Advances in Fetal Cardiac Imaging and Intervention.

The field of fetal cardiology has evolved significantly in recent years. This review focuses on specific advances in fetal cardiac imaging and intervention that are increasingly used in clinical practice. On the imaging frontier, updated screening guidelines and artificial intelligence hold promise for improving prenatal detection of congenital heart disease. Advances in ultrasound technology and magnetic resonance imaging techniques have enabled greater diagnostic and prognostic accuracy of fetal heart disease from the first to third trimesters, and maternal hyperoxygenation can offer additional physiological insights. Fetal cardiac therapy has also seen great progress, with advances in transplacental pharmacologic treatments, infusions of enzyme replacement therapy, and fetal surgery for select rare and severe conditions.

La cardiologie fœtale a connu un essor fulgurant ces dernières années. Nous nous penchons ici sur certaines avancées réalisées en imagerie et en thérapie cardiaque fœtale dont l'usage est de plus en plus répandu en pratique clinique. Du côté de l'imagerie, on se tourne vers les nouvelles recommandations sur le dépistage et vers l'intelligence artificielle pour améliorer le dépistage prénatal de la cardiopathie congénitale. Grâce aux avancées technologiques, l'échographie et l'IRM permettent de diagnostiquer une cardiopathie fœtale et d'établir le pronostic avec un plus haut degré de précision, et ce, du premier au troisième trimestre. L'hyperoxygénation maternelle, quant à elle, apporte un éclairage sur les effets physiologiques. La thérapie cardiaque fœtale a elle aussi fait des bonds de géant avec les traitements pharmacologiques transplacentaires, l'enzymothérapie de remplacement et la chirurgie fœtale pour certaines maladies rares et graves.

Advanced imaging of fetal cardiac function.

Over recent decades, a variety of advanced imaging techniques for assessing cardiovascular physiology and cardiac function in adults and children have been applied in the fetus. In many cases, technical development has been required to allow feasibility in the fetus, while an appreciation of the unique physiology of the fetal circulation is required for proper interpretation of the findings. This review will focus on recent advances in fetal echocardiography and cardiovascular magnetic resonance (CMR), providing examples of their application in research and clinical settings. We will also consider future directions for these technologies, including their ongoing technical development and potential clinical value.

Dysphagia in the elderly population: A Videofluoroscopic study.

OBJECTIVE: To examine the impact of age and underlying comorbid conditions on swallowing in elderly patients with dysphagia. METHODS: Charts of consecutive patients aged >64 studied by Videofluoroscopic swallowing study (VFSS) between 2010 and 2018 at our institution were reviewed (n = 731). Patients were categorized based on age into young old (aged 65-74), older old (aged 75-84) and oldest old (aged 85+). The underlying comorbidities and VFSS results were compared between different age groups. RESULTS: Dysphagia was more likely to be caused by presbyphagia (p < 0.01) and dementia (p < 0.0001) in the oldest old, whereas, head and neck cancers (p < 0.0001) were more common in the young old cohort. In the absence of organic disease (e.g. cancer, stroke, dementia), aging was associated with prolonged oral transit time (OTT) (p < 0.05) and aspiration after swallow (p < 0.05). Compared to those with presbyphagia, patients with organic disease were more likely to have delayed pharyngeal swallow response (p < 0.05) and aspiration during swallow (p < 0.005). CONCLUSION: There are significant differences in the etiology of dysphagia between different age cohorts amongst the dysphagic elderly population. In addition, organic diseases affect swallowing differently than does mere aging. The rate of prolonged OTT and post-swallow aspiration increase with aging in patients with presbyphagia, likely due to age-related sarcopenia of the swallowing muscles. Whereas, those with organic diseases have a higher rate of delayed pharyngeal swallow response and aspiration during swallow, likely due to sensorineural impairment. Thus, it is important to view the elderly as a heterogeneous group when evaluating patients with dysphagia.

Longitudinal 3D Blood Flow Distribution Provided by Diffuse Correlation Tomography during Bone Healing in a Murine Fracture Model.

Noninvasive monitoring of vascularization can potentially diagnose impaired bone healing earlier than current radiographic methods. In this study, a noncontact diffuse correlation tomography (DCT) technique was employed to measure longitudinal blood flow changes during bone healing in a murine femoral fracture model. The three-dimensional distribution of the relative blood flow was quantified from one day pre-fracture to 48 days post-fracture. For three mice, frequent DCT measurements were performed every other day for one week after fracture, and then weekly thereafter. A decrease in blood flow was observed in the bone fracture region at one day post-fracture, followed by a monotonic increase in blood flow beyond the pre-injury baseline until five to seven days post-fracture. For the remaining 12 mice, only weekly DCT measurements were performed. Data collected on a weekly basis show the blood flow for most mice was elevated above baseline during the first two post-fracture weeks, followed by a subsequent decrease. Torsional strength of the excised femurs was measured for all 15 mice after 7 weeks of healing. A metric based on the early blood flow changes shows a statistically significant difference between the high strength group and the low strength group.

A comprehensive characterization of myocardial and vascular phenotype in pediatric chronic kidney disease using cardiovascular magnetic resonance imaging.

BACKGROUND: Children with chronic kidney disease (CKD) have increased cardiovascular mortality. Identifying high-risk children who may benefit from further therapeutic intervention is difficult as cardiovascular abnormalities are subtle. Although transthoracic echocardiography may be used to detect sub-clinical abnormalities, it has well-known problems with reproducibility that limit its ability to accurately detect these changes. Cardiovascular magnetic resonance (CMR) is the reference standard method for assessing blood flow, cardiac structure and function. Furthermore, recent innovations enable the assessment of radial and longitudinal myocardial velocity, such that detection of sub-clinical changes is now possible. Thus, CMR may be ideal for cardiovascular assessment in pediatric CKD. This study aims to comprehensively assess cardiovascular function in pediatric CKD using CMR and determine its relationship with CKD severity. METHODS: A total of 120 children (40 mild, 40 moderate, 20 severe pre-dialysis CKD subjects and 20 healthy controls) underwent CMR with non-invasive blood pressure (BP) measurements. Cardiovascular parameters measured included systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular (LV) structure, ejection fraction (EF), cardiac timings, radial and longitudinal systolic and diastolic myocardial velocities. Between group comparisons and regression modelling were used to identify abnormalities in CKD and determine the effects of renal severity on myocardial function. RESULTS: The elevation in mean BP in CKD was accompanied by significantly increased afterload (SVR), without evidence of arterial stiffness (TAC) or increased fluid overload. Left ventricular volumes and global function were not abnormal in CKD. However, there was evidence of LV remodelling, prolongation of isovolumic relaxation time and reduced systolic and diastolic myocardial velocities. CONCLUSION: Abnormal cardiovascular function is evident in pre-dialysis pediatric CKD. Novel CMR biomarkers may be useful for the detection of subtle abnormalities in this population. Further studies are needed to determine to prognostic value of these biomarkers.

Overnight auto-adjusting continuous airway pressure + standard care compared with standard care alone in the prevention of morbidity in sickle cell disease phase II (POMS2b): study protocol for a randomised controlled trial.

BACKGROUND: In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life. METHODS/DESIGN: Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16-22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment. DISCUSSION: Altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events. TRIAL REGISTRATION: ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.

Magnetic Resonance-Augmented Cardiopulmonary Exercise Testing: Comprehensively Assessing Exercise Intolerance in Children With Cardiovascular Disease.

BACKGROUND: Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)-augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease. METHODS AND RESULTS: Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute; P=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute; P=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m2) and peak (5.3±1.2 L/min per m2) values compared with controls (resting 4.3±1.2 L/min per m2 and peak 6.6±1.2 L/min per m2) and PAH patients (resting 4.5±1.1 L/min per m2 and peak 5.9±1.1 L/min per m2). Both the PAH and tetralogy of Fallot patients had blunted exercise-induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL; P=0.005). CONCLUSIONS: MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference.

Non-Invasive Monitoring of Temporal and Spatial Blood Flow during Bone Graft Healing Using Diffuse Correlation Spectroscopy.

Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1-2 weeks for the autograft group, and at 2-4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts.

MR augmented cardiopulmonary exercise testing-a novel approach to assessing cardiovascular function.

The purposes of this study were: (1) to evaluate feasibility and acceptability of MRI augmented cardiopulmonary exercise testing (MR-CPET) in healthy adults and (2) to test whether peak values obtained at conventional and MR-CPET correlate and to demonstrate variation in peak oxygen consumption (VO2) relates to both peak cardiac output (CO) and peak oxygen extraction (ΔcO2). Seventeen healthy adults underwent CPET and MR-CPET using an MR compatible ergometer and CPET system customised for MR use. Continuous aortic flow measurement used a validated UNFOLD-SENSE spiral phase contrast magnetic resonance (PCMR) sequence.Fifteen of 17 volunteers completed exercise; exclusions were due to claustrophobia and inability to effectively master exercise technique. Measures of acceptability were lower but still satisfactory for MR-CPET.There were strong correlations between conventional and MR-CPET for peak VO2 (r = 0.94, p < 0.001); VCO2 (r = 0.87, p < 0.001) and VE (r = 0.88, p < 0.001).Multiple linear regression analysis demonstrated peak CO and ΔcO2 were independent predictors of peak VO2 measured during MR-CPET (ß = 0.73 and 0.38 p < 0.0001) and conventional CPET (ß = 0.78, 0.28 p < 0.0001).MR-CPET is feasible, acceptable and demonstrates physiology not apparent with conventional CPET. MR-CPET allows differentiation of the contributions of CO and ΔcO2 to variation in peak VO2. We believe that this will be useful in understanding the origin of reduced exercise capacity in cardiac disease.

Rifampicin pharmacokinetics in extreme prematurity to treat congenital tuberculosis.

Little evidence is available on the pharmacokinetics of antituberculous medication in premature infants. We report rifampicin (RMP) pharmacokinetics in an extremely premature, low-birthweight female infant born to a mother with known miliary tuberculosis. Intravenous RMP, isoniazid (INH), ciprofloxacin and amikacin were used, as the enteral route was not possible. Area under the curve calculations revealed low average RMP concentrations at doses of 5-10 mg/kg. We review the literature with regard to the dosing regimen and therapeutic drug levels of RMP and INH in premature infants and discuss issues of management. Evidence from this case suggests 10 mg/kg/day is the minimum dose required.