: 80 [60-97] beats per minute [bpm] vs. 58 [38-92] bpm; p = 0.0036). CAVB reappeared in all 5 responders either prenatally (n = 1) or postnatally before (n = 3) or after (n = 1) the first year of life. When compared with infants with treatment-resistant CAVB (median follow-up 10.3 years), responders (median follow-up 12.3 years) required postnatal pacing less frequent (2/5 [40%] vs. 45/49 [92%]; p = 0.013). CONCLUSIONS: In a subgroup of CAVB fetuses, dexamethasone transiently restored AV conduction. This was associated with a lower rate of postnatal pacing when compared with nonresponders.

Mixed-reality view of cardiac specimens: a new approach to understanding complex intracardiac congenital lesions.

Digital reality is an emerging platform for three-dimensional representation of medical imaging data. In this technical innovation paper, the authors evaluated the accuracy and utility of mixed-reality technology in the morphological evaluation of complex congenital heart disease. The authors converted CT datasets of 12 heart specimens with different subtypes of double-outlet right ventricle to stereoscopic images and interrogated them using a mixed-reality system. The morphological features identified on the stereoscopic models were compared with findings at macroscopic examination of the actual heart specimens. The results showed that the mixed-reality system provided highly accurate stereoscopic display of spatially complex congenital cardiac lesions, with interactive features that might enhance 3-D understanding of morphology. Additionally, the authors found that high-resolution digital reproduction of cardiac specimens using clinical CT scanners is feasible for preservation and educational purposes.

Isolated Congenital Right Atrial Aneurysm: Monitoring Parameters for Asymptomatic Patients.

Isolated congenital right atrial aneurysm is rare. Indications for surgery in asymptomatic patients with moderate-size right atria remain controversial. Evidence in support of medical management and timing of prophylactic surgery is reviewed. We propose the use of three echocardiographic indices to help identify inappropriate atrial growth and facilitate surgical decision-making.

Improving Prenatal Diagnosis of Coarctation of the Aorta.

BACKGROUND: The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta. METHODS: A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves. RESULTS: Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention. CONCLUSIONS: In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler.

Effect of Obstructive Sleep Apnea on Cardiovascular Function in Obese Youth.

The increasing prevalence of overweight or obese children and adolescents is a significant global health concern. Although the effect of obesity on cardiovascular function has been investigated, little is known on the impact of associated obstructive sleep apnea (OSA) in obese youth. The aim of the present study was to investigate the influence of OSA on cardiovascular functional parameters in obese youth. This is a prospective single-center observational cross-sectional study. Forty-four obese patients and 44 age- and gender-matched control subjects were included. All patients underwent polysomnography and cardiovascular assessment including functional echocardiography and carotid-femoral pulse wave velocity (PWV). Obese patients had higher left ventricular (LV) mass/height2.7, preserved LV systolic parameters, differences in LV diastolic parameters, and increased PWV and systolic blood pressure at rest compared with control group. In obese youth, 14 of 44 (32%) had OSA. There was no correlation between obesity and the apnea-hypopnea index (AHI). LV mass/height2.7 significantly correlated with body mass index z-score (r = 0.648, p <0.001) whereas PWV correlated with AHI (r = 0.352, p = 0.038). In obese patients, body mass index z-score was an independent predictor for LV mass/height2.7 (r = 0.61, p <0.001) and AHI was an independent predictor for higher PWV (r = 0.352, p = 0.038). In conclusion, both obesity and OSA influence cardiovascular performance in obese youth. Although obesity is associated with increased LV mass and reduced LV diastolic function, OSA is associated with changes in arterial stiffness.