Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.

BACKGROUND: The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood. METHODS: Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1). RESULTS: There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE. CONCLUSION: An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.

Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

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.

Bex-Nikaidoh operation and the impact of double root translocation on outcomes.

OBJECTIVES: The Bex-Nikaidoh operation can effectively relieve left ventricular outflow tract obstruction. However, if a conduit is used for right ventricular outflow tract reconstruction, a late reoperation can be anticipated. We examined the impact of double root translocation on outcomes. METHODS: We performed a retrospective single-centre study of patients who underwent aortic root translocation between 2006 and 2019. RESULTS: Aortic root translocation was performed in 23 patients at a median age of 1.6 years [interquartile range (IQR) 0.9-2.5]. Concomitant repairs were done in 52.2% of patients (12/23) including the Senning atrial switch in 34.8% (8/23). The right ventricular outflow tract was reconstructed with valved conduits in 39.1% (9/23), direct anastomoses in 4.35% (1/23) and pulmonary autografts in 56.5% of patients (13/23). Aortic cross-clamp time was significantly longer in patients with double root translocation [308 min (IQR 270-259) vs 209 min (IQR 179-281), P = 0.02]; 2 patients in this group required temporary mechanical circulatory support. There were no early deaths. Median follow-up time was 7.5 years (IQR 3.3-10.5). The estimated 10-year survival was 90% [95% confidence interval (CI): 47.3%, 98.5%]. There was no recurrent left ventricular outflow tract obstruction. Freedom from any reoperation was 64.2% (95% CI: 40.8%, 80.3%) at 3 years and 44.5% (95% CI: 21.2%, 65.5%) at 6 years. The main indication for late reoperation was conduit degeneration. Freedom from a right ventricular outflow tract reoperation was significantly higher, and the number of reoperations per patient was lower when a double root translocation had been performed (P = 0.03). CONCLUSIONS: The Bex-Nikaidoh operation effectively relieved left ventricular outflow tract obstruction. A double root translocation further increased procedural complexity but was associated with better mid-term freedom from a right ventricular outflow tract reoperation. It should be considered in suitable patients.

Potential benefits of prenatal diagnosis of TGA in Australia may be outweighed by the adverse effects of earlier delivery: likely causation and potential solutions.

OBJECTIVE: Prenatal diagnosis of transposition of great arteries (TGA) is expected to improve postoperative outcomes after neonatal arterial switch operation (ASO); however, published reports give conflicting results. We aimed to determine the association between prenatal diagnosis and early postoperative outcomes after neonatal ASO. METHODS: Cohort study involving 243 newborns who underwent ASO (70% prenatally diagnosed) between 2010 and 2019. Multivariable regression was used to determine the association between prenatal diagnosis and (a) birth characteristics and (b) postoperative outcomes. RESULTS: Gestational age and birthweight centile were lower and small-for-gestational-age more common (11.8% vs 1.4%) in those diagnosed prenatally. Among births which followed labour induction or prelabour caesarean, prenatal diagnosis was associated with earlier gestation at birth (mean (SD), 38.5 (1.6) vs 39.2 (1.4), p=0.01). Among births which followed spontaneous labour, prenatal diagnosis was associated with earlier gestation at labour onset (38.2 (1.8) vs 39.2 (1.4), p=0.01). Prenatal diagnosis was associated with longer postoperative mechanical ventilation (incidence rate ratio 1.74, 95% CI 1.37 to 2.21), intensive care (1.70, 1.31 to 2.21) and hospital length of stay (1.37, 1.14 to 1.66) after ASO. Gestational age mediated up to 60% of the effect of prenatal diagnosis on postoperative outcomes. CONCLUSION: Among newborns undergoing ASO for TGA, prenatal diagnosis is associated with poorer early postoperative outcomes. In addition to minimising iatrogenic factors (such as planned births) resulting in earlier births, evaluation of other dynamics following a prenatal diagnosis which may result in poor fetal growth and earlier onset of spontaneous labour is important.

Safety and feasibility of adjunct autologous cord blood stem cell therapy during the Norwood heart operation.

BACKGROUND: We conducted this phase I, open-label safety and feasibility trial of autologous cord blood (CB) stem cell (CBSC) therapy via a novel blood cardioplegia-based intracoronary infusion technique during the Norwood procedure in neonates with an antenatal diagnosis of hypoplastic left heart syndrome (HLHS). CBSC therapy may support early cardiac remodeling with enhancement of right ventricle (RV) function during the critical interstage period. METHODS: Clinical grade CB mononucleated cells (CBMNCs) were processed to NetCord-FACT International Standards. To maximize yield, CBSCs were not isolated from CBMNCs. CBMNCs were stored at 4 °C (no cryopreservation) for use within 3 days and delivered after each cardioplegia dose (4 × 15 mL). RESULTS: Of 16 patients with antenatal diagnosis, 13 were recruited; of these 13 patients, 3 were not treated due to placental abruption (n = 1) or conditions delaying the Norwood for >4 days (n = 2) and 10 received 644.9 ± 134 × 106 CBMNCs, representing 1.5 ± 1.1 × 106 (CD34+) CBSCs. Interstage mortality was 30% (n = 3; on days 7, 25, and 62). None of the 36 serious adverse events (53% linked to 3 deaths) were related to CBMNC therapy. Cardiac magnetic resonance imaging before stage 2 (n = 5) found an RV mass index comparable to that in an exact-matched historical cohort (n = 22), with a mean RV ejection fraction of 66.2 ± 4.5% and mean indexed stroke volume of 47.4 ± 6.2 mL/m2 versus 53.5 ± 11.6% and 37.2 ± 10.3 mL/m2, respectively. All 7 survivors completed stage 2 and are alive with normal RV function (6 with ≤mild and 1 with moderate tricuspid regurgitation). CONCLUSIONS: This trial demonstrated that autologous CBMNCs delivered in large numbers without prior cryopreservation via a novel intracoronary infusion technique at cardioplegic arrest during Norwood palliation on days 2 to 3 of life is feasible and safe.

Numerical simulation of the cavopulmonary connection flow with conduit stenoses of varying configurations.

The circulation in the total cavopulmonary connection (TCPC) is a low-energy system which operation and efficiency are subjected to multiple factors. Some retrospective studies report that the abnormal narrowing of vessels in the system, i.e. stenosis, is one of the most dangerous geometric factors which can result in heart failure. In the present study, the effect of varying extracardiac conduit (ECC) stenosis on the hemodynamics in a surrogate TCPC model is investigated using high-fidelity numerical simulations. The efficiency of the surrogate TCPC model was quantified according to the power loss, relative perfusion in lungs and the percentage of conduit surface area with abnormally low and high wall shear stress for venous flow. Additionally, the impact of respiration and asymmetry in the stenosis geometry to the system was examined. The results show that the flow in the TCPC model exhibits pronounced unsteadiness even under the steady initial boundary conditions, while the uneven pulmonary flow distribution and the presence of the ECC stenosis amplify the chaotic nature of the flow. Energy efficiency of the system is shown to strongly correlate with amount of vortical structures in the model and their range of scales. Finally, the study demonstrates that the presence of respiration in the model adds to perturbations in the flow which causes increase in the power loss. Results obtained in the study provide valuable insights on how the ECC stenosis effect the flow in the surrogate TCPC model under different flow conditions.

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.

Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm.

Background: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. Methods: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. Findings: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. Interpretation: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic health may provide a window for intervention. Funding: National Health and Medical Research Council of Australia.

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.

Acute rheumatic fever and rheumatic heart disease in children and adolescents in Victoria, Australia.

AIM: To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia. METHODS: A retrospective audit was undertaken of children and adolescents with ARF and RHD attending the Royal Children's and Monash Children's Hospitals in Victoria, Australia between 2010 and 2019. Potential cases were identified by searching multiple sources for relevant ICD-10-AM codes and keywords, then reviewed manually. For confirmed cases, we collected data on patient demographics, clinical features, comorbidities and management. RESULTS: Of 179 participants included, there were 108 Victorian residents and 71 non-Victorian residents. 126 had at least one episode of ARF during the study period and 128 were diagnosed with RHD. In the Victorian resident group, the overall incidence of ARF was 0.8 per 100 000 5-14 year olds. This incidence was higher in Victorian Aboriginal and/or Torres Strait Islander (3.8 per 100 000) and Pacific Islander (32.1 per 100 000) sub-populations. Of 83 Victorian residents who had an ARF episode, 11 (13%) had a recurrence. Most Victorian residents with RHD had mixed aortic and mitral valve pathology (69.4%) and moderate to severe disease (61.9%). Most non-Victorian residents were Aboriginal and/or Torres Strait Islander people (80.3%) and were commonly transferred for tertiary or surgical management of RHD (83.1%). CONCLUSIONS: ARF and RHD continue to affect the health of significant numbers of children and adolescents living in Victoria, including severe and recurrent disease. Specialised services and a register-based control program may help to prevent complications and premature death.

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.

Preserved Left Ventricular Function despite Myocardial Fibrosis and Myopathy in the Dystrophin-Deficient D2.B10-Dmd mdx /J Mouse.

Duchenne muscular dystrophy involves an absence of dystrophin, a cytoskeletal protein which supports cell structural integrity and scaffolding for signalling molecules in myocytes. Affected individuals experience progressive muscle degeneration that leads to irreversible loss of ambulation and respiratory diaphragm function. Although clinical management has greatly advanced, heart failure due to myocardial cell loss and fibrosis remains the major cause of death. We examined cardiac morphology and function in D2.B10-Dmd mdx /J (D2-mdx) mice, a relatively new mouse model of muscular dystrophy, which we compared to their wild-type background DBA/2J mice (DBA/2). We also tested whether drug treatment with a specific blocker of mitochondrial permeability transition pore opening (Debio-025), or ACE inhibition (Perindopril), had any effect on dystrophy-related cardiomyopathy. D2-mdx mice were treated for six weeks with Vehicle control, Debio-025 (20 mg/kg/day), Perindopril (2 mg/kg/day), or a combination (n = 8/group). At 18 weeks, compared to DBA/2, D2-mdx hearts displayed greater ventricular collagen, lower cell density, greater cell diameter, and greater protein expression levels of IL-6, TLR4, BAX/Bcl2, caspase-3, PGC-1α, and notably monoamine oxidases A and B. Remarkably, these adaptations in D2-mdx mice were associated with preserved resting left ventricular function similar to DBA/2 mice. Compared to vehicle, although Perindopril partly attenuated the increase in heart weight and collagen at 18 weeks, the drug treatments had no marked impact on dystrophic cardiomyopathy.

Poorer Self-Reported Physical Health and Higher Anxiety Trait in Young Adults With Previous Coarctation Repair.

BACKGROUND: Little is known about the impact of a coarctation repair on the functional outcomes of young adults. This study aimed to determine (1) the functional and mental health status in young adults with previous coarctation repair, and (2) the impact of late hypertension on their quality of life. METHODS: A cross-sectional study using validated self-reported questionnaires (Short Form 36 version 2 [SF-36v2], Beck Depression Inventory [BDI], and State-Trait Anxiety Inventory [STAI]) was performed in 54 patients aged 15-47 years with previous paediatric coarctation repair. Questionnaire scores were compared to healthy age- and gender-matched controls. Patients' previously published 24-hour blood pressure monitoring results were included. RESULTS: Late hypertension was present in 64% (34/54) at a mean of 29±8 years after coarctation repair. SF-36v2 mean physical component summary score was significantly lower in coarctation patients compared with controls (53.1±6.8 vs 56.0±4.7, p=0.02), but there was no significant difference in mean mental component summary score (p=0.2). SF-36v2 mean role emotional score tended to be associated with 10 mmHg increases in mean 24-hour systolic blood pressure (regression coefficient 4.3 p=0.06). STAI mean trait anxiety score tended to be higher in coarctation patients compared with controls (36.6±9.0 vs 33.5±7.8, p=0.06). There was no significant difference in BDI scores between patients and controls. CONCLUSIONS: Young adults with previous coarctation repair report poorer physical health and tended towards higher anxiety trait compared to healthy controls. Strategies to improve self-reported physical health and anxiety should be explored. Long-term assessment of quality of life outcomes in coarctation patients is warranted.

S-Nitrosoglutathione Limits Apoptosis and Reduces Pulmonary Vascular Dysfunction After Bypass.

BACKGROUND: During hypoxia or acidosis, S-nitrosoglutathione (GSNO) has been shown to protect the cardiomyocyte from ischemia-reperfusion injury. In a randomized double-blinded control study of a porcine model of paediatric cardiopulmonary bypass (CPB), we aimed to evaluate the effects of 2 different doses (low and high) of GSNO. METHODS: Pigs weighing 15-20 kg were exposed to CPB with 1 hour of aortic cross-clamp. Prior to and during CPB, animals were randomized to receive low-dose (up to 20 nmol/kg/min) GSNO (n = 8), high-dose (up to 60 nmol/kg/min) GSNO (n = 6), or normal saline (n = 7). Standard cardiac intensive care management was continued for 4 hours post-bypass. RESULTS: There was a reduction in myocyte apoptosis after administration of GSNO (P = .04) with no difference between low- and high-dose GSNO. The low-dose GSNO group had lower pulmonary vascular resistance post-CPB (P = .007). Mitochondrial complex I activity normalized to citrate synthase activity was higher after GSNO compared with control (P = .02), with no difference between low- and high-dose GSNO. CONCLUSIONS: In a porcine model of CPB, intravenous administration of GSNO limits myocardial apoptosis through preservation of mitochondrial complex I activity, and improves pulmonary vascular resistance. There appears to be a dose-dependent effect to this protection.

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.