Arterial structure and function in children with inflammatory bowel disease.

Background and Aim: People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. Methods: We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. Results: We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. Conclusion: We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40 s, n = 11), moderate (∼2 min, n = 11) or extended (∼5 min, n = 12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P = 0.005) that persisted for 4 min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40 s), moderate (∼2 min) or extended (∼5 min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.

Carotid wave analysis in young adults with a history of adolescent anorexia nervosa: a case control study.

BACKGROUND: Anorexia nervosa (AN) is associated with abnormalities that may increase the risk of future cardiovascular disease. This study assessed the cardiovascular health of individuals who recovered from AN during adolescence by conducting wave power analysis. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospitals (N = 17) in Melbourne, Australia underwent ultrasound imaging of the right carotid artery. Wave power analysis was conducted to assess biomechanical interactions of the cardiovascular system. Patient measures were compared to healthy controls (N = 51). RESULTS: Eighty-eight percent of the former AN patients and controls were female, aged approximately 25 years, with a healthy body mass index. Mean carotid flow and pulsatility index were not different between groups. Carotid arterial strain and distensibility were lower, and the wave speed and beta stiffness index higher in the former AN patients. Characteristic impedance was not different nor were the forward and backward wave amplitudes. However, wave reflection indices (ratios of backward-to-forward compression wave area, and wave-related effect on pressure and hydraulic power) were 12-18% lower in the former AN patients (p < 0.05). CONCLUSIONS: Increased carotid artery stiffness and reduced wave reflection are evident in young adults who recovered from adolescent AN. This may relate to an adaptive process that helps to maintain or restore flow and characteristic impedance despite increased vessel stiffness, with this warranting future investigation.

Anorexia nervosa (AN) is an eating disorder which may cause permanent changes in the heart and blood vessels. Blood flow properties can provide information on the health of a patient's heart and blood vessels. In this study of young adults who recovered from adolescent AN, blood flow analysis revealed altered properties compared to controls who had never experienced an eating disorder. These alterations may help to maintain or restore blood flow despite unhealthy changes in the blood vessels themselves. Further investigation is needed to better understand how the heart and blood vessels change during and after AN to guide treatments and ongoing care. Regular assessment of the heart and blood vessels after AN recovery could identify and monitor possible health risks early.

Noninvasive pediatric blood pressure assessment: exploring the clinicians' perspective.

BACKGROUND: Obtaining accurate and reliable blood pressure (BP) readings in pediatric patients is challenging, given difficulties in adhering to measurement guidelines, limited device validation and variable patient cooperation. This study aimed to investigate clinicians' perspectives surrounding noninvasive pediatric BP assessment to identify opportunities for improvement in BP technology and clinical practice. METHOD: Based on an adapted version of the extended Technology Acceptance Model 2, semi-structured interviews were conducted with clinicians involved in noninvasive pediatric BP assessment in a major Australian children's hospital. Transcripts were analyzed thematically and guided by Technology Acceptance Model 2. RESULTS: Clinician responses ( n  = 20) revealed that poor patient tolerance of BP measurement resulting from excessive cuff inflation is a major hindrance to reliable pediatric BP assessment. Clinicians described low trust in BP readings from automated devices, often relating to poor patient tolerance to cuff inflation, thereby diminishing the clinical utility of these readings in informing treatment decisions. Auscultatory measurement was regarded as more trustworthy and better tolerated, but less convenient to perform as compared with oscillometric measurement. CONCLUSION: A dissonance exists between (1) low trust and clinical utility of the most common and easy-to-use BP measurement approach (automated devices), versus (2) higher trust and clinical utility, but efficiency and user-related impediments, for the auscultatory method. Based on our results, we have developed the Blood Pressure Acceptance Model, which can be used to explain and predict clinicians' acceptance of BP technology. Further work is needed to improve the tolerability and accuracy of automated BP devices in real-world pediatric settings.

Superiority of a Representative MRI Flow Waveform over Doppler Ultrasound for Aortic Wave Reflection Assessment in Children and Adolescents With/Without a History of Heart Disease.

Wave separation analysis (WSA) reveals the impact of forward- and backward-running waves on the arterial pressure pulse, but the calculations require a flow waveform. This study investigated (1) the variability of the ascending aortic flow waveform in children and adolescents with/without a childhood heart disease history (CHD); (2) the accuracy of WSA obtained with a representative flow waveform (RepFlow), compared with the triangulation method and published ultrasound-derived adult representative flow; (3) the impact of limitations in Doppler ultrasound on WSA; and (4) generalizability of results to adults with a history of CHD. Phase contrast MRI was performed in youth without (n = 45, Group 1, 10-19 years) and with CHD (n = 79, Group 2, 7-18 years), and adults with CHD history (n = 29, Group 3, 19-59 years). Segmented aortic cross-sectional area was used as a surrogate for the central pressure waveform in WSA. A subject-specific virtual Doppler ultrasound was performed on MRI data by extracting velocities from a sample volume. Time/amplitude-normalized ascending aortic flow waveforms were highly consistent amongst all groups. WSA with RepFlow therefore yielded errors < 10% in all groups for reflected wave magnitude and return time. Absolute errors were typically 1.5-3 times greater with other methods, including subject-specific (best-case/virtual) Doppler ultrasound, for which velocity profile skewing introduced waveform errors. Our data suggest that RepFlow is the optimal approach for pressure-only WSA in children and adolescents with/without CHD, as well as adults with CHD history, and may even be more accurate than subject-specific Doppler ultrasound in the ascending aorta.

From fetus to neonate: A review of cardiovascular modeling in early life.

Computational modeling has well-established utility in the study of cardiovascular hemodynamics, with applications in medical research and, increasingly, in clinical settings to improve the diagnosis and treatment of cardiovascular diseases. Most cardiovascular models developed to date have been of the adult circulatory system; however, the perinatal period is unique as cardiovascular physiology undergoes drastic changes from the fetal circulation, during the birth transition, and into neonatal life. There may also be further complications in this period: for example, preterm birth (defined as birth before 37 completed weeks of gestation) carries risks of short-term cardiovascular instability and is associated with increased lifetime cardiovascular risk. Here, we review computational models of the cardiovascular system in early life, their applications to date and potential improvements and enhancements of these models. We propose a roadmap for developing an open-source cardiovascular model that spans the fetal, perinatal, and postnatal periods. This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Congenital Diseases > Computational Models.

Long-term cardiovascular consequences of adolescent anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with maladaptive cardiovascular changes. This study investigated whether individuals who recovered from AN during adolescence experience long-term cardiovascular risk in early adulthood. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospital Eating Disorder Services in Melbourne, Australia underwent cardiovascular testing. Measurements were performed using an oscillometric device for blood pressure and pulse wave velocity, ultrasound for carotid wall structure/function, resting electrocardiogram for heart-rate variability, and the EndoPat 2000 (Itamar) system for endothelial function. Patient measures were compared to healthy controls and/or normal thresholds. RESULTS: Ninety-one percent of the former AN patients (N = 22) and controls (N = 66) were female, aged approximately 25 years, with a healthy body mass index. The mean time interval from AN recovery to participation was 7.4 years. Pulse wave velocity was lower in the former AN patients than controls. Carotid intima-media thickness was not different; however, carotid distensibility and compliance were lower, and the elastic modulus higher in the former AN patients. Greater vagal tone was observed and endothelial dysfunction was evident in 46% of the former patients. CONCLUSIONS: Young adults who recovered from adolescent AN exhibit persistent cardiovascular adaptations. Routine cardiovascular monitoring could manage potential disease risk. IMPACT: Cardiovascular complications are common in patients with anorexia nervosa (AN) and population studies have revealed that developmental adaptations in response to undernutrition have long-term consequences for cardiovascular health. In this study of young adults treated for AN during adolescence, there was evidence of increased carotid artery stiffness, reduced aortic stiffness, vagal hyperactivity, and endothelial dysfunction in early adulthood when compared to healthy controls. It is important to consider the cardiovascular health of patients with AN beyond achieving medical stability. Interventions that monitor cardiovascular health could minimise the burden of future cardiovascular disease.

Novel Centroid Method for Robust Evaluation of Return Time of Reflected Waves in the Systemic Arterial Network.

GOAL: A diastolic-to-systolic shift in the return time (RT) of backward waves to central arteries is expected with ageing. However, current methods of estimating RT-inflection point, zero crossing, and foot-depend on a single waveform feature and produce systolic RT throughout life. We propose a novel centroid method that accounts for the entire backward pressure waveform. We assess the accuracy of the various methods against a ground truth RT (GTRT) and their sensitivity to diastolic/systolic RT. METHODS: Linear wave tracking was implemented in a one-dimensional systemic arterial tree model and GTRT was calculated as the amplitude-weighted mean RT of backward waves at the ascending aorta. The sensitivity of the methods to diastolic/systolic RT was also assessed in ten sheep. A balloon catheter in the descending thoracic aorta generated a backward-running pulse that arrived at the ascending aorta at different times during diastole or systole, allowing the 'bulk' RT of the backward-running wave ensemble to be manipulated. RESULTS: Using a virtual cohort of 1200 patients, the centroid RT was closest to GTRT compared to the zero crossing, inflection point, and foot methods; mean differences (limits of agreement) were -8 (-47, 30), vs -42 (-136, 52), -78 (-305, 149), and -197 (-379,-15) ms, respectively. Furthermore, only the centroid method was sensitive to both diastolic and systolic RT; other methods were only sensitive to systolic RT. CONCLUSION: The centroid method had the highest accuracy and robustness in estimating RT. SIGNIFICANCE: This can provide insight into the diastolic-to-systolic shift in RT of backward waves with ageing.

Cardiac cycle: an observational/interventional study protocol to characterise cardiopulmonary function and evaluate a home-based cycling program in children and adolescents born extremely preterm.

INTRODUCTION: Extremely preterm (EP)/extremely low birthweight (ELBW) individuals may have an increased risk for adverse cardiovascular outcomes. Compared with term-born controls, these individuals have poorer lung function and reduced exercise capacity. Exercise interventions play an important role in reducing cardiopulmonary risk, however their use in EP/ELBW cohorts is unknown. This study, cardiac cycle, aims to characterise the cardiopulmonary system of children and adolescents who were born EP compared with those born at term, following acute and chronic exercise bouts. METHODS AND ANALYSIS: The single-centre study comprises a home-based exercise intervention, with physiological characterisation at baseline and after completion of the intervention. Fifty-eight children and adolescents aged 10-18 years who were born EP and/or with ELBW will be recruited. Cardiopulmonary function assessed via measures of blood pressure, arterial stiffness, capillary density, peak oxygen consumption, lung clearance indexes and ventricular structure/function, will be compared with 58 age-matched and sex-matched term-born controls at baseline and post intervention. The intervention will consist of a 10-week stationary cycling programme, utilising Zwift technology. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the Royal Children's Hospital Melbourne under HREC2019.053. Results will be disseminated via peer-reviewed journal regardless of outcome. TRIAL REGISTRATION NUMBER: 12619000539134, ANZCTR.

Optimized design of an arterial network model reproduces characteristic central and peripheral haemodynamic waveform features of young adults.

The arterial network in healthy young adults is thought to be structured to optimize wave reflection in the arterial system, producing an ascending aortic pressure waveform with three key features: early systolic peak, negative systolic augmentation and diastolic hump. One-dimensional computer models have provided significant insights into arterial haemodynamics, but no previous models of the young adult have exhibited these three features. Given that this issue was likely to be related to unrepresentative or non-optimized impedance properties of the model arterial networks, we developed a new 'YoungAdult' model that incorporated the following features: (i) a new and more accurate empirical equation for approximating wave speeds, based on area and relative distance to elastic-muscular arterial transition points; (ii) optimally matched arterial junctions; and (iii) an improved arterial network geometry that eliminated 'within-segment' taper (which causes wave reflection in conduit arteries) whilst establishing 'impedance-preserving' taper. These properties of the model led to wave reflection occurring predominantly at distal vascular beds, rather than in conduit arteries. The model predicted all three typical characteristics of an ascending aortic pressure waveform observed in young adults. When compared with non-invasively acquired pressure and velocity measurements (obtained via tonometry and Doppler ultrasound in seven young adults), the model was also shown to reproduce the typical waveform morphology observed in the radial, brachial, carotid, temporal, femoral and tibial arteries. The YoungAdult model provides support for the concept that the arterial tree impedance in healthy young adults is exquisitely optimized, and it provides an important baseline model for investigating cardiovascular changes in ageing and disease states. KEY POINTS: The origin of wave reflection in the arterial system is controversial, but reflection properties are likely to give rise to characteristic haemodynamic features in healthy young adults, including an early systolic peak, negative systolic augmentation and diastolic hump in the ascending aortic pressure waveform, and triphasic velocity profiles in peripheral arteries. Although computational modelling provides insights into arterial haemodynamics, no previous models have predicted all these features. An established arterial network model was optimized by incorporating the following features: (i) a more accurate representation of arterial wave speeds; (ii) precisely matched junctions; and (iii) impedance-preserving tapering, thereby minimizing wave reflection in conduit arteries in the forward direction. Comparison with in vivo data (n = 7 subjects) indicated that the characteristic waveform features in young adults were predicted accurately. Our findings strongly imply that a healthy young arterial system is structured to optimize wave reflection in the main conduit arteries and that reflection of forward waves occurs primarily in the vicinity of vascular beds.

Inter-arm differences in regional arterial stiffness and geometry lead to inter-arm systolic blood pressure differences: A modelling study.

An inter-arm systolic blood pressure difference (ISBPD), if substantial in magnitude (typically defined as ≥10 mmHg), is a potential cardiovascular risk factor in adults, due to its association with cardiovascular events/mortality. A substantial ISBPD occurs in approximately 10% of the adult population, and, although associations with vascular disease and elevated stiffness have been reported, the mechanisms underlying ISBPD remain unknown. The aim of this study was to investigate whether inter-arm differences in segmental pulse wave velocity, cross-sectional area, or vascular bed compliance/resistance could give rise to substantial differences in brachial pressures between arms; for example, due to differences in pulse wave transmission and reflection. Using an established one-dimensional model of the major systemic arteries, pulse wave velocity (PWV) was uniformly increased or decreased in arteries of 1) the supra-aortic region leading up to the arm, 2) the brachial region, 3) the forearm, and 4) all of these (entire arm pathway); for the left arm, right arm, and both arms. Cross-sectional area and vascular bed compliance and resistance of the arms were similarly varied. Inter-arm differences in segmental PWV and cross-sectional area (but not bilateral changes) led to associated substantial inter-arm SBP differences, which were observed with changes to brachial, forearm and/or entire arm pathways and were related to altered transmission of forward waves and amplitude/timing of reflected waves. Vascular bed compliance and resistance had minimal influence. We conclude that inter-arm differences in arterial stiffness and geometry may contribute to inter-arm systolic blood pressure differences, warranting further investigation.

Ventricular wall stress and wall shear stress homeostasis predicts cardiac remodeling during pregnancy: A modeling study.

Pregnancy is a unique and dynamic process characterized by significant changes in the maternal cardiovascular system that are required to satisfy the increased maternal and fetal metabolic demands. Profound structural and hemodynamic adaptations occur during healthy pregnancy that allows the mother to maintain healthy hemodynamics and provide an adequate uteroplacental blood circulation to ensure physiological fetal development. Investigating these adaptations is crucial for understanding the physiology of pregnancy and may provide important insights for the management of high-risk pregnancies. However, no previous modeling studies have investigated the maternal cardiac structural changes that occur during gestation. This study, therefore, had two aims. The first was to develop a lumped parameter model of the whole maternal circulation that is suitable for studying global hemodynamics and cardiac function at different stages of gestation. The second was to test the hypothesis that myofiber stress and wall shear stress homeostasis principles can be used to predict cardiac remodeling that occurs during normal pregnancy. Hemodynamics and cardiac variables predicted from simulations with and without controlled cardiac remodeling algorithms were compared and evaluated with reference clinical data. While both models reproduced the hemodynamic variations that arise in pregnancy, importantly, we show that the structural changes that occur with pregnancy could be predicted by assuming invariant homeostatic "target" values of myocardial wall stress and chamber wall shear stress.

Normative blood pressure response to exercise stress testing in children and adolescents.

OBJECTIVE: To describe normative values for blood pressure (BP) response to maximal exercise in children/adolescents undergoing a treadmill stress test. METHODS: From a retrospective analysis of medical records, patients who had undergone a Bruce protocol exercise stress test, with (1) normal cardiovascular system and (2) a body mass index percentile rank below 95% were included for analysis. Sex, age, height, weight, resting and peak heart rate, resting and peak systolic blood pressure (SBP), test duration, stage of Bruce protocol at termination, reason for undergoing the test and reason for termination of test were collected. Percentiles for exercise-induced changes in SBP were constructed by age and height for each sex with the use of quantile regression models. RESULTS: 648 patients with a median age of 12.4 years (range 6-18 years) were included. Typical indications for stress testing were investigation of potential rhythm abnormalities, syncope/dizziness and chest pain and were deemed healthy by an overseeing cardiologist. Mean test duration was 12.6±2.2 min. Reference percentiles for change in SBP by sex, age and height are presented. CONCLUSION: The presented reference percentiles for the change in SBP for normal children and adolescents will have utility for detecting abnormally high or low BP responses to exercise in these age groups.

Arterial Stiffness in Congenital Heart Disease.

Transposition of the great arteries (TGA), coarctation of the aorta (CoA), single ventricle (SV) and tetralogy of Fallot (ToF) are forms of congenital heart disease (CHD). Despite advances in treatment, cardiovascular and cerebrovascular complications in patients with repaired CHD occur earlier in life compared to healthy subjects. A factor that may contribute to this increased risk is elevated arterial stiffness. This systematic review provides a critical assessment of current evidence on central arterial stiffness in patients with CHD compared to healthy controls. In July 2020, Medline OVID, EMBASE and Scopus were searched using keywords and MeSH terms. Articles were included if they reported indices of aortic or carotid artery stiffness in patients with TGA, CoA, SV or ToF, and compared these to controls. Additional studies were screened from the reference lists of included articles. Of 1,033 studies identified, 43 were included in the final review. Most studies identified at least one index of central arterial stiffness, commonly in the aortic root or ascending aorta, that was higher in patients with CHD compared to controls. The commonly reported surrogate markers of stiffness were pulse wave velocity, aortic distensibility and the ß stiffness index. There was a relatively small number of original studies, and synthesis of data was limited by methodological heterogeneity, highlighting the need for further studies with standardised methods. However, there was consistent evidence of early and/or accelerated arterial stiffening in CHD patients, which may contribute to the increased risk of adverse cardiovascular and cerebrovascular events in this population.