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To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia.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.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%).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.

OBJECTIVE. The purpose of this systematic review was to evaluate the evidence for the effectiveness of parent-mediated interventions on occupational performance of children with autism spectrum disorder (ASD). METHOD. We conducted a search of academic databases using terms such as autism spectrum disorder, parent, caregiver, and intervention. Five hundred eighty-two articles were reviewed, and 109 were selected for full-text review. The final analysis included 13 articles. RESULTS. Strong evidence was found for the efficacy of parent-mediated intervention for increasing child joint attention. Moderate evidence was found for the improvement of language scores, expressive language, nonverbal communication, initiation and response to interaction, behavior, play, adaptive functioning, ASD symptoms, and social communication. CONCLUSION. This systematic review suggests that parent-mediated interventions for children with ASD can improve various aspects of communication and ASD symptoms, with emerging support for occupational performance. Occupational therapy practitioners are well suited to facilitate these interventions to support families with children with autism.

Although early antiretroviral therapy (ART) reduces HIV-related mortality in children by up to 75%, almost half of HIV-positive children younger than 1 year old in Swaziland do not initiate ART. This study was conducted to identify barriers to early ART initiation among HIV-positive infants. This was a case-control study among HIV-positive infants, aged 2 to 18 months, who either did not initiate ART (cases), or initiated ART (controls), during 18 months after testing. Multivariable logistic regression showed that infants who visited the clinic every month, or every 2 months, were 5.78 and 6.20 times more likely to initiate ART than those who visited less often (OR 5.78, 95% CI 1.82–18.33 and OR 6.20, 95% CI 1.30–29.60 respectively). Children who lived ≤30 and 31–60 minutes from the nearest clinic were 84% and 79% less likely respectively to initiate ART (OR 0.16, 95% CI 0.03–0.78 and OR 0.21, 95% CI 0.04–0.98) compared with those who lived more than 60 minutes away. Children who received immunisation after 6 months were 22.59 times more likely to initiate ART (OR 22.59, 95% CI 7.00–21.72) than those who did not. Infants of caregivers who had excellent or good relationships with their healthcare provider were 4.32 times more likely to initiate ART (OR 4.32, 95% CI 1.01–18.59) than those of caregivers who had average or poor relationships with healthcare providers. The significant predictors of ART initiation identified in this study should be regarded as priority areas for intervention among HIV-positive women in Swaziland.Keywords: ART initiation, clinic visits, HIV, HIV-positive infants, healthcare providers, immunisation, predictors

Objectives The study sought to evaluate the late outcomes of a policy of transatrial repair delayed beyond the neonatal period. Background Long-term outcomes of transatrial repair of tetralogy of Fallot are unknown. Methods The records of 675 consecutive patients undergoing a transatrial repair of tetralogy of Fallot between 1980 and 2005 were reviewed, their follow-up updated and survival confirmed from national death registries. One-third (220 of 675) had undergone previous palliation. Median age at repair was 2 years in the first 8 years, and 1 year from 1988 onward. A transannular incision was performed in 75% of cases and autologous pericardium was the material used to patch this incision in 92% of cases. Results There were 7 hospital deaths (1%). Eight patients died during follow-up (2 sudden unexpected and 6 noncardiac deaths). Mean follow-up was 11.7 ± 6.3 years. Twenty-five years' survival was 97% (95% confidence interval [CI]: 95% to 98%). Twenty-five years' freedom from implantation of a valved conduit was 84.6% (95% CI: 77.8% to 89.5%). By multivariable analysis, prior palliation and younger age at repair were predictive of implantation of a valved conduit (hazard ratio: 2.4, 95% CI: 1.3 to 4.6, p = 0.008; hazard ratio: 0.70, 95% CI: 0.50 to 0.96, p = 0.03, respectively). Conclusions During long-term follow-up, transatrial repair of tetralogy of Fallot was associated with a minimal risk of sudden death and low rate of reintervention for right ventricular dilation and residual outflow tract obstruction.

Aims Adenosine stress computed tomography myocardial perfusion imaging (CTP) is an emerging non-invasive method for detecting myocardial ischaemia. Its value when compared with fractional flow reserve (FFR), a highly accurate index of ischaemia, is unknown. Our aim was to determine the diagnostic accuracy of CTP and its incremental value when used with computed tomography coronary angiography (CTA) for detecting ischaemia compared with FFR. Methods and results Forty-two patients (126 vessel territories), who had at least one ≥50% angiographic stenosis on invasive angiography considered for non-urgent revascularization, were included and underwent FFR and CT assessment, including CTP, delayed contrast enhancement scan and CTA all acquired using 320-detector row CT, and prospective ECG gating. Fractional flow reserve was determined in 86 territories subtended by vessels with ≥50% stenosis upon visual assessment. Fractional flow reserve ≤0.8 was considered to indicate significant ischaemia. Computed tomography myocardial perfusion imaging correctly identified 31/41 (76%) ischaemic territories and 38/45 (84%) non-ischaemic territories. Per-vessel territory sensitivity, specificity, positive, and negative predictive values of CTP were 76, 84, 82, and 79%, respectively. The combination of a ≥50% stenosis on CTA and perfusion defect on CTP was 98% specific for ischaemia, while the presence of

Date Presented 4/21/2018 Findings from this study provide preliminary confirmation of the construct validity of the Feeding Assessment for Children With Autism, providing researchers and clinicians with a comprehensive and psychometrically sound assessment tool to assess the unique feeding challenges of children with autism. Primary Author and Speaker: Karla Ausderau Additional Authors and Speakers: Muhammad Al-Heizan, Caitlin Dammann, Sarah Hope, Colleen Althoff, Katelyn Dorrance, Molly Hamre, Brittany St. John

We sought to evaluate the diagnostic accuracy of noninvasive coronary angiography using 320-detector row computed tomography, which provides 16-cm craniocaudal coverage in 350 ms and can image the entire coronary tree in a single heartbeat, representing a significant advance from previous-generation scanners. We evaluated 63 consecutive patients who underwent 320-detector row computed tomography and invasive coronary angiography for the investigation of suspected coronary artery disease. Patients with known coronary artery disease were excluded. Computed tomographic (CT) studies were assessed by 2 independent observers blinded to results of invasive coronary angiography. A single observer unaware of CT results assessed invasive coronary angiographic images quantitatively. All available coronary segments were included in the analysis, regardless of size or image quality. Lesions with >50% diameter stenoses were considered significant. Mean heart rate was 63 ± 7 beats/min, with 6 patients (10%) in atrial fibrillation during image acquisition. Thirty-three patients (52%) and 70 of 973 segments (7%) had significant coronary stenoses on invasive coronary angiogram. Seventeen segments (2%) were nondiagnostic on computed tomogram and were assumed to contain significant stenoses on an "intention-to-diagnose" analysis. Sensitivity, specificity, and positive and negative predictive values of computed tomography for detecting significant stenoses were 94%, 87%, 88%, and 93%, respectively, by patient (n = 63), 89%, 95%, 82%, and 97%, respectively, by artery (n = 260), and 87%, 97%, 73%, and 99%, respectively, by segment (n = 973). In conclusion, noninvasive 320-detector row CT coronary angiography provides high diagnostic accuracy across all coronary segments, regardless of size, cardiac rhythm, or image quality.

Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. Twenty children aged 3-17 yr referred for investigation of sleep-disordered breathing (10 DS, and 10 OSA controls) matched for age and obstructive apnea/hypopnea index underwent routine overnight polysomnography. In addition, 10 nonsnoring controls from the general community were studied. Beat-by-beat HR was analyzed from 15 s pre- to 15 s post-spontaneous arousals and compared between groups using two-way ANOVA with repeated measures. Data are presented as means + or - SE. For both rapid eye movement (REM) and non-REM (NREM), arousals were associated with a significant increase in HR in all groups (peak response NREM: DS, 118 + or - 1% at 3 s; OSA controls, 124 + or - 2% at 4 s; and healthy controls, 125 + or - 3% at 4 s; and peak response REM: DS, 116 + or - 2% at 4 s; OSA controls, 123 + or - 3% at 4 s; and healthy controls, 125 + or - 4 at 4 s; P0.001 for all). Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.

Continuing reports in the literature regarding the potential of central pulse wave analysis in clinical practice and a recent consensus statement demonstrate the increasing interest in the clinical application of arterial transfer functions. A number of misconceptions, however, persist regarding their use. In spite of ongoing controversy, there are considerable published data that would permit users to assess the validity and accuracy of the technique. We provide a comprehensive review of available data, all of which appear to be clear and consistent. The technique does not permit accurate reconstruction of central waveforms from entirely non-invasively acquired data. We should move on from the misconception that what is being studied is central aortic data when transfer functions are applied non-invasively, and accept that it is radial waveform data that have been passed through a single mathematical transformation. We have a readily applicable, non-invasive and reproducible technique for acquiring radial waveform data, with or without the application of a generalized arterial transfer function. We must explore the potential of this technique in an analytical manner, and without untenable preconceptions, if we are to learn the secrets that it may yet reveal.

1. Arteries become stiffer with increasing age and various disease states. A complete description of arterial mechanical properties in vivo is not possible, although a number of methods have been used. 2. Detailed discussion in the present review is limited to pulse wave velocity and estimates of central waveform morphology derived by the application of a generalized arterial transfer function. 3. Many drugs affect these parameters, either increasing or decreasing apparent stiffness. However, the extent to which changes reflect changes in blood pressure rather than more fundamental vessel wall properties remains unclear. Similarly, it is as yet unknown whether determining the need for, or assessing the effectiveness of, drug treatment by the assessment of arterial mechanical properties will offer any advantage and the usefulness of these techniques as routine clinical tools remains to be established.

Nervous wreck (Nwk) is a conserved F-BAR protein that attenuates synaptic growth and promotes synaptic function in Drosophila. In an effort to understand how Nwk carries out its dual roles, we isolated interacting proteins using mass spectrometry. We report a conserved interaction between Nwk proteins and BAR-SH3 sorting nexins, a family of membrane-binding proteins implicated in diverse intracellular trafficking processes. In mammalian cells, BAR-SH3 sorting nexins induce plasma membrane tubules that localize NWK2, consistent with a possible functional interaction during the early stages of endocytic trafficking. To study the role of BAR-SH3 sorting nexins in vivo, we took advantage of the lack of genetic redundancy in Drosophila and employed CRISPR-based genome engineering to generate null and endogenously tagged alleles of SH3PX1. SH3PX1 localizes to neuromuscular junctions where it regulates synaptic ultrastructure, but not synapse number. Consistently, neurotransmitter release was significantly diminished in SH3PX1 mutants. Double-mutant and tissue-specific-rescue experiments indicate that SH3PX1 promotes neurotransmitter release presynaptically, at least in part through functional interactions with Nwk, and might act to distinguish the roles of Nwk in regulating synaptic growth and function., Summary: A loss-of-function study of the SNX9, SNX18 and SNX33 homolog SH3PX1 in Drosophila reveals a new role in the development of presynaptic active zones and regulation of neurotransmitter release.

During mammalian follicle development, a fluid-filled antrum develops in the avascular centre of the follicle. We investigated the hypothesis that follicular fluid contains osmotically-active molecules, sufficiently large so as to not freely escape the follicular fluid. Such molecules could generate an osmotic differential and thus recruit fluid from the surrounding vascularised stroma into the antrum. Follicular fluid was collected from bovine follicles classified histologically as healthy (n= 4 pools) or atretic (n= 4 pools). Dialysis of the follicular fluid at 300 kDa or 500 kDa resulted in a reduction in colloid osmotic pressure of 35% and 60%, respectively, in fluid from healthy follicles and 29% and 80% from atretic follicles. Digestion of follicular fluid withStreptomyceshyaluronidase, chondroitinase ABC or DNase 1 followed by dialysis resulted in reductions in osmotic pressure of 43%, 53% and 43% respectively for fluids from healthy follicles and 34%, 20% and 31% for atretic follicles. Digestion with collagenase I, proteinase K, heparanase 1 or keratanase had no significant effect on the osmotic pressure of follicular fluid of healthy follicles. Ion exchange and size exclusion, Western blotting and ELISA identified the proteoglycans versican and inter-alpha trypsin inhibitor and the glycosaminoglycan hyaluronan in follicular fluid. We conclude that these molecules or aggregates of them are of sufficient size to contribute to the osmotic potential of follicular fluid and thus recruit fluid into the follicular antrum. DNA may also contribute but it is probably not a component that is regulated for this role.

Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61±8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3–30 μg/min) and SNP (sodium nitroprusside; 0.3–3 μg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanolrich cocoa does not modify vascular function in patients with established CAD.

The role of cellular adhesion molecules in the patho­genesis of atherosclerosis has now been clearly demonstrated. Plasma levels of adhesion molecules, which have been shed from the cell surface, have also been associated with the presence of clinical atherosclerotic disease, cardiovascular risk factors and acute coronary syndromes. However, there is little consensus in the literature, including between the large well-designed population studies. This may be explained either by unrecognized confounding factors or, alternatively, by the unpredictable relationship between cell surface expression and activity of cellular adhesion molecules and their shedding into the plasma under different circumstances. Probably for the latter reasons, there is at present little evidence that the measurement of circulating adhesion molecules is likely to offer any additional benefit for individual patients above the assessment of conventional cardiovascular risk factors in the assessment of either the extent of, or future risk from, cardiovascular disease. (Intern Med J 2003; 33: 450−462)

Atherosclerosis is now recognized to be an inflammatory disease, and several inflammatory markers have been shown to be associated with both the presence and future risk of symptomatic cardiovascular disease. Cellular adhesion molecules, particularly members of the selectin family and immunoglobulin superfamily, are intimately involved in the recruitment of leucocytes to sites of inflammation, including developing atherosclerotic lesions. Their role in the pathogenesis of atherosclerosis has been clearly demonstrated using knockout mice models. Plasma levels of adhesion molecules, which have been shed from the cell surface, have been associated with the presence of clinical atherosclerotic disease, although published studies differ in their findings. This limited consensus in the literature may be explained either by unrecognized confounding factors, or perhaps by the unpredictable relationship between cell surface expression and activity of cellular adhesion molecules and their shedding into the plasma. While cell surface activity of adhesion molecules appears critical in the development of atherosclerotic lesions, the measurement of plasma levels of soluble adhesion molecules may offer little additional benefit for individual patients in the prediction of the extent of atherosclerotic disease above the assessment of conventional cardiovascular risk factors.

Nervous wreck (Nwk) is a conserved F-BAR protein that attenuates synaptic growth and promotes synaptic function in Drosophila. In an effort to understand how Nwk carries out its dual roles, we isolated interacting proteins through mass spectrometry. We report a conserved interaction between Nwk proteins and BAR-SH3 Sorting nexins, a family of membrane-binding proteins implicated in diverse intracellular trafficking processes. In mammalian cells, BAR-SH3 Sorting nexins induce plasma membrane tubules that colocalize Nwk2, consistent with a possible functional interaction during early stages of endocytic trafficking. To study the role of BAR-SH3 Sorting nexins in vivo, we took advantage of the lack of genetic redundancy in Drosophila and employed CRISPR-based genome engineering to generate null and endogenously tagged alleles of SH3PX1. SH3PX1 localizes to neuromuscular junctions where it regulates synaptic ultrastructure, but not synapse number. Consistently, neurotransmitter release is significantly diminished in SH3PX1 mutants. Double mutant and tissue-specific rescue experiments indicate that SH3PX1 promotes neurotransmitter release presynaptically, at least in part through functional interactions with Nwk, and may act to distinguish Nwk's roles in regulating synaptic growth and function.

Arterial transfer functions have been promoted for the derivation of central aortic waveform characteristics not usually accessible noninvasively, but possibly of prognostic significance. The utility of generalized rather than gender-specific transfer functions has not been assessed. Invasive central aortic and noninvasive radial (Millar Mikro-tip tonometer) blood pressure waveforms were recorded simultaneously in 78 subjects (61 male and 17 female). Average transfer functions were obtained for the whole group and for each gender by two methods. Reverse transformation was performed with the use of each transfer function. Measured aortic waveform parameters were compared with those derived using average, gender-appropriate, and gender-inappropriate transfer functions. Differences in central waveform characteristics were demonstrated between men and women. Derived waveform parameters were significantly different from measured values [e.g., subendocardial viability index and augmentation index ( P < 0.001)]. A gender-appropriate transfer function significantly improved the derivation of some parameters, including systolic pressure and systolic and diastolic pressure time integrals ( P < 0.05). Generalized arterial transfer functions may not be universally applicable across all waveform parameters of potential interest, and gender-specific transfer functions may be more appropriate.

Background— The life expectancy of patients undergoing a Fontan procedure is unknown. Methods and Results— Follow-up of all 1006 survivors of the 1089 patients who underwent a Fontan procedure in Australia and New Zealand was obtained from a binational population-based registry including all pediatric and adult cardiac centers. There were 203 atriopulmonary connections (AP; 1975–1995), 271 lateral tunnels (1988–2006), and 532 extracardiac conduits (1997–2010). The proportion with hypoplastic left heart syndrome increased from 1/173 (1%) before 1990 to 80/500 (16%) after 2000. Survival at 10 years was 89% (84%–93%) for AP and 97% (95% confidence interval [CI], 94%–99%) for lateral tunnels and extracardiac conduits. The longest survival estimate was 76% (95% CI, 67%–82%) at 25 years for AP. AP independently predicted worse survival compared with extracardiac conduits (hazard ratio, 6.2; P P Conclusions— The long-term survival of the Australia and New Zealand Fontan population is excellent. Patients with an AP Fontan experience survival of 76% at 25 years. Technical modifications have further improved survival. Patients with hypoplastic left heart syndrome are at higher risk of failure. Large, comprehensive registries such as this will further improve our understanding of late outcomes after the Fontan procedure.

Hypertrophic obstructive cardiomyopathy is a complex disorder with serious clinical implications. Percutaneous transluminal septal myocardial ablation is a promising new addition to existing therapies for this condition. It is a catheter-based approach that involves instilling alcohol into the septal branches of the left anterior descending artery to induce a ‘controlled’ septal myocardial infarct. The result is a decrease in thickness of the hypertrophied interventricular septum and a reduction of the left ventricular outflow tract gradient. To date, the results from several series have been promising, with improvements in haemodynamic and clinical parameters without prohibitive complication rates. In this article, the indications, technique and outcomes of this procedure are reviewed.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) occurs at an increased incidence in children with Down Syndrome (DS) compared to the general pediatric population. We hypothesized that, compared with typically developing (TD) children with SDB, children with DS have a reduced cardiovascular response with delayed reoxygenation after obstructive respiratory events, and reduced sympathetic drive, providing a potential explanation for their increased risk of pulmonary hypertension. DESIGN: Beat-by-beat heart rate (HR) was analyzed over the course of obstructive events (pre, early, late, post-event) and compared between groups. Also compared were the time for oxygen resaturation post-event and overnight urinary catecholamines. SETTING: Pediatric sleep laboratory. PATIENTS: Sixty-four children aged 2-17 y referred for investigation of SDB (32 DS; 32 TD) matched for age and obstructive apnea/hypopnea index. MEASUREMENT AND RESULTS: Children underwent overnight polysomnography with overnight urine collection. Compared to TD children, those with DS had significantly reduced HR changes post-event during NREM (DS: 21.4% ± 1.8%, TD: 26.6% ± 1.6%, change from late to post-event, P < 0.05). The time to resaturation post-event was significantly increased in the DS group (P < 0.05 for both NREM and REM sleep). Children with DS had significantly reduced overnight urinary noradrenaline (P < 0.01), adrenaline (P < 0.05) and dopamine levels (P < 0.01) compared with TD children. CONCLUSION: Children with DS and SDB exhibit a compromised acute cardio-respiratory response and dampened sympathetic response to SDB compared with TD children with SDB. These data may reflect autonomic dysfunction in children with DS that may place them at increased risk for cardiovascular complications such as pulmonary hypertension.

Endothelial cells derived from induced pluripotent stem cells (iPSC-ECs) have been shown to promote angiogenesis in vivo. Recently, an alternative method of generating endothelial cells has been developed, by directly differentiating fibroblasts into endothelial cells (iECs), bypassing the pluripotent intermediate. Here we compared survival, engraftment and pro-angiogenic potential of iECs versus iPSC-ECs in a mouse model of hindlimb ischaemia. Human iPSC-ECs and iECs were transduced with a firefly luciferase and green fluorescent protein reporter for bioluminescence imaging. They exhibited endothelial behavior in vitro, assessed by migration towards VEGF, uptake of acetylated-LDL and tubule formation on matrigel. NODSCID mice (n=7-9) underwent unilateral femoral artery ligation and received either control vehicle or 1x106 iPSCECs or iECs, via intramuscular injection. Recovery of the ischaemic limb was tracked for 14 days. Laser Doppler imaging after femoral artery ligation revealed enhanced blood perfusion recovery in the iEC group vs. control at day 7 (p

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased sympathetic activity and hypertension in adults. We tested the hypothesis that children with OSA also have increased sympathetic activity as measured by overnight urinary catecholamines, and that this increase is related to the severity of OSA and to blood pressure (BP). METHODS: Seventy snoring children referred for assessment of sleep disordered breathing and 26 healthy non-snoring control children (age range: 3-12 years, 59 M/37 F) were studied. Overnight polysomnography was performed coincident with a 12h overnight urine collection. Urinary catecholamine levels were determined using high performance liquid chromatography (noradrenaline, adrenaline and dopamine, with levels adjusted for creatinine excretion). Simple linear and stepwise multiple linear regressions were used to determine the independent associations between catecholamine levels and age, gender, BMI z-score, systolic BP z-score, diastolic BP z-score, and apnea hypopnea index (AHI). RESULTS: Simple linear regressions revealed significant associations between noradrenaline and AHI (r = 0.32) and age (r = -0.20, p < 0.05 for both). Significant associations were also found between adrenaline and AHI (r = 0.27) and age (r = -0.25, p < 0.05 for both). Systolic BP z-score and diastolic z-score were both significantly associated with adrenaline (r = 0.22 and r = 0.20 respectively, p < 0.05 for both). Multivariate analysis revealed that only AHI was a significant independent predictor of noradrenaline (model R(2) = 0.10, p = 0.001). Similarly, only AHI and age were significant independent predictors of adrenaline (model R(2) = 0.12, p < 0.05). CONCLUSIONS: This study demonstrates that levels of overnight urinary noradrenaline and adrenaline are related to the severity of OSA in children. These data indicate that children with OSA have increased sympathetic tone that may contribute to the cardiovascular consequences of the condition.

Applanation tonometry evaluation of pulse wave velocity is widely accepted as the 'gold standard' method for noninvasively assessing arterial stiffness. Newer noninvasive tools such as cardiovascular magnetic resonance can also evaluate arterial stiffness, but have not been validated. The aim of this study was to validate cardiovascular magnetic resonance-derived aortic distensibility with pulse wave velocity and to investigate age-related changes in regional aortic distensibility.Ten young (20-30 years) and ten old (60-70 years) patients underwent applanation tonometry assessment of pulse wave velocity. Cardiovascular magnetic resonance measurements of arterial stiffness were evaluated by aortic distensibility (10-3 mmHg-1) at three separate locations, the ascending aorta, proximal descending aorta and distal descending aorta.Pulse wave velocity correlated strongly with aortic distensibility measurements at each site: ascending aorta R2 = 0.57, proximal descending aorta R2 = 0.60 and distal descending aorta R2 = 0.72. As expected, the old cohort had significantly increased aortic stiffness compared with the young cohort (P0.01). Post-hoc comparison showed an increase in proximal stiffness in the old cohort compared with the young cohort (P = 0.018).Cardiovascular magnetic resonance-derived aortic distensibility is an accurate measure of arterial stiffness and can evaluate regional stiffness through the aorta. Furthermore, our results suggest that aortic stiffening may preferentially occur in the proximal aortic segments in the elderly.

Percutaneous Transluminal Septal Myocardial Ablation (PTSMA) may reduce symptoms in patients with obstructive hypertrophic cardiomyopathy. Limited quantitative and qualitative data exists on the effects of PTSMA on the resting electrocardiograph. We report repolarisation and conduction abnormalities and incidence of arrhythmia post-PTSMA. Twelve-lead electrocardiographs from subjects without pre-procedural pacemakers who underwent successful procedures (37 procedures, mean age 61+/-14 years) were analysed for rhythm, heart rate, PR and QTc intervals, QRS duration and left or right bundle branch block (RBBB, LBBB). Four subjects developed permanent complete AV block, 19 subjects developed new RBBB and two subjects developed new LBBB pre-discharge. At a median follow-up of 34 (range 1-84) months, no new AV block, ventricular arrhythmias or deaths occurred. Post-PTSMA PR, QRS and QTc intervals lengthened (PR 180+/-33 ms, 204+/-40 ms, QRS 105+/-20 ms, 132+/-27 ms and QTc 454+/-32 ms, 491+/-37 ms (pre- and post-PTSMA respectively, all p=0.001). Predictors of permanent complete AV block included female gender (p=0.013), older age (p=0.013) and pre-existing LBBB (p

The aim of this study was to test the hypothesis that coronary artery disease extent and severity are associated with central aortic pressure waveform characteristics.Although it is thought that central aortic pressure waveform characteristics, particularly augmentation index, may influence cardiovascular disease progression and predict cardiovascular risk, little is known of the relationship between central waveform characteristics and the severity and extent of coronary artery disease.Central aortic waveforms (2F Millar pressure transducer-tipped catheters) were acquired at the time of coronary angiography for suspected native coronary artery disease in 40 patients (24 male). The severity and extent of disease were assessed independently by two observers using two previously described scoring systems (modified Gensini's stenosis and Sullivan's extent scores). Relationships between disease scores, aortic waveform characteristics, aorto-radial pulse wave velocity and subject demographic features were assessed by regression techniques.Both extent and severity scores were associated with increasing age and male sex (P0.001), but no other risk factors. Both scores were independently associated with aorto-radial pulse wave velocity (P0.001), which entered a multiple regression model prior to age and sex. This association was not dependent upon blood pressure. Neither score was associated with central aortic augmentation index, by either simple or multiple linear regression techniques including heart rate, subject demographic features and cardiovascular risk factors.Aorto-radial pulse wave velocity, but not central aortic augmentation index, is associated with both the extent and severity of coronary artery disease. This has potentially important implications for applicability of a generalized arterial transfer function.

Arterial transfer functions (TFs) describe the relationship between the pressure waveform at different arterial sites. Generalized TFs are used to reconstruct central aortic waveforms from non-invasively obtained peripheral waveforms and have been promoted as potentially clinically useful. A limitation is the paucity of information on their 'generalizability' with no information existing on the number of subjects required to construct a satisfactory TF, nor is adequate prospective validation available. We therefore investigated the uniformity of radial-aortic TFs and prospectively estimated the capacity of a generalized TF to reconstruct individual central blood pressure parameters.Ninety-three subjects (64 male) were studied by simultaneous radial applanation and high-fidelity (Millar Mikro-tip catheter) direct measurement of central aortic BP during elective coronary procedures. Subjects were prospectively randomized to either a derivation or validation group.Increasing numbers of individual TFs from the derivation group were averaged to form a generalized TF. There was minimal change with greater than 20 TFs averaged. In the validation group, the error in most reconstructed parameters related to the absolute value of the directly measured parameter [systolic blood pressure (SBP) and pulse pressure, P0.05; systolic pressure-time interval, subendocardial viability index, augmentation index, and times to the inflection point, peak and end systole, all P0.01]. Aorto-radial delay was related to error in reconstructed central aortic SBP and pulse pressure (negatively) and time to peak systole (positively) (all P0.001). Reconstruction of augmentation index was poor.Inclusion of more than 20 individual TFs in the construction of a generalized TF does not improve 'generalizability'. There appear to be systematic errors in derived central pressure waveforms and derived aortic augmentation index is inaccurate compared to the directly measured value.

To the Editor: We read with interest the report of the Conduit Artery Function Evaluation (CAFE) study1 showing a difference in SphygmoCor-derived central systolic blood pressure (SBP) between the 2 arms of an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy (despite similar brachial blood pressure changes). We would make 3 points. First, the authors seem to have misinterpreted our work (authors’ Reference 53)2 as showing a “precision” of 1 mm Hg between calculated central aortic and directly measured SBP in the context of noninvasive studies. This figure relates to …

The objective of this study was to investigate the determinants of aortic pressure waveform morphology in the thoracoabdominal aorta with specific reference to features of potential prognostic value for cardiovascular disease. In particular, we aimed to determine the location of major pressure wave reflection sites within the aorta. Aortic pressure waveforms were acquired with 2-Fr Millar Mikro-tip catheter transducers in 40 subjects (26 men, 14 women), and repeated in 10 subjects, at five predetermined points within the aorta: aortic root, transverse arch, and at the levels of the diaphragm, renal arteries, and aortic bifurcation. Waveforms were analyzed for augmentation index (AI), time to inflection point ( Ti), and pressure parameters. AI decreased progressively between the aortic root and bifurcation ( P < 0.001), and Ti increased ( P < 0.01). There was the expected progressive peripheral amplification of systolic and pulse pressures and fall in time to peak pressure (all P < 0.001). There was no difference on repeat pullback or between sexes. These data are at variance with the concept that central AI results solely from pressure wave reflection, when Ti would be expected to decrease and AI increase with distal progression. Pressure wave propagation phenomena may contribute, and the potential role of frequency dispersion merits investigation.

Transfer function techniques are increasingly used for non-invasive estimation of central aortic waveform characteristics. Non-invasive radial waveforms must be calibrated for this purpose. Most validation studies have used invasive pressures for calibration, with little data on the impact of non-invasive calibration on transfer-function-derived aortic waveform characteristics. In the present study, simultaneous invasive central aortic (Millar Mikro-tip® catheter transducer) and non-invasive radial (Millar® Mikro-tip® tonometer) pressure waveforms and non-invasive brachial pressures (Dinamap®) were measured in 42 subjects. In this cohort, radial waveforms were calibrated to both invasive and non-invasive mean and diastolic pressures. From each of these, central waveforms were reconstructed using a generalized transfer function obtained by us from a previous cohort [Hope, Tay, Meredith and Cameron (2002) Am. J. Physiol. Heart Circ. Physiol. 283, H1150–H1156]. Waveforms were analysed for parameters of potential clinical interest. For calibrated radial and reconstructed central waveforms, different methods of calibration were associated with differences in pressure (P

OBJECTIVE—Optimal blood pressure control in subjects with diabetes reduces cardiovascular complications. There is theoretical benefit in the assessment of central aortic waveforms including the augmentation index, which is taken as a putative index of stiffness. Transfer functions may be used to reconstruct aortic from radial pressure waveforms; however, a single generalized transfer function may not be appropriate for all patients. We aimed to evaluate the technique in subjects with diabetes. RESEARCH DESIGN AND METHODS—Simultaneous invasive central aortic and noninvasive radial waveforms were acquired in 19 subjects with type 2 diabetes, and a diabetes-specific transfer function was derived. Similar data were acquired from 38 age- and sex-matched subjects without diabetes. Central waveforms were reconstructed using a generalized transfer function in all patients and the diabetes-specific transfer function in individuals with diabetes. RESULTS—There was no difference between groups in measured central pressures. The error in generalized transfer function-derived systolic pressure was greater in individuals with diabetes (6 ± 7 mmHg) (mean ± SD) than without diabetes (2 ± 8 mmHg) (P < 0.05). Errors in other parameters were no different. The diabetes-specific transfer function reduced the error in derived systolic pressure to 0 ± 7 mmHg in individuals with diabetes—no different than that with the generalized transfer function in individuals without diabetes. The central augmentation index reconstructed by either transfer function was unrelated to that directly measured. CONCLUSIONS—A generalized transfer function is inappropriate for the derivation of central waveforms in subjects with type 2 diabetes. Errors in subjects with diabetes might be reduced with a diabetes-specific transfer function.

To the Editor: We read with interest the paper by Millasseau et al,1 which raises the question of whether the application of an arterial transfer function to noninvasively acquired radial artery pressure waveform data is necessary for the estimation of central aortic waveform characteristics. Although the conclusion that this approach offers no advantage over the simple analysis of untransformed radial artery pressure waveforms is valid, it should be remembered that the approach of these authors demonstrates only comparability and does not add to the debate as to whether arterial transfer function techniques enable accurate estimation of central aortic waveform parameters, because no directly measured central aortic waveforms were available for comparison. Our own findings, derived from noninvasive radial waveforms compared with directly measured central aortic waveforms, have demonstrated close relationships between several radial and measured central aortic waveform parameters proposed to be of potential clinical value, such as systolic and diastolic pressure time integrals.2,3 However, the radial artery augmentation index (AI) was unrelated to, or at best weakly correlated with, the …

We describe a young adult with an underlying diagnosis of pulmonary atresia with intact ventricular septum and Fontan physiology who presented with extreme dyspnoea on exertion. Coronary artery to right ventricular fistulae and reversible myocardial ischaemia secondary to a right ventricular steal phenomenon were present. The right coronary artery to right ventricular fistula was completely occluded with coils, by a transcoronary approach, with amelioration of symptoms. However, one coil embolised and lodged uneventfully in the left atrium during the procedure. This case demonstrates that a transcatheter approach may be successfully employed not only in patients with isolated coronary artery fistulae, but also in patients with coexistent complex congenital heart disease.

BACKGROUND Atherosclerosis is an inflammatory process in which adhesion molecules play an intimate role in both the initiation and progression of lesions. It is postulated that they also play a role in the presentation of acute coronary syndromes and that plasma levels thereafter may be of potential prognostic significance. The stability of sample levels under different laboratory conditions is unknown. METHODS Stability of plasma levels was assessed in six healthy subjects under four different laboratory conditions. The time course of levels was studied in 57 patients with acute chest pain, 21 of non-cardiac aetiology, 23 unstable angina and 13 acute myocardial infarction, at mean times of 2.3, 8.2 and 17.3 h after the onset of pain. Samples were assayed for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, E-selectin and C-reactive protein (CRP). RESULTS ICAM-1, VCAM-1, P-selectin and E-selectin levels did not differ under different laboratory conditions. Levels were similar at presentation in patients with acute chest pain of non-cardiac aetiology, unstable angina or acute myocardial infarction (median levels ICAM-1 269 microg/l, VCAM-1 379 microg/l, P-selectin 167 microg/l and E-selectin 53 microg/l). Levels did not change in the 24 h following the onset of pain. CRP levels did not differ at presentation between groups (median level 2.1 mg/l), but rose more than 12 h after the onset of pain in the group with acute myocardial infarction (P < 0.05). CONCLUSION Adhesion molecule levels are stable under normal laboratory sample handling conditions. Levels do not change in the 24 h following the onset of chest pain of non-cardiac or acute ischaemic aetiology.

Methods: Consecutive patients presenting with TTC over 14 months were evaluated. Putative myocardial inflammation was assessed acutely utilizing Technetium-99m (Tc-99m) pyrophosphate scintigraphy. We also assessed plasma CRP levels and platelet function: both aggregability and responsiveness to nitric oxide (NO). Results: Nine patients (eight women, one man; mean age 63± 11(S.D.) years) with TTC were investigated 1–7 days post-symptom onset. At acute imaging peri-apical myocardial Tc-99m pyrophosphate accumulation was increased in 6 patients. Mean CRP level was 44± 70mg/L. Mean adenosine 5′-diphosphate (2.5 mol/L)-induced platelet aggregation in whole blood (9.7± 2.7 ) was in the normal range (9.4± 2.8 ). However, response to the inhibitory effect of the NO donor sodium nitroprusside was diminished, in comparison with a normal referencegroup (25± 19%vs. 54± 24% inhibitionof aggregation, respectively) constituting platelet NO resistance. At a median follow up of 73 days, left ventricular wall motion had normalized in all cases. However, platelet NO response had normalized in only one patient. Conclusions: TTC is characterized by acute myocardial inflammatory activation and impairment of platelet response to NO, consistent with systemic redox stress. Intriguingly, in majority of the patients, platelet NO resistance persists after restoration of normal systolic function. Results: One hundred twenty-two cases have been performed (acute coronary syndromes and elective outpatients). Procedural success was 95% (116/122). There were no deaths or ST-elevation myocardial infarctions. There has been one retrieval to Sydney, which was for observation only. Groin complications were uncommon with 75% of patients receiving closure devices. There was one retroperitoneal bleed requiring blood transfusion and surgery (which was done locally). The utilisation of this service locally has improved access to PCI services for those patients unwilling or unable to travel to the city, and during times of transfer delay (particularly winter months). Conclusion: Elective and urgent PCI can be safely and effectively performed in a rural setting with careful planning and support. doi:10.1016/j.hlc.2008.05.214 214 Factors that Influence Patients’ Adherence to Medical Therapy Following Percutaneous Coronary Intervention Mary-Anne Austin ∗, Joshua Casan, Mauro Baldi, Ian Meredith, Sarah Hope MonashHeart, SouthernHealth,Melbourne, Victoria, Australia Background: Evidence based medical therapy followdoi:10.1016/j.hlc.2008.05.213 213 Percutaneous Coronary Interventions in a Rural Australian Hospital Without Surgical Backup: First Year’s Experience Jason Kaplan2,∗, David Amos2, Ruth Arnold2, Michael Ward5, Sidney Lo3, Craig Juergens3, Harry Lowe4, Mark Adams1, Ghasson Charbel 2 1 Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2 Orange Base Hospital, Orange, NSW, Australia; 3 Liverpool Hospital, Sydney, NSW, Australia; 4 Concord Hospital, Sydney, NSW, Australia; 5 Royal North Shore Hospital, Sydney, NSW, Australia Background: Elective and emergent percutaneous coronary intervention (PCI) have been shown to be safely and effectively provided in settings without surgical backup, however there is less experience in centres far remote from surgical centres. We aimed to assess the safety of this practice in a regional setting. Methods:OrangeBaseHospital is a 200bedruralbasehospital 3 h via road and 40min via helicopter from Sydney. Planning was done in close consultation with CSANZ and with the support of three major teaching hospitals. Staff training, patient care protocols and a formalized program for emergent transfer were developed with these centres. Interventionalists were all attached to large centres and agreed to exclude heavily calcified lesions and chronic total occlusions. Cases were selected with the aid of a web based angiogram viewer. ing Percutaneous Coronary Intervention (PCI) includes a range of medications. Data suggests that clinical and socioeconomic factors have a modest affect on adherence to prescribed therapy, whilst an individual’s beliefs pertaining to medication are more predictive. Is this relevant in an Australian tertiary hospital? Methods:Onehundred sixteenpatients from three indication groups (34% primary, 30% semi-urgent, 36% elective) were contacted 6 months following PCI. They described their social and clinical circumstances and answered the Medication Adherence Scale (MAS 0–4), with 86 completing the written Beliefs in Medication Questionnaire (BMQ—beliefs re harm, overuse, necessity and concerns regarding medications). Results: Discharge and 6 months medications were similar between indication groups. Demographic and risk factors were similar between groups, excepting lower rates of known Coronary Heart Disease (CHD) (P= 0.001), hypertension (P< 0.01) and hypercholesteremia (P< 0.05) and greater prevalence of current smoking (P< 0.05) in the primary PCI group. BMQ scores were similar to previously published data for cardiac patients, with no difference in BMQorMAS scores between groups. Thirtythree percentages of patients reported “forgetting to take medication”, and 13% reported “carelessness”. Social circumstances were not associated with MAS or BMQ scores. Patients with previously known CHD described greater belief in the necessity (BMQ) of cardiac medication (P< 0.01). Less adherent patients (MAS≥ 2) expressed greater concern (BMQ) regarding medications (P< 0.01). Conclusions: In this cohort demographic, social and clinical factorshadminimal impact on self-reportedadherence A B S T R A C T S Heart, Lung and Circulation Abstracts S91 2008;17S:S1–S209 rates. Medication beliefs may be amore reliable predictor of adherence. doi:10.1016/j.hlc.2008.05.215